Author Report for: Zhang XNo contact information in database for Zhang X
Guo B, Shen T, Liu Y, Jing J, Shao C, Zhang X Ref: Spectrochim Acta A Mol Biomol Spectrosc, 291:122389, 2023 : PubMed ESTHER: Guo_2023_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_291_122389 PubMedSearch: Guo 2023 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 291 122389 PubMedID: 36689909 Abstract Esterase is primarily distributed in the endoplasmic reticulum (ER) and often overexpressed in cancer cells. Therefore, the detection of esterase in ER is significant for monitoring the metabolic process of various esters and evaluating the efficacy of chemotherapeutic prodrugs. However, only few fluorescent probes can detect esterase in the ER due to the lack of ER-specificity. More seriously, these probes are often limited by low pearson's colocalization coefficient and one single wavelength emission. To solve those problems, an ER-specific ratiometric fluorescent probe (ER-EST) is designed for detecting esterase in living cells. The ER-EST shows a ratiometric and red-shifted emission (125snm) from 435 to 560snm after hydrolysis by esterase. The fluorescence intensity ratio of ER-EST displays quantitative response to the esterase activity (0-0.5 U/mL) with low detection limit of 1.8sxs10(-4) U/mL. Importantly, the ER-EST with good biocompatibility and excellent ER-targeted ability was successfully employed to ratiometric image the endogenous endoplasmic reticulum esterase in living cells. Title: Targeting ANGPTL3 by GalNAc-conjugated siRNA ANGsiR10 lowers blood lipids with long-lasting and potent efficacy in mice and monkeys Wang J, Zheng W, Zheng S, Yuan Y, Wen W, Cui W, Xue L, Sun X, Shang H and Zhang X <3 more author(s)> Wang J, Zheng W, Zheng S, Yuan Y, Wen W, Cui W, Xue L, Sun X, Shang H, Zhang H, Xiao RP, Gao S, Zhang X (- 3) Ref: Mol Ther Nucleic Acids, 31:68, 2023 : PubMed ESTHER: Wang_2023_Mol.Ther.Nucleic.Acids_31_68 PubMedSearch: Wang 2023 Mol.Ther.Nucleic.Acids 31 68 PubMedID: 36618267 Abstract Angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipoproteins by inhibiting both lipoprotein and endothelial lipases. It has been intensively investigated as a drug target for the treatment of dyslipidemia. In the present study, a modified small interfering RNA (siRNA) conjugated with GalNAc ANGsiR10 was characterized by insvivo and insvitro studies for its effect on ANGPTL3 silencing, the reduction of plasma triglycerides (TGs), and cholesterol levels in disease models. The results showed that ANGsiR10 displayed a significant and long-lasting efficacy in reducing blood TG and cholesterol levels in both mice and monkeys. Remarkably, the maximal reductions of plasma TG levels in the hApoC3-Tg mice, a model with high TG levels, and the spontaneous dyslipidemia model of rhesus monkey were 96.3% and 67.7%, respectively, after a single dose of ANGsiR10, with long-lasting effects up to 15sweeks. The cholesterol levels were also reduced in response to treatment, especially the non-HDL-c level, without altering the ApoA/ApoB ratio. This study showed that ANGsiR10 is effective in treating dyslipidemia and is worth further development. Title: Rosmarinic acid potentiates and detoxifies tacrine in combination for Alzheimer's disease Yang M, Zhang X, Qiao O, Ji H, Zhang Y, Han X, Wang W, Li X, Wang J and Gao W <2 more author(s)> Yang M, Zhang X, Qiao O, Ji H, Zhang Y, Han X, Wang W, Li X, Wang J, Guo L, Huang L, Gao W (- 2) Ref: Phytomedicine, 109:154600, 2023 : PubMed ESTHER: Yang_2023_Phytomedicine_109_154600 PubMedSearch: Yang 2023 Phytomedicine 109 154600 PubMedID: 36610144 Abstract BACKGROUND: There is no doubt that Alzheimer's disease (AD) is one of the greatest threats facing mankind today. Within the next few decades, Acetylcholinesterase inhibitors (AChEIs) will be the most widely used treatment for Alzheimer's disease. The withdrawal of the first generation AChEIs drug Tacrine (TAC)/ Cognex from the market as a result of hepatotoxicity has always been an interesting case study. Rosmarinic acid (RA) is a natural compound of phenolic acids that has pharmacological activity for inhibiting Alzheimer's disease, as well as liver protection. PURPOSE AND STUDY DESIGN: In this study, we determined that RA can reduce the hepatotoxicity of TAC, and both of them act synergistically to inhibit the progression of AD in mice. METHODS: In addition to the wild type mice (WT) group, the 6-month-old APP/PS1 (APPswe/PSEN1dE9) double-transgenic (Tg) mice were randomly divided into 6 groups: Tg group, TAC group, RA group, TAC+Silymarin (SIL) group, TAC+RA-L (Rosmarinic Acid Low Dose) goup and TAC+RA-H (Rosmarinic Acid High Dose) group. A series of experiments were carried out, including open field test, Morris water maze test, Hematoxylin - Eosin (HE) staining, Nissl staining, biochemical analysis, immunofluorescence analysis, western blotting analysis and so on. RESULTS: RA combined with TAC could enter the brain tissue of AD mice, and the combination of drugs could better improve the cognitive behavior and brain pathological damage of AD mice, reduce the expression of A beta oligomer, inhibit the deposition of A beta, inhibit the activity of AChE and enhance the level of Ach in hippocampus. Both in vivo and in vitro experiments showed that RA could alleviate the hepatotoxicity or liver injury induced by TAC. The Western blot analysis of the liver of AD mice showed that RA combined with TAC might inhibit the apoptosis of Bcl-2/Bax, reduce the programmed apoptosis mediated by caspase-3 and reduce the burden of liver induced by TAC, could inhibit the development of liver apoptosis by alleviating the hepatotoxicity of TAC and inhibiting the phosphorylation of JNK. CONCLUSION: The potential drug combination that combines rosmarinic acid with tacrine could reduce tacrine's hepatotoxicity as well as enhance its therapeutic effect on Alzheimer's disease. Title: A novel monoacylglycerol lipase-targeted (18)F-labeled probe for positron emission tomography imaging of brown adipose tissue in the energy network Cheng R, Fujinaga M, Yang J, Rong J, Haider A, Ogasawara D, Van RS, Shao T, Chen Z and Liang SH <14 more author(s)> Cheng R, Fujinaga M, Yang J, Rong J, Haider A, Ogasawara D, Van RS, Shao T, Chen Z, Zhang X, Calderon Leon ER, Zhang Y, Mori W, Kumata K, Yamasaki T, Xie L, Sun S, Wang L, Ran C, Shao Y, Cravatt B, Josephson L, Zhang MR, Liang SH (- 14) Ref: Acta Pharmacol Sin, :, 2022 : PubMed ESTHER: Cheng_2022_Acta.Pharmacol.Sin__ PubMedSearch: Cheng 2022 Acta.Pharmacol.Sin PubMedID: 35513432 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: FEPAD Abstract Monoacylglycerol lipase (MAGL) constitutes a serine hydrolase that orchestrates endocannabinoid homeostasis and exerts its function by catalyzing the degradation of 2-arachidonoylglycerol (2-AG) to arachidonic acid (AA). As such, selective inhibition of MAGL represents a potential therapeutic and diagnostic approach to various pathologies including neurodegenerative disorders, metabolic diseases and cancers. Based on a unique 4-piperidinyl azetidine diamide scaffold, we developed a reversible and peripheral-specific radiofluorinated MAGL PET ligand [(18)F]FEPAD. Pharmacokinetics and binding studies on [(18)F]FEPAD revealed its outstanding specificity and selectivity towards MAGL in brown adipose tissue (BAT) - a tissue that is known to be metabolically active. We employed [(18)F]FEPAD in PET studies to assess the abundancy of MAGL in BAT deposits of mice and found a remarkable degree of specific tracer binding in the BAT, which was confirmed by post-mortem tissue analysis. Given the negative regulation of endocannabinoids on the metabolic BAT activity, our study supports the concept that dysregulation of MAGL is likely linked to metabolic disorders. Further, we now provide a suitable imaging tool that allows non-invasive assessment of MAGL in BAT deposits, thereby paving the way for detailed mechanistic studies on the role of BAT in endocannabinoid system (ECS)-related pathologies. Title: Guaiane-type sesquiterpenoids with various ring skeletons from Daphne bholua uncovered by molecular networking and structural revisions of previously reported analogues Dong SH, Duan ZK, Ai YF, Zhou XF, Zhang X, Lian MY, Huang XX, Bai M, Song SJ Ref: Bioorg Chem, 129:106208, 2022 : PubMed ESTHER: Dong_2022_Bioorg.Chem_129_106208 PubMedSearch: Dong 2022 Bioorg.Chem 129 106208 PubMedID: 36272251 Abstract The genus Daphne is a treasure-house of secondary metabolites with various biological effects, which inspired Daphne bholua being fully investigated phytochemically and biologically for the first time. Here, seven undescribed guaiane-type sesquiterpenoids (1-7) along with thirteen known analogues (8-20) were targeted and isolated from D. bholua using molecular networking. Their chemical structure and configurations were established via NMR spectroscopy analysis, NMR and ECD calculations, Snatzke's method, along with single-crystal X-ray diffraction technique. Moreover, two pairs of sesquiterpene isomers, either with prominent biological properties or with unprecedented skeleton, were revised by means of computer-assisted structure elucidation, chemical shift calculator using deep learning, etc. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico. Title: Coumarins from Sarcandra glabra (Thunb.) Nakai and Acetylcholinesterase Inhibiting Activity Du NN, Bai M, Zhang X, Zhou L, Huang XX, Song SJ Ref: Chem Biodivers, :, 2022 : PubMed ESTHER: Du_2022_Chem.Biodivers__ PubMedSearch: Du 2022 Chem.Biodivers PubMedID: 36036517 Abstract Nine coumarins including a pair of new enantiomers ( 1a / 1b ) and seven known compounds ( 2-8 ) were isolated from Sarcandra glabra (Thunb.) Nakai. Among them, compounds 1a and 1b were naturally occurring coumarin-phenylpropanoid conjugate enantiomers. Their structures were identified by NMR and ECD calculations. Compounds 1-8 were tested for acetylcholinesterase (AchE) inhibiting activity. The results of the enzymology experiment showed that compound 3 demonstrated obvious AchE inhibitory activity which showed an IC 50 value of 1.982 +/- 0.003 micro M, and the binding sites were predicted by molecular docking. Title: Similarities and differences among the responses to three chlorinated organophosphate esters in earthworm: Evidences from biomarkers, transcriptomics and metabolomics Gao Y, Wang L, Zhang X, Shi C, Ma L, Wang G Ref: Sci Total Environ, 815:152853, 2022 : PubMed ESTHER: Gao_2022_Sci.Total.Environ_815_152853 PubMedSearch: Gao 2022 Sci.Total.Environ 815 152853 PubMedID: 34998776 Abstract The wide use of chlorinated organophosphate esters (Cl-OPEs) as additive flame retardants has aroused concern about their potential risks on ecosystem and human health. However, knowledge about the toxicity of Cl-OPEs on soil organisms remains limited. In this study, earthworms, Eisenia fetida, were exposed to three representative Cl-OPEs, i.e., tris(2-chloroethyl) phosphate (TCEP), tris(2-chloro-1-methylethyl) phosphate (TCPP), and tris(1,3-dichloro-2-propyl) phosphate (TDCPP) in artificial soil. Using a combination of biochemical indicators (biomarkers), transcriptomics, and metabolomics, we compared the Cl-OPE-induced toxicity to E. fetida and provide new insight into the related molecular mechanism. All three Cl-OPEs elicited immune defense by the earthworms, as evidenced by increased acid phosphatase and alkaline phosphatase activities, and the genes involved in immune-related pathways (e.g., lysosomal and interleukin-17 signaling pathways). Furthermore, no effects on acetylcholinesterase activity were observed among the three Cl-OPEs. However, the TCPP and TDCPP treatments significantly decreased the neurotransmitter serotonin, suggesting the potential neurotoxicity of Cl-OPEs. Although TCEP affected the genes involved in carbohydrate and amino acid metabolism, the changes in the corresponding metabolites were not statistically significant. In contrast, exposure to TCPP and TDCPP induced oxidative stress, and affected xenobiotic metabolism and energy metabolism, leading to the decreased body weight in E. fetida. Based on these toxic effects, TCPP and TDCPP were more severely toxic than TCEP, despite their structural similarity. Given that the use of TCEP has been tightly regulated, our results suggest the potentially toxic effects of TCPP and TDCPP should not be ignored in future risk assessments of flame retardants. Title: Synthesis and Biological Evaluation of Water-Soluble Esterase-Activated CO-Releasing Molecules Targeting Mitochondria Hemmersbach L, Schreiner Y, Zhang X, Dicke F, Hunemeyer L, Neudorfl JM, Fleming T, Yard B, Schmalz HG Ref: Chemistry, :, 2022 : PubMed ESTHER: Hemmersbach_2022_Chemistry__ PubMedSearch: Hemmersbach 2022 Chemistry PubMedID: 35771078 Abstract Due to the beneficial effects of carbon monoxide (CO) as a cell-protective and anti-inflammatory agent, CO-releasing molecules (CORMs) offer promising potential applications in medicine. We synthesized a set of acyloxy-cyclohexadiene-Fe(CO)3 complexes, all displaying a N-methyl-pyridinium triflate moiety in the ester side chain, as mitochondria-targeting esterase-triggered CORM prodrugs. While the compounds in which the acyloxy substituent is attached to the 2-position of the diene-Fe(CO)3 unit (A series) spontaneously release CO upon dissolution in phosphate buffer, which is partly suppressed in the presence of porcine liver esterase (PLE), the 1-substituted isomers (B series) show the expected PLE-induced release of CO (up to 3 equiv.). The biological activity of Mito-CORMs 2 / 3-B and their isophorone-derived analogs 2/3-A' was assessed using human umbilical vein endothelial cells (HUVEC). While Mito-CORMs 2/3-B were not cytotoxic up to 500 microM (MTT assay), Mito-CORMs 2/3-A' caused significant toxicity at concentrations above 50 microM. The anti-inflammatory potential of both Mito-CORM variants was demonstrated by concentration-dependent down-regulation of the pro-inflammatory markers as well as induction of HO-1 in TNFalpha stimulated HUVEC. Energy phenotyping by Seahorse Real-Time Cell Metabolic Analysis, revealed opposing shifts of metabolic potentials (mitochondrial respiration/glycolytic activity) in cells treated either with Mito-CORMs 2/3-B or Mito-CORMs 2/3-A'. Thus, the Mito-CORMs represent valuable tools for the safe and targeted delivery of CO to mitochondria as a subcellular compartment to induce anti-inflammatory effects with only minor shifts in cellular energy metabolism. Also, due to their water solubility, these compounds provide promising options for further pharmacological studies. Title: Identification and Comparative Genomic Analysis of Type VI Secretion Systems and Effectors in Klebsiella pneumoniae Li W, Liu X, Tsui W, Xu A, Li D, Zhang X, Li P, Bian X, Zhang J Ref: Front Microbiol, 13:853744, 2022 : PubMed ESTHER: Li_2022_Front.Microbiol_13_853744 PubMedSearch: Li 2022 Front.Microbiol 13 853744 PubMedID: 35633723 Abstract Klebsiella pneumoniae is a nosocomial opportunistic pathogen that can cause pneumonia, liver abscesses, and infections of the bloodstream. The resistance and pathogenicity of K. pneumoniae pose major challenges to clinical practice. However, the ecology and pathogenic mechanisms of K. pneumoniae have not been fully elucidated. Among these mechanisms, the secretion systems encoded by strains of the bacteria confer adaptive advantages depending on the niche occupied. The type VI secretion system (T6SS) is a multi-protein complex that delivers effector proteins to the extracellular environment or directly to eukaryotic or prokaryotic cells. T6SSs are widely distributed in Gram-negative bacteria and play an important role in bacterial virulence and the interactions between bacteria and other microorganisms or the environment. This study aimed to enhance the understanding of the characteristics of T6SSs in K. pneumoniae through an in-depth comparative genomic analysis of the T6SS in 241 sequenced strains of K. pneumoniae. We identified the T6SS loci, the synteny of the loci in different species, as well as the effectors and core T6SS-related genes in K. pneumoniae. The presence of a T6SS was a common occurrence in K. pneumoniae, and two T6SS clusters are the most prevalent. The variable region downstream of the gene vgrG usually encodes effector proteins. Conserved domain analysis indicated that the identified putative effectors in K. pneumoniae had the functions of lipase, ribonuclease, deoxyribonuclease, and polysaccharide hydrolase. However, some effectors did not contain predicted functional domains, and their specific functions have yet to be elucidated. This in silico study represents a detailed analysis of T6SS-associated genes in K. pneumoniae and provides a foundation for future studies on the mechanism(s) of T6SSs, especially effectors, which may generate new insights into pathogenicity and lead to the identification of proteins with novel antimicrobial properties. Title: Probiotic effect of ferulic acid esterase-producing Lactobacillus plantarum inoculated alfalfa silage on digestion, antioxidant, and immunity status of lactating dairy goats Li F, Zhang B, Zhang Y, Zhang X, Usman S, Ding Z, Hao L, Guo X Ref: Anim Nutr, 11:38, 2022 : PubMed ESTHER: Li_2022_Anim.Nutr_11_38 PubMedSearch: Li 2022 Anim.Nutr 11 38 PubMedID: 36091259 Abstract A feeding experiment was conducted to determine the effects of inoculating alfalfa silage with a ferulic acid esterase-producing inoculum on feed digestibility, rumen fermentation, antioxidant, and immunity status of lactating dairy goats. Twenty dairy goats were distributed into 2 experimental groups consisting of control diet (Lp MTD/1, including Lactobacillus plantarum MTD/1 inoculated silage) against diet containing silage treated with ferulic acid esterase-producing L. plantarum A1 (Lp A1). Alfalfa silage inoculated with a ferulic acid esterase-producing Lp A1 had better fermentation quality than the Lp MTD/1 inoculation. The application of Lp A1 improved silage antioxidant capacity as indicated by greater total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) activities in Lp A1 treated silage versus Lp MTD/1 treatment. Compared with Lp MTD/1 treated group, inoculation of silage with Lp A1 increased apparent total tract digestibility of dietary dry matter, organic matter and crude protein, and ruminal concentrations of total volatile fatty acids, acetate, propionate and isobutyrate as well. The results of current study also demonstrated improved antioxidant capacity and immune performance of dairy goats with Lp A1 inoculation. Feeding Lp A1-treated silage increased dairy goats' serum antioxidase activity, such as T-AOC, SOD, GSH-Px and catalase, and the serum concentration of immunoglobulin A, while decreased tumor necrosis factor alpha, interleukin (IL)-2 and IL-6. In addition, compared with Lp MTD/1, diet containing alfalfa silage inoculated with Lp A1 endowed dairy goats' milk with greater fat and protein contents, improved dairy goat milk quality without affecting feed efficiency. Title: The Aptamer Ob2, a novel AChE inhibitor, restores cognitive deficits and alleviates amyloidogenesis in 5FAD transgenic mice Liang Z, Li X, Luo X, Luo H, Chen Y, Cai M, Zhong X, Fang Y, Guo T and Zhang X <1 more author(s)> Liang Z, Li X, Luo X, Luo H, Chen Y, Cai M, Zhong X, Fang Y, Guo T, Shi Y, Zhang X (- 1) Ref: Mol Ther Nucleic Acids, 28:114, 2022 : PubMed ESTHER: Liang_2022_Mol.Ther.Nucleic.Acids_28_114 PubMedSearch: Liang 2022 Mol.Ther.Nucleic.Acids 28 114 PubMedID: 35402070 Abstract Loss of cerebral cholinergic neurons and decreased levels of acetylcholine (ACh) are considered to be major factors causing cognitive dysfunction in Alzheimer's disease (AD). Abnormally elevated levels of acetylcholinesterase (AChE) resulting in decreased levels of ACh are common in AD patients; thus, AChE inhibitors (AChEIs) are widely used for the treatment of AD. In our previous work, we acquired DNA aptamers Ob1, Ob2, and Ob3 against human brain AChE from systematic evolution of ligands by exponential enrichment (SELEX). In this study, we investigated the effect of these aptamers on learning and memory abilities, as well as the underlying mechanism in a 5xFAD transgenic AD mouse model. Here, we showed that only aptamer Ob2 exhibits a good inhibitory effect on both mouse and human AChE activity. In addition, chronic treatment with aptamer Ob2 significantly improved cognitive ability of 5xFAD mice in the Morris water maze. Moreover, the mechanism of aptamer Ob2 in 5xFAD mice may be associated with its inhibition of AChE activity, alleviation of the levels of Abeta by lowering the expression of beta-secretase (BACE1), and activation of astrocytes in the brains of 5xFAD mice. These results indicate that aptamer Ob2 exhibits potential as an effective AChEI for the treatment of AD. Title: Discovery of novel 3-butyl-6-benzyloxyphthalide Mannich base derivatives as multifunctional agents against Alzheimer's disease Liu Z, Shi Y, Zhang X, Yu G, Li J, Cong S, Deng Y Ref: Bioorganic & Medicinal Chemistry, 58:116660, 2022 : PubMed ESTHER: Liu_2022_Bioorg.Med.Chem_58_116660 PubMedSearch: Liu 2022 Bioorg.Med.Chem 58 116660 PubMedID: 35183029 Inhibitor(s) related to this paper: 3-butyl-6-benzyloxyphthalide-Mannich-base-7d Abstract Based on the multitarget-directed ligands strategy, a series of 3-butyl-6-benzyloxyphthalide Mannich base derivatives were designed, synthesized and identified for Alzheimer's disease (AD). Biological activity studies demonstrated that the designed hybrids showed multitarget activities toward AD. Among them, compound 7d was the most potent agent with excellent inhibitory activities on EeAChE (IC(50) = 0.087 microM), HuAChE (IC(50) = 0.041 microM) and MAO-B (IC(50) = 0.30 microM). Furthermore, molecular docking studies were conducted to investigate the interaction mode with enzymes. Besides, 7d also possessed good effects of Cu(2+) chelation, ameliorate oxidative stress, and anti-neuroinflammation, desirable BBB permeability and eligible drug-like properties. Altogether, the multifunctional profiles of 7d prove that it deserves further investigation as a novel drug candidate for AD treatment. Title: Insight into Isolation and Characterization of Phenolic Compounds from Hawthorn (Crataegus pinnatifida Bge.) with Antioxidant, Anti-Acetylcholinesterase, and Neuroprotective Activities Liu DF, Bai M, Du NN, Shen S, Li ZY, Zhang X, Guo R, Yao GD, Song SJ, Huang XX Ref: Plant Foods Hum Nutr, :, 2022 : PubMed ESTHER: Liu_2022_Plant.Foods.Hum.Nutr__ PubMedSearch: Liu 2022 Plant.Foods.Hum.Nutr PubMedID: 35986175 Abstract Recent epidemiologic studies have demonstrated a link between the consumption of daily functional fruits rich in phenols and the prevention of disease for neurodegenerative disorders. Hawthorn products are derived from the functional fruit hawthorn, which is rich in phenols and has been used around the world for centuries. In order to explore the phenolic components in hawthorn, the investigation of the ethanol extract led to the separation of five new phenol compounds (1a/1b, 2-4), including one pair of enantiomers (1a/1b), along with seven disclosed analogs (5-11). Their structures were elucidated based on extensive spectroscopic analyses and electronic circular dichroism (ECD). The compounds (1-11) were tested for antioxidant activities by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) (ABTS), and ferric reducing antioxidant power (FRAP) methods. Apart from that, monomeric compounds 2, 4, and 6 exhibited more potent protective capabilities against H(2)O(2) (hydrogen peroxide)-induced SH-SY5Y cells. Meanwhile, electronic analyses were performed using the highest occupied molecular orbital (HOMO), and the lowest unoccupied molecular orbital (LUMO) to analyze compounds 2, 4, and 6. Furthermore, compounds (1-11) measured acetylcholinesterase (AChE) inhibitory activities, and 2, 4, and 6 possessed greater AChE inhibitory activity than donepezil. At the same time, molecular docking was used to investigate the possible mechanism of the interaction between active compounds (2, 4, and 6) and AChE. Title: Molecular Mechanisms Underlying Metabolic Resistance to Cyflumetofen and Bifenthrin in Tetranychus urticae Koch on Cowpea Liu TT, Liu XT, Huang GL, Liu L, Chen QX, Wang Q, Liu P, Zheng Y, Yuan Y and Huang J <17 more author(s)> Liu TT, Liu XT, Huang GL, Liu L, Chen QX, Wang Q, Liu P, Zheng Y, Yuan Y, Zhang T, Li Q, Liang Q, Su T, Qi Q, Liu G, Meng X, Ren Y, Zhang M, Chen Z, Zhang Z, Pang X, Zhang X, Liu Z, Wu F, Liang W, Zhou L, Huang J (- 17) Ref: Int J Mol Sci, 23:, 2022 : PubMed ESTHER: Liu_2022_Int.J.Mol.Sci_23_ PubMedSearch: Liu 2022 Int.J.Mol.Sci 23 PubMedID: 35269668 36232310 36233017 36555861 Inhibitor(s) related to this paper: Caffeine Abstract Tetranychus urticae Koch (T. urticae) is one of the most tremendous herbivores due to its polyphagous characteristics, and is resistant to most acaricides. In this study, enzyme-linked immunosorbent assay (ELISA), transcriptome sequencing (RNA-seq) and quantitative real-time PCR (qRT-PCR) were carried out to analyze the mechanisms of T. urticae metabolic resistance to cyflumetofen and bifenthrin on cowpea. The enzyme activity of UDP-glucuronosyltransferases (UGTs) and carboxylesterases (CarEs) in the cyflumetofen-resistant (R_cfm) strain significantly decreased, while that of cytochrome P450 monooxygenases (P450s) significantly increased. Meanwhile, the activities of glutathione-S-transferases (GSTs), CarEs and P450s in the bifenthrin-resistant (R_bft) strain were significantly higher than those in the susceptible strain (Lab_SS). According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses, in the R_cfm mite strain, two carboxyl/cholinesterase (CCE) genes and two P450 genes were upregulated and one gene was downregulated, namely CYP392E7; in the R_bft mite strain, eleven CCE, nine UGT, two P450, four GST and three ABC genes were upregulated, while four CCE and three P450 genes were downregulated. Additionally, 94 differentially expressed genes (DEGs) were common to the two resistant groups. Specifically, TuCCE46 and TuCCE70 were upregulated in both resistant groups. Furthermore, the qRT-PCR validation data were consistent with those from the transcriptome sequencing analysis. Specifically, TuCCE46 (3.37-fold) was significantly upregulated in the R_cfm strain, while in the R_bft strain, TeturUGT22 (5.29-fold), teturUGT58p (1.74-fold), CYP392A11 (2.89-fold) and TuGSTd15 (5.12-fold) were significantly upregulated and TuCCE01 (0.13-fold) and CYP392A2p (0.07-fold) were significantly downregulated. Our study indicates that TuCCE46 might play the most important role in resistance to cyflumetofen, and TuCCE01, teturUGT58p, teturUGT22, CYP392A11, TuGSTd15, TuGSTm09 and TuABCG-13 were prominent in the resistance to bifenthrin. These findings provide further insight into the critical genes involved in the metabolic resistance of T. urticae to cyflumetofen and bifenthrin. Title: Synthesis, Characterization and Biological Evaluation of Benzothiazole-Isoquinoline Derivative Liu C, Guan S, E J, Yang Z, Zhang X, Ju J, Wang S, Zhang H, Liu W and Guan L <6 more author(s)> Liu C, Guan S, E J, Yang Z, Zhang X, Ju J, Wang S, Zhang H, Liu W, Zhao D, He Z, Hu Y, Zhu Y, Zhang L, Jin L, Guan L (- 6) Ref: Molecules, 27:, 2022 : PubMed ESTHER: Liu_2022_Molecules_27_ PubMedSearch: Liu 2022 Molecules 27 PubMedID: 36364337 36558194 Abstract Currently, no suitable clinical drugs are available for patients with neurodegenerative diseases complicated by depression. Based on a fusion technique to create effective multi-target-directed ligands (MTDLs), we synthesized a series of (R)-N-(benzo[d]thiazol-2-yl)-2-(1-phenyl-3,4-dihydroisoquinolin-2(1H)-yl) acetamides with substituted benzothiazoles and (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline. All compounds were tested for their inhibitory potency against monoamine oxidase (MAO) and cholinesterase (ChE) by in vitro enzyme activity assays, and further tested for their specific inhibitory potency against monoamine oxidase B (MAO-B) and butyrylcholinesterase (BuChE). Among them, six compounds (4b-4d, 4f, 4g and 4i) displayed excellent activity. The classical antidepressant forced swim test (FST) was used to verify the in vitro results, revealing that six compounds reduced the immobility time significantly, especially compound 4g. The cytotoxicity of the compounds was assessed by the MTT method and Acridine Orange (AO) staining, with cell viability found to be above 90% at effective compound concentrations, and not toxic to L929 cells reversibility, kinetics and molecular docking studies were also performed using compound 4g, which showed the highest MAO-B and BuChE inhibitory activities. The results of these studies showed that compound 4g binds to the primary interaction sites of both enzymes and has good blood-brain barrier (BBB) penetration. This study provides new strategies for future research on neurodegenerative diseases complicated by depression. Title: Dwarf and High Tillering1 represses rice tillering through mediating the splicing of D14 pre-mRNA Liu T, Zhang X, Zhang H, Cheng Z, Liu J, Zhou C, Luo S, Luo W, Li S and Wan J <12 more author(s)> Liu T, Zhang X, Zhang H, Cheng Z, Liu J, Zhou C, Luo S, Luo W, Li S, Xing X, Chang Y, Shi C, Ren Y, Zhu S, Lei C, Guo X, Wang J, Zhao Z, Wang H, Zhai H, Lin Q, Wan J (- 12) Ref: Plant Cell, 34:3301, 2022 : PubMed ESTHER: Liu_2022_Plant.Cell_34_3301 PubMedSearch: Liu 2022 Plant.Cell 34 3301 PubMedID: 35670739 Abstract Strigolactones (SLs) constitute a class of plant hormones that regulate many aspects of plant development, including repressing tillering in rice (Oryza sativa). However, how SL pathways are regulated is still poorly understood. Here, we describe a rice mutant dwarf and high tillering1 (dht1), which exhibits pleiotropic phenotypes (such as dwarfism and increased tiller numbers) similar to those of mutants defective in SL signaling. We show that DHT1 encodes a monocotyledon-specific hnRNP-like protein that acts as a previously unrecognized intron splicing factor for many precursor mRNAs (pre-mRNAs), including for the SL receptor gene D14. We find that the dht1 (DHT1I232F) mutant protein is impaired in its stability and RNA binding activity, causing defective splicing of D14 pre-mRNA and reduced D14 expression, and consequently leading to the SL signaling-defective phenotypes. Overall, our findings deepen our understanding of the functional diversification of hnRNP-like proteins and establish a connection between posttranscriptional splicing and SL signaling in the regulation of plant development. Title: Identification of novel immune-related targets mediating disease progression in acute pancreatitis Liu Q, Li L, Xu D, Zhu J, Huang Z, Yang J, Cheng S, Gu Y, Zheng L and Shen H <1 more author(s)> Liu Q, Li L, Xu D, Zhu J, Huang Z, Yang J, Cheng S, Gu Y, Zheng L, Zhang X, Shen H (- 1) Ref: Front Cell Infect Microbiol, 12:1052466, 2022 : PubMed ESTHER: Liu_2022_Front.Cell.Infect.Microbiol_12_1052466 PubMedSearch: Liu 2022 Front.Cell.Infect.Microbiol 12 1052466 PubMedID: 36590588 Abstract INTRODUCTION: Acute pancreatitis (AP) is an inflammatory disease with very poor outcomes. However, the order of induction and coordinated interactions of systemic inflammatory response syndrome (SIRS) and compensatory anti-inflammatory response syndrome (CARS) and the potential mechanisms in AP are still unclear. METHODS: An integrative analysis was performed based on transcripts of blood from patients with different severity levels of AP (GSE194331), as well as impaired lung (GSE151572), liver (GSE151927) and pancreas (GSE65146) samples from an AP experimental model to identify inflammatory signals and immune response-associated susceptibility genes. An AP animal model was established in wild-type (WT) mice and Tlr2-deficient mice by repeated intraperitoneal injection of cerulein. Serum lipase and amylase, pancreas impairment and neutrophil infiltration were evaluated to assess the effects of Tlr2 in vivo. RESULTS: The numbers of anti-inflammatory response-related cells, such as M2 macrophages (P = 3.2 x 10(-3)), were increased with worsening AP progression, while the numbers of pro-inflammatory response-related cells, such as neutrophils (P = 3.0 x 10(-8)), also increased. Then, 10 immune-related AP susceptibility genes (SOSC3, ITGAM, CAMP, FPR1, IL1R1, TLR2, S100A8/9, HK3 and MMP9) were identified. Finally, compared with WT mice, Tlr2-deficient mice exhibited not only significantly reduced serum lipase and amylase levels after cerulein induction but also alleviated pancreatic inflammation and neutrophil accumulation. DISCUSSION: In summary, we discovered SIRS and CARS were stimulated in parallel, not activated consecutively. In addition, among the novel susceptibility genes, TLR2might be a novel therapeutic target that mediates dysregulation of inflammatory responses during AP progression. Title: The Chemical Composition Characteristics and Health Risk Assessment of Cooking Fume Condensates from Residential Kitchens in Different Regions of China Liu Q, Zhang X, Yang Y, Tang Q, Zheng L, Lou H, Chen H, Yang Q Ref: Foods, 12:, 2022 : PubMed ESTHER: Liu_2022_Foods_12_ PubMedSearch: Liu 2022 Foods 12 PubMedID: 36613322 Abstract The aim of this study was to explore the similarities and differences of volatile organic pollutants (VOCs) in cooking fumes (COF) of residential buildings in different regions of China, as well as to evaluate their potential health risks. COF condensates were collected from 10 representative cities in China and analyzed by a GC-MS method. Their effects on alpha-glucosidase, acetylcholinesterase (AchE), and lactate dehydrogenase (LDH) activities were then detected to evaluate potential health risks. A total of 174 kinds of VOCs, including aldehydes, esters, hydrocarbons, alcohols, and carboxylic acid, were identified. There were 59 identical compounds in the northern and southern regions, and 56 common compounds in spicy and non-spicy regions. Health risk assessment results showed that COF condensate could inhibit the activity of alpha-glucosidase to varying degrees (61.73-129.25%), suggesting that it had a potential risk of causing hypoglycemia. Daily and 3 and 6 month intakes of COF in minors, adults, and the elderly had both activated and inhibited effects on AchE. The activated effect in the southern and spicy areas was higher than that in northern and non-spicy areas, revealing that different regions and dietary habits had different effects on the risk of neurological diseases caused by changes in AchE activity. For minors, adults, and the elderly, COF had different degrees of activation of LDH at different exposure times and regions. Activation in the northern and non-spicy areas was higher than that in southern and spicy areas, suggesting that the health risks caused by changes in LDH activity levels were significantly increased. Title: Formation of thyroid hormone revealed by a cryo-EM structure of native bovine thyroglobulin Marechal N, Serrano BP, Zhang X, Weitz CJ Ref: Nat Commun, 13:2380, 2022 : PubMed ESTHER: Marechal_2022_Nat.Commun_13_2380 PubMedSearch: Marechal 2022 Nat.Commun 13 2380 PubMedID: 35501346 Gene_locus related to this paper: bovin-thyro Abstract Thyroid hormones are essential regulators of metabolism, development, and growth. They are formed from pairs of iodinated tyrosine residues within the precursor thyroglobulin (TG), a 660-kDa homodimer of the thyroid gland, by an oxidative coupling reaction. Tyrosine pairs that give rise to thyroid hormones have been assigned within the structure of human TG, but the process of hormone formation is poorly understood. Here we report a ~3.3-A cryo-EM structure of native bovine TG with nascent thyroid hormone formed at one of the predicted hormonogenic sites. Local structural rearrangements provide insight into mechanisms underlying thyroid hormone formation and stabilization. Title: Bladder epithelial cell phosphate transporter inhibition protects mice against uropathogenic Escherichia coli infection Pang Y, Cheng Z, Zhang S, Li S, Li X, Zhang X, Feng Y, Cui H, Chen Z and Feng L <6 more author(s)> Pang Y, Cheng Z, Zhang S, Li S, Li X, Zhang X, Feng Y, Cui H, Chen Z, Liu L, Li Q, Huang J, Zhang M, Zhu S, Wang L, Feng L (- 6) Ref: Cell Rep, 39:110698, 2022 : PubMed ESTHER: Pang_2022_Cell.Rep_39_110698 PubMedSearch: Pang 2022 Cell.Rep 39 110698 PubMedID: 35443182 Abstract Urinary tract infections are predominantly caused by uropathogenic Escherichia coli (UPEC). UPEC infects bladder epithelial cells (BECs) via fusiform vesicles, escapes into the cytosol to evade exocytosis, and establishes intracellular bacterial communities (IBCs) for the next round of infection. The UPEC vesicle escape mechanism remains unclear. Here we show that UPEC senses host immune responses and initiates escape by upregulating a key phospholipase. The UPEC phospholipase PldA disrupts the vesicle membrane, and pldA expression is activated by phosphate reduction in vesicles. The host phosphate transporter PIT1 is located on the fusiform vesicle membrane, transporting phosphate into the cytosol. UPEC infection upregulates PIT1 via nuclear factor kappaB (NF-kappaB), resulting in phosphate reduction. Silencing PIT1 blocks UPEC vesicle escape in BECs, inhibits IBC formation in mouse bladders, and protects mice from UPEC infection. Our results shed light on pathogenic bacteria responding to intracellular phosphate shortage and tackling host defense and provide insights for development of new therapeutic agents to treat UPEC infection. Title: Tanshinone IIA regulates glycogen synthase kinase-3beta-related signaling pathway and ameliorates memory impairment in APP/PS1 transgenic mice Peng X, Chen L, Wang Z, He Y, Ruganzu JB, Guo H, Zhang X, Ji S, Zheng L, Yang W Ref: European Journal of Pharmacology, :174772, 2022 : PubMed ESTHER: Peng_2022_Eur.J.Pharmacol__174772 PubMedSearch: Peng 2022 Eur.J.Pharmacol 174772 PubMedID: 35090935 Inhibitor(s) related to this paper: Tanshinone-IIA Abstract Our previous findings indicated that tanshinone IIA (tan IIA), a natural component extracted from the root and rhizome of danshen, significantly attenuated beta-amyloid accumulation, neuroinflammation, and endoplasmic reticulum stress, as well as improved learning and memory deficits in APP/PS1 transgenic mouse model of Alzheimer's disease (AD). However, whether tan IIA can ameliorate tau pathology and the underlying mechanism in APP/PS1 mice remains unclear. In the current study, tan IIA (15 mg/kg and 30 mg/kg) or saline was intraperitoneally administered to the 5-month-old APP/PS1 mice once daily for 4 weeks. The open-field test, novel object recognition test, Y-maze test, and Morris water maze test were performed to assess the cognitive function. Nissl staining, immunohistochemistry, TUNEL, and western blotting were conducted to explore tau hyperphosphorylation, neuronal injury, and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt)/glycogen synthase kinase-3beta (GSK-3beta) signaling pathway. The activity of GSK-3beta, acetylcholinesterase (AChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px), and the level of malondialdehyde (MDA) were measured using commercial kits. Our results revealed that tan IIA treatment significantly ameliorated behavioral deficits and improved spatial learning and memory ability of APP/PS1 mice. Additionally, tan IIA markedly attenuated tau hyperphosphorylation and prevented neuronal loss and apoptosis in the parietal cortex and hippocampus. Simultaneously, tan IIA reversed cholinergic dysfunction and reduced oxidative stress. Furthermore, tan IIA activated the PI3K/Akt signaling pathway and suppressed GSK-3beta. Taken together, the above findings suggested that tan IIA improves cognitive decline and tau pathology may through modulation of PI3K/Akt/GSK-3beta signaling pathway. Title: The Relationship between Intracarotid Plaque Neovascularization and Lp (a) and Lp-PLA2 in Elderly Patients with Carotid Plaque Stenosis Sun C, Xi N, Sun Z, Zhang X, Wang X, Cao H, Jia X Ref: Dis Markers, 2022:6154675, 2022 : PubMed ESTHER: Sun_2022_Dis.Markers_2022_6154675 PubMedSearch: Sun 2022 Dis.Markers 2022 6154675 PubMedID: 35493296 Abstract The aim of this study was to investigate the relationship between carotid plaque neovascularization and lipoprotein (a) [Lp (a)], lipoprotein-associated phospholipase A2 (Lp-PLA2) in elderly patients with carotid plaque stenosis. One hundred elderly patients with carotid plaque stenosis diagnosed in our hospital from January 2020 to January 2022 were retrospectively analyzed and divided into stable (n = 62) and unstable (n = 38) groups according to whether the plaque was stable or not. Plasma Lp (a), Lp-PLA2, apoA, and apoB levels were measured; intraplaque angiogenesis (IPN) scores were examined by contrast-enhanced ultrasound (CEUS) to assess IPN grade in patients; and Pearson correlation was used to analyze the relationship between plasma Lp (a) and Lp-PLA2 levels and plaque characteristics and angiogenesis. The maximum thickness and total thickness of carotid plaque in the unstable group were significantly greater than those in the stable group (P < 0.05); the IPN grade was mainly grade III and IV in the unstable group and grade II in the stable group, and the IPN score was significantly higher in the unstable group than in the stable group (P < 0.05); there was no significant difference in the plasma apoA and apoB levels between the two groups (P > 0.05), and the plasma Lp (a) and Lp-PLA2 levels were significantly higher in the unstable group than in the stable group (P < 0.05); the neovascular grade, plasma Lp-PLA2, and Lp (a) levels were significantly increased (P < 0.05); the plasma Lp (a) and Lp-PLA2 levels were positively correlated with the maximum plaque thickness, total plaque thickness, degree of stenosis, and angiogenesis (P < 0.05). The plasma levels of Lp (a) and Lp-PLA2 are positively correlated with intraplaque angiogenesis, and their levels can reflect the stability of carotid plaques. Title: Improving Effect of the Policosanol from Ericerus pela Wax on Learning and Memory Impairment Caused by Scopolamine in Mice Sun L, Li X, Ma C, He Z, Zhang X, Wang C, Zhao M, Gan J, Feng Y Ref: Foods, 11:, 2022 : PubMed ESTHER: Sun_2022_Foods_11_ PubMedSearch: Sun 2022 Foods 11 PubMedID: 35885338 Abstract Policosanol (PC) is a mixture of long-chain fatty alcohols that exhibits multiple biological activities, such as reducing blood lipid and cholesterol levels, lowering blood pressure, and extenuating liver inflammation. To assess PC's impact on cognitive behavior and function, PC was prepared from Ericerus pela wax using a reduction method and analyzed using gas chromatography (GC). A total of 60 mice were randomly divided into six groups of 10 animals each: control (0.5% CMC-Na solution, i.g.), model (0.5% CMC-Na solution, i.g.), donepezil (3 mg/kg, i.g.), PC low- (2 g/kg, i.g.), medium (4 g/kg, i.g.), and high- (6 g/kg, i.g.) dose groups. All the groups were administered daily for 28 consecutive days. There were four parameters-escape latency, crossings of platform, swimming distance, and time spent in the target quadrant-that were recorded to evaluate the cognitive performance of mice in the Morris Water Maze (MWM). After MWM testing, the levels of acetylcholine (ACh), acetylcholinesterase (AChE), superoxide dismutase (SOD), malondialdehyde (MDA), and glutathione (GSH) that were present in brain tissue were determined using assay kits. The GC data showed that PC consisted of four major components: tetracosanol (14.40%), hexacosanol (48.97%), octacosanol (25.40%), and triacontanol (4.80%). In the MWM test, PC significantly decreased the escape latency (p < 0.05) and increased the crossings of the platform (p < 0.05) and swimming distance (p < 0.05) and time in the target quadrant (p < 0.05) in rodents compared to that in the model group. Moreover, PC increased the levels of ACh, SOD, and GSH; inhibited AChE; and reduced MDA in the brain tissue of the tested animals. This is the first report to evaluate the efficacy of PC for cognitive behavior and function in animals. Our findings demonstrate that PC from E. pela wax is likely to exert an enhancing effect on learning and memory by promoting the cholinergic system and attenuating oxidative stress, which will provide a new insight into the efficacy of PC and expand its application in the food, nutraceutical, and beverage industries. Title: Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K and Qian Z <1 more author(s)> Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K, Zhu E, Qian Z (- 1) Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Wang_2022_Anal.Chem__ PubMedSearch: Wang 2022 Anal.Chem PubMedID: 35315662 Abstract Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca(2+) by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells. Title: Impact of AADAC gene expression on prognosis in patients with Borrmann type III advanced gastric cancer Wang Y, Fang T, Yin X, Zhang L, Zhang X, Zhang D, Zhang Y, Wang X, Wang H, Xue Y Ref: BMC Cancer, 22:635, 2022 : PubMed ESTHER: Wang_2022_BMC.Cancer_22_635 PubMedSearch: Wang 2022 BMC.Cancer 22 635 PubMedID: 35681154 Gene_locus related to this paper: human-AADAC Abstract BACKGROUND: The prognosis of Borrmann type III advanced gastric cancer (AGC) is known to vary significantly among patients. This study aimed to determine which differentially expressed genes (DEGs) are directly related to the survival time of Borrmann type III AGC patients and to construct a prognostic model. METHODS: We selected 25 patients with Borrmann type III AGC who underwent radical gastrectomy. According to the difference in overall survival (OS), the patients were divided into group A (OS<1 year, n=11) and group B (OS>3 years, n=14). DEGs related to survival time in patients with Borrmann type III AGC were determined by mRNA sequencing. The prognosis and functional differences of DEGs in different populations were determined by The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases. The expression of mRNA and protein in cell lines was detected by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) and Western blot (WB). Immunohistochemical (IHC) staining was used to detect protein expression in the paraffin-embedded tissues of 152 patients with Borrmann type III AGC who underwent radical gastrectomy. After survival analysis, nomograms were constructed to predict the prognosis of patients with Borrmann type III AGC. RESULTS: Arylacetamide deacetylase (AADAC) is a survival-related DEG in patients with Borrmann type III AGC. The higher the expression level of its mRNA and protein is, the better the prognosis of patients. Bioinformatics analysis found that AADAC showed significant differences in prognosis and function in European and American populations and Asian populations. In addition, the mRNA and protein expression levels of AADAC were high in differentiated gastric cancer (GC) cells. We also found that AADAC was an independent prognostic factor for patients with Borrmann type III AGC, and its high expression was significantly correlated with better OS and disease-free survival (DFS). Nomogram models of AADAC expression level combined with clinicopathological features can be used to predict the OS and DFS of Borrmann type III AGC. CONCLUSION: AADAC can be used as a biomarker to predict the prognosis of Borrmann type III AGC and has the potential to become a new therapeutic target for GC. Title: From Function to Metabolome: Metabolomic Analysis Reveals the Effect of Probiotic Fermentation on the Chemical Compositions and Biological Activities of Perilla frutescens Leaves Wang Z, Jin X, Zhang X, Xie X, Tu Z, He X Ref: Front Nutr, 9:933193, 2022 : PubMed ESTHER: Wang_2022_Front.Nutr_9_933193 PubMedSearch: Wang 2022 Front.Nutr 9 933193 PubMedID: 35898707 Abstract This study aimed to investigate the impact of probiotic fermentation on the active components and functions of Perilla frutescens leaves (PFL). PFL was fermented for 7 days using six probiotics (Lactobacillus Plantarum SWFU D16, Lactobacillus Plantarum ATCC 8014, Lactobacillus Rhamnosus ATCC 53013, Streptococcus Thermophilus CICC 6038, Lactobacillus Casei ATCC 334, and Lactobacillus Bulgaricus CICC 6045). The total phenol and flavonoid contents, antioxidant abilities, as well as alpha-glucosidase and acetylcholinesterase inhibition abilities of PFL during the fermentation process were evaluated, and its bioactive compounds were further quantified by high-performance liquid chromatography (HPLC). Finally, non-targeted ultra-HPLC-tandem mass spectroscopy was used to identify the metabolites affected by fermentation and explore the possible mechanisms of the action of fermentation. The results showed that most of the active component contents and functional activities of PFL exhibited that it first increased and then decreased, and different probiotics had clearly distinguishable effects from each other, of which fermentation with ATCC 53013 for 1 day showed the highest enhancement effect. The same trend was also confirmed by the result of the changes in the contents of 12 phenolic acids and flavonoids by HPLC analysis. Further metabolomic analysis revealed significant metabolite changes under the best fermentation condition, which involved primarily the generation of fatty acids and their conjugates, flavonoids. A total of 574 and 387 metabolites were identified in positive ion and negative ion modes, respectively. Results of Spearman's analysis indicated that some primary metabolites and secondary metabolites such as flavonoids, phenols, and fatty acids might play an important role in the functional activity of PFL. Differential metabolites were subjected to the KEGG database and 97 metabolites pathways were obtained, of which biosyntheses of unsaturated fatty acids, flavonoid, and isoflavonoid were the most enriched pathways. The above results revealed the potential reason for the differences in metabolic and functional levels of PFL after fermentation. This study could provide a scientific basis for the further study of PFL, as well as novel insights into the action mechanism of probiotic fermentation on the chemical composition and biological activity of food/drug. Title: Design, Synthesis, Calculation and Biological Activity Studies Based on Privileged Coumarin Derivatives as Multifunctional Anti-AD Lead Compound Wang H, Su M, Shi X, Li X, Zhang X, Yang A, Shen R Ref: Chem Biodivers, :, 2022 : PubMed ESTHER: Wang_2022_Chem.Biodivers__ PubMedSearch: Wang 2022 Chem.Biodivers PubMedID: 36461922 Abstract Coumarins and their derivatives possessed a variety of biological activities and some of coumarin-based drugs have been approved by the US Food and Drug Administration. Alzheimer's disease (AD) has caused great losses to human society. However, due to its complex pathogenesis, the ideal therapeutic approach has not been found yet. Free radical scavenging activity which is one of the main activities of coumarin core structure is closely related to other anti-AD activities. Therefore, in this work coumarins was chosen as privileged lead compounds for the development of anti-AD drugs based on strategy of multi-target directed ligands (MTDLs). Derivatives 1-3 which could modulate multiple targets simultaneously, including ROS, cholinesterase, beta amyloid (Abeta) aggregation, and metal ions were designed and for the first time synthesized. Their anti-AD activities were studied both in vitro and in silico. Results showed that 1-3 possessed potent antioxidant activities and 7-OH group did change the electron distribution of the molecule and enhance the antioxidant activities. They also have good inhibition activities on acetylcholinesterase (AChE) and Abeta aggregation and compound 1 had the strongest AChE inhibitory effect among the three compounds (AChE IC 50 =11.15 microM). Compound 1-3 could also selectively chelate with Cu 2+ and Al 3+ to regulate the metal homeostasis. In silico simulations, including molecular docking and prediction of ADMET performance, indicated that 1-3 could interact with target proteins and cross the blood brain barrier. In conclusion, 1-3 could be promising MTDLs applied as anti-AD candidate drugs. Title: Discovery of Novel Non-Oxime Reactivators Showing In Vivo Antidotal Efficiency for Sarin Poisoned Mice Wei Z, Zhang X, Nie H, Yao L, Liu Y, Zheng Z, Ouyang Q Ref: Molecules, 27:, 2022 : PubMed ESTHER: Wei_2022_Molecules_27_ PubMedSearch: Wei 2022 Molecules 27 PubMedID: 35164361 Abstract A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imidazole to the ortho position of phenols would dramatically enhance reactivation efficiency. Moreover, the in vivo experiment was conducted, and the results demonstrated that Mannich phenol L10R1 (30 mg/kg, ip) could afford 100% 48 h survival for mice of 2*LD(50) sarin exposure, which is promising for the development of non-oxime reactivators with central efficiency. Title: Lethal and Sublethal Toxicity Assessment of Cyclosporin C (a Fungal Toxin) against Plutella xylostella (L.) Wu J, Zhang X, Bashir MH, Ali S Ref: Toxins (Basel), 14:, 2022 : PubMed ESTHER: Wu_2022_Toxins.(Basel)_14_ PubMedSearch: Wu 2022 Toxins.(Basel) 14 PubMedID: 36006176 Abstract Secondary metabolites/toxins produced by Purpeocillium lilacinum (Hypocreales; Phiocordycipitaceae), a well-known insect pathogen, can be used for the management of different insect pests. We report the lethal and sublethal effects of cyclosporin C (a toxin produced by P. lilacinum) against a major vegetable pest, Plutella xylostella, at specific organismal (feeding rate, larval growth, adult emergence, fecundity, and adult longevity) and sub-organismal levels (changes in antioxidant and neurophysiological enzyme activities). The toxicity of cyclosporin C against different larval instars of P. xylostella increased with increasing concentrations of the toxin and the maximum percent mortality rates for different P. xylostella larval instars at different times were observed for the 300 microg/mL cyclosporin C treatment, with an average mortality rate of 100% for all larval instars. The median lethal concentrations (LC(50)) of cyclosporin C against the first, second, third, and fourth larval instars of P. xylostella 72 h post-treatment were 78.05, 60.42, 50.83, and 83.05 microg/mL, respectively. Different concentrations of cyclosporin C caused a reduction in the average leaf consumption and average larval weight. Different life history parameters, such as the pupation rate (%), adult emergence (%), female fecundity, and female longevity were also inhibited when different concentrations of cyclosporin C were applied topically. The cyclosporin C concentrations inhibited the activities of different detoxifying (glutathione S-transferase, carboxylesterase, and acetylcholinesterase) and antioxidant enzyme (superoxide dismutase, catalase, and peroxidase) activities of P. xylostella when compared to the control. These findings can serve as baseline information for the development of cyclosporin C as an insect control agent, although further work on mass production, formulation, and field application is still required. Title: Phosphoproteomic of the acetylcholine pathway enables discovery of the PKC-beta-PIX-Rac1-PAK cascade as a stimulatory signal for aversive learning Yamahashi Y, Lin YH, Mouri A, Iwanaga S, Kawashima K, Tokumoto Y, Watanabe Y, Faruk MO, Zhang X and Kaibuchi K <5 more author(s)> Yamahashi Y, Lin YH, Mouri A, Iwanaga S, Kawashima K, Tokumoto Y, Watanabe Y, Faruk MO, Zhang X, Tsuboi D, Nakano T, Saito N, Nagai T, Yamada K, Kaibuchi K (- 5) Ref: Mol Psychiatry, :, 2022 : PubMed ESTHER: Yamahashi_2022_Mol.Psychiatry__ PubMedSearch: Yamahashi 2022 Mol.Psychiatry PubMedID: 35665767 Abstract Acetylcholine is a neuromodulator critical for learning and memory. The cholinesterase inhibitor donepezil increases brain acetylcholine levels and improves Alzheimer's disease (AD)-associated learning disabilities. Acetylcholine activates striatal/nucleus accumbens dopamine receptor D2-expressing medium spiny neurons (D2R-MSNs), which regulate aversive learning through muscarinic receptor M1 (M1R). However, how acetylcholine stimulates learning beyond M1Rs remains unresolved. Here, we found that acetylcholine stimulated protein kinase C (PKC) in mouse striatal/nucleus accumbens. Our original kinase-oriented phosphoproteomic analysis revealed 116 PKC substrate candidates, including Rac1 activator beta-PIX. Acetylcholine induced beta-PIX phosphorylation and activation, thereby stimulating Rac1 effector p21-activated kinase (PAK). Aversive stimulus activated the M1R-PKC-PAK pathway in mouse D2R-MSNs. D2R-MSN-specific expression of PAK mutants by the Cre-Flex system regulated dendritic spine structural plasticity and aversive learning. Donepezil induced PAK activation in both accumbal D2R-MSNs and in the CA1 region of the hippocampus and enhanced D2R-MSN-mediated aversive learning. These findings demonstrate that acetylcholine stimulates M1R-PKC-beta-PIX-Rac1-PAK signaling in D2R-MSNs for aversive learning and imply the cascade's therapeutic potential for AD as aversive learning is used to preliminarily screen AD drugs. Title: Acetylcholinesterase-Cu(3)(PO(4))(2) hybrid nanoflowers for electrochemical detection of dichlorvos using square-wave voltammetry Yang L, Zhang X, Li M, Qu L, Liu Z Ref: Anal Methods, :, 2022 : PubMed ESTHER: Yang_2022_Anal.Methods__ PubMedSearch: Yang 2022 Anal.Methods PubMedID: 36169013 Abstract Immobilization of enzymes is one of the key steps in the development of high-performance enzymatic electrochemical biosensors, and various nanostructured materials have been designed and developed to achieve this goal. Herein, hybrid nanoflowers (HNFs) were synthesized using acetylcholinesterase (AChE) as an organic component and copper phosphate (Cu(3)(PO(4))(2)) as an inorganic component. These AChE-Cu(3)(PO(4))(2) HNFs exhibit a three-dimensional hierarchical flower-like structure, which not only has a large specific surface area but also promotes the affinity between AChE and its substrate with better catalytic activity. Not only that, the surface modification of the glassy carbon electrode (GCE) by the joint use of gold nanoparticles (AuNPs) and graphene oxide (GO) extended the electroactive area. Using square-wave voltammetry (SWV), the as-prepared biosensor (i.e., AChE-Cu(3)(PO(4))(2) HNF/AuNP/GO/GCE) demonstrated superior sensing performance in the detection of dichlorvos. The detection limit is as low as 0.07 pM, and the linear detection range can range from 0.5 pM to 10 microM. In addition, the biosensor was feasible in real agricultural samples with satisfactory recoveries (98.65% to 103.43%). The reported biosensor provides an alternative tool for the direct measurements of AChE activity and its inhibition. Besides organophosphorus pesticides represented by dichlorvos, this biosensor has the potential to detect other AChE inhibitors, such as carbamate pesticides, drugs for Alzheimer's disease, etc., thus having broader applications in food safety and drug screening. Title: Notum Leads to Potential Pro-survival of OSCC Through Crosstalk Between Shh and Wnt/beta-catenin Signaling Via p-GSK3beta Yang P, Li C, Zhou Q, Zhang X, Kou Y, Feng Q, Wang H, Su R, Hasegawa T and Li M <1 more author(s)> Yang P, Li C, Zhou Q, Zhang X, Kou Y, Feng Q, Wang H, Su R, Hasegawa T, Liu H, Li M (- 1) Ref: International Journal of Biochemistryistry & Cell Biology, :106316, 2022 : PubMed ESTHER: Yang_2022_Int.J.Biochem.Cell.Biol__106316 PubMedSearch: Yang 2022 Int.J.Biochem.Cell.Biol 106316 PubMedID: 36280040 Abstract Notum, which belongs to the alpha/beta hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms. Various approaches including bioinformatics analysis, enzyme-linked immunosorbent assay and immunohistochemical staining were used to detect the expression of Notum in OSCC cells and tissues. Cell counting kit-8 assay, clone formation assay, wound healing assay, transwell assay and in-gel zymography assay were explored to evaluate the regulation of Notum in OSCC proliferation and migration. Hoechst 33342/PI assay, cell immunofluorescence, flow cytometry and in vivo tumorigenesis experiment were applied for OSCC apoptosis. Real-time quantitative polymerase chain reaction analysis was performed for mRNA level while western blotting was conducted to detect protein expression. The results showed that Notum was highly expressed in OSCC tissues and cells, and Notum promoted the proliferation and migration of OSCC cells while it inhibited their apoptosis. Furthermore, signaling pathway analysis showed that Notum led to potential pro-survival of OSCC through crosstalk between sonic hedgehog (Shh) and Wnt/beta-catenin signaling via phosphorylation of glycogen synthase kinase-3 beta. These results will help to elucidate the mechanism and also provide new ideas for targeted treatment of OSCC. Title: A preliminary study of the chemical composition and bioactivity of Bombax ceiba L. flower and its potential mechanism in treating type 2 diabetes mellitus using ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry and network pharmacology analysis Yin K, Yang J, Wang F, Wang Z, Xiang P, Xie X, Sun J, He X, Zhang X Ref: Front Nutr, 9:1018733, 2022 : PubMed ESTHER: Yin_2022_Front.Nutr_9_1018733 PubMedSearch: Yin 2022 Front.Nutr 9 1018733 PubMedID: 36313078 Abstract This study aimed to preliminary investigate the phytochemistry, bioactivity, hypoglycemic potential, and mechanism of action of Bombax ceiba L. flower (BCF), a wild edible and food plant in China. By using methanol extraction and liquid-liquid extraction, the crude extract (CE) of BCF and its petroleum ether (PE), dichloromethane (DCM), ethyl acetate (EtOAc), n-butanol (n-BuOH), and aqueous (AQ) fractions were obtained, and their chemical components and biological activities were evaluated. Further high-performance liquid chromatography (HPLC) analysis was carried out to identify and quantify the active constituents of BFC and its five fractions, and the phytochemical composition of the best-performing fraction was then analyzed by ultra-performance liquid chromatography quadrupole-time-flight mass spectrometry (UPLC/Q-TOF-MS). Finally, a network pharmacology strategy based on the chemical profile of this fraction was applied to speculate its main hypoglycemic mechanism. Results revealed the excellent biological activities of BCF, especially the EtOAc fraction. In addition to the highest total flavonoid content (TFC) (367.72 microg RE/mg E) and total phenolics content (TPC) (47.97 microg GAE/mg E), EtOAc showed the strongest DPPH scavenging ability (IC(50) value = 29.56 microg/mL), ABTS (+) scavenging ability (IC(50) value = 84.60 microg/mL), and ferric reducing antioxidant power (FRAP) (889.62 microg FeSO(4)/mg E), which were stronger than the positive control BHT. EtOAc also exhibited the second-best alpha-glucosidase inhibitory capacity and second-best acetylcholinesterase (AChE) inhibitory capacity with the IC(50) values of 2.85 and 3.27 mg/mL, respectively. Also, EtOAc inhibited HepG2, MCF-7, Raw264.7, and A549 cell with IC(50) values of 1.08, 1.62, 0.77, and 0.87 mg/mL, which were the second or third strongest in all fractions. Additionally, HPLC analysis revealed significant differences in the compounds' abundance between different fractions. Among them, EtOAc had the most detected compounds and the highest content. According to the results of UPLC/Q-TOF-MS, 38 compounds were identified in EtOAc, including 24 phenolic acids and 6 flavonoids. Network pharmacological analysis further confirmed 41 potential targets of EtOAc in the treatment of type 2 diabetes, and intracellular receptor signaling pathways, unsaturated fatty acid, and DNA transcription pathways were the most possible mechanisms. These findings suggested that BCF was worthwhile to be developed as an antioxidant and anti-diabetic food/drug. Title: Chemical profile, anti-hepatoma activity, anti-acetylcholinesterase and antioxidant activity of aerial part of Aconitum carmichaeli Debx Yu J, Xia J, Xu J, Chen S, Zhang Y, Yin F, Fang J, Cai L, Zhang B and Liang Z <3 more author(s)> Yu J, Xia J, Xu J, Chen S, Zhang Y, Yin F, Fang J, Cai L, Zhang B, Zhan Y, Zhang X, Zeng Z, Liang Z (- 3) Ref: Nat Prod Res, :1, 2022 : PubMed ESTHER: Yu_2022_Nat.Prod.Res__1 PubMedSearch: Yu 2022 Nat.Prod.Res 1 PubMedID: 36503283 Abstract Five extracts of the aerial parts of Aconitum carmichaeli were obtained by different solvent extraction or macroporous adsorption resin purification: ethyl acetate layer extract (EAE), n-butanol layer extract (BuE), water layer extract (WE), extract eluted by 10% ethanol from macroporous resin (10%EE), extract eluted by 80% ethanol from macroporous resin (80%EE). Antioxidant activities of the five extracts were determined by ABTS, DPPH, FRAP assays, anti-AChE activities by modified Ellman's method, insvitro anti-hepatoma activities by CCK-8 assay, and chemical constituents of 80%EE were identified by UPLC-QE-Orbitrap-MS. The results demonstrated that the 80%EE showed the best insvitro anti-hepatoma activity on Huh-7 cell line with an IC(50) of 103.91+/-11.02microg/mL. 10%EE and 80%EE gave the highest antioxidant activity. Furthermore, current findings demonstrated that the aerial part of Aconitum carmichaeli Debx. has high medicinal value and may be a good natural medicine. Title: UHPLC-QTOF/MS-based comparative metabolomics in pectoralis major of fast- and slow-growing chickens at market ages Zhang J, Cao J, Geng A, Wang H, Chu Q, Yan Z, Zhang X, Zhang Y, Liu H Ref: Food Sci Nutr, 10:487, 2022 : PubMed ESTHER: Zhang_2022_Food.Sci.Nutr_10_487 PubMedSearch: Zhang 2022 Food.Sci.Nutr 10 487 PubMedID: 35154685 Abstract The molecular regulatory mechanism underlying meat quality between different chicken genotypes remains elusive. This study aimed to identify the differences in metabolites and pathways in pectoralis major (breast muscle) between a commercial fast-growing chicken genotype (Cobb500) and a slow-growing Chinese native chicken genotype (Beijing-You chickens, BYC) at market ages respectively based on ultra-high-performance liquid chromatography-quadrupole/time of flight mass spectrometry (UHPLC-QTOF/MS). Eighteen metabolites were identified as potential biomarkers between BYC and Cobb500 at market ages. Among them, L-cysteine exhibited a higher relative intensity in BYC compared with Cobb500 and was enriched into 10 potential flavor-associated KEGG pathways. In addition, the glycerophospholipid metabolism pathway was found to be associated with chicken meat flavor and the accumulation of sn-glycerol 3-phosphate and acetylcholine was more predominant in BYC than that in Cobb500, which were catalyzed by glycerophosphocholine phosphodiesterase (GPCPD1, EC:3.1.4.2), choline O-acetyltransferase (CHAT, EC:2.3.1.6), and acetylcholinesterase (ACHE, EC:3.1.1.7). Overall, the present study provided some metabolites and pathways for further investigating the roles of the differences in meat flavor quality in breast muscle between Cobb500 and BYC at market ages. Title: Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues Zhang X, Xu W, Xu R, Wang Z, Wang P, Peng K, Li M, Li J, Tan Y and Pei H <1 more author(s)> Zhang X, Xu W, Xu R, Wang Z, Wang P, Peng K, Li M, Li J, Tan Y, Wang X, Pei H (- 1) Ref: Oxid Med Cell Longev, 2022:4594956, 2022 : PubMed ESTHER: Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956 PubMedSearch: Zhang 2022 Oxid.Med.Cell.Longev 2022 4594956 PubMedID: 35401929 Abstract Cytoplasmic lipid droplets (LDs) can store neutral lipids as an energy source when needed and also regulate the key metabolic processes of intracellular lipid accumulation, which is associated with several metabolic diseases. The perilipins (Plins) are a family of proteins that associate with the surface of LDs. As a member of Plins superfamily, perilipin 5 (Plin5) coats LDs in cardiomyocytes, which is significantly related to reactive oxygen species (ROS) production originated from mitochondria in the heart, consequently determining the progression of diabetic cardiomyopathy. Plin5 may play a bidirectional function in lipid metabolism which is in a state of dynamic balance. In the basic state, Plin5 inhibited the binding of comparative gene identification-58 (CGI-58) to adipose triglyceride lipase (ATGL) by binding CGI-58, thus inhibiting lipolysis. However, when the body is under stress (such as cold, fasting, exercise, and other stimuli), protein kinase A (PKA) phosphorylates and activates Plin5, which then causes Plin5 to release the binding site of CGI-58 and ATGL, prompting CGI-58 to bind to ATGL and activate ATGL activity, thus accelerating the lipolysis process, revealing the indispensable role of Plin5 in lipid turnover. Here, the purpose of this review is to summarize the present understanding of the bidirectional regulation role of Plin5 in oxidative tissues and to reveal its potential role in diabetic cardiomyopathy protection. Title: Modulation of oxidative stress and gut microbiota by selenium-containing peptides from Cardamine enshiensis and structural-based characterization Zhang X, Jia L, He H, Yin H, Ming J, Hou T, Xiang J Ref: Food Chem, 395:133547, 2022 : PubMed ESTHER: Zhang_2022_Food.Chem_395_133547 PubMedSearch: Zhang 2022 Food.Chem 395 133547 PubMedID: 35780669 Abstract The antioxidant properties of Se-containing peptides from Cardamine enshiensis (SeCPPs) and their impact on gut microbiota were studied in d-galactose (d-gal)- injected mice and antibiotic-treated mice. The structures of SeCPPs were identified by UPLC-Q-Extractive Orbitrap MS. In d-gal ageing mice, SeCPPs were associated with significantly decreased acetyl cholinesterase (AchE) activity, malondialdehyde (MDA) content, increased glutathione peroxidase (GSH-Px) activity, downregulated tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) levels (p < 0.05), and improved memory. In antibiotic-treated mice, SeCPPs were associated with reduced Proteobacteria and evaluated Akkermansia abundances (p < 0.01). Eighty-five Se-containing peptides were identified in SeCPPs. Peptides such as RV-SeM-I, RA-SeM-T and R-SeC-K showed low binding energy with 1,1-diphenyl-2-picrylhydrazyl (DPPH), and their binding affinities were confirmed by molecular docking. Overall, compared with Na(2)SeO(3) and SeMet, SeCPPs showed superior antioxidant activity via their association with higher antioxidant enzyme activity, scavenging free radical properties and gut microbiome modulation. Title: Huperzine-A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation Zhang T, Kim MJ, Wu X, Yang HJ, Yuan H, Huang S, Yoon SM, Kim KN, Park S and Wang J <46 more author(s)> Zhang T, Kim MJ, Wu X, Yang HJ, Yuan H, Huang S, Yoon SM, Kim KN, Park S, Zhang Y, Yao J, Yin K, Liu Z, Deng C, Liu J, Hou S, Zhang H, Yu D, Zhao N, Zhao R, Chen S, Zhang ZP, Bai X, Cui WB, Chen XH, Liu X, Zhi DJ, Zhang ZX, Fei DQ, Wang DS, Zhang X, Wang Y, Zhu H, Zhong Z, Zhang CY, Tan XH, Yang HH, Jin L, Hong JR, Zhou Y, Huang XT, Zhang M, Xiang R, Glorieux C, Huang P, Young C, Morishita Y, Kim K, Kabil OO, Clarke OB, Di Jeso B, Arvan P, Wang D, Sun J, Wu S, Wang J (- 46) Ref: Int J Mol Sci, 23:, 2022 : PubMed ESTHER: Zhang_2022_Int.J.Mol.Sci_23_ PubMedSearch: Zhang 2022 Int.J.Mol.Sci 23 PubMedID: 35328781 35563299 35743309 35887300 35897843 36233022 36362390 36555825 Abstract Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1beta, IL-18, CD16, and TNF-alpha). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation. Title: Translocation of Specific DNA Nanocarrier through an Ultrasmall Nanopipette: Toward Single-Protein-Molecule Detection with Superior Signal-to-Noise Ratio Zhang X, Luo D, Zheng YW, Li XQ, Song J, Zhao WW, Chen HY, Xu JJ Ref: ACS Nano, :, 2022 : PubMed ESTHER: Zhang_2022_ACS.Nano__ PubMedSearch: Zhang 2022 ACS.Nano PubMedID: 36047811 Abstract The use of functional DNA nanostructures as carriers to ship proteins through solid-state nanopores has recently seen substantial growth in single-protein-molecule detection (SPMD), driven by the potential of this methodology and implementations that it may enable. Ultrasmall nanopores have exhibited obvious advantages in spatiotemporal biological detection due to the appropriate nanoconfined spaces and unique properties. Herein, a 6.8 nm DNA tetrahedron (TDN) with a target-specific DNA aptamer (TDN-apt) was engineered to carry the representative target of acetylcholinesterase (AChE) through an ultrasmall nanopipet with a 30 nm orifice, underpinning the advanced SPMD of AChE with good performance in terms of high selectivity, low detection limit (0.1 fM), and especially superior signal-to-noise ratio (SNR). The kinetic interaction between TDN-apt and AChE was studied and the practical applicability of the as-developed SPMD toward real samples was validated using serum samples from patients with Alzheimer's disease. This work not only presented a feasible SPMD solution toward low-abundance proteins in complex samples and but also was envisioned to inspire more interest in the design and implementation of synergized DNA nanostructure-ultrasmall nanopore systems for future SPMD development. Title: Toxicological and Biochemical Description of Synergism of Beauveria bassiana and Emamectin Benzoate against Megalurothrips usitatus (Bagrall) Zhang Y, Zhang X, Tian Q, Ali S, Tang L, Wu J Ref: J Fungi (Basel), 8:, 2022 : PubMed ESTHER: Zhang_2022_J.Fungi.(Basel)_8_ PubMedSearch: Zhang 2022 J.Fungi.(Basel) 8 PubMedID: 36135641 Abstract The prophylactic application of synthetic insecticides to manage Megalurothrips usitatus (Bagrall) has resulted in insecticide resistance and negative impacts upon natural ecosystems. This has driven the need for developing alternative pest control strategies. In the present study, we investigated the synergistic interaction between the entomopathogenic fungus Beauveria bassiana and the insecticide emamectin benzoate on M. usitatus. The results of our research exhibited that higher doses of emamectin benzoate inhibited the germination rate and colony growth of B. bassiana. The percentage of M. usitatus mortality following B. bassiana and emamectin benzoate treatment indicated a dose-mortality effect. All concentrations of emamectin benzoate combined with different concentrations of B. bassiana demonstrated a synergistic effect five days post-treatment. When B. bassiana and emamectin benzoate were applied alone or in combination, antioxidant enzyme activities, including acetylcholinesterase, catalase, superoxide dismutase, and peroxidase, were significantly lower in M. usiatus than in the controls at the end of the experimental period. The findings of our study confirm the synergistic effect of B. bassiana and emamectin benzoate on M. usitatus, as well as the biochemical process that might be involved in the regulation of the synergistic effect. Title: Structurally diverse lignans from Solanum lyratum: chemical evidence for their acetylcholinease inhibitory activity Zhang X, Bai M, Chang Y, Huang XX, Song SJ Ref: Nat Prod Res, :1, 2022 : PubMed ESTHER: Zhang_2022_Nat.Prod.Res__1 PubMedSearch: Zhang 2022 Nat.Prod.Res 1 PubMedID: 36345975 Abstract A chemical investigation of Solanum lyratum Thumb. (Solanace) afforded two new lignans (1b and 3) and eleven known lignan analogues (1a, 2a/2b and 4-11). Compounds 1a/1b and 2a/2b were separated as two pairs of enantiomers by chiral high-performance liquid chromatography (HPLC). Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. The absolute configurations of compounds 1a/1b and 2a/2b were determined by comparing the experimental ECD data with the calculated values. All compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Notably, compared to the positive control, compounds 4 and 9 showed obvious AChE inhibition with their IC(50) values of 1.30 +/- 0.25 and 0.89 +/- 0.04 microM, respectively. In addition, the possible interaction between acetylcholinesterase and the active compounds was also investigated by molecular docking. Title: Correlation of lipoprotein-associated phospholipase A2 and cerebral microbleeds in patients with acute ischaemic stroke Zhang X, Liu L, Jiang N, Liu Y, Wang Q, Tang X, Zhai Q, Zhao L Ref: BMC Neurol, 22:482, 2022 : PubMed ESTHER: Zhang_2022_BMC.Neurol_22_482 PubMedSearch: Zhang 2022 BMC.Neurol 22 482 PubMedID: 36517761 Abstract BACKGROUND AND AIMS: Cerebral microbleeds (CMBs) increase the risk of stroke occurrence and recurrence,and affect the prognosis of stroke patients. Therefore, identifying biological markers that predict CMBs after stroke is urgently needed. This study explored whether high levels of lipoprotein-associated phospholipase A2(Lp-PLA2) are associated with an increased risk of CMBs in patients with acute ischaemic stroke (AIS). METHODS: From April 2020 to October 2021, we enrolled 242 patients with AIS. At admission, the plasma levels of Lp-PLA2 were measured in all patients as well as the number of CMBs and white matter lesions. According to the results of the Susceptibility Weighted Imaging (SWI), the patients were divided into a CMB group and a no-CMB group. The groups were compared with univariate and multivariate analyses to clarify the correlation between Lp-PLA2 levels and CMBs, and the optimal cut-off value of Lp-PLA2 that predicted CMBs was determined from the receiver-operating characteristic curve. RESULTS: CMBs were detected in 71 (29.3%) of the 242 AIS patients. The median Lp-PLA2 level was 182.79ng/ml. Using the 1st quartile of Lp-PLA2 levels (the lowest levels) as the reference group, univariate logistic regression analysis showed that individuals in the 4th quartile (the highest levels) had a higher risk of CMBs (odds ratio [OR]=1.460, 95% confidence interval [CI]: 1.188-1.795, P=0.000). This correlation persisted after adjusting for relevant risk factors (OR=1.370, 95% CI: 1.096-1.713, P=0.006). The optimal cut-off value of Lp-PLA2 that predicted the occurrence of CMBs was 184.36ng/ml; at this threshold, the sensitivity was 69.0%, and the specificity was 60.2%. CONCLUSIONS: Our data suggest that a high level of Lp-PLA2 in patients with AIS is a potential risk factor for CMBs. Title: Screening and identification of anti-acetylcholinesterase ingredients from Tianzhi granule based on ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry and in silico analysis Zhao N, Liu D, Wang Y, Zhang X, Zhang L Ref: J Ethnopharmacol, :115641, 2022 : PubMed ESTHER: Zhao_2022_J.Ethnopharmacol__115641 PubMedSearch: Zhao 2022 J.Ethnopharmacol 115641 PubMedID: 35973628 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Tianzhi granule (TZG) is a traditional Chinese formula that is widely used for the treatment of vascular dementia (VaD). AIM OF THE STUDY: To discover the herbs in TZG possessing acetylcholinesterase (AChE) inhibitory activity and to screen the anti-acetylcholinesterase ingredients from active herbs. MATERIALS AND METHODS: In vitro AChE inhibitory activity assay of eleven herbal extracts was conducted. An ultrafiltration combined with ultra-performance liquid chromatography-mass spectrometry method was established to screen and identify the anti-acetylcholinesterase ingredients from active extracts. In addition, in vitro AChE inhibitory activity assay and molecular docking were adopted for further investigation. Moreover, ultra-performance liquid chromatography-mass spectrometry was performed for the content determination of active compounds in TZG. RESULTS: Three herbs in TZG showed significant AChE inhibitory activity. A total of thirteen active ingredients were screened out and identified, and all of these compounds were present in TZG. Five available commercial standards presented moderate AChE inhibitory activity, and all of which have a relatively high content in TZG. CONCLUSION: A number of herbs and compounds with acetylcholinesterase inhibitory activity were found in TZG, which provided a scientific basis for the material basis and quality control research of TZG. Title: Atomically dispersed Fe/Bi dual active sites single-atom nanozymes for cascade catalysis and peroxymonosulfate activation to degrade dyes Chen Q, Liu Y, Lu Y, Hou Y, Zhang X, Shi W, Huang Y Ref: J Hazard Mater, 422:126929, 2021 : PubMed ESTHER: Chen_2021_J.Hazard.Mater_422_126929 PubMedSearch: Chen 2021 J.Hazard.Mater 422 126929 PubMedID: 34523499 Abstract Constructing single-atom nanozymes (SAzymes) with densely exposed and dispersed double metal-N(x) catalytic sites for pollution remediation remains rare and challenging. Herein, we report a novel Fe-Bi bimetallic MOF-derived carbon supported Fe-N(4) and Bi-N(4) dual-site FeBi-NC SAzyme for cascade catalysis and peroxymonosulfate activation to degrade dye pollutants, which is synthesized from the Fe-doped Bi-MOF as a precursor. The formation of both Fe-N(4) and Bi-N(4) sites is demonstrated by XANES and EXAFS. The FeBi-NC SAzyme has high single atoms loadings of Fe (2.61 wt%) and Bi (8.01 wt%), and displays 5.9- and 9.8-fold oxidase mimicking activity enhancement relative to the Fe-NC and Bi-NC SAzymes, respectively. When integrated acetylcholinesterase (AChE) and FeBi-NC SAzyme, a cascade enzyme-nanozyme system is developed for selective and sensitive screening of AChE activity with a low detection limit of 1 x 10(-4) mU mL(-1). Both Fe-N(4) and Bi-N(4) in FeBi-NC display a strong binding energy and electron donating capability to promote peroxymonosulfate activation to generate highly active intermediates for rhodamine B degradation. 100% rhodamine B removal occurs within 5 min via FeBi-NC mediated activation of peroxymonosulfate. The DFT calculations reveal that high activity of FeBi-NC is due to the isolated Fe-N(4) and Bi-N(4) sites and their synergy. Title: Notum deletion from late-stage skeletal cells increases cortical bone formation and potentiates skeletal effects of sclerostin inhibition Choi RB, Bullock WA, Hoggatt AM, Horan DJ, Pemberton EZ, Hong JM, Zhang X, He X, Robling AG Ref: J Bone Miner Res, :, 2021 : PubMed ESTHER: Choi_2021_J.Bone.Miner.Res__ PubMedSearch: Choi 2021 J.Bone.Miner.Res PubMedID: 34223673 Gene_locus related to this paper: human-NOTUM, mouse-notum Abstract Wnt signaling plays a vital role in the cell biology of skeletal patterning, differentiation, and maintenance. Notum is a secreted member of the alpha/beta-hydrolase superfamily that hydrolyzes the palmitoleoylate modification on Wnt proteins, thereby disrupting Wnt signaling. As a secreted inhibitor of Wnt, Notum presents an attractive molecular target for improving skeletal health. To determine the cell type of action for Notum's effect on the skeleton, we generated mice with Notum deficiency globally (Notum(-/-) ) and selectively (Notum(f/f) ) in limb bud mesenchyme (Prx1-Cre) and late osteoblasts/osteocytes (Dmp1-Cre). Late-stage deletion induced increased cortical bone properties, similar to global mutants. Notum expression was enhanced in response to sclerostin inhibition, so dual inhibition (Notum/sclerostin) was also investigated using a combined genetic and pharmacologic approach. Co-suppression increased cortical properties beyond either factor alone. Notum suppressed Wnt signaling in cell reporter assays, but surprisingly, also enhanced Shh signaling independent of effects on Wnt. Notum is an osteocyte-active suppressor of cortical bone formation that is likely involved in multiple signaling pathways important for bone homeostasis. Title: Inhibition of Soluble Epoxide Hydrolase Attenuates Bosutinib-Induced Blood Pressure Elevation Cui Z, Li B, Zhang Y, He J, Shi X, Wang H, Zhao Y, Yao L, Ai D and Zhu Y <1 more author(s)> Cui Z, Li B, Zhang Y, He J, Shi X, Wang H, Zhao Y, Yao L, Ai D, Zhang X, Zhu Y (- 1) Ref: Hypertension, 78:1527, 2021 : PubMed Title: Detection of carboxylesterase 1 and carbamates with a novel fluorescent protein chromophore based probe Dai J, Zhao Y, Hou Y, Zhong G, Gao R, Wu J, Shen B, Zhang X Ref: Dyes and Pigments, 192:109444, 2021 : PubMed ESTHER: Dai_2021_Dyes.Pigments_192_109444 PubMedSearch: Dai 2021 Dyes.Pigments 192 109444 Abstract An aggregation-induced emission (AIE) fluorescent protein chromophore-based probe (CBZ-FP) for detection of human carboxylesterases (CESs) was designed and synthesized. CBZ -FP exhibited good cell permeability with a large stokes shift (116snm) and can be applied to reveal the actual activities of CES1 in living cells associated with pesticide s detoxification process. CBZ-FP can also serve as a fluorescence indicator of pesticide exposure in the way of hydrolyzing the carboxylic acid ester group in CBZ-FP. There fore, CBZ-FP has high selectivity for CESs and can detect real-time activity of CES1 in biological samples. Molecular docking study was used to explore the binding of CESs and CBZ-FP. Finding that only one specific activity site of CESs can bind with probe. In view of the fact that, the biotransformation of drugs and poisons containing ester groups can carry out normally depending on CESs, Carboxylesterase probes are expected to contribute to the characterization of relevant disease. Title: ((E)-N-(4-(((2-Amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) Ameliorated Abeta(1-42)-Induced Alzheimer's Disease in SD Rats by Inhibiting Oxidative Stress and Apoptosis Ding Y, Wang X, Ji J, Zhang X, Chen M, Li S, Zhang Q, Liu P Ref: ACS Chem Neurosci, :, 2021 : PubMed ESTHER: Ding_2021_ACS.Chem.Neurosci__ PubMedSearch: Ding 2021 ACS.Chem.Neurosci PubMedID: 33517657 Abstract Our study investigated the protective effects of ((E)-N-(4-(((2-amino-5-phenylpyridin-3-yl)imino)methyl)pyridin-2-yl)cyclopropanecarboxamide) 9b, a novel glycogen synthase kinase-3beta (GSK-3beta) inhibitor, on the learning and memory function of rats with amyloid-beta(1-42) (Abeta(1-42))-induced Alzheimer's disease (AD) and explored the possible mechanisms. Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups: the control, Abeta, donepezil, and low-dose and high-dose 9b groups. The rats in the Abeta, donepezil, and two 9b intervention groups received a single microinjection of 10 microg of Abeta(1-42) into the hippocampus followed by intragastric administration of 0.5% sodium carboxymethyl cellulose (CMC-Na), 12 (mg/kg)/d donepezil hydrochloride and 6 or 18 (mg/kg)/d compound 9b for 28 days, while the rats in the control group were treated with the vehicles. Learning and memory impairment were attenuated, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), acetylcholinesterase (AChE), and adenosine triphosphatase (ATPase) in the brain tissue were significantly increased (p < 0.05), and the concentrations of Abeta(1-42), phospho-tau (p-tau), and malondialdehyde (MDA) in the brain tissue were significantly decreased (p < 0.05) in the compound 9b group compared to the Abeta group. In addition, compound 9b regulated the imbalance in the concentrations of neurotransmitters and alleviated severe damage and apoptosis in the brains of the rats exposed to Abeta(1-42). The novel GSK-3beta inhibitor 9b could improve learning and memory dysfunction caused by Abeta(1-42) through its antioxidant and antiapoptotic effects. Title: Structural and biochemical mechanisms of NLRP1 inhibition by DPP9 Huang M, Zhang X, Toh GA, Gong Q, Wang J, Han Z, Wu B, Zhong F, Chai J Ref: Nature, :, 2021 : PubMed ESTHER: Huang_2021_Nature__ PubMedSearch: Huang 2021 Nature PubMedID: 33731929 Gene_locus related to this paper: rat-dpp9 Abstract Nucleotide-binding domain, leucine-rich repeat receptors (NLRs) mediate innate immunity by forming inflammasomes. Activation of the NLR protein NLRP1 requires autocleavage within its function-to-find domain (FIIND)(1-7). In resting cells, the dipeptidyl peptidases DPP8 and DPP9 interact with the FIIND of NLRP1 and suppress spontaneous NLRP1 activation(8,9); however, the mechanisms through which this occurs remain unknown. Here we present structural and biochemical evidence that full-length rat NLRP1 (rNLRP1) and rat DPP9 (rDPP9) form a 2:1 complex that contains an autoinhibited rNLRP1 molecule and an active UPA-CARD fragment of rNLRP1. The ZU5 domain is required not only for autoinhibition of rNLRP1 but also for assembly of the 2:1 complex. Formation of the complex prevents UPA-mediated higher-order oligomerization of UPA-CARD fragments and strengthens ZU5-mediated NLRP1 autoinhibition. Structure-guided biochemical and functional assays show that both NLRP1 binding and enzymatic activity are required for DPP9 to suppress NLRP1 in human cells. Together, our data reveal the mechanism of DPP9-mediated inhibition of NLRP1 and shed light on the activation of the NLRP1 inflammasome. Title: A non-integrated iPSC line (SDQLCHi042-A) from a boy suffering from familial combined hyperlipidemia with compound heterozygous mutations of lipoprotein lipase gene Li Z, Zhang X, Li X, Yang Y, Xin H, Yang X, Liu N, Gai Z, Liu Y Ref: Stem Cell Res, 53:102313, 2021 : PubMed ESTHER: Li_2021_Stem.Cell.Res_53_102313 PubMedSearch: Li 2021 Stem.Cell.Res 53 102313 PubMedID: 34087978 Gene_locus related to this paper: human-LPL Abstract In this study, peripheral blood monouclear cells (PBMCs) were donated from a boy suffering from familial combined hyperlipidemia confirmed by clinical and genetic diagnosis, which carried compound heterozygous mutations of lipoprotein lipase (LPL) gene. The induced pluripotent stem cell (iPSC) was generated with non-integrated episomal vectors carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The iPSCs presented the morphology of pluripotent cells, highly expressed mRNA and protein of pluripotent markers, excellent differentiation potency in vitro and normal karyotype, and bore LPL gene mutations. Title: Phytochemical Composition, Antioxidant Activity, and Enzyme Inhibitory Activities (alpha-Glucosidase, Xanthine Oxidase, and Acetylcholinesterase) of Musella lasiocarpa Li R, Ru Y, Wang Z, He X, Kong KW, Zheng T, Zhang X Ref: Molecules, 26:, 2021 : PubMed ESTHER: Li_2021_Molecules_26_ PubMedSearch: Li 2021 Molecules 26 PubMedID: 34361630 Abstract In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) were tested for their total antioxidant capacity, followed by their alpha-glucosidase, acetylcholinesterase, and xanthine oxidase inhibitory activities. Among the samples, the highest total phenolic and total flavonoid contents were found in the ethyl acetate (EtOAc) fraction (224.99 mg GAE/g DE) and crude methanol extract (187.81 mg QE/g DE), respectively. The EtOAc fraction of Musella lasiocarpa exhibited the strongest DPPH. scavenging ability, ABTS.(+) scavenging ability, and alpha-glucosidase inhibitory activity with the IC(50) values of 22.17, 12.10, and 125.66 microg/mL, respectively. The EtOAc fraction also showed the strongest ferric reducing antioxidant power (1513.89 mg FeSO(4)/g DE) and oxygen radical absorbance capacity ability (524.11 mg Trolox/g DE), which were higher than those of the control BHT. In contrast, the aqueous fraction demonstrated the highest acetylcholinesterase inhibitory activity (IC(50) = 10.11 microg/mL), and the best xanthine oxidase inhibitory ability (IC(50) = 5.23 microg/mL) was observed from the crude methanol extract as compared with allopurinol (24.85 microg/mL). The HPLC-MS/MS and GC-MS analyses further revealed an impressive arsenal of compounds, including phenolic acids, fatty acids, esters, terpenoids, and flavonoids, in the most biologically active EtOAc fraction. Taken together, this is the first report indicating the potential of Musella lasiocarpa as an excellent natural source of antioxidants with possible therapeutic, nutraceutical, and functional food applications. Title: Antioxidant Effects of Sophora davidi (Franch.) Skeels on d-Galactose-Induced Aging Model in Mice via Activating the SIRT1/p53 Pathway Lin B, Xu D, Wu S, Qi S, Xu Y, Liu X, Zhang X, Chen C Ref: Front Pharmacol, 12:754554, 2021 : PubMed ESTHER: Lin_2021_Front.Pharmacol_12_754554 PubMedSearch: Lin 2021 Front.Pharmacol 12 754554 PubMedID: 34938181 Abstract This study investigated the protective effect of Sophora davidi (Franch.) Skeels fruits extract (SDE) on d-galactose-induced acute aging in mice. Ultra performance liquid chromatography coupled with tine-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to identify the composition of compounds in SDE. KM mice were divided stochastically into the normal control group (NC, saline), d-galactose (D-gal) model group, vitamin C (Vc) group (positive control), low-, medium-and high-dose SDE treat groups. After 28 days administration and fasting overnight, the serum, liver, and brain samples of mice were collected. The levels of inducible nitric oxide synthase (iNOS), acetylcholinesterase (AChE) activity in the brain, malondialdehyde (MDA) and reduced glutathione (GSH) content, superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) activity in the liver and brain were measured. Immunohistochemistry was applied to detect silent information regulator 1 (SIRT1) and p53 protein expression in the liver and brain, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression of nuclear factor kappaB (NF-kappaB), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), interleukin-1beta (IL-1beta), and anti-aging factor Klotho in the liver and brain. The results showed that UPLC-Q-TOF/MS identified 78 compounds in SDE. SDE could reduce the iNOS activity in serum and AChE activity in the brain, upregulate the levels of SOD, T-AOC and GSH in liver and brain, and debase the MDA content in liver and brain. SDE could downregulate the mRNA expressions of TNF-alpha, NF-kB, IL-1beta, and IL-6 in the liver and brain, and elevate the mRNA expression of Klotho. SDE improved the pathological changes of the liver and brain induced by D-gal, increased the expression of SIRT1 protein in the liver and brain, and inhibited the expression of p53 protein induced by D-gal. To summarize, SDE demonstrated clear anti-aging effect, and its mechanism may be relevant to the activation of the SIRT1/p53 signal pathway. Title: Chemical Constituents and their Antioxidant, Anti-Inflammatory and Anti-Acetylcholinesterase Activities from Pholidota cantonensis Liu L, Zou M, Zeng K, Ye X, Wang R, Wang W, Zhang X Ref: Plant Foods Hum Nutr, 76:105, 2021 : PubMed ESTHER: Liu_2021_Plant.Foods.Hum.Nutr_76_105 PubMedSearch: Liu 2021 Plant.Foods.Hum.Nutr 76 105 PubMedID: 33620638 Abstract Alzheimer's disease (AD) has the third highest health expenditures after heart disease and cancer. It has emerged as a serious global health issue. The discovery of new drugs to prevent and treat AD is of utmost importance. Pholidota cantonensis is an edible medicinal plant consumed in China. It is widely used in traditional Chinese medicine to treat various diseases. P. cantonensis has been reported to have antioxidant, anti-inflammatory, antitumor and antibacterial activities. Among these properties, its potent antioxidant activity has attracted our attention, since oxidative stress is one of the important pathological mechanisms involved in AD. This study aimed to isolate the compounds from the active extract and evaluate their bioactivities. Fifteen compounds, including one new compound, were obtained. The isolates were tested for 2,2'-diphenyl-1-picrylhydrazyl (DPPH)/2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activities, anti-acetylcholinesterase (anti-AChE) activities and inhibitory effects on nitrogen monoxide (NO) release in the BV-2 cells. Compounds 1, 2, 4, 6, 8, and 13-15 exhibited two kinds of AD-associated bioactivities. More importantly, compound 13 showed more potent NO inhibitory activity (IC(50) = 0.72 +/- 0.08 microM) than the positive control quercetin (IC(50) = 12.94 +/- 0.08 microM). Compound 13 also had a higher inhibitory rate (99.59 +/- 0.43%) on AChE than that of the positive control galantamine (78.32 +/- 1.16%) at the concentrate of 50 microg/mL. Our studies provide new insights into this plant in terms of its potential in the development of new multi-target anti-Alzheimer's disease (anti-AD) drugs. Title: Association of TaD14-4D, a Gene Involved in Strigolactone Signaling, with Yield Contributing Traits in Wheat Liu R, Hou J, Li H, Xu P, Zhang Z, Zhang X Ref: Int J Mol Sci, 22:, 2021 : PubMed ESTHER: Liu_2021_Int.J.Mol.Sci_22_ PubMedSearch: Liu 2021 Int.J.Mol.Sci 22 PubMedID: 33916852 Abstract Tillering is a crucial agronomic trait of wheat; it determines yield and plant architecture. Strigolactones (SLs) have been reported to inhibit plant branching. D14, a receptor of SLs, has been described to affect tillering in rice, yet it has seldomly been studied in wheat. In this study, three TaD14 homoeologous genes, TaD14-4A, TaD14-4B, and TaD14-4D, were identified. TaD14-4A, TaD14-4B, and TaD14-4D were constitutively expressed, and TaD14-4D had a higher expression level in most tissues. TaD14 proteins were localized in both cytoplasm and nucleus. An SNP and a 22 bp insertion/deletion (Indel) at the exon regions of TaD14-4D were detected, forming three haplotypes, namely 4D-HapI, 4D-HapII, and 4D-HapIII. Due to the frameshift mutation in the coding region of 4D-HapII, the interaction of 4D-HapII with TaMAX2 and TaD53 was blocked, which led to the blocking of SL signal transduction. Based on the two variation sites, two molecular markers, namely dCAPS-250 and Indel-747, were developed. Association analysis suggested that haplotypes of TaD14-4D were associated with effective tillering number (ETN) and thousand kernel weight (TKW) simultaneously in four environments. The favorable haplotype 4D-HapIII underwent positive selection in global wheat breeding. This study provides insights into understanding the function of natural variations of TaD14-4D and develops two useful molecular markers for wheat breeding. Title: Elsholtzia rugulosa: Phytochemical Profile and Antioxidant, Anti-Alzheimer's Disease, Antidiabetic, Antibacterial, Cytotoxic and Hepatoprotective Activities Liu L, Gao Q, Zhang Z, Zhang X Ref: Plant Foods Hum Nutr, :, 2021 : PubMed ESTHER: Liu_2021_Plant.Foods.Hum.Nutr__ PubMedSearch: Liu 2021 Plant.Foods.Hum.Nutr PubMedID: 34853948 Abstract Elsholtzia rugulosa Hemsl., a species of the Labiatae family, has a long history of use as a honey plant, herbal tea, and folk medicine in China. However, little is known about its composition and biological activities. The present study aimed to investigate the total phenol and flavonoid contents, phytochemical composition, and multiple biological activities of this plant. The total flavonoid content of the ethyl acetate fraction (EAF) was higher than those of the petroleum ether fraction (PEF), n-butanol fraction (NBF), and water fraction (WF). The EAF also had much stronger antioxidant, cytotoxic, hepatoprotective, and acetylcholinesterase (AChE) and alpha-glucosidase inhibitory activities than the PEF, NBF, and WF. More importantly, the IC(50) values of the EAF and NBF against alpha-glucosidase were much lower than that of the positive control acarbose, indicating their potent alpha-glucosidase inhibitory activities. The isolation of the EAF led to the acquisition of 9 compounds, four of which (beta-daucosterol, methyl rosmarinate, betulinic acid, and oleanolic acid) possessed significant alpha-glucosidase inhibitory activities. Maltol 6'-O-(5-O-p-coumaroyl)-beta-D-apiofuranosyl-beta-D-glucopyranoside and rosmarinic acid were the major phenolic compounds in the EAF according to the HPLC-DAD analysis. All these findings indicate that the EAF, NBF, and some isolated compounds have the potential to be developed as antidiabetic drugs. Moreover, the dual inhibition of AChE and butyrylcholinesterase (BChE) of certain fractions indicates their potential in the development of anti-Alzheimer's disease drugs. The present study provides a new understanding of the phytochemistry and bioactivity of E. rugulosa. Title: Androgen-dependent miR-125a-5p targets LYPLA1 and regulates global protein palmitoylation level in late-onset hypogonadism males Qu M, Zhao Y, Qing X, Zhang X, Li H Ref: Journal of Cellular Physiology, 236:4738, 2021 : PubMed ESTHER: Qu_2021_J.Cell.Physiol_236_4738 PubMedSearch: Qu 2021 J.Cell.Physiol 236 4738 PubMedID: 33284463 Abstract Late-onset hypogonadism (LOH) is defined as a clinical and biochemical syndrome with multiple symptoms caused by testosterone deficiency in aging males. An in-depth exploration of the molecular mechanism underlying LOH development is insufficient. We previously identified miR-125a-5p as a dysregulated microRNA in LOH patients and potential diagnostic biomarker for LOH. The present study demonstrated that plasma miR-125a-5p was upregulated after testosterone supplementation in both LOH patients and castrated mice, and positively associated with the testosterone concentrations, suggesting direct regulation of miR-125a-5p expression by testosterone. Androgen response element in the promoter of miR-125a-5p was subsequently identified. Target gene screening and confirmation verified that LYPLA1, encoding acyl-protein thioesterase 1 which catalyzed protein depalmitoylation process, was a target gene of miR-125a-5p. Furthermore, in cells cultured with testosterone deprivation and organs from castrated mice, testosterone deficiency led to decreased global protein palmitoylation level. In aging males, global protein palmitoylation in peripheral blood showed a notable decline in LOH patients contrast to the normal elderly males. And the palmitoylation level was positively correlative with serum testosterone concentrations. Our results suggested that testosterone could regulate global palmitoylation level through miR-125a-5p/LYPLA1 signaling pathway. Given that protein palmitoylation is pivotal for protein function and constitutes the pathogenesis of various diseases, testosterone/miR-125a-5p/LYPLA1 may contribute to the molecular mechanism underlying multiple symptoms caused by testosterone deficiency in LOH patients, and aberrant global palmitoylation could be a potential biomarker for LOH. Title: The role of N-cadherin/c-Jun/NDRG1 axis in the progression of prostate cancer Quan Y, Zhang X, Butler W, Du Z, Wang M, Liu Y, Ping H Ref: Int J Biol Sci, 17:3288, 2021 : PubMed ESTHER: Quan_2021_Int.J.Biol.Sci_17_3288 PubMedSearch: Quan 2021 Int.J.Biol.Sci 17 3288 PubMedID: 34512147 Abstract The dysregulation of androgen receptor (AR) signaling is a critical event in the progression of prostate cancer (PCa) and hormone therapy consisting of androgen deprivation (ADT) or AR inhibition is therefore used to treat advanced cases. It is known that N-cadherin becomes upregulated following ADT and can directly induce PCa transformation to the castration-resistant stage (CRPC). However, the relationship between AR and N-cadherin is unclear and may promote better understanding of CRPC pathogenesis and progression. Here, we demonstrate a new axis of N-cadherin/c-Jun/N-myc downstream regulated gene 1 (NDRG1) that N-cadherin promotes c-Jun expression and suppresses NDRG1 to promote invasion and migration of PCa cells through epithelial to mesenchymal transition (EMT). Targeting N-cadherin in combination with enzalutamide (ENZ) treatment synergistically suppressed PC3 cell proliferation in vivo and in vitro. Further studies showed that compared to lower Gleason score (GS) (GS < 7) cases, high GS (GS > 7) cases exhibited elevated N-cadherin expression and reduced NDRG1 expression, corroborating our in vitro observations. We further demonstrate that c-Jun, AR, and DNA methyltransferase-1 (DNMT1) form a complex in the 12-O-tetradecanoyl phorbol-13-acetate (TPA) response elements (TREs) region of the NDRG1 promoter, which suppresses NDRG1 transcription through DNA hypermethylation. In conclusion, we demonstrate an underlying mechanism for how N-cadherin collaborates with AR and NDRG1 to promote CRPC progression. Controlling N-cadherin/c-Jun/NDRG1 axis may help to overcome resistance to commonly used hormone therapy to improve long-term patient outcomes. Title: Detection of Carboxylesterase 1 and Chlorpyrifos with ZIF-8 Metal-Organic Frameworks Using a Red Emission BODIPY-Based Probe Shen B, Ma C, Ji Y, Dai J, Li B, Zhang X, Huang H Ref: ACS Appl Mater Interfaces, :, 2021 : PubMed ESTHER: Shen_2021_ACS.Appl.Mater.Interfaces__ PubMedSearch: Shen 2021 ACS.Appl.Mater.Interfaces PubMedID: 33569946 Abstract In this work, a red emission fluorescent probe CBZ-BOD@zeolitic imidazolate framework-8 (ZIF-8) was fabricated based on metal-organic frameworks (MOFs) for detecting carboxylesterase 1 (CES1). The small molecule probe CBZ-BOD was first synthesized and then used to prepare the functionalized MOF material. ZIF-8 was chosen as an encapsulation shell to improve the detection properties of CBZ-BOD. Using this unique porous materials, ultrasensitive quantification of CES1 and chlorpyrifos was successfully realized. The low detection limit and high fluorescence quantum yield were calculated as 1.15 ng/mL and 0.65 for CBZ-BOD@ZIF-8, respectively. CBZ-BOD@ZIF-8 has good biocompatibility and was successfully applied to monitor the activity of CES1 in living cells. A molecular docking study was used to explore the binding of CES1 and CBZ-BOD, finding that CES1 can bind with the probe before and after hydrolysis. This type of materialized probe can inspire the development of fluorescent tools for further exploration of many pathological processes. Title: A strategy to discover lead chemome from traditional Chinese medicines based on natural chromatogram-effect correlation (NCEC) and natural structure-effect correlation (NSEC): Mahonia bealei and Mahonia fortunei as a case study Song HP, Zhang H, Hu R, Xiao HH, Guo H, Yuan WH, Han XT, Xu XY, Zhang X and Xie M <6 more author(s)> Song HP, Zhang H, Hu R, Xiao HH, Guo H, Yuan WH, Han XT, Xu XY, Zhang X, Ding ZX, Zhao MY, Kang TG, Sun HY, Chang A, Chen YH, Xie M (- 6) Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 1181:122922, 2021 : PubMed ESTHER: Song_2021_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_1181_122922 PubMedSearch: Song 2021 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 1181 122922 PubMedID: 34500403 Abstract Lead compound is an important concept for modern drug discovery. In this study, a new concept of lead chemome and an efficient strategy to discover lead chemome were proposed. Compared with the concept of lead compound, lead chemome can provide not only the starting point for drug development, but also the direction for structure optimization. Two traditional Chinese medicines of Mahonia bealei and Mahonia fortunei were used as examples to illustrate the strategy. Based on natural chromatogram-effect correlation (NCEC), berberine, palmatine and jatrorrhizine were discovered as acetylcholinesterase (AchE) inhibitors. Taking the three compounds as template molecules, a lead chemome consisting of 10 structurally related natural compounds were generated through natural structure-effect correlation (NSEC). In the lead chemome, the IC(50) values of jatrorrhizine, berberine, coptisine, palmatine and epiberberine are at nanomolar level, which are comparable to a widely used drug of galantamine. Pharmacophore modeling shows that the positive ionizable group and aromatic rings are important substructures for AchE inhibition. Molecular docking further shows that pi-cation interaction and pi-pi stacking are critical for compounds to maintain nanomolar IC(50) values. The structure-activity information is helpful for drug design and structure optimization. This work also expanded the traditional understanding of "stem is the medicinal part of Mahonia bealei and Mahonia fortunei". Actually, all parts except the leaf of Mahonia bealei exhibited potent AchE-inhibitory activity. This study provides not only a strategy to discover lead chemome for modern drug development, but also a reference for the application of different parts of medicinal plants. Title: Sublethal Effects of Abamectin on the Development, Reproduction, Detoxification Enzyme Activity, and Related Gene Expression of the Oriental Fruit Moth (Lepidoptera: Tortricidae) Su S, Jian C, Zhang X, Fang S, Peng X, Pinero JC, Chen M Ref: J Econ Entomol, :, 2021 : PubMed ESTHER: Su_2021_J.Econ.Entomol__ PubMedSearch: Su 2021 J.Econ.Entomol PubMedID: 34672347 Abstract Grapholita molesta is one of the most important fruit pests worldwide. Abamectin is a biological pesticide frequently used to control fruit borers like G. molesta in part owing to its translaminar properties. In this study, we characterized the toxicity of abamectin to G. molesta larvae using the diet incorporation method. The sublethal effects of abamectin on the development, reproduction, detoxification enzyme activity, and related gene expression of G. molesta were assessed. The results showed that the LC20 and LC50 values of the insecticide against G. molesta 72 h post-treatment were 1.17 mg L-1 and 5.85 mg L-1, whereas the LC20 and LC50 values 96 h post-treatment were 0.34 mg L-1 and 3.63 mg L-1. When compared to the control, sublethal concentrations of abamectin 1) significantly increased the mortality of the larvae, prepupae, and pupae of G. molesta, 2) prolonged the duration of 3rd to 5th instar larva, prepupal and pupal periods, 3) shortened the longevity of adults, and 4) reduced female fecundity. The enzymatic activity of glutathione S-transferase (GST) varied significantly after exposure to sublethal concentrations of abamectin, but the cytochrome P450 monooxygenases and carboxylesterase activity were not significantly affected. Thirteen of the 25 GST genes were significantly upregulated under different sublethal concentrations of abamectin. The combined findings increase our understanding of the effects of abamectin on G. molesta and the potential role of GSTs in the metabolic interactions of abamectin in this pest, and have applications for more rational and effective use of abamectin to control G. molesta. Title: UHPLC With On-Line Coupled Biochemical Detection for High Throughput Screening of Acetylcholinesterase Inhibitors in Coptidis Rhizoma and Cortex Phellodendri Tan J, Zhang X, Fang J, Shen H, Ding X, Zheng G Ref: Journal of Chromatography Sci, :, 2021 : PubMed ESTHER: Tan_2021_J.Chromatogr.Sci__ PubMedSearch: Tan 2021 J.Chromatogr.Sci PubMedID: 34664067 Abstract We developed a new on-line method of ultra-performance liquid chromatography coupled with biochemical detection (UHPLC-BCD) to screen acetylcholinesterase (AChE) inhibitors in complex matrixes. Chromatography separation was performed using an Xtimate UHPLC C18 column (100 mm x 2.1 mm, 1.8 microm) and a gradient elution with methanol-0.1% formic acid at a flow rate of 0.08 mL/min. The BCD was based on a colorimetric method using Ellman's reagent, and the detection wavelength was at 405 nm. Galanthamine was used as a positive reference to validate the methodology. The detection and quantitation limits of the UHPLC-BCD method were 0.018 and 0.060 microg, respectively. A functional equation was generated in terms of the negative peak area (X) and galanthamine concentration (Y, microg/mL). The regression equation was Y = 0.0028X2 + 0.4574X + 50.7776, R2 = 0.9993. UHPLC-fourier-transform mass spectrometry detection results revealed that five alkaloids showed obvious AChE inhibitory activities including coptisin, epiberberine, jatrorrhizine, berberine and palmatine. The relative AChE inhibitory activities of jatrorrhizine, berberine and palmatine in the Coptidis Rhizoma sample were equal to that of 257.0, 2355 and 283.9 microg/mL of galanthamine, respectively. This work demonstrated that the UHPLC-BCD method was convenient and feasible, and could be widely used for the screening and activity evaluation of the bioactive components in the complex extracts. Title: Synergistic Interaction between the Entomopathogenic Fungus Akanthomyces attenuatus (Zare & Gams) and the Botanical Insecticide Matrine against Megalurothrips usitatus (Bagrall) Wu J, Yang B, Zhang X, Cuthbertson AGS, Ali S Ref: J Fungi (Basel), 7:, 2021 : PubMed ESTHER: Wu_2021_J.Fungi.(Basel)_7_ PubMedSearch: Wu 2021 J.Fungi.(Basel) 7 PubMedID: 34356915 Abstract The excessive use of synthetic chemicals for Megalurothrips usitatus (Bagrall) management has resulted in the development of insecticide resistance as well as adverse effects to the natural ecosystem. This has driven the need to develop alternative pest control strategies. This study reports a synergistic interaction between the entomopathogenic fungus Akanthomyces attenuatus (Zare & Gams) and the botanical insecticide matrine against M. usitatus. The results revealed that the germination rate and colony growth of A. attenuatus were inhibited by higher matrine concentrations. Percentage mortalities of M. usitatus following application of A. attenuatus and matrine showed a dose mortality effect. After five days of treatment, all concentrations of matrine combined with different concentrations of A. attenuatus, except one combination (matrine 0.25 mg/mL + 1 x 10(7) conidia/mL), showed synergistic effect. The activities of acetylcholinesterase and antioxidant enzymes (superoxide dismutase, catalase and peroxidase) in M. usitatus, in response to individual or combined application of A. attenuatus and matrine at the end of the experimental period, were significantly lower than controls. The findings confirm the synergistic action of A. attenuatus and matrine against M. usitatus along with the biochemical phenomenon possibly regulating the synergistic effect. Title: Catabolism of strigolactones by a carboxylesterase Xu E, Chai L, Zhang S, Yu R, Zhang X, Xu C, Hu Y Ref: Nat Plants, 7:1495, 2021 : PubMed ESTHER: Xu_2021_Nat.Plants_7_1495 PubMedSearch: Xu 2021 Nat.Plants 7 1495 PubMedID: 34764442 Gene_locus related to this paper: arath-CXE15 Abstract Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants. Title: Neurotoxicity induced by combined exposure of microcystin-LR and nitrite in male zebrafish (Danio rerio): Effects of oxidant-antioxidant system and neurotransmitter system Yang L, Guo H, Kuang Y, Yang H, Zhang X, Tang R, Li D, Li L Ref: Comparative Biochemistry & Physiology C Toxicol Pharmacol, 253:109248, 2021 : PubMed ESTHER: Yang_2021_Comp.Biochem.Physiol.C.Toxicol.Pharmacol_253_109248 PubMedSearch: Yang 2021 Comp.Biochem.Physiol.C.Toxicol.Pharmacol 253 109248 PubMedID: 34826614 Abstract With the intensification of water eutrophication around the world, cyanobacterial blooms have been becoming a common environmental pollution problem. The levels of microcystin-LR (MC-LR) and nitrite rise sharply during the cyanobacterial bloom period, which may have potential joint toxicity on aquatic organisms. In this study, adult male zebrafish were immersed into different joint solutions of MC-LR (0, 3, 30 microg/L) and nitrite (0, 2, 20 mg/L) for 30 days to explore the neurotoxic effects and underlying mechanisms. The results showed that single factor MC-LR or nitrite caused a concentration-dependent damage in brain ultrastructure and the effects of their joint exposure were much more intense. Downregulated expression of mbp and bdnf associated with myelination of nerve fibers further confirmed that MC-LR and nitrite could damage the structure and function of neuron. The decreases in dopamine content, acetylcholinesterase activity and related gene mRNA levels indicated that MC-LR and nitrite adversely affected the normal function of the dopaminergic and cholinergic systems in zebrafish brain. In addition, the significant increase in malondialdehyde content suggested the occurrence of oxidative stress caused by MC-LR, nitrite and their joint-exposure, which paralleled a significant decrease in antioxidant enzymemanganese superoxide dismutase activity and its transcription level. In conclusion, MC-LR + Nitrite joint-exposure has synergistic neurotoxic effects on the structure and neurotransmitter systems of fish brain, and antioxidant capacity disruption caused by these two factors might be one of the underlying synergistic mechanisms. Therefore, there is a risk of being induced neurotoxicity in fish during sustained cyanobacterial bloom events. Title: Putative carboxylesterase gene identification and their expression patterns in Hyphantria cunea (Drury) Ye J, Mang D, Kang K, Chen C, Zhang X, Tang Y, E RP, Song L, Zhang QH, Zhang L Ref: PeerJ, 9:e10919, 2021 : PubMed ESTHER: Ye_2021_PeerJ_9_e10919 PubMedSearch: Ye 2021 PeerJ 9 e10919 PubMedID: 33717687 Gene_locus related to this paper: cname-a0a1u9x1s5, cname-a0a1u9x1s9, cname-a0a1u9x1t4, cname-a0a1u9x1t5, cname-a0a1u9x1t2, cname-a0a1u9x1t3, cname-a0a1u9x1t0, cname-a0a1u9x1s7, cname-a0a1u9x1t1, cname-a0a1u9x1s8, cname-a0a1u9x1t9, cname-a0a1u9x1t7, cname-a0a1u9x1t8, cname-a0a1u9x1u2, cname-a0a1u9x1u1 Abstract The olfactory system of insects is important for behavioral activities as it recognizes internal and external volatile stimuli in the environment. Insect odorant degrading enzymes (ODEs), including antennal-specific carboxylesterases (CXEs), are known to degrade redundant odorant molecules or to hydrolyze important olfactory sex pheromone components and plant volatiles. Compared to many well-studied Type-I sex pheromone-producing lepidopteran species, the molecular mechanisms of the olfactory system of Type-II sex pheromone-producing Hyphantria cunea (Drury) remain poorly understood. In the current study, we first identified a total of ten CXE genes based on our previous H. unea antennal transcriptomic data. We constructed a phylogenetic tree to evaluate the relationship of HcunCXEs with other insects' CXEs, and used quantitative PCR to investigate the gene expression of H. cunea CXEs (HcunCXEs). Our results indicate that HcunCXEs are highly expressed in antennae, legs and wings, suggesting a potential function in degrading sex pheromone components, host plant volatiles, and other xenobiotics. This study not only provides a theoretical basis for subsequent olfactory mechanism studies on H. cunea, but also offers some new insights into functions and evolutionary characteristics of CXEs in lepidopteran insects. From a practical point of view, these HcunCXEs might represent meaningful targets for developing behavioral interference control strategies against H. cunea. Title: Association analysis between FASN genotype and milk traits in Mediterranean buffalo and its expression among different buffalo tissues Ye T, Deng T, Hosseini SM, Raza SHA, Du C, Chen C, Zhang X, Hu X, Yang L Ref: Trop Anim Health Prod, 53:366, 2021 : PubMed ESTHER: Ye_2021_Trop.Anim.Health.Prod_53_366 PubMedSearch: Ye 2021 Trop.Anim.Health.Prod 53 366 PubMedID: 34156604 Abstract Fatty acid synthase (FASN) is a multifunctional protein that catalyzes the synthesis of long-chain saturated fatty acid. In this study, we identified the single nucleotide polymorphisms (SNPs), and their association with milk traits in Mediterranean buffalo, and the expression of FASN gene in different tissues was measured. Nine SNPs (g.-1640G > A, g.-1099C > T, g.1095C > A, g.3221G > A, g.4762G > A, g.5299G > A, g.7164G > A, g.7272 T > C, and g.8927 T > C) were identified by DNA pooled sequencing and then genotyped. Seven identified SNPs except g.3221G > A and g.8927 T > C were found significantly associated with both fat and protein percentage, and also the g.7164G > A and g.8927 T > C had significant association with peak milk yield and protein percentage, respectively. One haplotype block was successfully constructed by linkage disequilibrium (LD) analysis and it showed a significant association with both fat percentage and protein percentage. Expression of FASN gene was found in almost all the buffalo tissues including mammary gland, heart, liver, spleen, lung, kidney, uterus, and ovary, and to be highest in lung and mammary gland. Our findings suggest that polymorphisms in the buffalo FASN gene are associated with milk production traits and can be used as a candidate gene for milk traits and marker-assisted selection in buffalo breeding program. Title: Identification of Candidate Carboxylesterases Associated With Odorant Degradation in Holotrichia parallela Antennae Based on Transcriptome Analysis Yi J, Wang S, Wang Z, Wang X, Li G, Zhang X, Pan Y, Zhao S, Zhang J and Xi J <2 more author(s)> Yi J, Wang S, Wang Z, Wang X, Li G, Zhang X, Pan Y, Zhao S, Zhang J, Zhou JJ, Wang J, Xi J (- 2) Ref: Front Physiol, 12:674023, 2021 : PubMed ESTHER: Yi_2021_Front.Physiol_12_674023 PubMedSearch: Yi 2021 Front.Physiol 12 674023 PubMedID: 34566671 Abstract Insects rely on their olfactory systems in antennae to recognize sex pheromones and plant volatiles in surrounding environments. Some carboxylesterases (CXEs) are odorant-degrading enzymes (ODEs), degrading odorant signals to protect the olfactory neurons against continuous excitation. However, there is no report about CXEs in Holotrichia parallela, one of the most major agricultural underground pests in China. In the present study, 20 candidate CXEs were identified based on transcriptome analysis of female and male antennae. Sequence alignments and phylogenetic analysis were performed to investigate the characterization of these candidate CXEs. The expression profiles of CXEs were compared by RT-qPCR analysis between olfactory and non-olfactory tissues of both genders. HparCXE4, 11, 16, 17, 18, 19, and 20 were antenna-biased expressed genes, suggesting their possible roles as ODEs. HparCXE6, 10, 11, 13, and 16 showed significantly higher expression profiles in male antennae, whereas HparCXE18 was expressed more in female antennae. This study highlighted candidate CXE genes linked to odorant degradation in antennae, and provided a useful resource for further work on the H. parallela olfactory mechanism and selection of target genes for integrative control of H. parallela. Title: Characterization and structural analysis of a thermophilic GH11 xylanase from compost metatranscriptome Yi Y, Xu S, Kovalevsky A, Zhang X, Liu D, Wan Q Ref: Applied Microbiology & Biotechnology, 105:7757, 2021 : PubMed ESTHER: Yi_2021_Appl.Microbiol.Biotechnol_105_7757 PubMedSearch: Yi 2021 Appl.Microbiol.Biotechnol 105 7757 PubMedID: 34553251 Abstract Xylanase is efficient for xylan degradation and widely applied in industries. We found a GH11 family xylanase (Xyn11A) with high thermostability and catalytic activity from compost metatranscriptome. This xylanase has the optimal reaction temperature at 80 degreesC with the activity of 2907.3 U/mg. The X-ray crystallographic structure shows a typical "right hand" architecture, which is the characteristics of the GH11 family enzymes. Comparing it with the mesophilic XYN II, a well-studied GH11 xylanase from Trichoderma reesei, Xyn11A is more compact with more H-bonds. Our mutagenic results show that the electrostatic interactions in the thumb and palm region of Xyn11A could result in its high thermostability and activity. Introducing a disulfide bond at the N-terminus further increased its optimal reaction temperature to 90 degreesC with augmented activity. KEY POINTS: A hyperthermophilic xylanase with high activity was discovered using the metatranscriptomic method. The mechanisms of thermophilicity and high activity were revealed using X-ray crystallography, mutagenesis, and molecular dynamics simulations. The thermostability and activity were further improved by introducing a disulfide bond. Title: Expression and kinetic analysis of carboxylesterase LmCesA1 from Locusta migratoria Yin F, Ma W, Li D, Zhang X, Zhang J Ref: Biotechnol Lett, :, 2021 : PubMed ESTHER: Yin_2021_Biotechnol.Lett__ PubMedSearch: Yin 2021 Biotechnol.Lett PubMedID: 33511494 Gene_locus related to this paper: locmi-l7su46 Abstract OBJECTIVE: To investigate the biochemical characterization of the carboxylesterase LmCesA1 from Locusta migratoria. RESULTS: We expressed recombinant LmCesA1 in Sf9 cells by using the Bac-to-bac baculovirus expression system. Enzyme kinetic assays showed that the K(m) values of LmCesA1 for alpha-naphthyl acetate (alpha-NA) and beta-naphthyl acetate (beta-NA) were 0.08 +/- 0.01 mM and 0.22 +/- 0.03 mM, respectively, suggesting that LmCesA1 has a higher affinity for alpha-NA. LmCesA1 retained its enzymatic activity during incubations at pH 7-10 and at 10-30 degreesC. In an inhibition experiment, two organophosphate pesticides (malaoxon and malathion) and one pyrethroid pesticide (deltamethrin) showed different inhibition profiles against purified LmCesA1. Recombinant LmCesA1 activity was significantly inhibited by malaoxon in vitro. UPLC analysis showed that no metabolites were detected. CONCLUSIONS: These results suggest that overexpression of LmCesA1 enhances malathion sequestration to confer malathion tolerance in L. migratoria. Title: Structural basis for substrate specificity of the peroxisomal acyl-CoA hydrolase MpaH' involved in mycophenolic acid biosynthesis You C, Li F, Zhang X, Ma L, Zhang YZ, Zhang W, Li S Ref: Febs J, :, 2021 : PubMed ESTHER: You_2021_FEBS.J__ PubMedSearch: You 2021 FEBS.J PubMedID: 33843134 Inhibitor(s) related to this paper: Mycophenolic-acid Abstract Mycophenolic acid (MPA) is a fungal natural product and first-line immunosuppressive drug for organ transplantations and autoimmune diseases. In the compartmentalized biosynthesis of MPA, the acyl-coenzyme A (CoA) hydrolase MpaH' located in peroxisomes catalyzes the highly specific hydrolysis of MPA-CoA to produce the final product MPA. The strict substrate specificity of MpaH' not only averts undesired hydrolysis of various cellular acyl-CoAs, but also prevents MPA-CoA from further peroxisomal beta-oxidation catabolism. To elucidate the structural basis for this important property, in this study, we solve the crystal structures of the substrate-free form of MpaH' and the MpaH'(S139A) mutant in complex with the product MPA. The MpaH' structure reveals a canonical alpha/beta-hydrolase fold with an unusually large cap domain and a rare location of the acidic residue D163 of catalytic triad after strand beta6. MpaH' also forms an atypical dimer with the unique C-terminal helices alpha13 and alpha14 arming the cap domain of the other protomer and indirectly participating in the substrate binding. With these characteristics, we propose that MpaH' and its homologues form a new subfamily of alpha/beta hydrolase fold protein. The crystal structure of MpaH'(S139A) /MPA complex and the modelled structure of MpaH'/MPA-CoA, together with the structure-guided mutagenesis analysis and isothermal titration calorimetry (ITC) measurements provide important mechanistic insights into the high substrate specificity of MpaH'. Title: Active site architecture of an acetyl xylan esterase indicates a novel cold adaptation strategy Zhang Y, Ding HT, Jiang WX, Zhang X, Cao HY, Wang JP, Li CY, Huang F, Zhang XY and Li PY <2 more author(s)> Zhang Y, Ding HT, Jiang WX, Zhang X, Cao HY, Wang JP, Li CY, Huang F, Zhang XY, Chen XL, Zhang YZ, Li PY (- 2) Ref: Journal of Biological Chemistry, :100841, 2021 : PubMed ESTHER: Zhang_2021_J.Biol.Chem__100841 PubMedSearch: Zhang 2021 J.Biol.Chem 100841 PubMedID: 34058201 Abstract SGNH-type acetyl xylan esterases (AcXEs) play important roles in marine and terrestrial xylan degradation, which are necessary for removing acetyl side groups from xylan. However, only a few cold-adapted AcXEs have been reported, and the underlying mechanisms for their cold adaptation are still unknown due to the lack of structural information. Here, a cold-adapted AcXE, AlAXEase, from the Arctic marine bacterium Arcticibacterium luteifluviistationis SM1504(T) was characterized. AlAXEase could deacetylate xylooligosaccharides and xylan, which, together with its homologs, indicates a novel SGNH-type carbohydrate esterase family. AlAXEase showed the highest activity at 30 degreesC and retained over 70% activity at 0 degreesC, but had unusual thermostability with a T(m) value of 56 degreesC. To explain the cold adaption mechanism of AlAXEase, we next solved its crystal structure. AlAXEase has similar noncovalent stabilizing interactions to its mesophilic counterpart at the monomer level and forms stable tetramers in solution, which may explain its high thermostability. However, a long loop containing the catalytic residues Asp200 and His203 in AlAXEase was found to be flexible due to the reduced stabilizing hydrophobic interactions and increased destabilizing asparagine and lysine residues, leading to a highly flexible active site. Structural and enzyme kinetic analyses combined with molecular dynamics simulations at different temperatures revealed that the flexible catalytic loop contributes to the cold adaptation of AlAXEase by modulating the distance between the catalytic His203 in this loop and the nucleophilic Ser32. This study reveals a new cold adaption strategy adopted by the thermostable AlAXEase, shedding light on the cold adaption mechanisms of AcXEs. Title: Thyroid hormone synthesis continues despite biallelic thyroglobulin mutation with cell death Zhang X, Kellogg AP, Citterio CE, Zhang H, Larkin D, Morishita Y, Targovnik HM, Balbi VA, Arvan P Ref: JCI Insight, 6:, 2021 : PubMed ESTHER: Zhang_2021_JCI.Insight_6_e148496 PubMedSearch: Zhang 2021 JCI.Insight 6 e148496 PubMedID: 33914707 Gene_locus related to this paper: human-TG Abstract Complete absence of thyroid hormone is incompatible with life in vertebrates. Thyroxine is synthesized within thyroid follicles upon iodination of thyroglobulin conveyed from the endoplasmic reticulum (ER), via the Golgi complex, to the extracellular follicular lumen. In congenital hypothyroidism from biallelic thyroglobulin mutation, thyroglobulin is misfolded and cannot advance from the ER, eliminating its secretion and triggering ER stress. Nevertheless, untreated patients somehow continue to synthesize sufficient thyroxine to yield measurable serum levels that sustain life. Here, we demonstrate that TGW2346R/W2346R humans, TGcog/cog mice, and TGrdw/rdw rats exhibited no detectable ER export of thyroglobulin, accompanied by severe thyroidal ER stress and thyroid cell death. Nevertheless, thyroxine was synthesized, and brief treatment of TGrdw/rdw rats with antithyroid drug was lethal to the animals. When untreated, remarkably, thyroxine was synthesized on the mutant thyroglobulin protein, delivered via dead thyrocytes that decompose within the follicle lumen, where they were iodinated and cannibalized by surrounding live thyrocytes. As the animals continued to grow goiters, circulating thyroxine increased. However, when TGrdw/rdw rats age, they cannot sustain goiter growth that provided the dying cells needed for ongoing thyroxine synthesis, resulting in profound hypothyroidism. These results establish a disease mechanism wherein dead thyrocytes support organismal survival. Title: Attenuation of virulence in multiple serotypes (M1, M3, and M28) of Group A Streptococcus after the loss of secreted esterase Zhang X, Zhao Y, Wang Y, Cai M, Song Y, Zhu H Ref: J Microbiol Immunol Infect, :, 2021 : PubMed ESTHER: Zhang_2021_J.Microbiol.Immunol.Infect__ PubMedSearch: Zhang 2021 J.Microbiol.Immunol.Infect PubMedID: 34674958 Abstract INTRODUCTION: Group A Streptococcus (GAS) can produce streptococcal secreted esterase (Sse), which inhibits neutrophil recruitment to the site of infection and is crucial for GAS pathogenesis. As an effective esterase, Sse hydrolyzes the sn-2 ester bond of human platelet-activating factor, inactivating it and abolishing its ability to recruit neutrophils. OBJECTIVES: The purpose of this study was to investigate the effects of sse deletion on the virulence of multiple serotypes of GAS. METHODS: Isogenic strains that lack the sse gene (deltasse) were derived from the parent strains MGAS5005 (serotype M1, CovRS mutant), MGAS2221 (serotype M1, wild-type CovRS), MGAS315 (serotype M3, CovRS mutant) and MGAS6180 (serotype M28, wild-type CovRS) and were used to study the differences in virulence and pathogenicity of GAS serotypes. RESULTS: In a subcutaneous infection model, mice infected with MGAS5005(deltasse) exhibited higher survival rates but decreased dissemination to the organs compared with mice infected with MGAS5005. When mice were infected with the four deltasse mutants, the MPO activity and IFN-gamma, TNF-alpha, IL-2 and IL-6 levels increased, but the skin lesion sizes decreased. In an intraperitoneal infection model, the absence of Sse significantly reduced the virulence of GAS, leading to increased mouse survival rates and decreased GAS burdens in the organs in most of the challenge experiments. In addition, the numbers of the four deltasse mutants were greatly reduced 60 min after incubation with isolated rat neutrophils. CONCLUSION: Our results suggest that Sse participates in the pathogenesis of multiple GAS serotypes (MGAS5005, MGAS2221, MGAS315 and MGAS6180), particularly the hypervirulent CovS mutant strains MGAS5005 and MGAS315. These strain differences were positively correlated with the virulence of the serotype. Title: Genome-Wide Identification of GDSL-Type Esterase/Lipase Gene Family in Dasypyrum villosum L. Reveals That DvGELP53 Is Related to BSMV Infection Zhang H, Zhang X, Zhao J, Sun L, Wang H, Zhu Y, Xiao J, Wang X Ref: Int J Mol Sci, 22:, 2021 : PubMed ESTHER: Zhang_2021_Int.J.Mol.Sci_22_ PubMedSearch: Zhang 2021 Int.J.Mol.Sci 22 PubMedID: 34830200 Abstract GDSL-type esterase/lipase proteins (GELPs) characterized by a conserved GDSL motif at their N-terminus belong to the lipid hydrolysis enzyme superfamily. In plants, GELPs play an important role in plant growth, development and stress response. The studies of the identification and characterization of the GELP gene family in Triticeae have not been reported. In this study, 193 DvGELPs were identified in Dasypyrum villosum and classified into 11 groups (clade A-K) by means of phylogenetic analysis. Most DvGELPs contain only one GDSL domain, only four DvGELPs contain other domains besides the GDSL domain. Gene structure analysis indicated 35.2% DvGELP genes have four introns and five exons. In the promoter regions of the identified DvGELPs, we detected 4502 putative cis-elements, which were associated with plant hormones, plant growth, environmental stress and light responsiveness. Expression profiling revealed 36, 44 and 17 DvGELPs were highly expressed in the spike, the root and the grain, respectively. Further investigation of a root-specific expressing GELP, DvGELP53, indicated it was induced by a variety of biotic and abiotic stresses. The knockdown of DvGELP53 inhibited long-distance movement of BSMV in the tissue of D. villosum. This research provides a genome-wide glimpse of the D. villosum GELP genes and hints at the participation of DvGELP53 in the interaction between virus and plants. Title: Genome sequencing of the Australian wild diploid species Gossypium australe highlights disease resistance and delayed gland morphogenesis Cai Y, Cai X, Wang Q, Wang P, Zhang Y, Cai C, Xu Y, Wang K, Zhou Z and Liu F <25 more author(s)> Cai Y, Cai X, Wang Q, Wang P, Zhang Y, Cai C, Xu Y, Wang K, Zhou Z, Wang C, Geng S, Li B, Dong Q, Hou Y, Wang H, Ai P, Liu Z, Yi F, Sun M, An G, Cheng J, Shi Q, Xie Y, Shi X, Chang Y, Huang F, Chen Y, Hong S, Mi L, Sun Q, Zhang L, Zhou B, Peng R, Zhang X, Liu F (- 25) Ref: Plant Biotechnol J, 18:814, 2020 : PubMed ESTHER: Cai_2020_Plant.Biotechnol.J_18_814 PubMedSearch: Cai 2020 Plant.Biotechnol.J 18 814 PubMedID: 31479566 Gene_locus related to this paper: gosra-a0a0d2pzd7 Abstract The diploid wild cotton species Gossypium australe possesses excellent traits including resistance to disease and delayed gland morphogenesis, and has been successfully used for distant breeding programmes to incorporate disease resistance traits into domesticated cotton. Here, we sequenced the G. australe genome by integrating PacBio, Illumina short read, BioNano (DLS) and Hi-C technologies, and acquired a high-quality reference genome with a contig N50 of 1.83 Mb and a scaffold N50 of 143.60 Mb. We found that 73.5% of the G. australe genome is composed of various repeat sequences, differing from those of G. arboreum (85.39%), G. hirsutum (69.86%) and G. barbadense (69.83%). The G. australe genome showed closer collinear relationships with the genome of G. arboreum than G. raimondii and has undergone less extensive genome reorganization than the G. arboreum genome. Selection signature and transcriptomics analyses implicated multiple genes in disease resistance responses, including GauCCD7 and GauCBP1, and experiments revealed induction of both genes by Verticillium dahliae and by the plant hormones strigolactone (GR24), salicylic acid (SA) and methyl jasmonate (MeJA). Experiments using a Verticillium-resistant domesticated G. barbadense cultivar confirmed that knockdown of the homologues of these genes caused a significant reduction in resistance against Verticillium dahliae. Moreover, knockdown of a newly identified gland-associated gene GauGRAS1 caused a glandless phenotype in partial tissues using G. australe. The G. australe genome represents a valuable resource for cotton research and distant relative breeding as well as for understanding the evolutionary history of crop genomes. Title: Correlation analysis between CARMEN variants and alcohol-induced osteonecrosis of the femoral head in the Chinese population Guo Y, Cao Y, Gong S, Zhang S, Hou F, Zhang X, Hu J, Yang Z, Yi J and Song J <2 more author(s)> Guo Y, Cao Y, Gong S, Zhang S, Hou F, Zhang X, Hu J, Yang Z, Yi J, Luo D, Chen X, Song J (- 2) Ref: BMC Musculoskelet Disord, 21:547, 2020 : PubMed ESTHER: Guo_2020_BMC.Musculoskelet.Disord_21_547 PubMedSearch: Guo 2020 BMC.Musculoskelet.Disord 21 547 PubMedID: 32799824 Abstract BACKGROUND: Osteonecrosis of the femoral head (ONFH) is a complicated disease associated with trauma, hormone abuse and excessive alcohol consumption. Polymorphisms of long non-coding RNAs have been also linked with the development of ONFH. Our research aimed to explore the relationship between CARMEN (Cardiac Mesoderm Enhancer-Associated Non-Coding RNA) variants and ONFH risk. METHODS: Our study used Agena MassARRAY Assay to genotype 6 selected single nucleotide polymorphisms (SNPs) in 731 participants (308 alcohol-induced ONFH patients and 423 controls). We used odds ratios (ORs) and 95% confidence intervals (CIs) to calculate the effect of gene polymorphisms on the occurrence of alcohol-induced ONFH by logistic regression analysis and haplotype analysis. RESULTS: Our overall analysis illustrated that rs13177623 and rs12654195 had an association with a reduced risk of ONFH after adjustment for age and gender. We also found that rs13177623, rs12654195 and rs11168100 were associated with a decreased susceptibility to alcohol-induced ONFH in people <=45 years. In addition, the necrotic sites stratification analysis showed that rs12654195 was only found to be related to alcohol-induced ONFH risk in the recessive model. In patients with different clinical stages, rs353300 was observed to be associated with a higher incidence of ONFH. Individuals with different genotypes of rs13177623, rs12654195 and rs11168100 had significantly different clinical parameters (cholinesterase, globulin, percentage of neutrophils and the absolute value of lymphocytes). CONCLUSIONS: Our data provided new light on the association between CARMEN polymorphisms and alcohol-induced ONFH risk in the Chinese Han population. Title: Combined Omics Approach Identifies Gambogic Acid and Related Xanthones as Covalent Inhibitors of the Serine Palmitoyltransferase Complex Hoch DG, Abegg D, Hannich JT, Pechalrieu D, Shuster A, Dwyer BG, Wang C, Zhang X, You Q and Adibekian A <1 more author(s)> Hoch DG, Abegg D, Hannich JT, Pechalrieu D, Shuster A, Dwyer BG, Wang C, Zhang X, You Q, Riezman H, Adibekian A (- 1) Ref: Cell Chemical Biology, 27:586, 2020 : PubMed ESTHER: Hoch_2020_Cell.Chem.Biol_27_586 PubMedSearch: Hoch 2020 Cell.Chem.Biol 27 586 PubMedID: 32330443 Abstract In this study, we identify the natural product gambogic acid as well as structurally related synthetic xanthones as first-in-class covalent inhibitors of the de novo sphingolipid biosynthesis. We apply chemoproteomics to determine that gambogic acid binds to the regulatory small subunit B of the serine palmitoyltransferase complex (SPTSSB). We then test structurally related synthetic xanthones to identify 18 as an equally potent but more selective binder of SPTSSB and show that 18 reduces sphingolipid levels in situ and in vivo. Finally, using various biological methods, we demonstrate that 18 induces cellular responses characteristic for diminished sphingosine-1-phosphate (S1P) signaling. This study demonstrates that SPTSSB may become a viable therapeutic target in various diseases with pathological S1P signaling. Furthermore, we believe that our compound will become a valuable tool for studying the sphingolipid metabolism and serve as a blueprint for the development of a new generation of sphingolipid biosynthesis inhibitors. Title: Improved production of recombinant Rhizomucor miehei lipase by coexpressing protein folding chaperones in Pichia pastoris, which triggered ER stress Huang J, Zhao Q, Chen L, Zhang C, Bu W, Zhang X, Zhang K, Yang Z Ref: Bioengineered, 11:375, 2020 : PubMed ESTHER: Huang_2020_Bioengineered_11_375 PubMedSearch: Huang 2020 Bioengineered 11 375 PubMedID: 32175802 Abstract Rhizomucor miehei lipase (RML) is a biocatalyst that widely used in laboratory and industrial. Previously, RML with a 70-amino acid propeptide (pRML) was cloned and expressed in P. pastoris. Recombinant strains with (strain containing 4-copy prml) and without ER stress (strain containing 2-copy prml) were obtained. However, the effective expression of pRML in P. pastoris by coexpressing ER-related elements in pRML-produced strain with or without ER stress has not been reported to date. In this study, an efficient way to produce functional pRML was explored in P. pastoris. The coexpression of protein folding chaperones, including PDI and ERO1, in different strains with or without ER stress, was investigated. PDI overexpression only increased pRML production in 4-copy strain from 705 U/mL to 1430 U/mL because it alleviated the protein folded stress, increased the protein concentration from 0.56 mg/mL to 0.65 mg/mL, and improved enzyme-specific activity from 1238 U/mg to 2186 U/mg. However, PDI coexpression could not improve pRML production in the 2-copy strain because it increased protein folded stress, while ERO1 coexpression in the two strains all had a negative effect on pRML expression. We also investigated the effect of the propeptide on the substrate specificity and the condition for pRML enzyme powder preparation. Results showed that the relative activity exceeded 80% when the substrates C8-C10 were detected at 35 degrees C and pH 6, and C8-C12 at 45 degrees C and pH 8. The optimal enzyme powder preparation pH was 7, and the maximum recovery rate for pRML was 73.19%. Title: Inhibition of acetylcholinesterase attenuated retinal inflammation via suppressing NF-kappaB activation Li J, Chen Y, Zhang X, Ye S, Yi J, Chen Q, Liu Q Ref: Experimental Eye Research, :108003, 2020 : PubMed ESTHER: Li_2020_Exp.Eye.Res__108003 PubMedSearch: Li 2020 Exp.Eye.Res 108003 PubMedID: 32184102 Abstract Elevated inflammatory cytokines contribute to the pathogenesis of various retinal diseases such as diabetic retinopathy, retinal vasculitis and retinitis. However, the underlying mechanism of retinal inflammation remains largely unknown. Recent studies demonstrated that acetylcholinesterase (ACHE) is an inflammatory indicator in central neural system. This study was aimed to dissect the role of ACHE in retinal inflammation, and its mechanism of action. Retinal inflammation was induced by intravitreal injection of tumor necrosis factor-alpha (TNF-alpha) in heterozygous ACHE knockout mice (ACHE(+/-)) and wild type mice (ACHE(+/+)). Donepezil, a well-known ACHE inhibitor, was administrated by daily gavage. Expression of ACHE and intercellular adherent molecule-1 (ICAM-1), infiltration of CD11b(+) inflammatory cells, retinal leukostasis and vascular leakage was determined in both ACHE (+/-) and ACHE(+/+) mice. ARPE-19cells, a human retinal pigment epithelial cell line, were cultured for in vitro assay. Knockdown of ACHE was achieved by lipofectamine-mediated siRNA transfection and pharmaceutical suppression of ACHE was manipulated by donepezil. Cellular expression and distribution of ACHE, ICAM-1, and phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta were detected by western-blot analysis or immunocytochemistry. Retinal expression of ACHE was dramatically upregulated, in parallel with increased ICAM-1 expression, enhanced leukostasis and augmented CD11b(+) inflammatory cells infiltration as well as vascular hyperpermeability in ACHE(+/+) mice injected with TNF-alpha. However, TNF-alpha-injected ACHE (+/-) mice showed lower level of ICAM-1, less leukostasis and fewer infiltrated CD11b(+) cells. Moreover, TNF-alpha-induced retinal vascular leakage was significantly reduced in ACHE (+/-) mice. Similarly, TNF-alpha-induced retinal inflammatory response were also attenuated by donepezil intervention. In addition, TNF-alpha treatment resulted in significant induction of ACHE, upregulation of ICAM-1 and nuclear translocation of NF-kappaB in cultured-ARPE-19cells. Genetic and pharmaceutical suppression of ACHE markedly attenuated TNF-alpha-induced ICAM-1 expression. Meanwhile, inhibition of ACHE reduced TNF-alpha-induced phosphorylation of NF-kappaB, IkappaB and IKKalpha/beta in ARPE-19cells. The present study reveals a pivotal role of ACHE in retinal inflammation. Inhibition of ACHE attenuates retinal inflammation and retinal leakage likely through suppressing NF-kappaB signaling activation. Title: Promoting Active Sites in MOF-Derived Homobimetallic Hollow Nanocages as a High-Performance Multifunctional Nanozyme Catalyst for Biosensing and Organic Pollutant Degradation Li S, Hou Y, Chen Q, Zhang X, Cao H, Huang Y Ref: ACS Appl Mater Interfaces, 12:2581, 2020 : PubMed ESTHER: Li_2020_ACS.Appl.Mater.Interfaces_12_2581 PubMedSearch: Li 2020 ACS.Appl.Mater.Interfaces 12 2581 PubMedID: 31854974 Abstract Nanozymes are one of the ideal alternatives to natural enzymes for various applications. The rational design of nanozymes with improved catalytic activity stimulates increasing attention to address the low activity of current nanozymes. Here, we reported a general strategy to fabricate the Co-based homobimetallic hollow nanocages (HNCs) (C-CoM-HNC, M = Ni, Mn, Cu, and Zn) by ion-assistant solvothermal reaction and subsequent low-temperature calcination from metal-organic frameworks. The C-CoM-HNCs are featured with HNCs composed of interlaced nanosheets with homogeneous bimetallic oxide dispersion. The hierarchical structure and secondary metallic doping endow the C-CoM-HNC highly active sites. In particular, the Cu-doped C-CoCu-HNCs nanostructures exhibit superior performances over the other C-CoM-HNC as both the oxidase mimicking and peroxymonosulfate (PMS) activator. A sensitive bioassay for acetylcholinesterase (AChE) was established based on the excellent oxidase-like activity of C-CoCu-HNC, offering a linear detection range from 0.0001 to 1 mU/mL with an ultralow detection limit of 0.1 mU/L. As the PMS activator, the C-CoCu-HNC was applied for targeted organic pollutant (rhodamine B, RhB) degradation. A highly efficient RhB degradation was realized, along with good adaptability in a wide pH range and good reusability during the eight-cycle run. The results suggest that C-CoCu-HNC holds a practical potential for clinical diagnostics and pollution removal. Further density functional theory calculation reveals that Cu doping leads to a tighter connection and more negative adsorption energy for O2/PMS, as well as an upshifted d-band center in the C-CoCu-HNCs nanostructures. These changes facilitated the adsorption of O2/PMS on the C-CoCu-HNC surface for dissociation. This work not only offers a promising multifunctional nanozyme catalyst for clinical diagnostics and pollution removal but also gives some clues for the further development of novel nanozymes with high catalytic activities. Title: Acetylcholinesterase inhibition ameliorates retinal neovascularization and glial activation in oxygen-induced retinopathy Liu QP, Zhang X, Qin YZ, Yi JL, Li JM Ref: Int J Ophthalmol, 13:1361, 2020 : PubMed ESTHER: Liu_2020_Int.J.Ophthalmol_13_1361 PubMedSearch: Liu 2020 Int.J.Ophthalmol 13 1361 PubMedID: 32953572 Abstract AIM: To investigate whether inhibition of acetylcholinesterase (AChE) by donepezil ameliorate aberrant retinal neovascularization (RNV) and abnormal glial activation in oxygen-induced retinopathy (OIR). METHODS: A mouse model of RNV was induced in postnatal day 7 (P7) mice by exposure to 75% oxygen. Donepezil was administrated to P12 mice by intraperitoneal injection. Expression and localization of AChE in mouse retinas were determined by immunofluorescence. RNV was evaluated by paraffin sectioning and hematoxylin and eosin (HE) staining. Activation of retinal Muller glial cells were examined by immunoblot of glial fibrillary acidic protein (GFAP). rMC-1, a retinal Muller cell line, was used for in vitro study. Expression of hypoxia-induced factor 1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) were determined by Western-blot analysis, enzyme-linked immunosorbent assay (ELISA) or immunostaining. RESULTS: Aberrant RNV and glial activation was observed after OIR. Of note, retinal AChE was mainly expressed by retinal Muller glial cells and markedly increased in OIR mice. Systemic administration of donepezil significantly reduced RNV and abnormal glial activation in mice with OIR. Moreover, ischemia-induced HIF-1alpha accumulation and VEGF upregulation in OIR mouse retinas and cultured rMC-1 were significantly inhibited by donepezil intervention. CONCLUSION: AchE is implicated in RNV with OIR. Inhibition of AChE by donepeizl is likely to be a potential therapeutic approach for retinal neovascular diseases. Title: Enantioselective toxicity and oxidative stress effects of acetochlor on earthworms (Eisenia fetida) by mediating the signaling pathway Liu Y, Fang K, Zhang X, Liu T, Wang X Ref: Sci Total Environ, :142630, 2020 : PubMed ESTHER: Liu_2020_Sci.Total.Environ__142630 PubMedSearch: Liu 2020 Sci.Total.Environ 142630 PubMedID: 33069465 Abstract Acetochlor (ACT) as a widely used chiral chloroacetamide herbicide is appropriate to evaluate the potential toxicity in soil ecosystems at enantiomeric level. The acute and subchronic toxicities of R-acetochlor (R-ACT) and S-acetochlor (S-ACT) on earthworms (Eisenia fetida) were investigated in the present study. Residual analyses showed that S-ACT degraded faster than R-ACT in artificial soil with half-lives of 16.5 and 21.7 d, respectively. Additionally, significant enantioselective acute toxicity in earthworms from between S-ACT and R-ACT (p < 0.05) was observed, and the acute toxicity of R-ACT were 1.9 and 1.5 times higher than those of S-ACT in the filter paper test and artificial soil test. The hydroxyl radical (OH(-)) content, superoxide dismutase (SOD) and antioxidant enzyme catalase (CAT) activities, and cytochrome P450 content in earthworms significantly increased under the influence of ACT enantiomers; however, the acetylcholinesterase (AchE) activity was significantly inhibited after exposure to the two enantiomers. Moreover, lipid peroxidation and DNA damage were induced by ACT enantiomers. The results of transcriptome sequencing indicated that R-ACT induced a stronger oxidative stress effect than S-ACT in earthworms by mediating signaling pathways, which may be the primary reason for the enantioselective toxicity between S-ACT and R-ACT. Overall, the results demonstrated that R-ACT has a higher risk than S-ACT in the soil environment, which is important for understanding the enantioselective behavior of chloroacetamide pesticides. Title: Huperzine A inhibits heroin-seeking behaviors induced by cue or heroin priming in rats Ma B, Cai Y, Zhang X, Wang F, Zhuang D, Liu H, Liu Y, Zhou W Ref: Neuroreport, 31:819, 2020 : PubMed ESTHER: Ma_2020_Neuroreport_31_819 PubMedSearch: Ma 2020 Neuroreport 31 819 PubMedID: 32576772 Abstract Cholinergic systems modulate dopaminergic function in brain pathways are thought to mediate heroin addiction. This study investigated whether huperzine A, an acetylcholinesterase inhibitor, has beneficial effects on heroin reward and heroin-seeking behavior. Rats were trained to self-administer heroin (50microg/kg/infusion) under the fixed ratio 1 schedule for 14days and then drug-seeking was extinguished for 10days, after which reinstatement of drug-seeking was induced by conditioned cues or heroin priming. Acute treatment with huperzine A at dose from 0.05 to 0.2mg/kg potently and dose-dependently suppressed the cue- and heroin-induced reinstatement of heroin-seeking behavior following extinction. Huperzine A at these doses failed to alter either heroin rewarding effect or spontaneous locomotion activity. The study demonstrated that acute treatment with huperzine A inhibited heroin-seeking behavior, suggesting that huperzine A may be used as an adjuvant treatment for heroin relapse and addiction. Title: Evaluation of physiological and biochemical effects of two Sophora alopecuroides alkaloids on pea aphids Acyrthosiphon pisum Ma T, Shi X, Ma S, Ma Z, Zhang X Ref: Pest Manag Sci, 76:4000, 2020 : PubMed ESTHER: Ma_2020_Pest.Manag.Sci_76_4000 PubMedSearch: Ma 2020 Pest.Manag.Sci 76 4000 PubMedID: 32506722 Abstract BACKGROUND: Sophora alopecuroides alkaloids are the main constituents for the broad bioactivities on insect pests, especially on aphids. However, the aphicidal mode of action of S. alopecuroides alkaloids remains unclear. To clarify the aphicidal action, avermectin was selected as a positive control, and matrine, sophocarpine were chosen as the representative alkaloids to determine the physiological and biochemical effects on pea aphids (Acyrthosiphon pisum). RESULTS: The aphids treated by matrine and sophocarpine developed the intoxication symptoms of convulsions, paralysis, and death. However, avermectin showed no convulsions. Moreover, the two alkaloids had a significant inducing effect on glutamic acid decarboxylase, and the specific enzyme activity was 1.14-1.22 times of the control group. In the meanwhile, both matrine and sophocarpine possessed a dose-response and time-response inhibitory effect on alanine aminotransferase in vivo and in vitro. Furthermore, the glutamate content in pea aphids treated with the two alkaloids increased significantly with time, which was about 1.5-2.0 times that of the control group. Similarly, the GABA content elevated significantly, with an increase of 1.0-1.3 times. In addition, all the treatments, except avermectin, presented inhibitory effects on Na(+) , K(+) -ATPase, Ca(2+) and Mg(2+) -ATPase, with dose-response and time-response effect. However, the three treatments had no significant effect on acetylcholinesterase and acetylcholine content. CONCLUSION: The toxicological action of matrine and sophocarpine is related to the regulation on glutamate and gamma-aminobutyric acid systems and has certain similarities to that of avermectin. These findings would provide a basis for further mechanism elucidation. 2020 Society of Chemical Industry. Title: The toxicity assessment of extract of Peganum harmala L. seeds in Caenorhabditis elegans Miao X, Zhang X, Yuan Y, Zhang Y, Gao J, Kang N, Liu X, Wu J, Liu Y, Tan P Ref: BMC Complement Med Ther, 20:256, 2020 : PubMed ESTHER: Miao_2020_BMC.Complement.Med.Ther_20_256 PubMedSearch: Miao 2020 BMC.Complement.Med.Ther 20 256 PubMedID: 32807143 Abstract BACKGROUND: Peganum harmala L. is a medicinal herb extensively used in traditional Chinese medicine (TCM). So far, relevant reports on the toxicity of Peganum harmala L. seeds (PHS) are hardly available. Especially, we still know little about the in vivo mechanism for PHS toxicity. This study aims to evaluate the toxicity effects of PHS in Caenorhabditis elegans (C. elegans), investigate the possible mechanism of the toxicity effects of PHS, and provide reference for the pharmacological research of PHS. METHODS: In the present study, the C. elegans was exposed to 0.25, 0.50, 1.00 mg/mL of PHS in nematode growth medium (NGM) at 22 degC in the presence of food. Lethality, lifespan, growth, reproduction, and locomotion behavior assays were performed to evaluate the toxicity effects of PHS in C. elegans. We then determined the mechanism of the toxicity effect of PHS by quantitative real-time polymerase chain reaction (qRT-PCR), acetylcholinesterase (AChE) activity assay, and oxidative stress resistance assays. The main components of PHS were detected by high performance liquid chromatography (HPLC). RESULTS: Compared with the control group, the lethality of C. elegans was significantly increased when they were exposed to the ethanol extract of PHS at 0.25, 0.50 and 1.00 mg/mL (P < 0.01), and the mean lifespan was significantly decreased (P < 0.01). We also observed that PHS exposure could induce the toxicity on body length, brood size, and locomotion behavior. CONCLUSION: Our study shows that the ethanol extract of PHS exerts obvious toxic effects on C. elegans, which would provide new ideas and methods for the biological evaluation of the toxicity of Chinese medicinal materials. Title: Novel turn on-off paper sensor based on nonionic conjugated polythiophene-coated CdTe QDs for efficient visual detection of cholinesterase activity Ou Q, Tawfik SM, Zhang X, Lee YI Ref: Analyst, :, 2020 : PubMed ESTHER: Ou_2020_Analyst__ PubMedSearch: Ou 2020 Analyst PubMedID: 32478771 Abstract An increasing number of patients are living with Alzheimer's disease (AD); thus, the need for a method to detect AD early and sensitively has become urgent, and the demand for an intelligent analytical platform is growing year by year. Abnormal levels of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be indicative of AD. In this work, a novel conjugated polythiophene (CP) compound was successfully combined with CdTe quantum dots (QDs) to improve their selectivity and sensitivity. The QDs successfully enabled the detection of low concentrations of AChE by turning on the fluorescence of the CdTe/CP via the interaction between CP and thiocholine produced by ATCh hydrolysis and aggregation induced emission enhancement (AIEE). Under optimal conditions, we reached a low detection limit of 0.14 U L-1, which is 7.9 times lower than that of pristine QDs. More importantly, an efficient, inexpensive, and disposable paper-based platform, which allows the efficient visual detection of AChE activity via the color variation of CdTe/CP, was designed. Moreover, the accuracy of the method was demonstrated by conducting a recovery test in human serum, in which the recoveries reached 107% and 110%, proving that CdTe/CP has considerable potential to be used for analyzing real biological samples. The advantages of this method are its simplicity, fast detection capability, affordability, and the fact that it can be used for on-site detection of AChE activity. Furthermore, it has certain guiding significance for detecting AD. Title: MLL5alpha activates AR/NDRG1 signaling to suppress prostate cancer progression Quan Y, Cui Y, Wahafu W, Liu Y, Ping H, Zhang X Ref: Am J Cancer Research, 10:1608, 2020 : PubMed ESTHER: Quan_2020_Am.J.Cancer.Res_10_1608 PubMedSearch: Quan 2020 Am.J.Cancer.Res 10 1608 PubMedID: 32509400 Abstract Prostate cancer (PCa) is one of the most prevalent malignancies in men. However, the molecular mechanism controlling the transformation of androgen-dependent PCa (ADPC) to castration-resistant PCa (CRPC) is largely unknown. Androgen receptor (AR) signaling has been reported to play a key role in this process; thus, searching for the novel AR co-activator is important for identifying the mechanism underlying PCa progression. In this study, we focused on the function of mixed lineage leukemia-5alpha (MLL5alpha), an epigenetic regulator that exhibits aberrant expression in PCa. MLL5alpha was the primary expressed form of MLL5 protein in PCa cells and it significantly suppressed proliferation, invasion, and migration in PCa cell lines. Upon stimulation with dihydrotestosterone (DHT), knockdown of MLL5alpha significantly suppressed N-myc downstream regulated gene 1 (NDRG1) and Kallikrein-related peptidase 3 (KLK3) expression. MLL5alpha directly bound with AR on the androgen response elements (AREs) and recruited H3K4me3 to the promoters of NDRG1 and KLK3. Downregulation of NDRG1 partially restored the cell invasion and migration suppressed by MLL5alpha. As evaluated by the proliferation of PCa cells, overexpression of MLL5alpha synergistically promoted sensitivity to enzalutamide (ENZ) treatment. In PCa patients, MLL5alpha expression was lower in the high Gleason score (GS) (GS > 7) group than in the low GS (GS < 7) group. In conclusion, suppression of AR/NDRG1 signaling via androgen deprivation therapy (ADT) may be a potential mechanism of CRPC progression. MLL5alpha significantly suppressed PCa progression by promoting AR/NDRG1 signaling, indicating that regulating MLL5alpha expression may be a potential treatment approach for patients with advanced PCa. Title: Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses Schintu N, Zhang X, Stroth N, Mathe AA, Andren PE, Svenningsson P Ref: Front Pharmacol, 11:304, 2020 : PubMed ESTHER: Schintu_2020_Front.Pharmacol_11_304 PubMedSearch: Schintu 2020 Front.Pharmacol 11 304 PubMedID: 32265703 Abstract Depression is a common comorbid condition in Parkinson's disease (PD). Patients with depression have a two-fold increased risk to develop PD. Further, depression symptoms often precede motor symptoms in PD and are frequent at all stages of the disease. However, the influence of a depressive state on the responses to antiparkinson treatments is largely unknown. In this study, the genetically inbred depression-like flinders sensitive line (FSL) rats and control flinders resistant line (FRL) rats were studied in models of experimental parkinsonism. FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor. We also studied rats lesioned with 6-OHDA to induce hemiparkinsonism. No baseline differences in dopaminergic response to acute apomorphine or L-DOPA was found. However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT1 A agonist/D2 partial agonist sarizotan. In contrast, FSL rats did not develop sensitization of turning and only minor AIMs in response to L-DOPA treatment. The roles of several non-dopamine systems underlying this discrepancy were studied. Unexpectedly, no differences of opioid neuropeptides or serotonin markers were found between FRL and FSL rats. The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression. Title: Lysosome targeting metal-organic framework probe LysFP@ZIF-8 for highly sensitive quantification of carboxylesterase 1 and organophosphates in living cells Shen B, Zhang X, Dai J, Ji Y, Huang H Ref: J Hazard Mater, :124342, 2020 : PubMed ESTHER: Shen_2020_J.Hazard.Mater__124342 PubMedSearch: Shen 2020 J.Hazard.Mater 124342 PubMedID: 33257119 Abstract Herein, a lysosomal targeting LysFP@ZIF-8 metal-organic framework (MOF) was fabricated using fluorescent protein chromophore-based probe (LysFP) for selectively detection of carboxylesterase 1 (CES1) in living cells. Unlike the regular small molecule fluorescent probes, LysFP@ZIF-8 showed wide range pH tolerabiligy, high selectivity and sensitivity to CES1 in bio-samples, and was successfully applied to achieve the visual monitoring of CES1 activity in living cells. Low detection limit and high fluorescence quantum yield was calculated as 79 ng/mL and 0.76 for LysFP@ZIF-8, respectively. Furthermore, LysFP@ZIF-8 can also serve as a fluorescence indicator of organophosphates pesticide exposure in the way of hydrolyzing the carboxylic acid ester group in LysFP. This type of probe can inspire the development of fluorescent tools for further explore many pathological processes. Title: Evaluation of modes of action of pesticides to Daphnia magna based on QSAR, excess toxicity and critical body residues Wang J, Yang Y, Huang Y, Zhang X, Qin WC, Wen Y, Zhao YH Ref: Ecotoxicology & Environmental Safety, 203:111046, 2020 : PubMed ESTHER: Wang_2020_Ecotoxicol.Environ.Saf_203_111046 PubMedSearch: Wang 2020 Ecotoxicol.Environ.Saf 203 111046 PubMedID: 32888614 Abstract Agricultural pesticides serve as effective controls of unwanted weeds and pests. However, these same chemicals can exert toxic effects in non-target organisms. To determine chemical modes of action, the toxicity ratio (TR) and critical body residues (CBRs) of 57 pesticides were calculated for Daphnia magna. Results showed that the CBR values of inert compounds were close to a constant while the CBR values of pesticides varied over a wider range. Although herbicides are categorized as specifically-acting compounds to plants, herbicides did not exhibit excess toxicity to Daphnia magna and were categorized as inert compounds with an average logTR = 0.41, which was less than a threshold of one. Conversely, fungicides and insecticides exhibited strong potential for toxic effects to Daphnia magna with an average logTR >2. Many of these chemicals act via disruption of the nervous, respiratory, or reproductive system, with high ligand-receptor binding activity which leads to higher toxicity for Daphnia magna. Molecular docking using acetylcholinesterase revealed that fungicides and insecticides bind more easily with the biological macromolecule when compared with inert compounds. Quantitative structure-activity relationship (QSAR) analysis revealed that the toxicity of fungicides was mainly dependent upon the heat of formation and polar surface area, while the toxicity of insecticides was more related to hydrogen-bond properties. This comprehensive analysis reveals that there are specific differences in toxic mechanisms between fungicides and insecticides. These results are useful for determining relative risk associated with pesticide exposure to aquatic crustaceans, such as Daphnia magna. Title: Efficacy and safety of DBPR108 monotherapy in patients with type 2 diabetes: a 12-week, randomized, double-blind, placebo-controlled, phase II clinical trial Wang W, Yao J, Guo X, Guo Y, Yan C, Liu K, Zhang Y, Wang X, Li H and Yuan J <22 more author(s)> Wang W, Yao J, Guo X, Guo Y, Yan C, Liu K, Zhang Y, Wang X, Li H, Wen Z, Li S, Xiao X, Liu W, Li Z, Zhang L, Shao S, Ye S, Qin G, Li Y, Li F, Zhang X, Li X, Peng Y, Deng H, Xu X, Zhou L, Huang Y, Cao M, Xia X, Shi M, Dou J, Yuan J (- 22) Ref: Curr Med Res Opin, 36:1107, 2020 : PubMed ESTHER: Wang_2020_Curr.Med.Res.Opin_36_1107 PubMedSearch: Wang 2020 Curr.Med.Res.Opin 36 1107 PubMedID: 32338063 Inhibitor(s) related to this paper: Prusogliptin Abstract Objective: DBPR108, a novel dipeptidyl-peptidase-4 inhibitor, has shown great antihyperglycemic effect in animal models. This study was to evaluate the efficacy and safety of DBPR108 monotherapy in type 2 diabetes mellitus (T2DM).Methods: This was a 12-week, double-blind, placebo-controlled phase II clinical trial. The newly diagnosed or inadequately controlled untreated T2DM patients were randomized to receive 50, 100, 200 mg DBPR108 or placebo in a ratio of 1:1:1:1. The primary efficacy outcome was HbA1c change from baseline to week 12. Relevant secondary efficacy parameters and safety were assessed. The clinical trial registration is NCT04124484.Results: Overall, 271 of the 276 randomized patients, who received 50 mg (n = 68), 100 mg (n = 67), 200 mg (n = 69) DBPR108 or placebo (n = 67), were included in full analysis set. At week 12, HbA1c change from baseline was -0.04 +/- 0.77 in placebo group, -0.51 +/- 0.71, -0.75 +/- 0.73, and -0.57 +/- 0.78 (%, p < .001 vs. placebo) in 50, 100, and 200 mg DBPR108 groups, respectively. Since week 4, DBPR108 monotherapy resulted in significant improvements in secondary efficacy parameters. At end of 12-week treatment, the goal of HbA1c >=7% was achieved in 29.85, 58.82, 55.22, and 47.83% of the patients in placebo, 50, 100, and 200 mg DBPR108 groups, respectively. The incidence of adverse events did not show significant difference between DBPR108 and placebo except mild hypoglycemia in DBPR108 200 mg group.Conclusions: The study results support DBPR108 100 mg once daily as the primary dosing regimen for T2DM patients in phase III development program. Title: Tacrine-hydroxamate derivatives as multitarget-directed ligands for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation Xu A, He F, Zhang X, Li X, Ran Y, Wei C, James Chou C, Zhang R, Wu J Ref: Bioorg Chem, 98:103721, 2020 : PubMed ESTHER: Xu_2020_Bioorg.Chem_98_103721 PubMedSearch: Xu 2020 Bioorg.Chem 98 103721 PubMedID: 32193030 Abstract In order to develop multitarget-directed ligands as potential treatments for Alzheimer's disease, twenty-eight new tacrine-hydroxamate derivatives were designed, synthesized, and biologically evaluated. As expected, most of the compounds exhibited inhibitory activities against cholinesterases (ChEs) and histone deacetylase (HDACs). Among the tested compounds, A10 showed not only potent and selective inhibition on AChE at sub-nanomolar potency (AChEIC50 = 0.12 nM, BChEIC50 = 361.52 nM) but also potent inhibition on HDAC (IC50 = 0.23 nM). Moreover, A10 exhibited inhibitory activity on Abeta1-42 self-aggregation as well as disaggregation activity on pre-formed Abeta fibrils. Furthermore, A10 exhibited antioxidant activity and metal chelating properties. Further mechanistic studies demonstrated that A10 is a pan-inhibitor of HDACs and a mixed-type inhibitor for AChE. It shown that A10 is a BBB penetrant by online prediction. Taken together, the results indicate that A10 can serve as a lead compound to develop promising candidate analogs as AD therapeutics. Title: The genome evolution and low-phosphorus adaptation in white lupin Xu W, Zhang Q, Yuan W, Xu F, Muhammad Aslam M, Miao R, Li Y, Wang Q, Li X and Cheng F <3 more author(s)> Xu W, Zhang Q, Yuan W, Xu F, Muhammad Aslam M, Miao R, Li Y, Wang Q, Li X, Zhang X, Zhang K, Xia T, Cheng F (- 3) Ref: Nat Commun, 11:1069, 2020 : PubMed ESTHER: Xu_2020_Nat.Commun_11_1069 PubMedSearch: Xu 2020 Nat.Commun 11 1069 PubMedID: 32103018 Gene_locus related to this paper: lupal-a0a6a5lz53, lupal-a0a6a5mjk3 Abstract White lupin (Lupinus albus) is a legume crop that develops cluster roots and has high phosphorus (P)-use efficiency (PUE) in low-P soils. Here, we assemble the genome of white lupin and find that it has evolved from a whole-genome triplication (WGT) event. We then decipher its diploid ancestral genome and reconstruct the three sub-genomes. Based on the results, we further reveal the sub-genome dominance and the genic expression of the different sub-genomes varying in relation to their transposable element (TE) density. The PUE genes in white lupin have been expanded through WGT as well as tandem and dispersed duplications. Furthermore, we characterize four main pathways for high PUE, which include carbon fixation, cluster root formation, soil-P remobilization, and cellular-P reuse. Among these, auxin modulation may be important for cluster root formation through involvement of potential genes LaABCG36s and LaABCG37s. These findings provide insights into the genome evolution and low-P adaptation of white lupin. Title: Monoterpene indole alkaloids with diverse skeletons from the stems of Rauvolfia vomitoria and their acetylcholinesterase inhibitory activities Zhan G, Miao R, Zhang F, Hao X, Zheng X, Zhang H, Zhang X, Guo Z Ref: Phytochemistry, 177:112450, 2020 : PubMed ESTHER: Zhan_2020_Phytochemistry_177_112450 PubMedSearch: Zhan 2020 Phytochemistry 177 112450 PubMedID: 32580106 Abstract Nine undescribed monoterpene indole alkaloids, rauvomitorine A-I, including an unprecedented C-9-methoxymethylene-sarpagine framework alkaloid, two rare suaveoline framework type alkaloids, and six yohimbine framework type alkaloids, as well as eleven known alkaloids, were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). The structures of the unreported alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis with Cu Kalpha radiation. Rauvomitorine A with an unreported framework type represents the first example of C-9-methoxymethylene-sarpagine alkaloids and its plausible biosynthetic pathway was proposed. All the isolated alkaloids were evaluated their acetylcholinesterase inhibitory (AChE) activities and cytotoxicity against five cancer cell lines and some of them exhibited potential anti-AChE activities with IC50 values ranging from 49.76 to 186.62 muM. Importantly, this is the first report of the AChE inhibitory activities on suaveoline framework type alkaloids, suggesting this type of alkaloids may be valuable sources for the discovery of AChE inhibitory agents. A preliminary structure-activity relationship for AChE inhibitory activities of the isolated alkaloids is also discussed, providing some clues to designing lead compounds for AChE inhibitors. Title: Monoterpene indole alkaloids with acetylcholinesterase inhibitory activity from the leaves of Rauvolfia vomitoria Zhan G, Miao R, Zhang F, Chang G, Zhang L, Zhang X, Zhang H, Guo Z Ref: Bioorg Chem, 102:104136, 2020 : PubMed ESTHER: Zhan_2020_Bioorg.Chem_102_104136 PubMedSearch: Zhan 2020 Bioorg.Chem 102 104136 PubMedID: 32738570 Abstract Seventeen monoterpene indole alkaloids, including seven new alkaloids (1-7) and ten known analogues (8-17), were isolated and identified from the leaves of R. vomitoria. The structures of new alkaloids were elucidated by extensive spectroscopic analysis and single-crystal X-ray diffraction analysis. Rauvomitorine I (1) represents the first example of an unprecedented C(22) yohimbine-type monoterpene indole alkaloid featuring a carboxymethyl at C-14. The exceedingly rare vobasenal (2-3) and affinisine oxindole (5-6) framework type alkaloids are first reported from the Rauvolfia genus. Most notably, the structure of vobasenal-type alkaloids (2-3) were first determined by single-crystal X-ray diffraction analyses. Alkaloids 1-17 were tested their cytotoxicity against five cancer cell lines, however, none of them showed significant cytotoxicity at a concentration of 40 muM. All the isolated alkaloids were evaluated their acetylcholinesterase (AChE) inhibitory activities. Alkaloid 3 exhibited significant anti-AChE activity with an IC(50) value of 16.39 +/- 1.41 muM and alkaloids 8 and 10 showed moderate anti-AChE activities whereas the others (2, 9, 13, and 17) were weak inhibitors. This is the first report of vobasenal-type alkaloids as AChE inhibitors, indicating this type of alkaloids may be important sources for the discovery of new AChE inhibitors. A preliminary structure-activity relationship for AChE inhibitory activities showed the presence of the N-methyl group in vobasenal-type alkaloids may be essential for anti-AChE activity. Further molecular docking studies of vobasenal-type alkaloids revealed that interaction with Trp133 and Trp86 residues at hydrophobic subsite are necessary for the AChE inhibitory activities. This study not only enriches the chemical diversity of alkaloids in Apocynaceae plants but also provides new potential leading compounds and versatile scaffolds for the design and development of new AChE inhibitors to treat AD. Title: Peraksine derivatives with potential anti-inflammatory activities from the stems of Rauvolfia vomitoria Zhan G, Miao R, Zhang F, Hao Y, Zhang Y, Khurm M, Zhang X, Guo Z Ref: Fitoterapia, :104704, 2020 : PubMed ESTHER: Zhan_2020_Fitoterapia__104704 PubMedSearch: Zhan 2020 Fitoterapia 104704 PubMedID: 32827693 Abstract Five new peraksine derivatives rauvomine C-G (1-5) along with four known analogues (6-9) were isolated from the stems of Rauvolfia vomitoria Afzel. (Apocynaceae). Structural determinations of the new monoterpene indole alkaloids were elucidated via comprehensive spectroscopic analyses and ECD calculations. Rauvomine C (1) with an unprecedented framework type represents the first example of C(18) peraksine-type nor-monoterpene indole alkaloid featuring a chlorine atom at C-16 and its plausible biosynthetic pathway was also proposed. All the isolates were evaluated for their anti-inflammatory, cytotoxic, and acetylcholinesterase inhibitory activities. Among them, the new framework alkaloid rauvomine C (1) showed significant anti-inflammatory activities on NO production in LPS-induced RAW264.7 mouse macrophages with IC(50) value of 10.76 muM. Additionally, peraksine-type alkaloids featuring pyran ring (5, 8, and 9) exhibited potential anti-inflammatory activities with IC(50) values ranging from 17.52 to 20.99 muM. Title: Neurotoxicity of perfluorooctanoic acid and post-exposure recovery due to blueberry anthocyanins in the planarians Dugesia japonica Zhang J, Shao X, Zhao B, Zhai L, Liu N, Gong F, Ma X, Pan X, Yuan Z, Zhang X Ref: Environ Pollut, 263:114471, 2020 : PubMed ESTHER: Zhang_2020_Environ.Pollut_263_114471 PubMedSearch: Zhang 2020 Environ.Pollut 263 114471 PubMedID: 32268227 Abstract Perfluorooctanoic acid (PFOA) is a widely used synthetic industrial chemical which accumulates in ecosystems and organisms. Our study have investigated the neurobehavioral effects of PFOA and the alleviation effects of PFOA-induced neurotoxicity by blueberry anthocyanins (ANT) in Dugesia japonica. The planarians were exposed to PFOA and ANT for ten days. Researchs showed that exposure to PFOA affected locomotor behavior and ANT significantly alleviated the reduction in locomotion induced by PFOA. The regeneration of eyespots and auricles was suppressed by PFOA and was promoted by ANT. Following exposure to PFOA, acetylcholinesterase activity continually decreased and was unaffected in the ANT group, but was elevated after combined administration of PFOA and ANT. Oxidative DNA damage was found in planarians exposed to PFOA and was attenuated after administration of ANT by the alkaline comet assay. Concentrations of three neurotransmitters increased following exposure to PFOA and decreased after administration of ANT. Furthermore, ANT promoted and PFOA inhibited neuronal regeneration. DjotxA, DjotxB, DjFoxG, DjFoxD and Djnlg associated with neural processes were up-regulated following exposure to PFOA. Our findings indicate that PFOA is a neurotoxicant while ANT can attenuate these detrimental effects. Title: Genomic Characterization and Expression of Juvenile Hormone Esterase-Like Carboxylesterase Genes in Pacific White Shrimp, Litopenaeus vannamei Zhang X, Yuan J, Xiang J, Li F Ref: Int J Mol Sci, 21:, 2020 : PubMed ESTHER: Zhang_2020_Int.J.Mol.Sci_21_ PubMedSearch: Zhang 2020 Int.J.Mol.Sci 21 PubMedID: 32751646 Abstract The sesquiterpenoid methyl farnesoate (MF), a juvenile hormone (JH) analog, plays important roles in many physiological processes of crustaceans, such as morphogenesis, molting and reproduction. Juvenile hormone esterase-like (JHE-like) carboxylesterase (CXE) is a key enzyme in MF degradation, playing a significant role in regulating MF titer. However, its function is barely known in shrimp. In this study, a total of 21 JHE-like CXEs (LvCXEs) were characterized in Pacific white shrimp Litopenaeus vannamei, based on the full genome and multi-transcriptomic data. LvCXE has a conserved triplet catalytic site (Ser-Glu-His) and a characteristic GxSxG motif. Most LvCXEs were highly expressed in the hepatopancreas, which was the main site for MF degradation. LvCXEs containing a GESAG motif showed a specific expansion in the L. vannamei genome. Those GESAG-containing LvCXEs presented differential expressions at different larvae stages and different molting stages of L. vannamei, which suggested their potential functions in development and molting. Additionally, when the transcription level of CXEs was inhibited, it could lead to failed molt and death of L. vannamei. When we further detected the expression levels of the key ecdysone responsive transcription factors including LvE75, LvBr-C, LvHr3 and LvFtz-f1 after the CXE inhibitor was injected into L. vannamei, they all showed apparent down-regulation. These results suggested that the expansion of LvCXEs in the L. vannamei genome should contribute to the regulation of metamorphosis at larvae stages and frequent molting during the growth of L. vannamei. Title: Co-expression of Pseudomonas alcaligenes Lipase and Its Specific Foldase in Pichia pastoris by a Dual Expression Cassette Strategy Zhang Z, Zhang X, Hao H, Gong X, Gu X Ref: Protein Expr Purif, :105721, 2020 : PubMed ESTHER: Zhang_2020_Protein.Expr.Purif__105721 PubMedSearch: Zhang 2020 Protein.Expr.Purif 105721 PubMedID: 32763465 Abstract Lipomax is a commercialized foldase-dependent Pseudomonas lipase that was previously expressed only in Pseudomonas strains. Here, using Pichia pastoris as the host, we report a new co-expression method that leads to the successful production of Lipomax. The active Lipomax is extracellularly co-expressed with its cognate foldase (LIM); and the purified enzyme mix has the optimum pH at pH 8.0 and an optimal temperature around 40degC. N-glycosylation was observed for Pichia produced Lipomax, and its reduction was shown to increase the lipolytic activity. With different p-nitrophenyl esters as the substrates, the substrate profiling analyses further indicate that Lipomax prefers esters with middle-long chain fatty acids, showing the highest specific activity to p-nitrophenyl caprylate (C8). The extracellular co-expression of Lipomax and LIM in Pichia will not only increase our ability to investigate additional eukaryotic hosts for lipase expression, but also be of considerable value in analyzing other foldase-dependent lipases. Title: A Soluble Epoxide Hydrolase Inhibitor Upregulated KCNJ12 and KCNIP2 by Downregulating MicroRNA-29 in a Mouse Model of Myocardial Infarction Zhang X, Liao C, Sun K, Liu L, Xu D Ref: Heart Surg Forum, 23:E579, 2020 : PubMed ESTHER: Zhang_2020_Heart.Surg.Forum_23_E579 PubMedSearch: Zhang 2020 Heart.Surg.Forum 23 E579 PubMedID: 32990585 Abstract BACKGROUND: Soluble epoxide hydrolase inhibitors (sEHi) have anti-arrhythmic effects, and we previously found that the novel sEHi t-AUCB (trans-4[-4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid) significantly inhibited ventricular arrhythmias after myocardial infarction (MI). However, the mechanism is unknown. It's known that microRNA-29 (miR-29) participates in the occurrence of arrhythmias. In this study, we investigated whether sEHi t-AUCB was protective against ischemic arrhythmias by modulating miR-29 and its target genes KCNJ12 and KCNIP2. METHODS: Male 8-week-old C57BL/6 mice were divided into five groups and fed distilled water only or distilled water with t-AUCB of different dosages for seven days. Then, the mice underwent MI or sham surgery. The ischemic region of the myocardium was obtained 24 hours after MI to detect miR-29, KCNJ12, and KCNIP2 mRNA expression levels via real-time PCR and KCNJ12 and KCNIP2 protein expression levels via western blotting. RESULTS: MiR-29 expression levels were significantly increased in the ischemic region of MI mouse hearts and the mRNA and protein expression levels of its target genes KCNJ12 and KCNIP2 were significantly decreased. T-AUCB prevented these changes dose-dependently. CONCLUSION: The sEHi t-AUCB regulates the expression levels of miR-29 and its target genes KCNJ12 and KCNIP2, suggesting a possible mechanism for its potential therapeutic application in ischemic arrhythmia. Title: Effect of Massa Medicata Fermentata on the Gut Microbiota of Dyspepsia Mice Based on 16S rRNA Technique Zhang X, Zhang H, Huang Q, Sun J, Yao R, Wang J Ref: Evid Based Complement Alternat Med, 2020:7643528, 2020 : PubMed ESTHER: Zhang_2020_Evid.Based.Complement.Alternat.Med_2020_7643528 PubMedSearch: Zhang 2020 Evid.Based.Complement.Alternat.Med 2020 7643528 PubMedID: 33029172 Abstract Massa Medicata Fermentata (MMF) is a traditional Chinese medicine (TCM) for treating indigestion and its related disorders. This study analyzes the effect of MMF on intestinal microorganisms in dyspepsia mice based on 16S rRNA technology. We take a dyspepsia model caused by a high-protein, high-calorie, high-fat diet. The 60 specific-pathogen free Kunming (SPF KM) mice were randomly divided into a model group (n=12), an MMF group (LSQ group, n=12), a Jianweixiaoshi group (JWXS group, n=12), a domperidone group (DP group, n=12), and a blank group (n=12). On the seventh day of administration, mice were fasted and deprived of water. After 24 h, take the second feces of stress defecation in mice under strict aseptic conditions and quickly transfer them to a sterile cryotube. This study comprehensively evaluates the alpha-diversity, beta-diversity, flora abundance and composition of each group of mice's intestinal microorganisms, and their correlation with functional dyspepsia based on the 16S rRNA gene sequencing technology. After modeling, some dyspepsia reactions, proximal gastric relaxation reduction, and intestinal microflora changes were noted. Dyspepsia mice showed dyspepsia reactions and proximal gastric relaxation reduction, characterized by a significant decrease of contents of gastrin (P < 0.01) and cholinesterase (P < 0.01). MMF can improve dyspepsia symptoms and promote proximal gastric relaxation. Significant intestinal flora disorders were found in dyspepsia mice, including downregulation of Bacteroidetes, Lactobacillus, and Prevotellaceae and upregulation of Proteobacteria, Verrucomicrobia, Epsilonbacteraeota, Firmicutes, Lachnospiraceae NK4A136 group, and Lachnospiraceae. MMF could alleviate intestinal microflora disturbance, and the regulation effect of MMF on Bacteroidetes, Verrucomicrobia, and Epsilonbacteraeota was more reliable than that of Jianweixiaoshi tables and domperidone. The intestinal microflora may be correlated with the promoted digestion of MMF. Title: A tunable bifunctional hollow Co(3)O(4)/MO(3) (M = Mo, W) mixed-metal oxide nanozyme for sensing H(2)O(2) and screening acetylcholinesterase activity and its inhibitor Zhang X, Lu Y, Chen Q, Huang Y Ref: J Mater Chem B, 8:6459, 2020 : PubMed ESTHER: Zhang_2020_J.Mater.Chem.B_8_6459 PubMedSearch: Zhang 2020 J.Mater.Chem.B 8 6459 PubMedID: 32597916 Abstract A self-templated strategy was adopted to design hollow Co3O4/MO3 (M = Mo, W) mixed-metal oxides via the Mo or W doping of ZIF-67, and subsequent pyrolysis under an atmosphere of air at a low temperature of 450 degreesC. The hollow Co3O4/MO3 (M = Mo, W) mixed-metal oxides displayed tunable oxidase-like and peroxidase-like activities able to efficiently catalyze the oxidation of TMB to generate a deep blue color in the absence or presence of H2O2. Relative to that of the un-doped Co3O4, the oxidase mimic activity of the Mo-doped Co3O4 increased to 1.3 to 2.1-fold, while its peroxidase mimic activity increased to 7.1 to 19.9-fold, depending on different Mo doping amounts. The oxidase mimic activity of the W-doped Co3O4 increased to 2.1 to 2.3-fold, while its peroxidase mimic activity increased to 4.8 to 5.9-fold, depending on the different W doping amounts. The Mo- and W-doped Co3O4 nanohybrid exhibited both higher O2 and H2O2 activating capability, and their H2O2 activating capacity was superior to the O2 activating capability. Furthermore, the Mo- and W-doped Co3O4 nanohybrids exhibited similar O2 activating abilities, while the Mo-doped one displayed a higher H2O2 activating capability than the W-doped one. The discrepant peroxidase-like nature of Mo- and W-doped Co3O4 nanohybrids is likely attributed to their different catalytic mechanisms. The peroxidase-like activity of Mo-doped Co3O4 is highly related to the OH free radical, while that of W-doped Co3O4 is likely ascribed to the electron transfer between TMB and H2O2. The Km values of Co3O4/MoO3 for TMB and H2O2 were 0.0352 mM and 0.134 mM, which were 3.2- and 1.9-fold lower than that of pure Co3O4, respectively. A Co3O4/MoO3-based colorimetric platform was developed for the determination of H2O2 in the 0.1-200 microM range, with a limit of detection of 0.08 microM (3sigma). Based on the thiocholine (TCh) inhibition of the excellent peroxidase-like activity of Co3O4/MoO3 and the TCh generation via acetylcholinesterase (AChE) catalyzed hydrolysis of acetylthiocholine chloride (ATCh), the colorimetric platform was extended to screen AChE activity and its inhibitor. Title: Genome assembly of wild tea tree DASZ reveals pedigree and selection history of tea varieties Zhang W, Zhang Y, Qiu H, Guo Y, Wan H, Zhang X, Scossa F, Alseekh S, Zhang Q and Wen W <11 more author(s)> Zhang W, Zhang Y, Qiu H, Guo Y, Wan H, Zhang X, Scossa F, Alseekh S, Zhang Q, Wang P, Xu L, Schmidt MH, Jia X, Li D, Zhu A, Guo F, Chen W, Ni D, Usadel B, Fernie AR, Wen W (- 11) Ref: Nat Commun, 11:3719, 2020 : PubMed ESTHER: Zhang_2020_Nat.Commun_11_3719 PubMedSearch: Zhang 2020 Nat.Commun 11 3719 PubMedID: 32709943 Gene_locus related to this paper: camsi-a0a7j7g2i2 Abstract Wild teas are valuable genetic resources for studying domestication and breeding. Here we report the assembly of a high-quality chromosome-scale reference genome for an ancient tea tree. The further RNA sequencing of 217 diverse tea accessions clarifies the pedigree of tea cultivars and reveals key contributors in the breeding of Chinese tea. Candidate genes associated with flavonoid biosynthesis are identified by genome-wide association study. Specifically, diverse allelic function of CsANR, CsF3'5'H and CsMYB5 is verified by transient overexpression and enzymatic assays, providing comprehensive insights into the biosynthesis of catechins, the most important bioactive compounds in tea plants. The inconspicuous differentiation between ancient trees and cultivars at both genetic and metabolic levels implies that tea may not have undergone long-term artificial directional selection in terms of flavor-related metabolites. These genomic resources provide evolutionary insight into tea plants and lay the foundation for better understanding the biosynthesis of beneficial natural compounds. Title: [Value of serum cholinesterase in the prognosis of septic shock] Zhao R, Zhang X, Wang H, Zhang R, Duan X, Liu S, Han B, Ding X, Wang D, Sun T Ref: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 32:44, 2020 : PubMed ESTHER: Zhao_2020_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_32_44 PubMedSearch: Zhao 2020 Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue 32 44 PubMedID: 32148230 Abstract OBJECTIVE: To investigate the relationship between serum cholinesterase (SChE) level and the prognosis of patients with septic shock (SS). METHODS: A total of 594 patients with SS admitted to the First Affiliated Hospital of Zhengzhou University from June 2013 to June 2017 were enrolled. General data such as gender, age, acute physiology and chronic health evaluation II (APACHE II) score were recorded as well as routine blood test, procalcitonin (PCT), hepatic function, renal function, coagulation function and blood gas analysis parameters within 48 hours of SS diagnosis. The patients were followed by telephone from September to October in 2019, and the outcome was recorded. The primary outcome was all-cause death 28 days after discharge. The secondary outcomes were all-cause death in intensive care unit (ICU) and 2 years after discharge, and the length of ICU stay. The patients were divided into two groups according to prognosis of 28 days: the survival group and the death group. The clinical data of the two groups were compared. Multivariate Cox regression analysis was used to screen prognostic risk factors of 28 days in patients with SS. The receiver operating characteristic (ROC) curve was used to explore predictive value of liver function parameter SChE for 28-day prognosis of patients with SS. The patients were divided into two groups according to the levels of SChE: the low SChE group (SChE 4 000 U/L). Kaplan-Meier survival curves were used to compare the cumulative survival rates without endpoint event of patients with different SChE levels. RESULTS: A total of 385 patients with SS were enrolled according to the inclusion and exclusion criteria, and a total of 356 patients were followed up successfully, with a follow-up rate of 92.5% (356/385). There were 142 survival patients and 214 death patients at 28 days, with a 28-day mortality rate of 60.1% (214/356). There were 116 survival patients and 240 death patients at 2 years, with a 2-year mortality rate of 67.4% (240/356). Compared with the 28-day survival group, the patients in the death group were older and had higher APACHE II score, partial hepatic and renal function parameters, higher level of blood lactate (Lac) and lower levels of white blood cell count (WBC), platelet count (PLT) and SChE with statistically significant differences. Multivariate Cox regression analysis showed that the age [relative risk (RR) = 1.444, 95% confidence interval (95%CI) was 1.090-1.914, P = 0.010], APACHE II score (RR = 2.249, 95%CI was 1.688-2.997, P = 0.000), SChE (RR = 1.469, 95%CI was 1.057-2.043, P = 0.022), and Lac (RR = 2.190, 95%CI was 1.636-2.931, P = 0.000) were independent risk factors for 28-day mortality of patients with SS. The ROC curve analysis showed that SChE had a weak prognostic value for 28-day prognosis of patients with SS [the area under ROC curve (AUC) was 0.574]. However, the combined predictive value of SChE, APACHE II score and Lac was greater than APACHE II score or Lac alone for prediction (AUC: 0.807 vs. 0.785, 0.697), with a sensitivity of 79.9% and a specificity of 68.5%. Compared with the normal SChE group (n = 88), the 28-day mortality of patients in the low SChE group (n = 268) was significantly increased [63.1% (169/268) vs. 51.1% (45/88), P < 0.05], but ICU mortality [59.7% (160/268) vs. 48.9% (43/88)], 2-year mortality [69.8% (187/268) vs. 60.2% (53/88)] or the length of ICU stay [days: 4 (2, 7) vs. 5 (2, 9)] between the two groups showed no statistical significance (all P > 0.05). Kaplan-Meier survival curve analysis showed that the cumulative survival rate without endpoint event of patients in the low SChE group was significantly lower than that in the normal SChE group (Log-Rank test: chi(2) = 5.852, P = 0.016). CONCLUSIONS: Increased risk of 28-day mortality in patients with SS whose SChE is below normal. The level of SChE is an independent risk factor for 28-day death in SS patients, and it is one of the indicators to evaluate the short-term prognosis of patients with SS. Title: No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19 Zhou JH, Wu B, Wang WX, Lei F, Cheng X, Qin JJ, Cai JJ, Zhang XJ, Zhou F and Li HL <6 more author(s)> Zhou JH, Wu B, Wang WX, Lei F, Cheng X, Qin JJ, Cai JJ, Zhang XJ, Zhou F, Liu YM, Li HM, Zhu LH, She ZG, Zhang X, Yang J, Li HL (- 6) Ref: World J Clin Cases, 8:5576, 2020 : PubMed ESTHER: Zhou_2020_World.J.Clin.Cases_8_5576 PubMedSearch: Zhou 2020 World.J.Clin.Cases 8 5576 PubMedID: 33344548 Abstract BACKGROUND: Dipeptidyl peptidase-4 (DPP4) is commonly targeted to achieve glycemic control and has potent anti-inflammatory and immunoregulatory effects. Recent structural analyses indicated a potential tight interaction between DPP4 and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), raising a promising hypothesis that DPP4 inhibitor (DPP4i) drugs might be an optimal strategy for treating coronavirus disease 2019 (COVID-19) among patients with diabetes. However, there has been no direct clinical evidence illuminating the associations between DPP4i use and COVID-19 outcomes. AIM: To illuminate the associations between DPP4i usage and the adverse outcomes of COVID-19. METHODS: We conducted a multicenter, retrospective analysis including 2563 patients with type 2 diabetes who were hospitalized due to COVID-19 at 16 hospitals in Hubei Province, China. After excluding ineligible individuals, 142 patients who received DPP4i drugs and 1115 patients who received non-DPP4i oral anti-diabetic drugs were included in the subsequent analysis. We performed a strict propensity score matching (PSM) analysis where age, sex, comorbidities, number of oral hypoglycemic agents, heart rate, blood pressure, pulse oxygen saturation (SpO(2)) < 95%, CT diagnosed bilateral lung lesions, laboratory indicators, and proportion of insulin usage were matched. Finally, 111 participants treated with DPP4i drugs were successfully matched to 333 non-DPP4i users. Then, a linear logistic model and mixed-effect Cox model were applied to analyze the associations between in-hospital DPP4i use and adverse outcomes of COVID-19. RESULTS: After rigorous matching and further adjustments for imbalanced variables in the linear logistic model and Cox adjusted model, we found that there was no significant association between in-hospital DPP4i use (DPP4i group) and 28-d all-cause mortality (adjusted hazard ratio = 0.44, 95%CI: 0.09-2.11, P = 0.31). Likewise, the incidences and risks of secondary outcomes, including septic shock, acute respiratory distress syndrome, or acute organ (kidney, liver, and cardiac) injuries, were also comparable between the DPP4i and non-DPP4i groups. The performance of DPP4i agents in achieving glucose control (e.g., the median level of fasting blood glucose and random blood glucose) and inflammatory regulation was approximately equivalent in the DPP4i and non-DPP4i groups. Furthermore, we did not observe substantial side effects such as uncontrolled glycemia or acidosis due to DPP4i application relative to the use of non-DPP4i agents in the study cohort. CONCLUSION: Our findings demonstrated that DPP4i use is not significantly associated with poor outcomes of COVID-19 or other adverse effects of anti-diabetic treatment. The data support the continuation of DPP4i agents for diabetes management in the setting of COVID-19. Title: Design, Synthesis, and Evaluation of Reversible and Irreversible Monoacylglycerol Lipase Positron Emission Tomography (PET) Tracers Using a Tail Switching Strategy on a Piperazinyl Azetidine Skeleton Chen Z, Mori W, Deng X, Cheng R, Ogasawara D, Zhang G, Schafroth MA, Dahl K, Fu H and Liang SH <24 more author(s)> Chen Z, Mori W, Deng X, Cheng R, Ogasawara D, Zhang G, Schafroth MA, Dahl K, Fu H, Hatori A, Shao T, Zhang Y, Yamasaki T, Zhang X, Rong J, Yu Q, Hu K, Fujinaga M, Xie L, Kumata K, Gou Y, Chen J, Gu S, Bao L, Wang L, Collier TL, Vasdev N, Shao Y, Ma JA, Cravatt BF, Fowler C, Josephson L, Zhang MR, Liang SH (- 24) Ref: Journal of Medicinal Chemistry, 62:3336, 2019 : PubMed ESTHER: Chen_2019_J.Med.Chem_62_3336 PubMedSearch: Chen 2019 J.Med.Chem 62 3336 PubMedID: 30829483 Gene_locus related to this paper: human-MGLL Abstract Monoacylglycerol lipase (MAGL) is a serine hydrolase that degrades 2-arachidonoylglycerol (2-AG) in the endocannabinoid system (eCB). Selective inhibition of MAGL has emerged as a potential therapeutic approach for the treatment of diverse pathological conditions, including chronic pain, inflammation, cancer, and neurodegeneration. Herein, we disclose a novel array of reversible and irreversible MAGL inhibitors by means of "tail switching" on a piperazinyl azetidine scaffold. We developed a lead irreversible-binding MAGL inhibitor 8 and reversible-binding compounds 17 and 37, which are amenable for radiolabeling with (11)C or (18)F. [(11)C]8 ([(11)C]MAGL-2-11) exhibited high brain uptake and excellent binding specificity in the brain toward MAGL. Reversible radioligands [(11)C]17 ([(11)C]PAD) and [(18)F]37 ([(18)F]MAGL-4-11) also demonstrated excellent in vivo binding specificity toward MAGL in peripheral organs. This work may pave the way for the development of MAGL-targeted positron emission tomography tracers with tunability in reversible and irreversible binding mechanisms. Title: Design, Synthesis, and Evaluation of (18)F-Labeled Monoacylglycerol Lipase Inhibitors as Novel Positron Emission Tomography Probes Chen Z, Mori W, Fu H, Schafroth MA, Hatori A, Shao T, Zhang G, Van RS, Zhang Y and Liang SH <17 more author(s)> Chen Z, Mori W, Fu H, Schafroth MA, Hatori A, Shao T, Zhang G, Van RS, Zhang Y, Hu K, Fujinaga M, Wang L, Belov V, Ogasawara D, Giffenig P, Deng X, Rong J, Yu Q, Zhang X, Papisov MI, Shao Y, Collier TL, Ma JA, Cravatt BF, Josephson L, Zhang MR, Liang SH (- 17) Ref: Journal of Medicinal Chemistry, 62:8866, 2019 : PubMed ESTHER: Chen_2019_J.Med.Chem_62_8866 PubMedSearch: Chen 2019 J.Med.Chem 62 8866 PubMedID: 31518130 Inhibitor(s) related to this paper: PF-06795071 Abstract Dysfunction of monoacylglycerol lipase (MAGL) is associated with several psychopathological disorders, including drug addiction and neurodegenerative diseases. Herein we design, synthesize, and evaluate several irreversible fluorine-containing MAGL inhibitors for positron emission tomography (PET) ligand development. Compound 6 (identified from a therapeutic agent) was advanced for (18)F-labeling via a novel spirocyclic iodonium ylide (SCIDY) strategy, which demonstrated high brain permeability and excellent specific binding. This work supports further development of novel (18)F-labeled MAGL PET probes. Title: Synthesis of flavor esters by a novel lipase from Aspergillus niger in a soybean-solvent system Cong S, Tian K, Zhang X, Lu F, Singh S, Prior B, Wang ZX Ref: 3 Biotech, 9:244, 2019 : PubMed ESTHER: Cong_2019_3.Biotech_9_244 PubMedSearch: Cong 2019 3.Biotech 9 244 PubMedID: 31168437 Abstract To find a lipase for synthesis of flavor esters in food processing, a total of 35 putative lipases from Aspergillus niger F0215 were heterologously expressed and their esterification properties in crude preparations were examined. One of them, named An-lipase with the highest esterification rate (23.1%) was selected for further study. The purified An-lipase had the maximal activity at 20s degreesC and pH 6.5 and the specific activity of 1293sU/mg. Sixty percent of the activity was maintained in a range of temperatures of 0-30s degreesC and pHs of 3.0-8.5. The highest hydrolysis activity of An-lipase was towards pNPC (C8), followed by pNPB (C4) and pNPA (C2), then pNPL (C12). K (m), V (max), k (cat,) and k (cat)/K (m) towards pNPC were 26.7smmol/L, 129.9smmol/(Lsh), 23.2ss(-1), and 0.8/mM/s, respectively. The ethyl lactate, butyl butyrate, and ethyl caprylate flavor esters were produced by esterification of the corresponding acids with conversion efficiencies of 15.8, 37.5, and 24.7%, respectively, in a soybean-oil-based solvent system. In conclusion, An lipase identified in this study significantly mediated synthesis of predominant flavor esters (ethyl lactate, butyl butyrate, and ethyl caprylate) in a soybean-oil-lacking other toxic organic solvents, which has potential application in food industries. Title: Functional Characterization of LIPA (Lysosomal Acid Lipase) Variants Associated With Coronary Artery Disease Evans TD, Zhang X, Clark RE, Alisio A, Song E, Zhang H, Reilly MP, Stitziel NO, Razani B Ref: Arterioscler Thromb Vasc Biol, 39:2480, 2019 : PubMed ESTHER: Evans_2019_Arterioscler.Thromb.Vasc.Biol_39_2480 PubMedSearch: Evans 2019 Arterioscler.Thromb.Vasc.Biol 39 2480 PubMedID: 31645127 Gene_locus related to this paper: human-LIPA Abstract OBJECTIVE: LIPA (lysosomal acid lipase) mediates cholesteryl ester hydrolysis, and patients with rare loss-of-function mutations develop hypercholesterolemia and severe disease. Genome-wide association studies of coronary artery disease have identified several tightly linked, common intronic risk variants in LIPA which unexpectedly associate with increased mRNA expression. However, an exonic variant (rs1051338 resulting in T16P) in linkage with intronic variants lies in the signal peptide region and putatively disrupts trafficking. We sought to functionally investigate the net impact of this locus on LIPA and whether rs1051338 could disrupt LIPA processing and function to explain coronary artery disease risk. Approach and Results: In monocytes isolated from a large cohort of healthy individuals, we demonstrate both exonic and intronic risk variants are associated with increased LIPA enzyme activity coincident with the increased transcript levels. To functionally isolate the impact of rs1051338, we studied several in vitro overexpression systems and consistently observed no differences in LIPA expression, processing, activity, or secretion. Further, we characterized a second common exonic coding variant (rs1051339), which is predicted to alter LIPA signal peptide cleavage similarly to rs1051338, yet is not linked to intronic variants. rs1051339 also does not impact LIPA function in vitro and confers no coronary artery disease risk. CONCLUSIONS: Our findings show that common LIPA exonic variants in the signal peptide are of minimal functional significance and suggest coronary artery disease risk is instead associated with increased LIPA function linked to intronic variants. Understanding the mechanisms and cell-specific contexts of LIPA function in the plaque is necessary to understand its association with cardiovascular risk. Title: Synthesis and biological evaluation of genistein-O-alkylamine derivatives as potential multifunctional anti-Alzheimer agents Hong C, Guo HY, Chen S, Lv JW, Zhang X, Yang YC, Huang K, Zhang YJ, Tian ZY and Chen YP <1 more author(s)> Hong C, Guo HY, Chen S, Lv JW, Zhang X, Yang YC, Huang K, Zhang YJ, Tian ZY, Luo W, Chen YP (- 1) Ref: Chemical Biology Drug Des, 93:188, 2019 : PubMed ESTHER: Hong_2019_Chem.Biol.Drug.Des_93_188 PubMedSearch: Hong 2019 Chem.Biol.Drug.Des 93 188 PubMedID: 30299583 Abstract A series of genistein derivatives were synthesized and evaluated as multifunctional anti-Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC50 value (0.034 muM) much lower than that of rivastigmine (6.53 muM). A Lineweaver-Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal-chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 muM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD. Title: Lipase member H is a downstream molecular target of hypoxia inducible factor-1alpha and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines Li Y, Zhou X, Zhang Q, Chen E, Sun Y, Ye D, Wang O, Zhang X, Lyu J Ref: Cancer Manag Res, 11:931, 2019 : PubMed ESTHER: Li_2019_Cancer.Manag.Res_11_931 PubMedSearch: Li 2019 Cancer.Manag.Res 11 931 PubMedID: 30774423 Abstract Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. Materials and methods: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. Results: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial-mesenchymal transition pathway in PTC. Conclusion: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future. Title: Genome sequence of Isaria javanica and comparative genome analysis insights into family S53 peptidase evolution in fungal entomopathogens Lin R, Zhang X, Xin B, Zou M, Gao Y, Qin F, Hu Q, Xie B, Cheng X Ref: Applied Microbiology & Biotechnology, 103:7111, 2019 : PubMed ESTHER: Lin_2019_Appl.Microbiol.Biotechnol_103_7111 PubMedSearch: Lin 2019 Appl.Microbiol.Biotechnol 103 7111 PubMedID: 31273397 Gene_locus related to this paper: 9hypo-a0a545vqi9 Abstract The fungus Isaria javanica is an important entomopathogen that parasitizes various insects and is effective for pest control. In this study, we sequenced and assembled the genomes (IJ1G and IJ2G) of two I. javanica strains isolated from different insects. The genomes were approximately 35 Mb in size with 11,441 and 11,143 protein-coding genes, respectively. Using a phylogenomic approach, we evaluated genome evolution across five entomopathogenic fungi in Cordycipitaceae. By comparative genome analysis, it was found that family S53 serine peptidases were expanded in Cordycipitaceae entomopathogens, particularly in I. javanica. Gene duplication events were identified based on phylogenetic relationships inferred from 82 S53 peptidases within six entomopathogenic fungal genomes. Moreover, we found that carbohydrate-active enzymes and proteinases were the largest secretory protein groups encoded in the I. javanica genome, especially chitinases (GH18), serine and aspartic peptidases (S53, S08, S10, A01). Pathogenesis-related genes and genes for bacterial-like toxins and secondary metabolites were also identified. By comparative transcriptome analysis, differentially expressed genes in response to insect nutrients (in vitro) were identified. Moreover, most S53 peptidases were detected to be significantly upregulated during the initial fungal infection process in insects (in vivo) by RT-qPCR. Our results provide new clues about understanding evolution of pathogenic proteases and may suggest that abundant S53 peptidases in the I. javanica genome may contribute to its effective parasitism on various insects. Title: Asatone and Isoasatone A Against Spodoptera litura Fab. by Acting on Cytochrome P450 Monoxygenases and Glutathione Transferases Ling R, Yang R, Li P, Zhang X, Shen T, Li X, Yang Q, Sun L, Yan J Ref: Molecules, 24:, 2019 : PubMed ESTHER: Ling_2019_Molecules_24_ PubMedSearch: Ling 2019 Molecules 24 PubMedID: 31683670 Abstract Asatone and isoasatone A from Asarum ichangense Cheng were determined to be defensive compounds to some insects in a previous investigation. However, the anti-insect activity mechanisms to caterpillar are still unclear. The compounds asatone and isoasatone A from A. ichangense were induced by Spodoptera litura. The anti-insect activity of asatone and isoasatone A to S. litura was further tested by weight growth rate of the insect through a diet experiment. Isoasatone A showed a more significant inhibitory effect on S. litura than asatone on the second day. The concentration of asatone was higher than isoasatone A in the second instar larvae of S. litura after 12 h on the feeding test diet. Both compounds caused mid-gut structural deformation and tissue decay as determined by mid-gut histopathology of S. litura. Furthermore, some detoxification enzyme activity were measured by relative expression levels of genes using a qPCR detecting system. Asatone inhibited the gene expression of the cytochrome P450 monooxygenases (P450s) CYP6AB14. Isoasatone A inhibited the relative expression levels of CYP321B1, CYP321A7, CYP6B47, CYP6AB14, and CYP9A39. Asatone increased the relative gene expression of the glutathione transferases (GSTs) SIGSTe1 and SIGSTo1, in contrast, isoasatone A decreased the relative gene expression of SIGSTe1 by about 33 fold. Neither compound showed an effect on acetylcholinesterase SIAce1 and SIAce2. The mechanism of anti-insect activity by both compounds could be explained by the inhibition of enzymes P450s and GSTs. The results provide new insights into the function of unique secondary metabolites asatone and isoasatone A in genus Asarum, and a new understanding of why A. ichangense is largely free of insect pests. Title: Designing of a Cofactor Self-Sufficient Whole-Cell Biocatalyst System for Production of 1,2-Amino Alcohols from Epoxides Liu S, Zhang X, Liu F, Xu M, Yang T, Long M, Zhou J, Osire T, Yang S, Rao Z Ref: ACS Synth Biol, 8:734, 2019 : PubMed ESTHER: Liu_2019_ACS.Synth.Biol_8_734 PubMedSearch: Liu 2019 ACS.Synth.Biol 8 734 PubMedID: 30840437 Abstract Optically pure 1,2-amino alcohols are highly valuable products as intermediates for chiral pharmaceutical products. Here we designed an environmentally friendly non-natural biocatalytic cascade for efficient synthesis of 1,2-amino alcohols from cheaper epoxides. A redesignated omega-transaminase PAKomega-TA was tested and showed good bioactivity at a lower pH than other reported transaminases. The cascade was efficiently constructed as a single one-pot E. coli recombinant, by coupling SpEH (epoxide hydrolase), MnADH (alcohol dehydrogenase), and PAKomega-TA. Furthermore, RBS regulation strategy was used to overcome the rate limiting step by increasing expression of MnADH. For cofactor regeneration and amino donor source, an interesting point was involved as that a cofactor self-sufficient system was designed by expression of GluDH. It established a "bridge" between the cofactor and the cosubstrate, such that the cofactor self-sufficient system could release cofactor (NADP(+)) and cosubstrate (l-Glutamine) regenerated simultaneously. The recombinant E. coli BL21 (SGMP) with cofactor self-sufficient whole-cell cascade biocatalysis showed high ee value (>99%) and high yield, with 99.6% conversion of epoxide ( S)-1a to 1,2-amino alcohol ( S)-1d in 10 h. It further converted ( S)-2a-5a to ( S)-2d-5d with varying conversion rates ranging between 65-96.4%. This study first provides one-step synthesis of optically pure 1,2-amino alcohols from ( S)-epoxides employing a synthetic redox-self-sufficient cascade. Title: A Compound Heterozygous Mutation of Lipase Maturation Factor 1 is Responsible for Hypertriglyceridemia of a Patient Liu Y, Xu J, Tao W, Yu R, Zhang X Ref: J Atheroscler Thromb, 26:136, 2019 : PubMed ESTHER: Liu_2019_J.Atheroscler.Thromb_26_136 PubMedSearch: Liu 2019 J.Atheroscler.Thromb 26 136 PubMedID: 29910226 Abstract AIM: Dyslipidemia is the most common lipid metabolism disorder in humans, and its etiology remains elusive. Hypertriglyceridemia (HTG) is a type of dyslipidemia that contributes to atherosclerosis and coronary heart disease. Previous studies have demonstrated that mutations in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), glycosylphosphatidylinositol anchored high-density lipoprotein-binding protein 1 (GPIHBP1), lipase maturation factor 1(LMF1), and glycerol-3 phosphate dehydrogenase 1 (GPD1) are responsible for HTG by using genomic microarrays and next-generation sequencing. The aim of this study was to identify genetic lesions in patients with HTG. METHOD: Our study included a family of seven members from Jiangsu province across three generations. The proband was diagnosed with severe HTG, with a plasma triglyceride level of 38.70 mmol/L. Polymerase chain reaction (PCR) and Sanger sequencing were performed to explore the possible causative gene mutations for this patient. Furthermore, we measured the post-heparin LPL and hepatic lipase (HL) activities using an antiserum inhibition method. RESULTS: A compound heterozygous mutation in the LMF1 gene (c.257CT/p.P86L and c.1184CT/p.T395I) was identified and co-segregated with the affected patient in this family. Both mutations were predicted to be deleterious by three bioinformatics programs (Polymorphism Phenotyping-2, Sorting Intolerant From Tolerant, and MutationTaster). The levels of the plasma post-heparin LPL and HL activities in the proband (57 and 177 mU/mL) were reduced to 24% and 75%, respectively, compared with those assayed in the control subject with normal plasma triglycerides. CONCLUSION: A compound heterozygous mutation of LMF1 was identified in the presenting patient with severe HTG. These findings expand on the spectrum of LMF1 mutations and contribute to the genetic diagnosis and counseling of families with HTG. Title: Electrochemical MIP Sensor for Butyrylcholinesterase Ozcelikay G, Kurbanoglu S, Zhang X, Kosak Soz C, Wollenberger U, Ozkan SA, Yarman A, Scheller FW Ref: Polymers (Basel), 11:, 2019 : PubMed ESTHER: Ozcelikay_2019_Polymers.(Basel)_11_ PubMedSearch: Ozcelikay 2019 Polymers.(Basel) 11 PubMedID: 31801184 Abstract Molecularly imprinted polymers (MIPs) mimic the binding sites of antibodies by substituting the amino acid-scaffold of proteins by synthetic polymers. In this work, the first MIP for the recognition of the diagnostically relevant enzyme butyrylcholinesterase (BuChE) is presented. The MIP was prepared using electropolymerization of the functional monomer o-phenylenediamine and was deposited as a thin film on a glassy carbon electrode by oxidative potentiodynamic polymerization. Rebinding and removal of the template were detected by cyclic voltammetry using ferricyanide as a redox marker. Furthermore, the enzymatic activity of BuChE rebound to the MIP was measured via the anodic oxidation of thiocholine, the reaction product of butyrylthiocholine. The response was linear between 50 pM and 2 nM concentrations of BuChE with a detection limit of 14.7 pM. In addition to the high sensitivity for BuChE, the sensor responded towards pseudo-irreversible inhibitors in the lower mM range. Title: [Isolation and identification of endophytic fungi from Huperzia serrata and their metabolites' inhibitory activities against acetylcholinesterase and anti-inflammatory activities] Qi BW, Mo T, Zhang X, Yan YR, Xu XP, Yang HY, Wang XH, Li J, Shi SP, Liu X Ref: Zhongguo Zhong Yao Za Zhi, 44:3213, 2019 : PubMed ESTHER: Qi_2019_Zhongguo.Zhong.Yao.Za.Zhi_44_3213 PubMedSearch: Qi 2019 Zhongguo.Zhong.Yao.Za.Zhi 44 3213 PubMedID: 31602874 Abstract A total of 27 endophytic fungal strains were isolated from Huperzia serrata,which were richly distributed in the stems and leaves while less distributed in roots. The 27 strains were identified by Internal Transcribed Spacer( ITS) r DNA molecular method and one of the strains belongs to Basidiomycota phylum,and other 26 stains belong to 26 species,9 general,6 families,5 orders,3 classes of Ascomycota Phylum. The dominant strains were Colletotrichum genus,belonging to Glomerellaceae family,Glomerellales order,Sordariomycetes class,Ascomycota Phylum,with the percentage of 48. 15%. The inhibitory activities of the crude extracts of 27 endophytic fungal strains against acetylcholinesterase( ACh E) and nitric oxide( NO) production were evaluated by Ellman's method and Griess method,respectively. Crude extracts of four fungi exhibited inhibitory activities against ACh E with an IC50 value of 42. 5-62. 4 mg.L~(-1),and some fungi's crude extracts were found to inhibit nitric oxide( NO) production in lipopolysaccharide( LPS)-activated RAW264. 7 macrophage cells with an IC50 value of 2. 2-51. 3 mg.L~(-1),which indicated that these fungi had potential anti-inflammatory activities.The chemical composition of the Et OAc extract of endophytic fungus HS21 was also analyzed by LCMS-IT-TOF. Seventeen compounds including six polyketides,four diphenyl ether derivatives and seven meroterpenoids were putatively identified. Title: Functional analysis of the GbDWARF14 gene associated with branching development in cotton Wang P, Zhang S, Qiao J, Sun Q, Shi Q, Cai C, Mo J, Chu Z, Yuan Y and Cai Y <3 more author(s)> Wang P, Zhang S, Qiao J, Sun Q, Shi Q, Cai C, Mo J, Chu Z, Yuan Y, Du X, Miao Y, Zhang X, Cai Y (- 3) Ref: PeerJ, 7:e6901, 2019 : PubMed ESTHER: Wang_2019_PeerJ_7_e6901 PubMedSearch: Wang 2019 PeerJ 7 e6901 PubMedID: 31143538 Abstract Plant architecture, including branching pattern, is an important agronomic trait of cotton crops. In recent years, strigolactones (SLs) have been considered important plant hormones that regulate branch development. In some species such as Arabidopsis, DWARF14 is an unconventional receptor that plays an important role in the SL signaling pathway. However, studies on SL receptors in cotton are still lacking. Here, we cloned and analysed the structure of the GbD14 gene in Gossypium barbadense and found that it contains the domains necessary for a SL receptor. The GbD14 gene was expressed primarily in the roots, leaves and vascular bundles, and the GbD14 protein was determined via GFP to localize to the cytoplasm and nucleus. Gene expression analysis revealed that the GbD14 gene not only responded to SL signals but also was differentially expressed between cotton plants whose types of branching differed. In particular, GbD14 was expressed mainly in the axillary buds of normal-branching cotton, while it was expressed the most in the leaves of nulliplex-branch cotton. In cotton, the GbD14 gene can be induced by SL and other plant hormones, such as indoleacetic acid, abscisic acid, and jasmonic acid. Compared with wild-type Arabidopsis, GbD14-overexpressing Arabidopsis responded more rapidly to SL signals. Moreover, we also found that GbD14 can rescue the multi-branched phenotype of Arabidopsis Atd14 mutants. Our results indicate that the function of GbD14 is similar to that of AtD14, and GbD14 may be a receptor for SL in cotton and involved in regulating branch development. This research provides a theoretical basis for a profound understanding of the molecular mechanism of branch development and ideal plant architecture for cotton breeding improvements. Title: Antioxidant Profile of 1-Monocaffeoyl Glycerol in Lipophobic/Lipophilic Media Weng L, Li L, Ji L, Zhao D, Xu Z, Su J, Li B, Zhang X Ref: J Food Sci, 84:2091, 2019 : PubMed ESTHER: Weng_2019_J.Food.Sci_84_2091 PubMedSearch: Weng 2019 J.Food.Sci 84 2091 PubMedID: 31313325 Abstract Oxidative stress has been generally considered as one trigger of organism imbalance, resulting in lipid peroxidation, DNA damage and protein oxidation, which could be relieved by antioxidant supplement or endogenous antioxidant system. In present study, 1-monocaffeoyl glycerol (1-MCG), an amphipathic caffeic acid natural derivative, was enzymatically synthesized by Lipozyme 435, and its antioxidant profile in both lipophilic and lipophobic media was evaluated. The 1-MCG was identified by HPLC-UV, HPLC-ESI-MS, and (1) H/(13) C-NMR. Subsequently, antioxidant assays in lipophilic (DPPH assay) and lipophobic (ABTS, ORAC, erythrocyte hemolysis, ROS, MDA, and GPx assays) systems were explored. The better and lasting DPPH. and ABTS(+.) inhibitions of 1-MCG than caffeic acid (CA) were related to its better solubilities in ethanol/water media and electron transfer ability. ORAC results suggested the radical scavenging activities of 1-MCG (5 to 40 microM) were higher than Trolox. Furthermore, the effectiveness of 1-MCG against AAPH-induced erythrocytes oxidation indicated that 1-MCG can effectively inhibit hemolysis. ESEM was also applied to verify the hemolysis inhibition and morphology preservation abilities of 1-MCG. Besides, results showed 1-MCG was able to prevent ROS from invasion, reduce production of MDA, up-regulated GPx activity, terminate lipid peroxidation, and maintain the integrity of the structure and function of erythrocytes. PRACTICAL APPLICATION: As an amphiphilic caffeic acid derivative, 1-monocaffeoyl glycerol was synthesized, purified, and identified. 1-Monocaffeoyl glycerol could significantly eliminate radicals including DPPH., ABTS(+.) , and AAPH in ethanol, water, and PBS system, respectively. 1-Monocaffeoyl glycerol could protect erythrocyte from AAPH induced hemolysis. Title: HEV-LFS : A novel scoring model for patients with hepatitis E virus-related liver failure Wu J, Guo N, Zhang X, Xiong C, Liu J, Xu Y, Fan J, Yu J, Zhao X and Li L <4 more author(s)> Wu J, Guo N, Zhang X, Xiong C, Liu J, Xu Y, Fan J, Yu J, Zhao X, Liu B, Wang W, Zhang J, Cao H, Li L (- 4) Ref: J Viral Hepat, 26:1334, 2019 : PubMed ESTHER: Wu_2019_J.Viral.Hepat_26_1334 PubMedSearch: Wu 2019 J.Viral.Hepat 26 1334 PubMedID: 31294523 Abstract A noninvasive assessment method for acute or acute-on-chronic liver failure in patients with hepatitis E virus (HEV) infection is urgently needed. We aimed to develop a scoring model for diagnosing HEV patients who developed liver failure (HEV-LF) at different stages. A cross-sectional set of 350 HEV-LF patients were identified and enrolled, and the Guidelines for Diagnosis and Treatment of Liver Failure in China and the Asian Pacific Association for the Study of the Liver were adopted as references. HEV-LFS , a novel scoring model that incorporates data on cholinesterase (CHE), urea nitrogen (UREA), platelets and international normalized ratio was developed using a derived dataset. For diagnosing HEV-LF stages F1 to F3, the HEV-LFS scoring model (F1: 0.87; F2: 0.90; F3: 0.92) had a significantly higher AUROC than did the CLIF-C-ACLFs (F1: 0.65; F2: 0.56; F3: 0.51) and iMELD (F1: 0.70; F2: 0.57; F3: 0.51) scoring models, of which the HEV-LFS scoring model had the best sensitivity and specificity. In addition, the HEV-LFS scoring model was correlated with mortality, length of hospitalization and ICU stay. As the GDTLF score increased, the CHE level decreased and the UREA increased gradually. Encouragingly, a calibration curve showed good agreement between the derivation and validation sets. Notably, we also established a nomogram to facilitate the practical operability of the HEV-LFS scoring model in clinical settings. In conclusion, both CHE and UREA may be indicators for HEV-LF patients. The HEV-LFS scoring model is an efficient and accessible model for classifying HEV-LF at different stages. Title: Central cholinergic neuronal degeneration promotes the development of postoperative cognitive dysfunction Xu H, Chen L, Zhang X, Jiang X, Tian W, Yu W, Wang X, Tian J, Su D Ref: Lab Invest, 99:1078, 2019 : PubMed ESTHER: Xu_2019_Lab.Invest_99_1078 PubMedSearch: Xu 2019 Lab.Invest 99 1078 PubMedID: 30626892 Abstract Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality. However, its mechanism remains poorly understood. We hypothesized that central cholinergic neuronal degeneration facilitates the development of POCD. The impact of anesthesia/surgery (appendectomy) on learning and memory and the levels of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), and choline transporter (CHT) in adult and aged mice were measured. Separate cohorts were analyzed after pretreatment with donepezil, an AChE inhibitor, in aged mice or with murine-p75-saporin (mu-p75-sap), a cholinergic-specific immunotoxin, in adult mice. Morris Water Maze was used to measure the learning and memory changes after anesthesia/surgery. Western blot was used to measure the changes in the protein levels of the biomarkers of the central cholinergic system. We found that anesthesia/surgery-induced memory decline and attenuation of central cholinergic biomarkers (ChAT and VAChT) in aged mice but not in adult mice. Donepezil pretreatment reduced central cholinergic impairment in the aged mice and prevented learning and memory declines after anesthesia/surgery. In contrast, when central cholinergic neurons were pre-injured with mu-p75-sap, cognitive dysfunction developed in the adult mice after anesthesia/surgery. These data suggest that central cholinergic neuronal degeneration facilitates the development of POCD. Title: Bialternacins A-F, Aromatic Polyketide Dimers from an Endophytic Alternaria sp Yang CL, Wu HM, Liu CL, Zhang X, Guo ZK, Chen Y, Liu F, Liang Y, Jiao RH and Ge HM <1 more author(s)> Yang CL, Wu HM, Liu CL, Zhang X, Guo ZK, Chen Y, Liu F, Liang Y, Jiao RH, Tan RX, Ge HM (- 1) Ref: Journal of Natural Products, 82:792, 2019 : PubMed ESTHER: Yang_2019_J.Nat.Prod_82_792 PubMedSearch: Yang 2019 J.Nat.Prod 82 792 PubMedID: 30794407 Abstract Six novel aromatic polyketide dimers, bialternacins A-F (1-6), were isolated from a plant endophytic Alternaria sp. The structures of compounds 1-6 were elucidated on the basis of extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism analysis. Compounds 1, 2, 5, and 6 were characterized as four pairs of racemic mixtures. Compound (+)-5 was demonstrated to show acetylcholinesterase inhibitory activity with an IC50 value of 15.5 muM. A putative biosynthetic pathway for these compounds was proposed. Title: Inhibition of soluble epoxide hydrolase ameliorates hyperhomocysteinemia-induced hepatic steatosis by enhancing beta-oxidation of fatty acid in mice Yao L, Cao B, Cheng Q, Cai W, Ye C, Liang J, Liu W, Tan L, Yan M and Zhu Y <7 more author(s)> Yao L, Cao B, Cheng Q, Cai W, Ye C, Liang J, Liu W, Tan L, Yan M, Li B, He J, Hwang SH, Zhang X, Wang C, Ai D, Hammock BD, Zhu Y (- 7) Ref: American Journal of Physiology Gastrointest Liver Physiol, 316:G527, 2019 : PubMed ESTHER: Yao_2019_Am.J.Physiol.Gastrointest.Liver.Physiol_316_G527 PubMedSearch: Yao 2019 Am.J.Physiol.Gastrointest.Liver.Physiol 316 G527 PubMedID: 30789748 Inhibitor(s) related to this paper: TPPU Abstract Hepatic steatosis is the beginning phase of nonalcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuating their cardiovascular protective effects. However, the involvement of sEH in HHcy-induced hepatic steatosis is unknown. The current study aimed to explore the role of sEH in HHcy-induced lipid disorder. We fed 6-wk-old male mice a chow diet or 2% (wt/wt) high-metnionine diet for 8 wk to establish the HHcy model. A high level of homocysteine induced lipid accumulation in vivo and in vitro, which was concomitant with the increased activity and expression of sEH. Treatment with a highly selective specific sEH inhibitor (0.8 mg.kg(-1).day(-1) for the animal model and 1 muM for cells) prevented HHcy-induced lipid accumulation in vivo and in vitro. Inhibition of sEH activated the peroxisome proliferator-activated receptor-alpha (PPAR-alpha), as evidenced by elevated beta-oxidation of fatty acids and the expression of PPAR-alpha target genes in HHcy-induced hepatic steatosis. In primary cultured hepatocytes, the effect of sEH inhibition on PPAR-alpha activation was further confirmed by a marked increase in PPAR-response element luciferase activity, which was reversed by knock down of PPAR-alpha. Of note, 11,12-EET ligand dependently activated PPAR-alpha. Thus increased sEH activity is a key determinant in the pathogenesis of HHcy-induced hepatic steatosis, and sEH inhibition could be an effective treatment for HHcy-induced hepatic steatosis. NEW & NOTEWORTHY In the current study, we demonstrated that upregulation of soluble epoxide hydrolase (sEH) is involved in the hyperhomocysteinemia (HHcy)-caused hepatic steatosis in an HHcy mouse model and in murine primary hepatocytes. Improving hepatic steatosis in HHcy mice by pharmacological inhibition of sEH to activate peroxisome proliferator-activated receptor-alpha was ligand dependent, and sEH could be a potential therapeutic target for the treatment of nonalcoholic fatty liver disease. Title: Design, synthesis and evaluation of chalcone Mannich base derivatives as multifunctional agents for the potential treatment of Alzheimer's disease Zhang X, Song Q, Cao Z, Li Y, Tian C, Yang Z, Zhang H, Deng Y Ref: Bioorg Chem, 87:395, 2019 : PubMed ESTHER: Zhang_2019_Bioorg.Chem_87_395 PubMedSearch: Zhang 2019 Bioorg.Chem 87 395 PubMedID: 30921741 Abstract A series of chalcone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease based on the multi-target directed ligands design strategy. In vitro assays demonstrated that most of the derivatives exerted potent selective inhibitory potency on AChE with good multifunctional properties. Among them, representative compound 7c exhibited moderate inhibitory potency for EeAChE (IC50=0.44muM) and MAO-B inhibition (IC50=1.21muM), good inhibitory effect on self-induced Abeta1-42 aggregation (55.0%, at 25muM), biometal chelating property, moderate antioxidant activity with a value 1.93-fold of Trolox. Moreover, both kinetic analysis of AChE inhibition and molecular modeling study revealed that 7c showed a mixed-type inhibition, binding simultaneously to CAS and PAS of AChE. In addition, 7c also displayed high BBB permeability. These properties indicated 7c may be a promising multifunctional agent for the treatment of AD. Title: Transcriptomic analysis of Chlorimuron-ethyl degrading bacterial strain Klebsiella jilinsis 2N3 Zhang C, Hao Q, Zhang S, Zhang Z, Zhang X, Sun P, Pan H, Zhang H, Sun F Ref: Ecotoxicology & Environmental Safety, 183:109581, 2019 : PubMed ESTHER: Zhang_2019_Ecotoxicol.Environ.Saf_183_109581 PubMedSearch: Zhang 2019 Ecotoxicol.Environ.Saf 183 109581 PubMedID: 31446172 Abstract Chlorimuron-ethyl is a sulfonylurea herbicide with a long residual period in the field and is toxic to rotational crops. Klebsiella jilinsis 2N3 is a gram-negative bacterium that can rapidly degrade Chlorimuron-ethyl. In this study, the gene expression changes in strain 2N3 during degradation of Chlorimuron-ethyl was analyzed by RNA-Seq. Results showed that 386 genes were up-regulated and 453 genes were down-regulated. KEGG pathway enrichment analysis revealed the highest enrichment ratio in the pathway of sulfur metabolism. On the basis of the functional annotation and gene expression, we predicted that carboxylesterase, monooxygenase, glycosyltransferase, and cytochrome P450 were involved in the metabolism of Chlorimuron-ethyl biodegradation. Results of qRT-PCR showed that the relative mRNA expression levels of these genes were higher in treatment group than those in control group. The cytochrome P450 encoded by Kj-CysJ and the alkanesulfonate monooxygenase encoded by Kj-SsuD were predicted and further experimentally confirmed by gene knockout as the key enzymes in the biodegradation process. Cultured in basal medium containing Chlorimuron-ethyl (5mgL(-1)) in 36h, the strains of DeltaKj-CysJ, DeltaKj-SsuD, and WT reached the highest OD600 values of 0.308, 0.873, and 1.085, and the highest degradation rates of Chlorimuron-ethyl of 11.83%, 96.21%, and 95.62%, respectively. Title: Whole Genome Sequencing and Analysis of Chlorimuron-Ethyl Degrading Bacteria Klebsiella pneumoniae 2N3 Zhang C, Hao Q, Zhang Z, Zhang X, Pan H, Zhang J, Zhang H, Sun F Ref: Int J Mol Sci, 20:, 2019 : PubMed ESTHER: Zhang_2019_Int.J.Mol.Sci_20_ PubMedSearch: Zhang 2019 Int.J.Mol.Sci 20 PubMedID: 31234527 Gene_locus related to this paper: klep7-a6tb98, klep7-mhpc Abstract Klebsiella pneumoniae 2N3 is a strain of gram-negative bacteria that can degrade chlorimuron-ethyl and grow with chlorimuron-ethyl as the sole nitrogen source. The complete genome of Klebsiella pneumoniae 2N3 was sequenced using third generation high-throughput DNA sequencing technology. The genomic size of strain 2N3 was 5.32 Mb with a GC content of 57.33% and a total of 5156 coding genes and 112 non-coding RNAs predicted. Two hydrolases expressed by open reading frames (ORFs) 0934 and 0492 were predicted and experimentally confirmed by gene knockout to be involved in the degradation of chlorimuron-ethyl. Strains of DeltaORF 0934, DeltaORF 0492, and wild type (WT) reached their highest growth rates after 8-10 hours in incubation. The degradation rates of chlorimuron-ethyl by both DeltaORF 0934 and DeltaORF 0492 decreased in comparison to the WT during the first 8 hours in culture by 25.60% and 24.74%, respectively, while strains DeltaORF 0934, DeltaORF 0492, and the WT reached the highest degradation rates of chlorimuron-ethyl in 36 hours of 74.56%, 90.53%, and 95.06%, respectively. This study provides scientific evidence to support the application of Klebsiella pneumoniae 2N3 in bioremediation to control environmental pollution. Title: Compartmentalized biosynthesis of mycophenolic acid Zhang W, Du L, Qu Z, Zhang X, Li F, Li Z, Qi F, Wang X, Jiang Y and Li S <6 more author(s)> Zhang W, Du L, Qu Z, Zhang X, Li F, Li Z, Qi F, Wang X, Jiang Y, Men P, Sun J, Cao S, Geng C, Wan X, Liu C, Li S (- 6) Ref: Proc Natl Acad Sci U S A, 116:13305, 2019 : PubMed ESTHER: Zhang_2019_Proc.Natl.Acad.Sci.U.S.A_116_13305 PubMedSearch: Zhang 2019 Proc.Natl.Acad.Sci.U.S.A 116 13305 PubMedID: 31209052 Gene_locus related to this paper: penbr-mpaH, penbr-mpac Abstract Mycophenolic acid (MPA) from filamentous fungi is the first natural product antibiotic to be isolated and crystallized, and a first-line immunosuppressive drug for organ transplantations and autoimmune diseases. However, some key biosynthetic mechanisms of such an old and important molecule have remained unclear. Here, we elucidate the MPA biosynthetic pathway that features both compartmentalized enzymatic steps and unique cooperation between biosynthetic and beta-oxidation catabolism machineries based on targeted gene inactivation, feeding experiments in heterologous expression hosts, enzyme functional characterization and kinetic analysis, and microscopic observation of protein subcellular localization. Besides identification of the oxygenase MpaB' as the long-sought key enzyme responsible for the oxidative cleavage of the farnesyl side chain, we reveal the intriguing pattern of compartmentalization for the MPA biosynthetic enzymes, including the cytosolic polyketide synthase MpaC' and O-methyltransferase MpaG', the Golgi apparatus-associated prenyltransferase MpaA', the endoplasmic reticulum-bound oxygenase MpaB' and P450-hydrolase fusion enzyme MpaDE', and the peroxisomal acyl-coenzyme A (CoA) hydrolase MpaH'. The whole pathway is elegantly comediated by these compartmentalized enzymes, together with the peroxisomal beta-oxidation machinery. Beyond characterizing the remaining outstanding steps of the MPA biosynthetic steps, our study highlights the importance of considering subcellular contexts and the broader cellular metabolism in natural product biosynthesis. Title: An Epistatic Interaction between Pnpla2 and Lipe Reveals New Pathways of Adipose Tissue Lipolysis Zhang X, Zhang CC, Yang H, Soni KG, Wang SP, Mitchell GA, Wu JW Ref: Cells, 8:395, 2019 : PubMed ESTHER: Zhang_2019_Cells_8_395 PubMedSearch: Zhang 2019 Cells 8 395 PubMedID: 31035700 Gene_locus related to this paper: mouse-hslip Abstract White adipose tissue (WAT) lipolysis contributes to energy balance during fasting. Lipolysis can proceed by the sequential hydrolysis of triglycerides (TGs) by adipose triglyceride lipase (ATGL), then of diacylglycerols (DGs) by hormone-sensitive lipase (HSL). We showed that the combined genetic deficiency of ATGL and HSL in mouse adipose tissue produces a striking different phenotype from that of isolated ATGL deficiency, inconsistent with the linear model of lipolysis. We hypothesized that the mechanism might be functional redundancy between ATGL and HSL. To test this, the TG hydrolase activity of HSL was measured in WAT. HSL showed TG hydrolase activity. Then, to test ATGL for activity towards DGs, radiolabeled DGs were incubated with HSL-deficient lipid droplet fractions. The content of TG increased, suggesting DG-to-TG synthesis rather than DG hydrolysis. TG synthesis was abolished by a specific ATGL inhibitor, suggesting that ATGL functions as a transacylase when HSL is deficient, transferring an acyl group from one DG to another, forming a TG plus a monoglyceride (MG) that could be hydrolyzed by monoglyceride lipase. These results reveal a previously unknown physiological redundancy between ATGL and HSL, a mechanism for the epistatic interaction between Pnpla2 and Lipe. It provides an alternative lipolytic pathway, potentially important in patients with deficient lipolysis. Title: Urinary biomarkers for assessment of human exposure to monomeric aryl phosphate flame retardants Zhao F, Kang Q, Zhang X, Liu J, Hu J Ref: Environ Int, 124:259, 2019 : PubMed ESTHER: Zhao_2019_Environ.Int_124_259 PubMedSearch: Zhao 2019 Environ.Int 124 259 PubMedID: 30660026 Inhibitor(s) related to this paper: EHDPP Abstract While monomeric aryl organophosphate flame retardants (m-aryl-OPFRs) are used worldwide in a variety of consumer products, specific biomarkers for epidemiologic studies are lacking. To explore the potential of urinary hydroxylated metabolites of m-aryl-OPFRs as the biomarkers, we detected triphenyl phosphate (TPHP), 2-ethylhexyl diphenyl phosphate (EHDPP), and tricresyl phosphate (TCrP) in 259 whole blood samples and their 5 hydroxylated and 2 diester metabolites in the paired urine samples from the general population. 2-Ethyl-5-hydroxyhexyl diphenyl phosphate (5-OH-EHDPP), 4-hydroxyphenyl diphenyl phosphate (4-OH-TPHP), and 3-hydroxy-4-methylphenyl di-p-tolyl phosphate (3-OH-MDTP) were detected in >80% of urine samples after enzymatic hydrolysis of conjugates, and their concentrations showed significant positive correlations with the blood concentrations of their corresponding parent compounds, respectively. To characterize the temporal reliability, the m-aryl-OPFRs metabolites were also determined in urine samples repeated nine times from six volunteers over 3 months. Urinary 5-OH-EHDPP showed strong temporal reliability (creatinine-corrected intraclass correlation coefficients (ICCs), 0.77; 95% confidence interval [CI], 0.58 to 0.90), and urinary 3-OH-MDTP (creatinine-corrected ICC, 0.52; 95% CI, 0.37 to 0.87) and 4-OH-TPHP (0.56; 95% CI, 0.32 to 0.80) showed moderate-to-strong temporal reliability, while relatively weak temporal reliability was found for urinary DPHP (creatinine-corrected ICC, 0.37; 95% CI, 0.12 to 0.62). This study confirmed specific, reliable, and frequently detected biomarkers for TPHP and EHDPP and developed new biomarker of TCrP for future epidemiological research on health effects of m-aryl-OPFRs. Title: A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice Berger JP, SinhaRoy R, Pocai A, Kelly TM, Scapin G, Gao YD, Pryor KAD, Wu JK, Eiermann GJ and Carr RD <5 more author(s)> Berger JP, SinhaRoy R, Pocai A, Kelly TM, Scapin G, Gao YD, Pryor KAD, Wu JK, Eiermann GJ, Xu SS, Zhang X, Tatosian DA, Weber AE, Thornberry NA, Carr RD (- 5) Ref: Endocrinol Diabetes Metab, 1:e00002, 2018 : PubMed ESTHER: Berger_2018_Endocrinol.Diabetes.Metab_1_e00002 PubMedSearch: Berger 2018 Endocrinol.Diabetes.Metab 1 e00002 PubMedID: 30815539 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: VildaSaxagliptin-analogue, Vildagliptin Abstract Aims: Since 2006, DPP-4 inhibitors have become established therapy for the treatment of type 2 diabetes. Despite sharing a common mechanism of action, considerable chemical diversity exists amongst members of the DPP-4 inhibitor class, raising the question as to whether structural differences may result in differentiated enzyme inhibition and antihyperglycaemic activity. Methods: We have compared the binding properties of the most commonly used inhibitors and have investigated the relationship between their inhibitory potency at the level of the enzyme and their acute glucose-lowering efficacy. Results: Firstly, using a combination of published crystal structures and in-house data, we demonstrated that the binding site utilized by all of the DPP-4 inhibitors assessed was the same as that used by neuropeptide Y, supporting the hypothesis that DPP-4 inhibitors are able to competitively inhibit endogenous substrates for the enzyme. Secondly, we ascertained that the enzymatic cleft of DPP-4 is a relatively large cavity which displays conformational flexibility to accommodate structurally diverse inhibitor molecules. Finally, we found that for all inhibitors, irrespective of their chemical structure, the inhibition of plasma DPP-4 enzyme activity correlates directly with acute plasma glucose lowering in mice. Conclusion: The common binding site utilized by different DPP-4 inhibitors enables similar competitive inhibition of the cleavage of the endogenous DPP-4 substrates. Furthermore, despite chemical diversity and a range of binding potencies observed amongst the DPP-4 inhibitors, a direct relationship between enzyme inhibition in the plasma and glucose lowering is evident in mice for each member of the classes studied. Title: TaEDS1 genes positively regulate resistance to powdery mildew in wheat Chen G, Wei B, Li G, Gong C, Fan R, Zhang X Ref: Plant Mol Biol, 96:607, 2018 : PubMed ESTHER: Chen_2018_Plant.Mol.Biol_96_607 PubMedSearch: Chen 2018 Plant.Mol.Biol 96 607 PubMedID: 29582247 Gene_locus related to this paper: wheat-a0a1d5zte7 Abstract KEY MESSAGE: Three EDS1 genes were cloned from common wheat and were demonstrated to positively regulate resistance to powdery mildew in wheat. The EDS1 proteins play important roles in plant basal resistance and TIR-NB-LRR protein-triggered resistance in dicots. Until now, there have been very few studies on EDS1 in monocots, and none in wheat. Here, we report on three common wheat orthologous genes of EDS1 family (TaEDS1-5A, 5B and 5D) and their function in powdery mildew resistance. Comparisons of these genes with their orthologs in diploid ancestors revealed that EDS1 is a conserved gene family in Triticeae. The cDNA sequence similarity among the three TaEDS1 genes was greater than 96.5%, and they shared sequence similarities of more than 99.6% with the respective orthologs from diploid ancestors. The phylogenetic analysis revealed that the EDS1 family originated prior to the differentiation of monocots and dicots, and EDS1 members have since undergone clear structural differentiation. The transcriptional levels of TaEDS1 genes in the leaves were obviously higher than those of the other organs, and they were induced by Blumeria graminis f. sp. tritici (Bgt) infection and salicylic acid (SA) treatment. The BSMV-VIGS experiments indicated that knock-down the transcriptional levels of the TaEDS1 genes in a powdery mildew-resistant variety of common wheat compromised resistance. Contrarily, transient overexpression of TaEDS1 genes in a susceptible common wheat variety significantly reduced the haustorium index and attenuated the growth of Bgt. Furthermore, the expression of TaEDS1 genes in the Arabidopsis mutant eds1-1 complemented its susceptible phenotype to powdery mildew. The above evidences strongly suggest that TaEDS1 acts as a positive regulator and confers resistance against powdery mildew in common wheat. Title: In Vitro and in Vivo Evaluation of (11)C-Labeled Azetidinecarboxylates for Imaging Monoacylglycerol Lipase by PET Imaging Studies Cheng R, Mori W, Ma L, Alhouayek M, Hatori A, Zhang Y, Ogasawara D, Yuan G, Chen Z and Liang SH <16 more author(s)> Cheng R, Mori W, Ma L, Alhouayek M, Hatori A, Zhang Y, Ogasawara D, Yuan G, Chen Z, Zhang X, Shi H, Yamasaki T, Xie L, Kumata K, Fujinaga M, Nagai Y, Minamimoto T, Svensson M, Wang L, Du Y, Ondrechen MJ, Vasdev N, Cravatt BF, Fowler C, Zhang MR, Liang SH (- 16) Ref: Journal of Medicinal Chemistry, 61:2278, 2018 : PubMed ESTHER: Cheng_2018_J.Med.Chem_61_2278 PubMedSearch: Cheng 2018 J.Med.Chem 61 2278 PubMedID: 29481079 Abstract Monoacylglycerol lipase (MAGL) is the principle enzyme for metabolizing endogenous cannabinoid ligand 2-arachidonoyglycerol (2-AG). Blockade of MAGL increases 2-AG levels, resulting in subsequent activation of the endocannabinoid system, and has emerged as a novel therapeutic strategy to treat drug addiction, inflammation, and neurodegenerative diseases. Herein we report a new series of MAGL inhibitors, which were radiolabeled by site-specific labeling technologies, including (11)C-carbonylation and spirocyclic iodonium ylide (SCIDY) radiofluorination. The lead compound [(11)C]10 (MAGL-0519) demonstrated high specific binding and selectivity in vitro and in vivo. We also observed unexpected washout kinetics with these irreversible radiotracers, in which in vivo evidence for turnover of the covalent residue was unveiled between MAGL and azetidine carboxylates. This work may lead to new directions for drug discovery and PET tracer development based on azetidine carboxylate inhibitor scaffold. Title: Interaction between nonsynonymous polymorphisms in PLA2G7 gene and smoking on the risk of coronary heart disease in a Chinese population Chi Y, Shi C, Zhang X, Xi Y Ref: J Thromb Thrombolysis, 46:125, 2018 : PubMed ESTHER: Chi_2018_J.Thromb.Thrombolysis_46_125 PubMedSearch: Chi 2018 J.Thromb.Thrombolysis 46 125 PubMedID: 29728838 Gene_locus related to this paper: human-PLA2G7 Abstract To investigate the impact of PLA2G7 polymorphism, and additional their interactions with smoking and drinking on coronary heart disease (CHD) risk based on Chinese population. GMDR model was used to screen the best gene-smoking and gene-drinking interaction combinations. Logistic regression was performed to investigate association between 4 SNPs and CHD, and the interaction effect between rs1805017 and smoking. For CHD patient-control haplotype analyses, the SHEsis online haplotype analysis software ( http://analysis.bio-x.cn/myAnalysis.php ) was employed. CHD risks were higher in carriers of homozygous mutant of rs1805017 and rs1805018 than those with wild-type homozygotes, OR (95% CI) were 1.45 (1.16-1.92) and 1.51 (1.23-1.97), respectively, but the other two SNPs, rs16874954 and rs1051931 were not significant associated with CHD risks. GMDR analysis indicated that there was a significant two-locus model (p = 0.0107) involving rs1805017 and smoking, indicating a potential gene-environment interaction between rs1805017 and smoking. But we did not found any gene-drinking and gene-gene interaction combinations in GMDR models. The haplotype R-I was observed most frequently in two groups, with 47.43 and 54.38% in the case and control group of the population, respectively. The results also indicated that the haplotype containing the rs1805017-H and rs1805018-T alleles were associated with a statistically increased CHD risk, OR (95% CI) 1.43 (1.10-1.86), p = 0.0021. Polymorphisms in rs1805017 and rs1805018, additional interaction between rs1805017 and smoking, and haplotype containing the rs1805017-H and rs1805018-T alleles were associated with increased CHD risk. Title: Drug Development for Alzheimer's Disease: Review Lao K, Ji N, Zhang X, Qiao W, Tang Z, Gou X Ref: J Drug Target, :1, 2018 : PubMed ESTHER: Lao_2018_J.Drug.Target__1 PubMedSearch: Lao 2018 J.Drug.Target 1 PubMedID: 29732929 Abstract Alzheimer's disease (AD) is a chronic neurodegenerative disease, which is considered one of the most intractable medical problems with heavy social and economic costs. The current drugs for AD, including acetylcholinesterase inhibitors (AChEIs) and memantine, a NMDA receptor antagonist, only temporarily ameliorate cognitive decline, but are unable to stop or reverse the progression of dementia. This paper reviewed the recent advance in AD drug development. The drug discovery programs under clinical trials targeting cholinergic system, alpha7 nicotinic acetylcholine receptors (nAChRs), N-methyl-D-aspartate receptor (NMDAR), beta-secretase, gamma-secretase modulators, tau, inflammatory mediators and glucagon-like peptide-1 (GLP-1) were discussed. Though several drug discovery programs are ongoing, the high failure rate is an outstanding issue. Novel techniques and strategies are desperately needed to to significantly accelerate this process. Title: Comprehensive Molecular Screening in Chinese Usher Syndrome Patients Sun T, Xu K, Ren Y, Xie Y, Zhang X, Tian L, Li Y Ref: Invest Ophthalmol Vis Sci, 59:1229, 2018 : PubMed ESTHER: Sun_2018_Invest.Ophthalmol.Vis.Sci_59_1229 PubMedSearch: Sun 2018 Invest.Ophthalmol.Vis.Sci 59 1229 PubMedID: 29625443 Gene_locus related to this paper: human-ABHD12 Abstract Purpose: Usher syndrome (USH) refers to a group of autosomal recessive disorders causing deafness and blindness. The objectives of this study were to determine the mutation spectrum in a cohort of Chinese patients with USH and to describe the clinical features of the patients with mutations. Methods: A total of 119 probands who were clinically diagnosed with USH were recruited for genetic analysis. All probands underwent ophthalmic examinations. A combination of molecular screening methods, including targeted next-generation sequencing, Sanger-DNA sequencing, and multiplex ligation probe amplification assay, was used to detect mutations. Results: We found biallelic mutations in 92 probands (77.3%), monoallelic mutations in 5 patients (4.2%), and 1 hemizygous mutation in 1 patient (0.8%), resulting in an overall mutation detection rate of 78.2%. Overall, 132 distinct disease-causing mutations involving seven USH (ABHD12, CDH23, GPR98, MYO7A, PCDH15, USH1C, and USH2A) genes; 5 other retinal degeneration genes (CHM, CNGA1, EYS, PDE6B, and TULP1); and 1 nonsyndromic hearing loss gene (MYO15A) were identified, and 78 were novel. Mutations of MYOA7 were responsible for 60% of USH1 families, followed by PCDH15 (20%) and USH1C (10%). Mutations of USH2A accounted for 67.7% of USH2 families, and mutation c.8559-2A>G was the most frequent one, accounting for 19.1% of the identified USH2A alleles. Conclusions: Our results confirm that the mutation spectrum for each USH gene in Chinese patients differs from those of other populations. The formation of the mutation profile for the Chinese population will enable a precise genetic diagnosis for USH patients in the future. Title: IMA Genome-F 9: Draft genome sequence of Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina, and Morchella septimelata Wingfield BD, Bills GF, Dong Y, Huang W, Nel WJ, Swalarsk-Parry BS, Vaghefi N, Wilken PM, An Z and Zhang X <22 more author(s)> Wingfield BD, Bills GF, Dong Y, Huang W, Nel WJ, Swalarsk-Parry BS, Vaghefi N, Wilken PM, An Z, de Beer ZW, De Vos L, Chen L, Duong TA, Gao Y, Hammerbacher A, Kikkert JR, Li Y, Li H, Li K, Li Q, Liu X, Ma X, Naidoo K, Pethybridge SJ, Sun J, Steenkamp ET, van der Nest MA, van Wyk S, Wingfield MJ, Xiong C, Yue Q, Zhang X (- 22) Ref: IMA Fungus, 9:199, 2018 : PubMed ESTHER: Wingfield_2018_IMA.Fungus_9_199 PubMedSearch: Wingfield 2018 IMA.Fungus 9 199 PubMedID: 30018880 Gene_locus related to this paper: 9pezi-a0a370tge3, 9helo-a0a3d8spg6, 9euro-a0a3d8t2t6, 9euro-a0a3d8t644, 9pezi-a0a370te58, 9helo-a0a370tt42, 9helo-a0a370u2s4, 9helo-a0a3d8s0y2, 9helo-a0a3d8stp9, 9helo-a0a370u370, 9euro-a0a3d8rk78, 9helo-a0a370tat5, 9helo-a0a3d8qpi0 Abstract Draft genomes of the species Annulohypoxylon stygium, Aspergillus mulundensis, Berkeleyomyces basicola (syn. Thielaviopsis basicola), Ceratocystis smalleyi, two Cercospora beticola strains, Coleophoma cylindrospora, Fusarium fracticaudum, Phialophora cf. hyalina and Morchella septimelata are presented. Both mating types (MAT1-1 and MAT1-2) of Cercospora beticola are included. Two strains of Coleophoma cylindrospora that produce sulfated homotyrosine echinocandin variants, FR209602, FR220897 and FR220899 are presented. The sequencing of Aspergillus mulundensis, Coleophoma cylindrospora and Phialophora cf. hyalina has enabled mapping of the gene clusters encoding the chemical diversity from the echinocandin pathways, providing data that reveals the complexity of secondary metabolism in these different species. Overall these genomes provide a valuable resource for understanding the molecular processes underlying pathogenicity (in some cases), biology and toxin production of these economically important fungi. Title: Multifunctional 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives with acetylcholinesterase, monoamine oxidases and beta-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease Xu R, Xiao G, Li Y, Liu H, Song Q, Zhang X, Yang Z, Zheng Y, Tan Z, Deng Y Ref: Bioorganic & Medicinal Chemistry, 26:1885, 2018 : PubMed ESTHER: Xu_2018_Bioorg.Med.Chem_26_1885 PubMedSearch: Xu 2018 Bioorg.Med.Chem 26 1885 PubMedID: 29500132 Abstract A series of 5,6-dimethoxybenzo[d]isothiazol-3(2H)-one-N-alkylbenzylamine derivatives were designed, synthesized and evaluated as potential multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro assays indicated that most of these derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compounds 11b and 11d displayed comprehensive advantages, with good AChE (IC50=0.29+/-0.01muM and 0.46+/-0.02muM, respectively), MAO-A (IC50=8.2+/-0.08muM and 7.9+/-0.07muM, respectively) and MAO-B (IC50=20.1+/-0.16muM and 43.8+/-2.0% at 10muM, respectively) inhibitory activities, moderate self-induced Abeta1-42 aggregation inhibitory potency (35.4+/-0.42% and 48.0+/-1.53% at 25muM, respectively) and potential antioxidant activity. In addition, the two representative compounds displayed high BBB permeability in vitro. Taken together, these multifunctional properties make 11b and 11d as a promising candidate for the development of efficient drugs against AD. Title: An iridium complex-based probe for photoluminescence lifetime imaging of human carboxylesterase 2 in living cells Yan Z, Wang J, Zhang Y, Zhang S, Qiao J, Zhang X Ref: Chem Commun (Camb), 54:9027, 2018 : PubMed ESTHER: Yan_2018_Chem.Commun.(Camb)_54_9027 PubMedSearch: Yan 2018 Chem.Commun.(Camb) 54 9027 PubMedID: 30047956 Abstract A novel photoluminescence lifetime probe (Ir-TB) has been developed for the detection and imaging of hCE2 in living cells. A large lifetime increase by around 300 ns after the enzymatic reaction makes it an ideal tool to distinguish hCE2-hydrolyzed probes from those non-hydrolyzed ones via PLIM for the first time. Title: Duplication of a Pks gene cluster and subsequent functional diversification facilitate environmental adaptation in Metarhizium species Zeng G, Zhang P, Zhang Q, Zhao H, Li Z, Zhang X, Wang C, Yin WB, Fang W Ref: PLoS Genet, 14:e1007472, 2018 : PubMed ESTHER: Zeng_2018_PLoS.Genet_14_E1007472 PubMedSearch: Zeng 2018 PLoS.Genet 14 E1007472 PubMedID: 29958281 Gene_locus related to this paper: metaq-pks1, metra-pks2, metmf-pks2, metaf-pks1, metbs-pks2, metas-pks1, metaq-pks2 Abstract The ecological importance of the duplication and diversification of gene clusters that synthesize secondary metabolites in fungi remains poorly understood. Here, we demonstrated that the duplication and subsequent diversification of a gene cluster produced two polyketide synthase gene clusters in the cosmopolitan fungal genus Metarhizium. Diversification occurred in the promoter regions and the exon-intron structures of the two Pks paralogs (Pks1 and Pks2). These two Pks genes have distinct expression patterns, with Pks1 highly expressed during conidiation and Pks2 highly expressed during infection. Different upstream signaling pathways were found to regulate the two Pks genes. Pks1 is positively regulated by Hog1-MAPK, Slt2-MAPK and Mr-OPY2, while Pks2 is positively regulated by Fus3-MAPK and negatively regulated by Mr-OPY2. Pks1 and Pks2 have been subjected to positive selection and synthesize different secondary metabolites. PKS1 is involved in synthesis of an anthraquinone derivative, and contributes to conidial pigmentation, which plays an important role in fungal tolerance to UV radiation and extreme temperatures. Disruption of the Pks2 gene delayed formation of infectious structures and increased the time taken to kill insects, indicating that Pks2 contributes to pathogenesis. Thus, the duplication of a Pks gene cluster and its subsequent functional diversification has increased the adaptive flexibility of Metarhizium species. Title: Use of low-dose neostigmine intravenously in the treatment of thyroid storm-induced severe tachycardia in patient during huge pelvic mass resection: A case report and review of literature Zhang X, Jiang H, Li S, Luo A, Zhao Y Ref: Medicine (Baltimore), 97:e0300, 2018 : PubMed ESTHER: Zhang_2018_Medicine.(Baltimore)_97_e0300 PubMedSearch: Zhang 2018 Medicine.(Baltimore) 97 e0300 PubMedID: 29620652 Abstract RATIONALE: Thyroid storm is a rare and life-threatening metabolic crisis because of an emergent release of excess thyroid hormone. Sinus tachycardia induced by excess thyroid hormone may result in congestive heart failure due to decreased diastolic filling time. PATIENT CONCERNS: A controlled hyperthyroidism patient with severe sinus tachycardia. DIAGNOSES: A controlled hyperthyroidism patient was induced thyroid storm during huge pelvic mass resection. INTERVENTIONS: Application of low-dose neostigmine and beta-antagonist esmolol to control the heart rate (HR) avoided hemodynamic collapse. OUTCOMES: The patient improved dramatically following application of low-dose neostigmine instead of esmolol to control the HR avoided hemodynamic collapse. LESSONS: Our case suggests that neostigmine, an acetylcholinesterase inhibitor, may warrant further investigation in patients with thyroid storm-induced severe sinus tachycardia. Title: Central cholinergic system mediates working memory deficit induced by anesthesia/surgery in adult mice Zhang X, Jiang X, Huang L, Tian W, Chen X, Gu X, Yu W, Tian J, Su D Ref: Brain Behav, 8:e00957, 2018 : PubMed ESTHER: Zhang_2018_Brain.Behav_8_e00957 PubMedSearch: Zhang 2018 Brain.Behav 8 e00957 PubMedID: 29761010 Abstract Background: Postoperative cognitive dysfunction (POCD) is consistently associated with increased morbidity and mortality, which has become a major concern of patients and caregivers. Although POCD occurs mainly in aged patients, it happens at any age. Previous studies demonstrated that anesthesia/surgery had no effects on reference memory of adult mice. However, whether it impairs working memory remains unclear. Working memory deficit would result in many deficits of executive function. We hypothesized that anesthesia/surgery impaired the working memory of adult mice and the central cholinergic system was involved. Method: Tibial fracture internal fixation under the anesthesia of isoflurane was performed in two-month-old C57BL/6 mice. Two days later, the spatial reference memory and working memory were measured by a Morris Water Maze (MWM). Donepezil, an inhibitor of acetylcholinesterase (AChE), was administered in another cohort mice for 4 weeks. Then, the working memory was measured by MWM 2 days after anesthesia/surgery. Western blot was used to detect the protein levels of acetylcholine transferase (ChAT), AChE, vesicular acetylcholine transporter (VAChT), and choline transporter (ChT) in the prefrontal cortex (PFC). Results: We found that anesthesia/surgery had no effects on the reference memory, but it impaired the working memory in adult mice. Meanwhile, we also found that the protein level of ChAT in PFC decreased significantly compared with that in control group. Donepezil pretreatment prevented working memory impairment and the decrease of the protein levels of ChAT induced by anesthesia/surgery. Conclusion: These results suggest that anesthesia/surgery leads to working memory deficits in adult mice and central cholinergic system impairment is involved. Title: Multi-targetable chalcone analogs to treat deadly Alzheimer's disease: Current view and upcoming advice Zhang X, Rakesh KP, Bukhari SNA, Balakrishna M, Manukumar HM, Qin HL Ref: Bioorg Chem, 80:86, 2018 : PubMed ESTHER: Zhang_2018_Bioorg.Chem_80_86 PubMedSearch: Zhang 2018 Bioorg.Chem 80 86 PubMedID: 29890362 Abstract The complications of Alzheimer's disease AD were deadly dangerous cause of neurodegenerative disorders connected with the decline of the cognitive functions and loss of memory. The common form of dementia is accounted as the sixth leading cause of the death affecting any stage of people in a lifetime. Synthetic natural chalcone analogs were currently a hot research topic for the treatment of (AD) which has affected millions of peoples throughout the world. The present aim was set to understand the important problems of the AD and its treatment based on natural derivatives of novel chalcones. One interesting strategy currently of searching for the treatment of AD is to find inhibitors for acetylcholinesterase (AChE) and using metal chelators to target amyloid-beta (Abeta) peptides, and then metal-Abeta complexes for the AD pathogenesis. The present compressed review focuses and highlights the design and synthesis of new approaches for the construction of important chalcones playing multiple beneficiary roles in the AD treatments. These hallmarks of concurred research represent the immediate needs of development of novel therapeutic drugs for effective treatment of ADs by understanding the specific pharmacology targets. Title: Alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function in diabetic rabbits Zhang X, Zhang Z, Yang Y, Suo Y, Liu R, Qiu J, Zhao Y, Jiang N, Liu C and Liu T <2 more author(s)> Zhang X, Zhang Z, Yang Y, Suo Y, Liu R, Qiu J, Zhao Y, Jiang N, Liu C, Tse G, Li G, Liu T (- 2) Ref: Cardiovasc Diabetol, 17:160, 2018 : PubMed ESTHER: Zhang_2018_Cardiovasc.Diabetol_17_160 PubMedSearch: Zhang 2018 Cardiovasc.Diabetol 17 160 PubMedID: 30591063 Abstract BACKGROUND: There are increasing evidence that left ventricle diastolic dysfunction is the initial functional alteration in the diabetic myocardium. In this study, we hypothesized that alogliptin prevents diastolic dysfunction and preserves left ventricular mitochondrial function and structure in diabetic rabbits. METHODS: A total of 30 rabbits were randomized into control group (CON, n = 10), alloxan-induced diabetic group (DM, n = 10) and alogliptin-treated (12.5 mg/kd/day for 12 weeks) diabetic group (DM-A, n = 10). Echocardiographic and hemodynamic studies were performed in vivo. Mitochondrial morphology, respiratory function, membrane potential and reactive oxygen species (ROS) generation rate of left ventricular tissue were assessed. The serum concentrations of glucagon-like peptide-1, insulin, inflammatory and oxidative stress markers were measured. Protein expression of TGF-beta1, NF-kappaB p65 and mitochondrial biogenesis related proteins were determined by Western blotting. RESULTS: DM rabbits exhibited left ventricular hypertrophy, left atrial dilation, increased E/e' ratio and normal left ventricular ejection fraction. Elevated left ventricular end diastolic pressure combined with decreased maximal decreasing rate of left intraventricular pressure (- dp/dtmax) were observed. Alogliptin alleviated ventricular hypertrophy, interstitial fibrosis and diastolic dysfunction in diabetic rabbits. These changes were associated with decreased mitochondrial ROS production rate, prevented mitochondrial membrane depolarization and improved mitochondrial swelling. It also improved mitochondrial biogenesis by PGC-1alpha/NRF1/Tfam signaling pathway. CONCLUSIONS: The DPP-4 inhibitor alogliptin prevents cardiac diastolic dysfunction by inhibiting ventricular remodeling, explicable by improved mitochondrial function and increased mitochondrial biogenesis. Title: Genome Mining and Comparative Biosynthesis of Meroterpenoids from Two Phylogenetically Distinct Fungi Zhang X, Wang TT, Xu QL, Xiong Y, Zhang L, Han H, Xu K, Guo WJ, Xu Q and Ge HM <1 more author(s)> Zhang X, Wang TT, Xu QL, Xiong Y, Zhang L, Han H, Xu K, Guo WJ, Xu Q, Tan RX, Ge HM (- 1) Ref: Angew Chem Int Ed Engl, 57:8184, 2018 : PubMed ESTHER: Zhang_2018_Angew.Chem.Int.Ed.Engl_57_8184 PubMedSearch: Zhang 2018 Angew.Chem.Int.Ed.Engl 57 8184 PubMedID: 29797385 Gene_locus related to this paper: necsz-ntng, artsz-atng Abstract Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10. Title: Mechanistic insight into the relationship between triacylglycerol and crystallization of lipase-catalyzed interesterified blend of palm stearin and vegetable oil Zhu TW, Weng HT, Zhang X, Wu H, Li B Ref: Food Chem, 260:306, 2018 : PubMed ESTHER: Zhu_2018_Food.Chem_260_306 PubMedSearch: Zhu 2018 Food.Chem 260 306 PubMedID: 29699674 Abstract To give a deep insight into the relationship between triacylglycerol and crystallization of interesterified fat, the blends of palm stearin and various vegetable oil were catalyzed by two different immobilized lipases in this study. After interesterification, the blends had wider plastic range indicated by the SFC results and more beta' crystal. The improved physicochemical characteristics of interesterified blends were attributed to their changed TAG profiles. The statistical analysis showed that the interesterified blends were more likely to form beta' crystal with the increase of SU2-type TAG content and the decrease of SSS-type TAG content (p<0.01). In addition, the decrease of ECN 42- and ECN 48-type TAGs and the increase of ECN 50-type TAGs also significantly enhanced the formation of beta' crystal (p<0.05). Furthermore, the sn-1,3-specific Lipozyme TL IM-catalyzed interesterified blends were favorable for the formation of beta' crystal than the non-specific Novozym 435-catalyzed interesterified blends. Title: MicroRNA-182 Promotes Lipoprotein Lipase Expression and Atherogenesisby Targeting Histone Deacetylase 9 in Apolipoprotein E-Knockout Mice Cheng HP, Gong D, Zhao ZW, He PP, Yu XH, Ye Q, Huang C, Zhang X, Chen LY and Tang CK <10 more author(s)> Cheng HP, Gong D, Zhao ZW, He PP, Yu XH, Ye Q, Huang C, Zhang X, Chen LY, Xie W, Zhang M, Li L, Xia XD, Ouyang XP, Tan YL, Wang ZB, Tian GP, Zheng XL, Yin WD, Tang CK (- 10) Ref: Circ J, 82:28, 2017 : PubMed ESTHER: Cheng_2017_Circ.J_82_28 PubMedSearch: Cheng 2017 Circ.J 82 28 PubMedID: 28855441 Abstract BACKGROUND: Lipoprotein lipase (LPL) expressed in macrophages plays an important role in promoting the development of atherosclerosis or atherogenesis. MicroRNA-182 (miR-182) is involved in the regulation of lipid metabolism and inflammation. However, it remains unclear how miR-182 regulates LPL and atherogenesis.Methods and Results:Using bioinformatics analyses and a dual-luciferase reporter assay, we identified histone deacetylase 9 (HDAC9) as a target gene of miR-182. Moreover, miR-182 upregulated LPL expression by directly targetingHDAC9in THP-1 macrophages. Hematoxylin-eosin (H&E), Oil Red O and Masson's trichrome staining showed that apolipoprotein E (ApoE)-knockout (KO) mice treated with miR-182 exhibited more severe atherosclerotic plaques. Treatment with miR-182 increased CD68 and LPL expression in atherosclerotic lesions in ApoE-KO mice, as indicated by double immunofluorescence staining in the aortic sinus. Increased miR-182-induced increases in LPL expression in ApoE-KO mice was confirmed by real-time quantitative polymerase chain reaction and western blotting analyses. Treatment with miR-182 also increased plasma concentrations of proinflammatory cytokines and lipids in ApoE-KO mice. CONCLUSIONS: The results of the present study suggest that miR-182 upregulates LPL expression, promotes lipid accumulation in atherosclerotic lesions, and increases proinflammatory cytokine secretion, likely through targetingHDAC9, leading to an acceleration of atherogenesis in ApoE-KO mice. Title: Highly sensitive GQDs-MnO2 based assay with turn-on fluorescence for monitoring cerebrospinal acetylcholinesterase fluctuation: A biomarker for organophosphorus pesticides poisoning and management Deng J, Lu D, Zhang X, Shi G, Zhou T Ref: Environ Pollut, 224:436, 2017 : PubMed ESTHER: Deng_2017_Environ.Pollut_224_436 PubMedSearch: Deng 2017 Environ.Pollut 224 436 PubMedID: 28258856 Abstract In this study, we demonstrated an assay with turn-on fluorescence for monitoring cerebrospinal acetylcholinesterase (AChE) fluctuation as a biomarker for organophosphorus pesticides (OPs) poisoning and management based on single layer MnO2 nanosheets with graphene quantum dots (GQDs) as signal readout. Initially, the fluorescence of GQDs was quenched by MnO2 nanosheets mainly due to the inner filter effect (IFE). However, with the presence of reductive thiocholine (TCh), the enzymatic product, hydrolyzed from acetylthiocholine (ATCh) by AChE, the redox reaction between MnO2 and TCh occurred, leading to the destruction of the MnO2 nanosheets, and thereby IFE was diminished gradually. As a consequence, the turn-on fluorescence of GQDs with the changes in the spectrum of the dispersion constituted a new mechanism for sensing of cerebrospinal AChE. With the method developed here, we could monitor cerebrospinal AChE fluctuation of rats exposed to OPs before and after therapy, and could thereby open up the pathway to a new sensing platform for better understanding the mechanism of brain dysfunctions associate with OPs poisoning. Title: The Cation-pi Interaction Enables a Halo-Tag Fluorogenic Probe for Fast No-Wash Live Cell Imaging and Gel-Free Protein Quantification Liu Y, Miao K, Dunham NP, Liu H, Fares M, Boal AK, Li X, Zhang X Ref: Biochemistry, 56:1585, 2017 : PubMed ESTHER: Liu_2017_Biochemistry_56_1585 PubMedSearch: Liu 2017 Biochemistry 56 1585 PubMedID: 28221782 Gene_locus related to this paper: rhoso-halo1 Inhibitor(s) related to this paper: P9-benzothiadiazole Abstract The design of fluorogenic probes for a Halo tag is highly desirable but challenging. Previous work achieved this goal by controlling the chemical switch of spirolactones upon the covalent conjugation between the Halo tag and probes or by incorporating a "channel dye" into the substrate binding tunnel of the Halo tag. In this work, we have developed a novel class of Halo-tag fluorogenic probes that are derived from solvatochromic fluorophores. The optimal probe, harboring a benzothiadiazole scaffold, exhibits a 1000-fold fluorescence enhancement upon reaction with the Halo tag. Structural, computational, and biochemical studies reveal that the benzene ring of a tryptophan residue engages in a cation-pi interaction with the dimethylamino electron-donating group of the benzothiadiazole fluorophore in its excited state. We further demonstrate using noncanonical fluorinated tryptophan that the cation-pi interaction directly contributes to the fluorogenicity of the benzothiadiazole fluorophore. Mechanistically, this interaction could contribute to the fluorogenicity by promoting the excited-state charge separation and inhibiting the twisting motion of the dimethylamino group, both leading to an enhanced fluorogenicity. Finally, we demonstrate the utility of the probe in no-wash direct imaging of Halo-tagged proteins in live cells. In addition, the fluorogenic nature of the probe enables a gel-free quantification of fusion proteins expressed in mammalian cells, an application that was not possible with previously nonfluorogenic Halo-tag probes. The unique mechanism revealed by this work suggests that incorporation of an excited-state cation-pi interaction could be a feasible strategy for enhancing the optical performance of fluorophores and fluorogenic sensors. Title: Neurexin Restricts Axonal Branching in Columns by Promoting Ephrin Clustering Liu L, Tian Y, Zhang XY, Zhang X, Li T, Xie W, Han J Ref: Dev Cell, 41:94, 2017 : PubMed ESTHER: Liu_2017_Dev.Cell_41_94 PubMedSearch: Liu 2017 Dev.Cell 41 94 PubMedID: 28366281 Abstract Columnar restriction of neurites is critical for forming nonoverlapping receptive fields and preserving spatial sensory information from the periphery in both vertebrate and invertebrate nervous systems, but the underlying molecular mechanisms remain largely unknown. Here, we demonstrate that Drosophila homolog of alpha-neurexin (DNrx) plays an essential role in columnar restriction during L4 axon branching. Depletion of DNrx from L4 neurons resulted in misprojection of L4 axonal branches into neighboring columns due to impaired ephrin clustering. The proper ephrin clustering requires its interaction with the intracellular region of DNrx. Furthermore, we find that Drosophila neuroligin 4 (DNlg4) in Tm2 neurons binds to DNrx and initiates DNrx clustering in L4 neurons, which subsequently induces ephrin clustering. Our study demonstrates that DNrx promotes ephrin clustering and reveals that ephrin/Eph signaling from adjacent L4 neurons restricts axonal branches of L4 neurons in columns. Title: AgHalo: A Facile Fluorogenic Sensor to Detect Drug-Induced Proteome Stress Liu Y, Fares M, Dunham NP, Gao Z, Miao K, Jiang X, Bollinger SS, Boal AK, Zhang X Ref: Angew Chem Int Ed Engl, 56:8672, 2017 : PubMed ESTHER: Liu_2017_Angew.Chem.Int.Ed.Engl_56_8672 PubMedSearch: Liu 2017 Angew.Chem.Int.Ed.Engl 56 8672 PubMedID: 28557281 Gene_locus related to this paper: rhoso-halo1 Inhibitor(s) related to this paper: P1-benzoxadiazole-fluorogenic-ligand Abstract Drug-induced proteome stress that involves protein aggregation may cause adverse effects and undermine the safety profile of a drug. Safety of drugs is regularly evaluated using cytotoxicity assays that measure cell death. However, these assays provide limited insights into the presence of proteome stress in live cells. A fluorogenic protein sensor is reported to detect drug-induced proteome stress prior to cell death. An aggregation prone Halo-tag mutant (AgHalo) was evolved to sense proteome stress through its aggregation. Detection of such conformational changes was enabled by a fluorogenic ligand that fluoresces upon AgHalo forming soluble aggregates. Using 5 common anticancer drugs, we exemplified detection of differential proteome stress before any cell death was observed. Thus, this sensor can be used to evaluate drug safety in a regime that the current cytotoxicity assays cannot cover and be generally applied to detect proteome stress induced by other toxins. Title: Complex pectin metabolism by gut bacteria reveals novel catalytic functions Ndeh D, Rogowski A, Cartmell A, Luis AS, Basle A, Gray J, Venditto I, Briggs J, Zhang X and Gilbert HJ <15 more author(s)> Ndeh D, Rogowski A, Cartmell A, Luis AS, Basle A, Gray J, Venditto I, Briggs J, Zhang X, Labourel A, Terrapon N, Buffetto F, Nepogodiev S, Xiao Y, Field RA, Zhu Y, O'Neil MA, Urbanowicz BR, York WS, Davies GJ, Abbott DW, Ralet MC, Martens EC, Henrissat B, Gilbert HJ (- 15) Ref: Nature, 544:65, 2017 : PubMed ESTHER: Ndeh_2017_Nature_544_65 PubMedSearch: Ndeh 2017 Nature 544 65 PubMedID: 28329766 Abstract The metabolism of carbohydrate polymers drives microbial diversity in the human gut microbiota. It is unclear, however, whether bacterial consortia or single organisms are required to depolymerize highly complex glycans. Here we show that the gut bacterium Bacteroides thetaiotaomicron uses the most structurally complex glycan known: the plant pectic polysaccharide rhamnogalacturonan-II, cleaving all but 1 of its 21 distinct glycosidic linkages. The deconstruction of rhamnogalacturonan-II side chains and backbone are coordinated to overcome steric constraints, and the degradation involves previously undiscovered enzyme families and catalytic activities. The degradation system informs revision of the current structural model of rhamnogalacturonan-II and highlights how individual gut bacteria orchestrate manifold enzymes to metabolize the most challenging glycan in the human diet. Title: Ndrg3 gene regulates DSB repair during meiosis through modulation the ERK signal pathway in the male germ cells Pan H, Zhang X, Jiang H, Jiang X, Wang L, Qi Q, Bi Y, Wang J, Shi Q, Li R Ref: Sci Rep, 7:44440, 2017 : PubMed ESTHER: Pan_2017_Sci.Rep_7_44440 PubMedSearch: Pan 2017 Sci.Rep 7 44440 PubMedID: 28290521 Abstract The N-myc downstream regulated gene (NDRG) family consists of 4 members, NDRG-1, -2, -3, -4. Physiologically, we found Ndrg3, a critical gene which led to homologous lethality in the early embryo development, regulated the male meiosis in mouse. The expression of Ndrg3 was enhanced specifically in germ cells, and reached its peak level in the pachytene stage spermatocyte. Haplo-insufficiency of Ndrg3 gene led to sub-infertility during the male early maturation. In the Ndrg3(+/-) germ cells, some meiosis events such as DSB repair and synaptonemal complex formation were impaired. Disturbances on meiotic prophase progression and spermatogenesis were observed. In mechanism, the attenuation of pERK1/2 signaling was detected in the heterozygous testis. With our primary spermatocyte culture system, we found that lactate promoted DSB repair via ERK1/2 signaling in the male mouse germ cells in vitro. Deficiency of Ndrg3 gene attenuated the activation of ERK which further led to the aberrancy of DSB repair in the male germ cells in mouse. Taken together, we reported that Ndrg3 gene modulated the lactate induced ERK pathway to facilitate DSB repair in male germ cells, which further regulated meiosis and subsequently fertility in male mouse. Title: Design, synthesis and evaluation of scutellarein-O-acetamidoalkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease Sang Z, Qiang X, Li Y, Xu R, Cao Z, Song Q, Wang T, Zhang X, Liu H and Deng Y <1 more author(s)> Sang Z, Qiang X, Li Y, Xu R, Cao Z, Song Q, Wang T, Zhang X, Liu H, Tan Z, Deng Y (- 1) Ref: Eur Journal of Medicinal Chemistry, 135:307, 2017 : PubMed ESTHER: Sang_2017_Eur.J.Med.Chem_135_307 PubMedSearch: Sang 2017 Eur.J.Med.Chem 135 307 PubMedID: 28458136 Abstract A series of scutellarein-O-acetamidoalkylbenzylamines derivatives were designed based on a multitarget-directed ligands strategy for the treatment of Alzheimer's disease. Among these compounds, compound T-22 demonstrated excellent acetylcholinesterase inhibitory, moderate inhibitory effects on self-induced Abeta1-42 aggregation, Cu2+-induced Abeta1-42 aggregation, human AChE-induced Abeta1-40 aggregation and disassembled Cu2+-induced aggregation of the well-structured Abeta1-42 fibrils, and also acted as potential antioxidant and biometals chelator. Both kinetic analysis of AChE inhibition and molecular modeling study suggested that T-22 interacted with both the catalytic active site and peripheral anionic site of AChE. Moreover, compound T-22 showed a good neuroprotective effect against H2O2-induced PC12 cell injury and low toxicity in SH-SY5Y cells. Furthermore, the step-down passive avoidance test indicated T-22 significantly reversed scopolamine-induced memory deficit in mice. Taken together, the data showed that T-22 was an interesting multifunctional lead compound worthy of further study for AD. Title: Screening and characterization of a novel thermostable lipase with detergent-additive potential from the metagenomic library of a mangrove soil Tang L, Xia Y, Wu X, Chen X, Zhang X, Li H Ref: Gene, 625:64, 2017 : PubMed ESTHER: Tang_2017_Gene_625_64 PubMedSearch: Tang 2017 Gene 625 64 PubMedID: 28457984 Abstract One clone (Lip906) exhibiting lipase activity was screened from a metagenomic library by using a medium containing tricaprylin. A novel lipase gene from the inserted fragment of Lip906 was obtained by sequencing. The phylogenetic analysis of Lip906 lipase exhibited 34% and 32% homologue to lipases from Streptomyces sp. MspMP-M5 and Rhodopirellula europaea. This gene was expressed in Escherichia coli (E. coli) BL21 (DE3), and the recombinant protein was purified and characterized. The best substrate of the recombinant Lip906 lipase was p-nitrophenyl myristate (C14). The lipase expressed maximum activity at 74 degrees C and pH7.8, and it was found to be stable at pH values and temperatures ranging from 6.0-8.0 and 4-78 degrees C, respectively. Furthermore, the lipase was found to be highly resistant to commercial detergent, DMSO, and EDTA, whereas its activity was stimulated in the presence of methanol and ethanol at low concentrations. The lipase showed enhanced activity in the presence of Hg2+, whereas the presence of the metal ions Fe2+, Ca2+, Co2+, and Mg2+ inhibited the activity. These beneficial characteristics of Lip906 lipase provide some advantages for its potential application in industry. Title: Transcriptome of the GSH-Depleted Lens Reveals Changes in Detoxification and EMT Signaling Genes, Transport Systems, and Lipid Homeostasis Whitson JA, Zhang X, Medvedovic M, Chen J, Wei Z, Monnier VM, Fan X Ref: Invest Ophthalmol Vis Sci, 58:2666, 2017 : PubMed ESTHER: Whitson_2017_Invest.Ophthalmol.Vis.Sci_58_2666 PubMedSearch: Whitson 2017 Invest.Ophthalmol.Vis.Sci 58 2666 PubMedID: 28525556 Abstract Purpose: To understand the effects of glutathione (GSH)-deficiency on genetic processes that regulate lens homeostasis and prevent cataractogenesis. Methods: The transcriptome of lens epithelia and fiber cells was obtained from C57BL/6 LEGSKO (lens GSH-synthesis knockout) and buthionine sulfoximine (BSO)-treated LEGSKO mice and compared to C57BL/6 wild-type mice using RNA-Seq. Transcriptomic data were confirmed by qPCR and Western blot/ELISA on a subset of genes. Results: RNA-Seq results were in excellent agreement with qPCR (correlation coefficients 0.87-0.94 and P < 5E-6 for a subset of 36 mRNAs). Of 24,415 transcripts mapped to the mouse genome, 441 genes showed significantly modulated expression. Pathway analysis indicated major changes in epithelial-mesenchymal transition (EMT) signaling, visual cycle, small molecule biochemistry, and lipid metabolism. GSH-deficient lenses showed upregulation of detoxification genes, including Aldh1a1, Aldh3a1 (aldehyde dehydrogenases), Mt1, Mt2 (metallothioneins), Ces1g (carboxylesterase), and Slc14a1 (urea transporter UT-B). Genes in canonical EMT pathways, including Wnt10a, showed upregulation in lens epithelia samples. Severely GSH-deficient lens epithelia showed downregulation of vision-related genes (including crystallins). The BSO-treated LEGSKO lens epithelia transcriptome has significant correlation (r = 0.63, P < 0.005) to that of lens epithelia undergoing EMT. Protein expression data correlated with transcriptomic data and confirmed EMT signaling activation. Conclusions: These results show that GSH-deficiency in the lens leads to expression of detoxifying genes and activation of EMT signaling, in addition to changes in transport systems and lipid homeostasis. These data provide insight into the adaptation and consequences of GSH-deficiency in the lens and suggest that GSH plays an important role in lenticular EMT pathology. Title: Novel Thiosemicarbazones Inhibit Lysine-Rich Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 (CEACAM1) Coisolated (LYRIC) and the LYRIC-Induced Epithelial-Mesenchymal Transition via Upregulation of N-Myc Downstream-Regulated Gene 1 (NDRG1) Xi R, Pun IH, Menezes SV, Fouani L, Kalinowski DS, Huang ML, Zhang X, Richardson DR, Kovacevic Z Ref: Molecular Pharmacology, 91:499, 2017 : PubMed ESTHER: Xi_2017_Mol.Pharmacol_91_499 PubMedSearch: Xi 2017 Mol.Pharmacol 91 499 PubMedID: 28275050 Abstract Tumor necrosis factor alpha (TNFalpha) plays a vital role in cancer progression as it is associated with inflammation and promotion of cancer angiogenesis and metastasis. The effects of TNFalpha are mediated by its downstream target, the oncogene lysine-rich CEACAM1 coisolated protein (LYRIC, also known as metadherin or astrocyte elevated gene-1). LYRIC plays an important role in activating the nuclear factor-kB (NF-kappaB) signaling pathway, which controls multiple cellular processes, including proliferation, apoptosis, migration, etc. In contrast, the metastasis suppressor N-myc downstream regulated gene 1 (NDRG1) has the opposite effect on the NF-kappaB pathway, being able to inhibit NF-kappaB activation and reduce angiogenesis, proliferation, migration, and cancer cell invasion. These potent anticancer properties make NDRG1 an ideal therapeutic target. Indeed, a novel class of thiosemicarbazone anticancer agents that target this molecule has been developed; the lead agent, di-2-pyridylketone 4-cyclohexyl-4-methyl-3-thiosemicarbazone, has recently entered clinical trials for advanced and resistant cancers. To further elucidate the interaction between NDRG1 and oncogenic signaling, this study for the first time assessed the effects of NDRG1 on the tumorigenic properties of TNFalpha and its downstream target, LYRIC. We have demonstrated that NDRG1 inhibits the TNFalpha-mediated epithelial-to-mesenchymal transition. Further, NDRG1 also potently inhibited LYRIC expression, with a negative feedback loop existing between these two molecules. Examining the mechanism involved, we demonstrated that NDRG1 inhibited phosphatidylinositol 3-kinase/AKT signaling, leading to reduced levels of the LYRIC transcriptional activator, c-Myc. Finally, we demonstrated that novel thiosemicarbazones that upregulate NDRG1 also inhibit LYRIC expression, further highlighting their marked potential for cancer treatment. Title: Novel chaetospirolactone and orsellide F from an endophytic fungus Chaetomium sp Xu QL, Xiao YS, Shen Y, Wu HM, Zhang X, Deng XZ, Wang TT, Li W, Tan RX and Ge HM <1 more author(s)> Xu QL, Xiao YS, Shen Y, Wu HM, Zhang X, Deng XZ, Wang TT, Li W, Tan RX, Jiao RH, Ge HM (- 1) Ref: J Asian Nat Prod Res, :1, 2017 : PubMed ESTHER: Xu_2017_J.Asian.Nat.Prod.Res__1 PubMedSearch: Xu 2017 J.Asian.Nat.Prod.Res 1 PubMedID: 28478698 Abstract Chaetospirolactone (1), a novel spiro-lactone bearing a rare 1-oxaspiro [4.4] non-7-ene-2,6-dione skeleton, and orsellide F (2), together with six known compounds (3-8), were isolated from an endophytic fungus Chaetomium sp. NF00754. Their structures were determined by interpretation of spectroscopic data. The absolute configurations of 1 and 2 were established by analysis of single X-ray crystallographic data and CD spectra. Compounds 3, 4, and 6 showed moderate acetylcholinesterase inhibitory activity with IC50 values of 7.34, 5.19, and 7.67 muM, respectively. Title: Not all neuroligin 3 and 4X missense variants lead to significant functional inactivation Xu X, Hu Z, Zhang L, Liu H, Cheng Y, Xia K, Zhang X Ref: Brain Behav, 7:e00793, 2017 : PubMed ESTHER: Xu_2017_Brain.Behav_7_e00793 PubMedSearch: Xu 2017 Brain.Behav 7 e00793 PubMedID: 28948087 Gene_locus related to this paper: human-NLGN4X Abstract INTRODUCTION: Neuroligins are postsynaptic cell adhesion molecules that interact with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, accumulating evidence, involving mutation analysis, cellular assays, and mouse models, has suggested that neuroligin (NLGN) mutations affect synapse maturation and function. Previously, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162K (NLGN4X), and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. Title: Increased Expression of NDRG3 in Mouse Uterus During Embryo Implantation and in Mouse Endometrial Stromal Cells During In Vitro Decidualization Yang Q, Zhang X, Shi Y, He YP, Sun ZG, Shi HJ, Wang J Ref: Reprod Sci, :1933719117737843, 2017 : PubMed ESTHER: Yang_2017_Reprod.Sci__1933719117737843 PubMedSearch: Yang 2017 Reprod.Sci 1933719117737843 PubMedID: 29096585 Gene_locus related to this paper: human-NDRG3, mouse-ndr3 Abstract Decidualization is an indispensable event in the embryo implantation process, but its underlying molecular mechanisms remain elusive. In this study, we showed that in mice, the uterine expression of N-myc downstream-regulated gene 3 (NDRG3), a member of the alpha/beta hydrolase superfamily, was induced by estradiol and progesterone. During the embryo implantation process, uterine Ndrg3 expression was remarkably upregulated, and its expression level at implantation sites (IS) was significantly higher than that at inter-IS. Increased uterine expression of Ndrg3 was associated with artificial decidualization and the activation of delayed implantation. The in vitro decidualization of mouse endometrial stromal cells (ESCs) induced by estradiol and progesterone was also accompanied by increased Ndrg3 expression, and downregulated Ndrg3 expression in ESCs effectively inhibited decidualization. miR-290b-5p was identified as an upstream regulator of Ndrg3, and the uterine expression level of miR-290b-5p was decreased during the implantation process. Furthermore, overexpression of miR-290b-5p in mouse ESCs inhibited their in vitro decidualization. Taken together, these data suggested that Ndrg3 might play an important role in embryo implantation by regulating decidualization potentially via the estrogen/progesterone/miR-290b-5p pathway. Title: Genome-wide identification of pathogenicity, conidiation and colony sectorization genes in Metarhizium robertsii Zeng G, Chen X, Zhang X, Zhang Q, Xu C, Mi W, Guo N, Zhao H, You Y and Fang W <4 more author(s)> Zeng G, Chen X, Zhang X, Zhang Q, Xu C, Mi W, Guo N, Zhao H, You Y, Dryburgh FJ, Bidochka MJ, St Leger RJ, Zhang L, Fang W (- 4) Ref: Environ Microbiol, 19:3896, 2017 : PubMed ESTHER: Zeng_2017_Environ.Microbiol_19_3896 PubMedSearch: Zeng 2017 Environ.Microbiol 19 3896 PubMedID: 28447400 Gene_locus related to this paper: metaf-pks1 Abstract Metarhizium robertsii occupies a wide array of ecological niches and has diverse lifestyle options (saprophyte, insect pathogen and plant symbiont), that renders it an unusually effective model for studying genetic mechanisms for fungal adaptation. Here over 20,000 M. robertsii T-DNA mutants were screened in order to elucidate genetic mechanism by which M. robertsii replicates and persists in diverse niches. About 287 conidiation, colony sectorization or pathogenicity loci, many of which have not been reported in other fungi were identified. By analysing a series of conidial pigmentation mutants, a new fungal pigmentation gene cluster, which contains Mr-Pks1, Mr-EthD and Mlac1 was identified. A conserved conidiation regulatory pathway containing Mr-BrlA, Mr-AbaA and Mr-WetA regulates expression of these pigmentation genes. During conidiation Mr-BlrA up-regulates Mr-AbaA, which in turn controls Mr-WetA. It was found that Hog1-MAPK regulates fungal conidiation by controlling the conidiation regulatory pathway, and that all three pigmentation genes exercise feedback regulation of conidiation. This work provided the foundation for deeper understanding of the genetic processes behind M. robertsii adaptive phenotypes, and advances our insights into conidiation and pigmentation in this fungus. Title: Effects of monocrotophos pesticide on cholinergic and dopaminergic neurotransmitter systems during early development in the sea urchin Hemicentrotus pulcherrimus Zhang X, Li S, Wang C, Tian H, Wang W, Ru S Ref: Toxicol Appl Pharmacol, 328:46, 2017 : PubMed ESTHER: Zhang_2017_Toxicol.Appl.Pharmacol_328_46 PubMedSearch: Zhang 2017 Toxicol.Appl.Pharmacol 328 46 PubMedID: 28479505 Abstract During early development in sea urchins, classical neurotransmitters, including acetylcholine (ACh), dopamine (DA), and serotonin (5-HT), play important roles in the regulation of morphogenesis and swimming behavior. However, the underlying mechanisms of how organophosphate pesticides cause developmental neurotoxicity by interfering with different neurotransmitter systems are unclear. In this study, we investigated the effects of 0.01, 0.10, and 1.00mg/L monocrotophos (MCP) pesticide on the activity of acetyltransferase (ChAT), acetylcholinesterase (AChE), monoamine oxidase, the concentration of DA, dopamine transporter, and the transcription activity of DA receptor D1 and tyrosine hydroxylase, during critical periods in cholinergic and dopaminergic nervous system development in sea urchin (Hemicentrotus pulcherrimus) embryos and larvae. At the blastula stages, MCP disrupted DA metabolism but not 5-HT metabolism, resulting in abnormal development. High ChAT and AChE activity were observed at the gastrulation-completed stage and the two-armed pluteus stage, respectively, MCP inhibited ChAT activity and AChE activity/distribution and resulted in developmental defects of the plutei. From the gastrula stage to the two-armed pluteus stage, we found ubiquitous disrupting effects of MCP on ACh, DA, and 5-HT metabolism, particularly at critical periods during the development of these neurotransmitter systems. Therefore, we propose that this disruption is one of the main mechanisms of MCP-related developmental neurotoxicity, which would contribute better understanding insight into the mechanism of MCP pesticide's toxic effects. Title: Cellular Transport of Esculin and Its Acylated Derivatives in Caco-2 Cell Monolayers and Their Antioxidant Properties in Vitro Zhang M, Xin X, Lai F, Zhang X, Li X, Wu H Ref: Journal of Agricultural and Food Chemistry, 65:7424, 2017 : PubMed ESTHER: Zhang_2017_J.Agric.Food.Chem_65_7424 PubMedSearch: Zhang 2017 J.Agric.Food.Chem 65 7424 PubMedID: 28805379 Abstract Esculin has many pharmacological effects, but these are difficult to observe after oral administration owing to poor lipid solubility. In our previous study, five acylated derivatives with different acyl chain lengths (EA, EP, EO, EL, and EM) were synthesized to improve the lipophilicity of esculin. In this study, the bioavailability and antioxidant activity of the five derivatives were investigated. The logP of esculin, EA, EP, EO, EL, and EM were -1.1 +/- 0.1, -0.3 +/- 0.14, 0.1 +/- 0.17, 1.6 +/- 0.09, 2.4 +/- 0.11, and 2.8 +/- 0.18, and their Papp were 0.71 +/- 0.02, 1.24 +/- 0.18, 1.74 +/- 0.11, 11.6 +/- 3.6, 4.11 +/- 1.03, and 2.64 +/- 0.97 x 10(-6) cm/s, respectively. Besides, the bioavailability of EO, EL, and EM were seriously affected by carboxylesterase. The results of ABTS, ORAC, and DPPH assays indicated that the antiradical ability of the five derivatives did not exceed that of esculin. However, EA, EP, and EO showed more effective inhibition of AAPH-induced oxidative hemolysis than esculin did (p < 0.05), and EL and EM were less effective than esculin (p < 0.05). The mechanism was related to the distribution and localization of the derivatives in "oil-water interface" between the cytomembrane and the aqueous phase. Title: Neuroligin 4 regulates synaptic growth via the bone morphogenetic protein (BMP) signaling pathway at the Drosophila neuromuscular junction Zhang X, Rui M, Gan G, Huang C, Yi J, Lv H, Xie W Ref: Journal of Biological Chemistry, 292:17991, 2017 : PubMed ESTHER: Zhang_2017_J.Biol.Chem_292_17991 PubMedSearch: Zhang 2017 J.Biol.Chem 292 17991 PubMedID: 28912273 Abstract The neuroligin (Nlg) family of neural cell adhesion molecules is thought to be required for synapse formation and development and has been linked to the development of autism spectrum disorders in humans. In Drosophila melanogaster, mutations in the neuroligin 1-3 genes have been reported to induce synapse developmental defects at neuromuscular junctions (NMJs), but the role of neuroligin 4 (dnlg4) in synapse development has not been determined. Here, we report that the Drosophila neuroligin 4 (DNlg4) is different from DNlg1-3 in that it presynaptically regulates NMJ synapse development. Loss of dnlg4 results in reduced growth of NMJs with fewer synaptic boutons. The morphological defects caused by dnlg4 mutant are associated with a corresponding decrease in synaptic transmission efficacy. All of these defects could only be rescued when DNlg4 was expressed in the presynapse of NMJs. To understand the basis of DNlg4 function, we looked for genetic interactions and found connections with the components of the bone morphogenetic protein (BMP) signaling pathway. Immunostaining and Western blot analyses demonstrated that the regulation of NMJ growth by DNlg4 was due to the positive modulation of BMP signaling by DNlg4. Specifically, BMP type I receptor thickvein (Tkv) abundance was reduced in dnlg4 mutants, and immunoprecipitation assays showed that DNlg4 and Tkv physically interacted in vivo Our study demonstrates that DNlg4 presynaptically regulates neuromuscular synaptic growth via the BMP signaling pathway by modulating Tkv. Title: The sea cucumber genome provides insights into morphological evolution and visceral regeneration Zhang X, Sun L, Yuan J, Sun Y, Gao Y, Zhang L, Li S, Dai H, Hamel JF and Xiang J <21 more author(s)> Zhang X, Sun L, Yuan J, Sun Y, Gao Y, Zhang L, Li S, Dai H, Hamel JF, Liu C, Yu Y, Liu S, Lin W, Guo K, Jin S, Xu P, Storey KB, Huan P, Zhang T, Zhou Y, Zhang J, Lin C, Li X, Xing L, Huo D, Sun M, Wang L, Mercier A, Li F, Yang H, Xiang J (- 21) Ref: PLoS Biol, 15:e2003790, 2017 : PubMed ESTHER: Zhang_2017_PLoS.Biol_15_E2003790 PubMedSearch: Zhang 2017 PLoS.Biol 15 E2003790 PubMedID: 29023486 Gene_locus related to this paper: stija-a0a2g8k9s2, stija-a0a2g8ka54, stija-a0a2g8jd52, stija-a0a2g8l0w8 Abstract Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs. Title: The Aegilops tauschii genome reveals multiple impacts of transposons Zhao G, Zou C, Li K, Wang K, Li T, Gao L, Zhang X, Wang H, Yang Z and Jia J <5 more author(s)> Zhao G, Zou C, Li K, Wang K, Li T, Gao L, Zhang X, Wang H, Yang Z, Liu X, Jiang W, Mao L, Kong X, Jiao Y, Jia J (- 5) Ref: Nat Plants, 3:946, 2017 : PubMed ESTHER: Zhao_2017_Nat.Plants_3_946 PubMedSearch: Zhao 2017 Nat.Plants 3 946 PubMedID: 29158546 Gene_locus related to this paper: horvv-m0utz9, wheat-a0a3b6c2m6, wheat-a0a3b5zwb6, wheat-a0a3b6bzs8, wheat-a0a1d5zte7 Abstract Wheat is an important global crop with an extremely large and complex genome that contains more transposable elements (TEs) than any other known crop species. Here, we generated a chromosome-scale, high-quality reference genome of Aegilops tauschii, the donor of the wheat D genome, in which 92.5% sequences have been anchored to chromosomes. Using this assembly, we accurately characterized genic loci, gene expression, pseudogenes, methylation, recombination ratios, microRNAs and especially TEs on chromosomes. In addition to the discovery of a wave of very recent gene duplications, we detected that TEs occurred in about half of the genes, and found that such genes are expressed at lower levels than those without TEs, presumably because of their elevated methylation levels. We mapped all wheat molecular markers and constructed a high-resolution integrated genetic map corresponding to genome sequences, thereby placing previously detected agronomically important genes/quantitative trait loci (QTLs) on the Ae. tauschii genome for the first time. Title: Association of plasma dipeptidyl peptidase-4 activity with non-alcoholic fatty liver disease in nondiabetic Chinese population Zheng T, Chen B, Yang L, Hu X, Zhang X, Liu H, Qin L Ref: Metabolism, 73:125, 2017 : PubMed ESTHER: Zheng_2017_Metabolism_73_125 PubMedSearch: Zheng 2017 Metabolism 73 125 PubMedID: 28637594 Abstract OBJECTIVE: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is attributed to a "multi-hits hypothesis" involving insulin resistance, oxidative stress and inflammation. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing the"multi-hits". Hence, we investigated the association between plasma DPP4 activity and NAFLD in nondiabetic Chinese population. DESIGN AND METHODS: We performed a cross-sectional study using data from 1105 subjects (36-79years) in Guilin between 2015 and 2016. Plasma DPP4 activity, homeostatic model assessment of insulin resistance (HOMA-IR), oxidative stress parameters, and inflammatory markers were measured in all participants. NAFLD and its severity were diagnosed by ultrasound after the exclusion of alcohol abuse and other liver diseases. RESULTS: Participants in the highest quartile of DPP4 activity had higher HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6, CRP, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase compared with those in the lowest quartile (all P<0.05). Plasma DPP4 activity gradually increased across the groups according to the ultrasonographic severity of steatosis (P<0.001 for the trend). In the highest DPP4 quartile, NAFLD risk was higher (odds ratio 1.88; 95% CI 1.04-3.37) than in the lowest quartile after adjustment for confounders. The risk for NAFLD increased more with higher levels of DPP4 activity, HOMA-IR, nitrotyrosine, 8-iso-PGF2a, interleukin-6 and CRP. CONCLUSIONS: Plasma DPP4 activity is significantly associated with NAFLD. The underlying mechanisms may be partly attributed to the interactions between insulin resistance, oxidative stress, inflammation, and DPP4. Title: The genome sequences of Arachis duranensis and Arachis ipaensis, the diploid ancestors of cultivated peanut Bertioli DJ, Cannon SB, Froenicke L, Huang G, Farmer AD, Cannon EK, Liu X, Gao D, Clevenger J and Ozias-Akins P <29 more author(s)> Bertioli DJ, Cannon SB, Froenicke L, Huang G, Farmer AD, Cannon EK, Liu X, Gao D, Clevenger J, Dash S, Ren L, Moretzsohn MC, Shirasawa K, Huang W, Vidigal B, Abernathy B, Chu Y, Niederhuth CE, Umale P, Araujo AC, Kozik A, Kim KD, Burow MD, Varshney RK, Wang X, Zhang X, Barkley N, Guimaraes PM, Isobe S, Guo B, Liao B, Stalker HT, Schmitz RJ, Scheffler BE, Leal-Bertioli SC, Xun X, Jackson SA, Michelmore R, Ozias-Akins P (- 29) Ref: Nat Genet, 48:438, 2016 : PubMed ESTHER: Bertioli_2016_Nat.Genet_48_438 PubMedSearch: Bertioli 2016 Nat.Genet 48 438 PubMedID: 26901068 Gene_locus related to this paper: aradu-a0a6p4dix2, aradu-a0a6p4dpj0, aradu-a0a6p4dix7 Abstract Cultivated peanut (Arachis hypogaea) is an allotetraploid with closely related subgenomes of a total size of -2.7 Gb. This makes the assembly of chromosomal pseudomolecules very challenging. As a foundation to understanding the genome of cultivated peanut, we report the genome sequences of its diploid ancestors (Arachis duranensis and Arachis ipaensis). We show that these genomes are similar to cultivated peanut's A and B subgenomes and use them to identify candidate disease resistance genes, to guide tetraploid transcript assemblies and to detect genetic exchange between cultivated peanut's subgenomes. On the basis of remarkably high DNA identity of the A. ipaensis genome and the B subgenome of cultivated peanut and biogeographic evidence, we conclude that A. ipaensis may be a direct descendant of the same population that contributed the B subgenome to cultivated peanut. Title: MAPK cascade-mediated regulation of pathogenicity, conidiation and tolerance to abiotic stresses in the entomopathogenic fungus Metarhizium robertsii Chen X, Xu C, Qian Y, Liu R, Zhang Q, Zeng G, Zhang X, Zhao H, Fang W Ref: Environ Microbiol, 18:1048, 2016 : PubMed ESTHER: Chen_2016_Environ.Microbiol_18_1048 PubMedSearch: Chen 2016 Environ.Microbiol 18 1048 PubMedID: 26714892 Gene_locus related to this paper: metra-pks2 Abstract Metarhizium robertsii has been used as a model to study fungal pathogenesis in insects, and its pathogenicity has many parallels with plant and mammal pathogenic fungi. MAPK (Mitogen-activated protein kinase) cascades play pivotal roles in cellular regulation in fungi, but their functions have not been characterized in M. robertsii. In this study, we identified the full complement of MAPK cascade components in M. robertsii and dissected their regulatory roles in pathogenesis, conidiation and stress tolerance. The nine components of the Fus3, Hog1 and Slt2-MAPK cascades are all involved in conidiation. The Fus3- and Hog1-MAPK cascades are necessary for tolerance to hyperosmotic stress, and the Slt2- and Fus3-MAPK cascades both mediate cell wall integrity. The Hog1 and Slt2-MAPK cascades contribute to pathogenicity; the Fus3-MAPK cascade is indispensable for fungal pathogenesis. During its life cycle, M. robertsii experiences multiple microenvironments as it transverses the cuticle into the haemocoel. RNA-seq analysis revealed that MAPK cascades collectively play a major role in regulating the adaptation of M. robertsii to the microenvironmental change from the cuticle to the haemolymph. The three MAPKs each regulate their own distinctive subset of genes during penetration of the cuticle and haemocoel colonization, but they function redundantly to regulate adaptation to microenvironmental change. Title: Susceptibility and potential biochemical mechanism of Oedaleus asiaticus to beta-cypermethrin and deltamethrin in the Inner Mongolia, China Dong W, Zhang X, Wu H, Zhang M, Ma E, Zhang J Ref: Pestic Biochem Physiol, 132:47, 2016 : PubMed ESTHER: Dong_2016_Pestic.Biochem.Physiol_132_47 PubMedSearch: Dong 2016 Pestic.Biochem.Physiol 132 47 PubMedID: 27521912 Abstract Oedaleus asiaticus is a highly destructive grass pest in Inner Mongolia, China, and likely developed resistance to pyrethroid insecticides due to their frequent application for control of this locust. In this study, the susceptibility of five field populations of O. asiaticus to two pyrethroid insecticides was investigated. The Wulate Middle Banner (WB) population was the least susceptible, whereas the Ewenki Banner (EB) population appeared to be the most sensitive. The WB population was 3.16 and 5.15-fold less sensitive to beta-cypermethrin and deltamethrin than EB population, respectively. Further, the enzyme activities and mRNA expression levels of carboxylesterase (CarE) and glutathione-S-transferase (GST) were determined and we found that their activities in the WB population were 5.15 and 2.8-fold higher than those in the EB population, respectively. Quantitative real-time PCR (qRT-PCR) analysis demonstrated that the mRNA expression levels of CarE and GST genes were positively correlated with the LD50 in the WB, Siziwang Banner (SB) and EB populations. Our findings suggest that differences in susceptibility to pyrethroids in O. asiaticus might be attributed to the elevated activities and mRNA expression levels of CarE and GST genes. Title: Comparative genomic and transcriptomic analyses of the Fuzhuan brick tea-fermentation fungus Aspergillus cristatus Ge Y, Wang Y, Liu Y, Tan Y, Ren X, Zhang X, Hyde KD, Liu Z Ref: BMC Genomics, 17:428, 2016 : PubMed ESTHER: Ge_2016_BMC.Genomics_17_428 PubMedSearch: Ge 2016 BMC.Genomics 17 428 PubMedID: 27267057 Gene_locus related to this paper: 9euro-a0a1e3ba25, 9euro-a0a1e3bs39, 9euro-a0a1e3bjz1, 9euro-a0a1e3b9q3, 9euro-a0a1e3bp23 Abstract BACKGROUND: Aspergillus cristatus is the dominant fungus involved in the fermentation of Chinese Fuzhuan brick tea. Aspergillus cristatus is a homothallic fungus that undergoes a sexual stage without asexual conidiation when cultured in hypotonic medium. The asexual stage is induced by a high salt concentration, which completely inhibits sexual development. The taxon is therefore appropriate for investigating the mechanisms of asexual and sexual reproduction in fungi. In this study, de novo genome sequencing and analysis of transcriptomes during culture under high- and low-osmolarity conditions were performed. These analyses facilitated investigation of the evolution of mating-type genes, which determine the mode of sexual reproduction, in A. cristatus, the response of the high-osmolarity glycerol (HOG) pathway to osmotic stimulation, and the detection of mycotoxins and evaluation of the relationship with the location of the encoding genes. Title: Calretinin, S100 and protein gene product 9.5 immunostaining of rectal suction biopsies in the diagnosis of Hirschsprung' disease Jiang M, Li K, Li S, Yang L, Yang D, Zhang X, Fang M, Cao G, Wang Y and Tang S <1 more author(s)> Jiang M, Li K, Li S, Yang L, Yang D, Zhang X, Fang M, Cao G, Wang Y, Chen W, Tang S (- 1) Ref: Am J Transl Res, 8:3159, 2016 : PubMed ESTHER: Jiang_2016_Am.J.Transl.Res_8_3159 PubMedSearch: Jiang 2016 Am.J.Transl.Res 8 3159 PubMedID: 27508037 Abstract Evaluation of rectal suction biopsies for the ganglion cells and neural hypertrophy is the basic modality for the diagnosis of Hirschsprung's disease (HD). However, the traditional hematoxylin and eosin staining coupled with acetylcholinesterase histochemistry remain challenging, especially in newborns. Thus we conducted a prospective study to evaluate the usefulness of calretinin combined with S100 and protein gene product 9.5 (PGP9.5) immunostaining of rectal suction biopsies for the diagnosis of HD. A total of 195 patients were enrolled in our study. Of the 195 patients 69% had ganglion cells on the initial diagnostic protocol. Sixty cases were devoid of ganglion cells, and of these, 90% and 91% showed submucosal neural hypertrophy on S-100 staining and PGP9.5 staining, respectively. Eighty-one patients underwent a colonic resection, and of these, 59 had confirmed aganglionic segment, the other 22 patients were diagnosed as intestinal neuronal dysplasia type B (n=13) and isolated hypoganglionosis (n=9). Of the rest 114 patients, 51 cases underwent a full-thickness biopsy, and HD was excluded; sixty-three patients were thoroughly followed-up with no evidence of HD. We encountered two false-negatives and they were proved to be short segment HD after the surgery. The sensitivity and specificity rates of our diagnostic protocol was 96.49% (95% CI, 0.88-0.99) and 100% (95% CI, 0.97-1.00), respectively, excluding 5 patients with inconclusive results. Our findings demonstrated that calretinin coupled with S100 and PGP9.5 immunostaining on suction rectal biopsies is sensitive and specific for diagnosing HD. Title: Ionic liquids as novel solvents for biosynthesis of octenyl succinic anhydride-modified waxy maize starch Li D, Zhang X, Tian Y Ref: Int J Biol Macromol, 86:119, 2016 : PubMed ESTHER: Li_2016_Int.J.Biol.Macromol_86_119 PubMedSearch: Li 2016 Int.J.Biol.Macromol 86 119 PubMedID: 26797225 Abstract Biosynthesis of octenyl succinic anhydride (OSA) starch was investigated using ionic liquids (ILs) as reaction media. Waxy maize starch was pretreated in 1-butyl-3-methylimidazolium chlorine and then esterified with OSA in 1-octyl-3-methylimidazolium nitrate by using Novozyme 435as catalyst. The degree of substitution of OSA starch reached 0.0130 with 5wt% starch concentration and 1wt% lipase dosage based on ILs weight at 50 degrees C for 3h. The formation of OSA starch was confirmed by fourier transform infrared spectroscopy. Scanning electron microscopy and X-ray diffraction revealed that the morphology and crystal structure of starch were significantly destroyed. Thermogravimetric analysis showed that esterification decreased the thermal stability of starch. The successful lipase-catalyzed synthesis of OSA starch in ILs suggests that ILs are potential replacement of traditional organic solvents for starch ester biosynthesis. Title: Bacterial Expression and Kinetic Analysis of Carboxylesterase 001D from Helicoverpa armigera Li Y, Liu J, Lu M, Ma Z, Cai C, Wang Y, Zhang X Ref: Int J Mol Sci, 17:, 2016 : PubMed ESTHER: Li_2016_Int.J.Mol.Sci_17_ PubMedSearch: Li 2016 Int.J.Mol.Sci 17 PubMedID: 27049381 Abstract Carboxylesterasesare an important class of detoxification enzymes involved in insecticide resistance in insects. A subgroup of Helicoverpa armigera esterases, known as Clade 001, was implicated in organophosphate and pyrethroid insecticide resistance due to their overabundance in resistant strains. In this work, a novel carboxylesterasegene 001D of H. armigera from China was cloned, which has an open reading frame of 1665 nucleotides encoding 554 amino acid residues. We used a series of fusion proteins to successfully express carboxylesterase 001D in Escherichia coli. Three different fusion proteins were generated and tested. The enzyme kinetic assay towards 1-naphthyl acetate showed all three purified fusion proteins are active with a Kcat between 0.35 and 2.29 s(-1), and a Km between 7.61 and 19.72 muM. The HPLC assay showed all three purified fusion proteins had low but measurable hydrolase activity towards beta-cypermethrin and fenvalerate insecticides (specific activities ranging from 0.13 to 0.67 muM.min(-1).(muM(-1).protein)). The enzyme was stable up to 40 degrees C and at pH 6.0-11.0. The results imply that carboxylesterase 001D is involved in detoxification, and this moderate insecticide hydrolysis may suggest that overexpression of the gene to enhance insecticide sequestration is necessary to allow carboxylesterases to confer resistance to these insecticides in H. armigera. Title: Inhibition of soluble epoxide hydrolase alleviated atherosclerosis by reducing monocyte infiltration in Ldlr(-/-) mice Li D, Liu Y, Zhang X, Lv H, Pang W, Sun X, Gan LM, Hammock BD, Ai D, Zhu Y Ref: Journal of Molecular & Cellular Cardiology, 98:128, 2016 : PubMed ESTHER: Li_2016_J.Mol.Cell.Cardiol_98_128 PubMedSearch: Li 2016 J.Mol.Cell.Cardiol 98 128 PubMedID: 27496380 Abstract RATIONALE: Circulating monocytes play pivotal roles in chronic inflammatory diseases. Epoxyeicosatrienoic acids (EETs), metabolites of arachidonic acid, are known to have anti-inflammatory effects and are hydrolyzed by soluble epoxide hydrolase (sEH). OBJECTIVE: We aimed to investigate the effect of sEH inhibition in atherogenesis. METHODS AND Title: Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication Li W, Zhu Z, Cao W, Yang F, Zhang X, Li D, Zhang K, Li P, Mao R and Zheng H <1 more author(s)> Li W, Zhu Z, Cao W, Yang F, Zhang X, Li D, Zhang K, Li P, Mao R, Liu X, Zheng H (- 1) Ref: Mol Immunol, 75:112, 2016 : PubMed ESTHER: Li_2016_Mol.Immunol_75_112 PubMedSearch: Li 2016 Mol.Immunol 75 112 PubMedID: 27267271 Abstract The enzymatic activities of esterase D (ESD) are involved in many human diseases. However, no antiviral property of ESD has been described to date. Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease. In this study, we showed that FMDV infection triggered ESD expression. Overexpression of ESD significantly suppressed FMDV replication and knockdown of ESD expression enhanced virus replication, showing an essential antiviral role of ESD. Furthermore, we found that Sendai-virus-induced interferon (IFN) signaling was enhanced by upregulation of ESD, and ESD promoted activation of the IFN-beta promoter simulated by IFN regulatory factor (IRF)3 or its upstream molecules (retinoic acid-inducible gene-I, melanoma differentiation-associated protein 5, virus-induced signaling adaptor and TANK binding kinase 1). Detailed analysis revealed that ESD protein enhanced IRF3 phosphorylation during FMDV infection. Overexpression of ESD also promoted the expression of various antiviral interferon-stimulated genes (ISGs) and knockdown of ESD impaired the expression of these antiviral genes during FMDV infection. Our findings demonstrate a new mechanism evolved by ESD to enhance type I IFN signal transduction and suppress viral replication during FMDV infection. Title: Macrophage ABHD5 promotes colorectal cancer growth by suppressing spermidine production by SRM Miao H, Ou J, Peng Y, Zhang X, Chen Y, Hao L, Xie G, Wang Z, Pang X and Liang H <6 more author(s)> Miao H, Ou J, Peng Y, Zhang X, Chen Y, Hao L, Xie G, Wang Z, Pang X, Ruan Z, Li J, Yu L, Xue B, Shi H, Shi C, Liang H (- 6) Ref: Nat Commun, 7:11716, 2016 : PubMed ESTHER: Miao_2016_Nat.Commun_7_11716 PubMedSearch: Miao 2016 Nat.Commun 7 11716 PubMedID: 27189574 Abstract Metabolic reprogramming in stromal cells plays an essential role in regulating tumour growth. The metabolic activities of tumour-associated macrophages (TAMs) in colorectal cancer (CRC) are incompletely characterized. Here, we identify TAM-derived factors and their roles in the development of CRC. We demonstrate that ABHD5, a lipolytic co-activator, is ectopically expressed in CRC-associated macrophages. We demonstrate in vitro and in mouse models that macrophage ABHD5 potentiates growth of CRC cells. Mechanistically, ABHD5 suppresses spermidine synthase (SRM)-dependent spermidine production in macrophages by inhibiting the reactive oxygen species-dependent expression of C/EBPvarepsilon, which activates transcription of the srm gene. Notably, macrophage-specific ABHD5 transgene-induced CRC growth in mice can be prevented by an additional SRM transgene in macrophages. Altogether, our results show that the lipolytic factor ABHD5 suppresses SRM-dependent spermidine production in TAMs and potentiates the growth of CRC. The ABHD5/SRM/spermidine axis in TAMs might represent a potential target for therapy. Title: Effects of abhydrolase domain containing 5 gene (ABHD5) expression and variations on chicken fat metabolism Ouyang H, Liu Q, Xu J, Zeng F, Pang X, Jebessa E, Liang S, Nie Q, Zhang X Ref: Poult Sci, 95:99, 2016 : PubMed ESTHER: Ouyang_2016_Poult.Sci_95_99 PubMedSearch: Ouyang 2016 Poult.Sci 95 99 PubMedID: 26574024 Abstract Abhydrolase domain containing 5 gene (ABHD5), also known as comparative gene identification 58 (CGI-58), is a member of the alpha/beta-hydrolase family as a protein cofactor of ATGL stimulating its triacylglycerol hydrolase activity. In this study, we aim to characterize the expression and variations of ABHD5 and to study their functions in chicken fat metabolism. We compared the ABHD5 expression level in various tissues and under different nutrition conditions, identified the variations of ABHD5, and associated them with production traits in an F2 resource population of chickens. Overexpression analysis with two different genotypes and siRNA interfering analysis of ABHD5 were performed in chicken preadipocytes. Chicken ABDH5 was expressed widely and most predominantly in adipose tissue. Five SNPs of the ABHD5 gene were identified and genotyped in the F2 resource population. The c.490C > T SNP was associated with subcutaneous fat thickness (P < 0.01), carcass weight (P < 0.05), body weight (P < 0.05), shank diameter (P < 0.05), and shank length (P < 0.05). The c.423T > C SNP was also associated with chicken body weight (P < 0.05) and shank diameter (P < 0.05). In chicken preadipocytes, overexpression of wild type ABDH5 did not affect the mRNA level of ATGL (adipose triglyceride lipase) but markedly decreased (P < 0.05) the TG (triglyceride) content of the cell, whereas overexpression of mutation type ABHD5 did not affect either ATGL expression or TG content of the cell. The expression of ATGL and TG content of the cell were decreased (P < 0.05) after ABHD5 knockdown in preadipocytes. The mRNA level of ABHD5 was regulated by both feeding and fasting, and by consumption of a high fat diet. It was increased greatly by fasting (P < 0.05) and was returned to control levels after re-feeding in the adipose tissues, and down-regulated in abdominal fat (P < 0.05) and the liver (P < 0.01) of chickens with a high fat diet. These results suggest that expression and variations of ABHD5 may affect fat metabolism through regulating the activity of ATGL in chickens. Title: Design, synthesis and evaluation of novel ferulic acid-memoquin hybrids as potential multifunctional agents for the treatment of Alzheimer's disease Pan W, Hu K, Bai P, Yu L, Ma Q, Li T, Zhang X, Chen C, Peng K and Sang Z <1 more author(s)> Pan W, Hu K, Bai P, Yu L, Ma Q, Li T, Zhang X, Chen C, Peng K, Liu W, Sang Z (- 1) Ref: Bioorganic & Medicinal Chemistry Lett, 26:2539, 2016 : PubMed ESTHER: Pan_2016_Bioorg.Med.Chem.Lett_26_2539 PubMedSearch: Pan 2016 Bioorg.Med.Chem.Lett 26 2539 PubMedID: 27072909 Inhibitor(s) related to this paper: Memoquin Abstract A novel series of ferulic acid-memoquin hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease (AD). The in vitro studies showed that most of the compounds exhibited a significant ability to inhibit acetylcholinesterase (AChE) (IC50 of 3.2-34.7muM) and self-induced beta-amyloid (Abeta1-42) aggregation (30.8-39.1%, 25muM), to act as potential antioxidants (ORAC-FL value of 0.9-1.3). In particular, compound 17d had the greatest ability to inhibit AChE (IC50=3.2muM), and Abeta1-42 aggregation (30.8%) was also an excellent antioxidant and neuroprotectant. Moreover, it is capable of disaggregating self-induced Abeta aggregation. Furthermore, 17d could cross the blood-brain barrier (BBB) in vitro. The results showed that compound 17d is a potential multifunctional agent for the treatment of AD. Title: Enriched environment improves post-stroke cognitive impairment in mice by potential regulation of acetylation homeostasis in cholinergic circuits Wang X, Chen A, Wu H, Ye M, Cheng H, Jiang X, Zhang X, Wu D, Gu X and Yu D <2 more author(s)> Wang X, Chen A, Wu H, Ye M, Cheng H, Jiang X, Zhang X, Wu D, Gu X, Shen F, Shan C, Yu D (- 2) Ref: Brain Research, 1650:232, 2016 : PubMed ESTHER: Wang_2016_Brain.Res_1650_232 PubMedSearch: Wang 2016 Brain.Res 1650 232 PubMedID: 27637156 Abstract Post-stroke cognitive impairment (PSCI), commonly seen in the clinical practice, is a major factor impeding patient rehabilitation. Enriched environment (EE) intervention is a simple and effective way to improve cognitive impairment, partially due to the rebalancing of the basal forebrain-hippocampus cholinergic signaling pathway. Epigenetic changes have been identified in many cognitive disorders. However, studies on the effects of EE on epigenetic regulation of cholinergic circuits in PSCI animal models have not yet been reported. In this study, we established a photothrombotic mouse PSCI model and showed that after EE intervention, mice with PSCI had significantly improved water maze performance, better induction of hippocampal long-term potentiation (LTP), enhanced function of the basal forebrain-hippocampus cholinergic circuits of contralateral side of stroke and relatively balanced acetylation homeostasis compared to those of PSCI mice in standard environments (SE). In addition, PSCI mice in EE expressed much higher levels of p-CREB and CBP than in SE, and the chromatins bound to M-type promoter of ChAT gene were more acetylated. These results demonstrate that EE plays an important role in the improvement of PSCI and the underlying mechanism may involve in the acetylation of histones bound to the ChAT gene promoter in cholinergic circuits. Title: Rapid eye movement sleep behavior disorder in patients with probable Alzheimer's disease Wang P, Wing YK, Xing J, Liu Y, Zhou B, Zhang Z, Yao H, Guo Y, Shang Y, Zhang X Ref: Aging Clin Exp Res, 28:951, 2016 : PubMed ESTHER: Wang_2016_Aging.Clin.Exp.Res_28_951 PubMedSearch: Wang 2016 Aging.Clin.Exp.Res 28 951 PubMedID: 26022447 Abstract BACKGROUND AND AIMS: Rapid eye movement (REM) sleep behavior disorder (RBD) is commonly associated with neurodegenerative disorders characterized by alpha-synuclein deposition, including Parkinson's disease, multiple system atrophy, and Lewy body dementia. However, this tendency in tauopathy-mediated diseases is rare and only sporadically reported. We systematically illustrate the occurrence of RBD and sleep features among a cohort of patients with Alzheimer's disease (AD), a non-synucleinopathy. Title: Fragment-Based Approach to the Development of an Orally Bioavailable Lactam Inhibitor of Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Woolford AJ, Day PJ, Beneton V, Berdini V, Coyle JE, Dudit Y, Grondin P, Huet P, Lee LY and Zhang X <11 more author(s)> Woolford AJ, Day PJ, Beneton V, Berdini V, Coyle JE, Dudit Y, Grondin P, Huet P, Lee LY, Manas ES, McMenamin RL, Murray CW, Page LW, Patel VK, Potvain F, Rich SJ, Sang Y, Somers DO, Trottet L, Wan Z, Zhang X (- 11) Ref: Journal of Medicinal Chemistry, 59:10738, 2016 : PubMed ESTHER: Woolford_2016_J.Med.Chem_59_10738 PubMedSearch: Woolford 2016 J.Med.Chem 59 10738 PubMedID: 27933945 Gene_locus related to this paper: human-PLA2G7 Inhibitor(s) related to this paper: 7BP-5LZ8, CHEMBL3924430, CHEMBL3983270, CHEMBL3975283, 3-cyano-N-cyclopropylbenzenesulfonamide, CHEMBL3908555, 5LZ9-7BR Abstract Lp-PLA2 has been explored as a target for a number of inflammation associated diseases, including cardiovascular disease and dementia. This article describes the discovery of a new fragment derived chemotype that interacts with the active site of Lp-PLA2. The starting fragment hit was discovered through an X-ray fragment screen and showed no activity in the bioassay (IC50 > 1 mM). The fragment hit was optimized using a variety of structure-based drug design techniques, including virtual screening, fragment merging, and improvement of shape complementarity. A novel series of Lp-PLA2 inhibitors was generated with low lipophilicity and a promising pharmacokinetic profile. Title: Rapid-releasing of HI-6 via brain-targeted mesoporous silica nanoparticles for nerve agent detoxification Yang J, Fan L, Wang F, Luo Y, Sui X, Li W, Zhang X, Wang Y Ref: Nanoscale, 8:9537, 2016 : PubMed ESTHER: Yang_2016_Nanoscale_8_9537 PubMedSearch: Yang 2016 Nanoscale 8 9537 PubMedID: 26730700 Abstract The toxic nerve agent (NA) soman is the most toxic artificially synthesized compound that can rapidly penetrate into the brain and irreversibly inhibit acetylcholinesterase (AChE) activity, leading to immediate death. However, there are currently few brain-targeted nanodrugs that can treat acute chemical brain poisoning owing to the limited drug-releasing speed. The present study investigated the effectiveness of a nanodrug against NA toxicity that has high blood-brain barrier penetration and is capable of rapid drug release. Transferrin-modified mesoporous silica nanoparticles (TF-MSNs) were conjugated with the known AChE reactivator HI-6. This nanodrug rapidly penetrated the blood-brain barrier in zebrafish and mice and restored cerebral AChE activity via the released HI-6, preventing the brain damage caused by soman poisoning and increasing the survival rate in mice. Furthermore, there was no toxicity associated with the MSNs in mice or rats. These results demonstrate that TF-MSNs loaded with HI-6 represent the most effective antidote against NA poisoning by soman reported to date, and suggest that MSNs are a safe alternative to conventional drugs and an optimal nanocarrier for treating brain poisoning, which requires acute pulse cerebral administration. Title: [Role of alpha7 nicotinic acetylcholine receptor in attenuation of endotoxin induced delirium with dexmedetomidine in mice] Zhang X, Li Z, Sun X, Jin F, Liu J, Li J Ref: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue, 28:127, 2016 : PubMed ESTHER: Zhang_2016_Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_28_127 PubMedSearch: Zhang 2016 Zhonghua.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue 28 127 PubMedID: 26911944 Abstract OBJECTIVE: To observe the role of alpha7 nicotinic acetylcholine receptor (alpha7nAChR) in the protection against delirium by the use of dexmedetomidine (DEX) in endotoxin derived delirium and its mechanism. Title: Pretreatment serum pseudocholinesterase level as a novel prognostic biomarker for upper tract urothelial carcinoma Zhang B, Shen C, Jin J, Song Y, Zhao Z, Zhang X, Wang G, Fan Y, Mi Y and Han W <5 more author(s)> Zhang B, Shen C, Jin J, Song Y, Zhao Z, Zhang X, Wang G, Fan Y, Mi Y, Hu S, Cui Y, Zhou L, He Z, Yu W, Han W (- 5) Ref: International Urology & Nephrology, 48:1993, 2016 : PubMed ESTHER: Zhang_2016_Int.Urol.Nephrol_48_1993 PubMedSearch: Zhang 2016 Int.Urol.Nephrol 48 1993 PubMedID: 27554671 Abstract PURPOSE: Pretreatment serum pseudocholinesterase (PChE) has been reported to be a prognostic predictor in several cancers. However, the prognostic significance of serum PChE level in patients with upper tract urothelial carcinoma (UTUC) remains unknown. Title: Methods for Studying Wnt Protein Modifications/Inactivations by Extracellular Enzymes, Tiki and Notum Zhang X, He X Ref: Methods Mol Biol, 1481:29, 2016 : PubMed ESTHER: Zhang_2016_Methods.Mol.Biol_1481_29 PubMedSearch: Zhang 2016 Methods.Mol.Biol 1481 29 PubMedID: 27590149 Abstract Wnt proteins are modified and inactivated by two extracellular enzymatic antagonists, Tiki and Notum. Tiki proteins act as membrane-tethered metalloproteases to cleave a fragment from the amino terminus of Wnt proteins. Notum is a Wnt deacylase that removes the lipid modification that is essential for Wnt activities. Here, we provide detailed procedures for preparing enzymatic active Tiki and Notum proteins and the in vitro enzymatic reactions. We also describe a metabolic labeling and click chemistry method for detection of Wnt protein acylation. Title: Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T and Chen X <19 more author(s)> Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T, Ding Y, Nie L, Li Q, Dong WR, Jiang L, Sun B, Zhang X, Li M, Zhang HQ, Xie S, Zhu Y, Jiang X, Wang X, Mu P, Chen W, Yue Z, Wang Z, Wang J, Shao JZ, Chen X (- 19) Ref: PLoS Genet, 11:e1005118, 2015 : PubMed ESTHER: Ao_2015_PLoS.Genet_11_E1005118 PubMedSearch: Ao 2015 PLoS.Genet 11 E1005118 PubMedID: 25835551 Gene_locus related to this paper: larcr-a0a0f8ay25, larcr-a0a0f8cf53, larcr-a0a0f8cir1, larcr-a0a0f8d1j2, larcr-a0a0f8alq6, larcr-a0a0f8bdu4, larcr-a0a0f8abw1, larcr-a0a0f8ahh1, larcr-a0a0f8avc6, larcr-a0a0f8al93, larcr-a0a0f8aed8, larcr-a0a0f7ir14, larcr-a0a0f8aje8, larcr-k9lsm3, larcr-a0a0f8but5, larcr-a0a0f8af44 Abstract The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea. Title: Genome sequence of cultivated Upland cotton (Gossypium hirsutum TM-1) provides insights into genome evolution Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X and Yu S <30 more author(s)> Li F, Fan G, Lu C, Xiao G, Zou C, Kohel RJ, Ma Z, Shang H, Ma X, Wu J, Liang X, Huang G, Percy RG, Liu K, Yang W, Chen W, Du X, Shi C, Yuan Y, Ye W, Liu X, Zhang X, Liu W, Wei H, Wei S, Zhu S, Zhang H, Sun F, Wang X, Liang J, Wang J, He Q, Huang L, Cui J, Song G, Wang K, Xu X, Yu JZ, Zhu Y, Yu S (- 30) Ref: Nat Biotechnol, 33:524, 2015 : PubMed ESTHER: Li_2015_Nat.Biotechnol_33_524 PubMedSearch: Li 2015 Nat.Biotechnol 33 524 PubMedID: 25893780 Gene_locus related to this paper: gosra-a0a0d2rxs2, gosra-a0a0d2tng2, gosra-a0a0d2twz7, goshi-a0a1u8hr03, gosra-a0a0d2vdc5, goshi-a0a1u8ljh5, gosra-a0a0d2vj24, goshi-a0a1u8pxd3, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8mt09, goshi-a0a1u8kis4, goshi-a0a1u8ibk3, goshi-a0a1u8ieg2, goshi-a0a1u8iki6, goshi-a0a1u8jvp4, goshi-a0a1u8jw35, gosra-a0a0d2pzd7 Abstract Gossypium hirsutum has proven difficult to sequence owing to its complex allotetraploid (AtDt) genome. Here we produce a draft genome using 181-fold paired-end sequences assisted by fivefold BAC-to-BAC sequences and a high-resolution genetic map. In our assembly 88.5% of the 2,173-Mb scaffolds, which cover 89.6% approximately 96.7% of the AtDt genome, are anchored and oriented to 26 pseudochromosomes. Comparison of this G. hirsutum AtDt genome with the already sequenced diploid Gossypium arboreum (AA) and Gossypium raimondii (DD) genomes revealed conserved gene order. Repeated sequences account for 67.2% of the AtDt genome, and transposable elements (TEs) originating from Dt seem more active than from At. Reduction in the AtDt genome size occurred after allopolyploidization. The A or At genome may have undergone positive selection for fiber traits. Concerted evolution of different regulatory mechanisms for Cellulose synthase (CesA) and 1-Aminocyclopropane-1-carboxylic acid oxidase1 and 3 (ACO1,3) may be important for enhanced fiber production in G. hirsutum. Title: Macrophage CGI-58 deficiency promotes IL-1beta transcription by activating the SOCS3-FOXO1 pathway Miao H, Ou J, Zhang X, Chen Y, Xue B, Shi H, Gan L, Yu L, Liang H Ref: Clinical Science (Lond), 128:493, 2015 : PubMed ESTHER: Miao_2015_Clin.Sci.(Lond)_128_493 PubMedSearch: Miao 2015 Clin.Sci.(Lond) 128 493 PubMedID: 25431838 Abstract Over-nutrition induces low-grade inflammation that dampens insulin sensitivity, but the underlying molecular mediators are not fully understood. Comparative gene identification-58 (CGI-58) is an intracellular lipolytic activator. In the present study, we show that in mouse visceral fat-derived macrophages or human peripheral blood monocytes, CGI-58 negatively and interleukin (IL)-1beta positively correlate with obesity. Saturated non-esterified fatty acid (NEFA) suppresses CGI-58 expression in macrophages and this suppression activates FOXO1 (forkhead box-containing protein O subfamily-1) through inhibition of FOXO1 phosphorylation. Activated FOXO1 binds to an insulin-responsive element in IL-1beta promoter region to potentiate IL-1beta transcription. Gain- and loss-of-function studies demonstrate that NEFA-induced CGI-58 suppression activates FOXO1 to augment IL-1beta transcription by dampening insulin signalling through induction of SOCS3 (suppressor of cytokine signalling 3) expression. CGI-58 deficiency-induced SOCS3 expression is NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome-dependent. Our data thus identified a vicious cycle (IL-1beta-SOCS3-FOXO1-IL-1beta) that amplifies IL-1beta secretion and is initiated by CGI-58 deficiency-induced activation of the NLRP3 inflammasome in macrophages. We further show that blocking this cycle with a FOXO1 inhibitor, an antioxidant that inhibits FOXO1 or IL-1 receptor antagonist alleviates chronic inflammation and insulin resistance in high-fat diet (HFD)-fed mice. Collectively, our data suggest that obesity-associated factors such as NEFA and lipopolysaccharide (LPS) probably adopt this vicious cycle to promote inflammation and insulin resistance. Title: Perilipin 5 improves hepatic lipotoxicity by inhibiting lipolysis Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P and Ye J <6 more author(s)> Wang C, Zhao Y, Gao X, Li L, Yuan Y, Liu F, Zhang L, Wu J, Hu P, Zhang X, Gu Y, Xu Y, Wang Z, Li Z, Zhang H, Ye J (- 6) Ref: Hepatology, 61:870, 2015 : PubMed ESTHER: Wang_2015_Hepatology_61_870 PubMedSearch: Wang 2015 Hepatology 61 870 PubMedID: 25179419 Abstract Abnormal metabolism of nonesterified fatty acids (NEFAs) and their derivatives has been reported to be the main cause of intracellular lipotoxic injury. Normally, NEFAs are stored in lipid droplets (LDs) in the form of triglyceride (TG), which could reduce the lipotoxicity of cytosolic NEFAs. Previous studies have implicated that Perilipin 5 (Plin5), an LD-binding protein, regulates the storage and hydrolysis of TG in LD. However, its roles and underlying mechanisms in the liver remain unknown. Here we found that Plin5 expression was increased in steatotic livers. Using Plin5 knockout mice, we found that Plin5 deficiency resulted in reduced hepatic lipid content and smaller-sized LDs, which was due to the elevated lipolysis rate and fatty acid utilization. Plin5-deficient hepatocytes showed increased mitochondria proliferation, which could be explained by the increased expression and activity of PPARalpha stimulated by the increased NEFA levels. Meanwhile, Plin5-deficient livers also exhibited enhanced mitochondrial oxidative capacity. We also found that Plin5 deficiency induces lipotoxic injury in hepatocytes, attributed to lipid peroxidation. Mechanistically, we found that Plin5 blocks adipose triglyceride lipase (ATGL)-mediated lipolysis by competitively binding to comparative gene identification-58 (CGI-58) and disrupting the interaction between CGI-58 and ATGL. CONCLUSION: Plin5 is an important protective factor against hepatic lipotoxicity induced by NEFAs generated from lipolysis. This provides an important new insight into the regulation of hepatic lipid storage and relation between lipid storage and lipotoxicity. Title: Genomic and transcriptomic analysis of the endophytic fungus Pestalotiopsis fici reveals its lifestyle and high potential for synthesis of natural products Wang X, Zhang X, Liu L, Xiang M, Wang W, Sun X, Che Y, Guo L, Liu G and Liu X <3 more author(s)> Wang X, Zhang X, Liu L, Xiang M, Wang W, Sun X, Che Y, Guo L, Liu G, Wang C, Yin WB, Stadler M, Liu X (- 3) Ref: BMC Genomics, 16:28, 2015 : PubMed ESTHER: Wang_2015_BMC.Genomics_16_28 PubMedSearch: Wang 2015 BMC.Genomics 16 28 PubMedID: 25623211 Gene_locus related to this paper: 9pezi-w3wud0, 9pezi-w3xja3, pesfw-w3wz53, pesfw-w3x341, pesfw-w3whp0, pesfw-w3xc39, pesfw-w3wrn9, pesfw-pfmab, pesfw-pfmae Abstract BACKGROUND: In recent years, the genus Pestalotiopsis is receiving increasing attention, not only because of its economic impact as a plant pathogen but also as a commonly isolated endophyte which is an important source of bioactive natural products. Pestalotiopsis fici Steyaert W106-1/CGMCC3.15140 as an endophyte of tea produces numerous novel secondary metabolites, including chloropupukeananin, a derivative of chlorinated pupukeanane that is first discovered in fungi. Some of them might be important as the drug leads for future pharmaceutics. Title: Correlation between PON1 gene polymorphisms and breast cancer risk: a Meta-analysis Wen Y, Huang Z, Zhang X, Gao B, He Y Ref: Int J Clin Exp Med, 8:20343, 2015 : PubMed ESTHER: Wen_2015_Int.J.Clin.Exp.Med_8_20343 PubMedSearch: Wen 2015 Int.J.Clin.Exp.Med 8 20343 PubMedID: 26884950 Abstract OBJECTIVE: A number of studies have investigated the relationship between the PON1 gene polymorphisms and breast cancer risk, but the conclusions are not consistent. In this paper, a meta-analysis was conducted to explore the possible reasons for these inconsistencies, expecting to further clarify the correlation between PON1 gene polymorphisms and breast cancer risk. Title: A cold-adapted, solvent and salt tolerant esterase from marine bacterium Psychrobacter pacificensis Wu G, Zhang X, Wei L, Kumar A, Mao T, Liu Z Ref: Int J Biol Macromol, 81:180, 2015 : PubMed ESTHER: Wu_2015_Int.J.Biol.Macromol_81_180 PubMedSearch: Wu 2015 Int.J.Biol.Macromol 81 180 PubMedID: 26231332 Abstract Lipolytic enzymes with unique physico-chemical characteristics are gaining more attention for their immense industrial importance. In this study, a novel lipolytic enzyme (Est11) was cloned from the genomic library of a marine bacterium Psychrobacter pacificensis. The enzyme was expressed in Escherichia coli and purified to homogeneity with molecular mass of 32.9kDa. The recombinant Est11 was able to hydrolyze short chain esters (C2-C8) and displayed an optimum activity against butyrate ester (C4). The optimal temperature and pH were 25 degrees C and 7.5, respectively. Est11 retained more than 70% of its original activity at 10 degrees C, suggesting that it was a cold-active esterase. The enzyme was highly active and stable at high concentration of NaCl (5M). Further, incubation with ethanol, isopropanol, propanediol, DMSO, acetonitrile, and glycerol rendered remarkable positive effects on Est11 activity. Typically, even at the concentration of 30% (v/v), ethanol, DMSO, and propanediol increased Est11 activity by 1.3, 2.0, and 2.4-folds, respectively. This new robust enzyme with remarkable properties like cold-adaptability, exceptional tolerance to salt and organic solvents provides us a promising candidate to meet the needs of some harsh industrial processes. Title: Anticancer drugs induce hypomethylation of the acetylcholinesterase promoter via a phosphorylated-p38-DNMT1-AChE pathway in apoptotic hepatocellular carcinoma cells Xi Q, Gao N, Yang Y, Ye W, Zhang B, Wu J, Jiang G, Zhang X Ref: International Journal of Biochemistryistry & Cell Biology, 68:21, 2015 : PubMed ESTHER: Xi_2015_Int.J.Biochem.Cell.Biol_68_21 PubMedSearch: Xi 2015 Int.J.Biochem.Cell.Biol 68 21 PubMedID: 26299326 Abstract Apoptosis, also known as programmed cell death, plays an essential role in eliminating excessive, damaged or harmful cells. Previous work has demonstrated that anticancer drugs induce cell apoptosis by inducing cytotoxicity. In recent years, several reports demonstrated modulated expression of DNA methyltransferases 1 (DNMT1) and acetylcholinesterase (AChE) in a variety of tumors. In this study, we showed that the expression of DNMT1 was decreased and the methylation of CpGs in the promoter of AChE was reduced in anticancer drugs-induced apoptotic hepatocellular carcinoma cells. Silencing of DNMT1 expression by AZA or RNA interference (RNAi) restored AChE production and inhibition of AChE expression by RNAi protected HCC cells from anticancer drugs-induced apoptosis. Furthermore, we demonstrated that the regulation of AChE by DNMT1 was involved in the phosphorylated p38 pathway in anticancer drugs-induced apoptosis. In addition, immunohistochemical staining showed that P-p38, DNMT1 and AChE were aberrantly expressed in a subset of HCC tumors. Taken together, we demonstrated the regulation of AChE by DNMT1 and further, we found that this regulation was involved in the phosphorylated p38 pathway in anticancer drugs-induced apoptosis. Title: Screening and identification of a cutinase-producing Rhodotorula mucilaginosa and properties of the cutinase Zhang XN, Ran QQ, Zhang X Ref: Appl Biochem Biotechnol, 175:1221, 2015 : PubMed ESTHER: Zhang_2015_Appl.Biochem.Biotechnol_175_1221 PubMedSearch: Zhang 2015 Appl.Biochem.Biotechnol 175 1221 PubMedID: 25377248 Abstract Eucommia leaf contains large amounts of natural active products. In extracting the substances, the most important is the removal of the cuticle layer on the leaves and the cell wall in the leaves of Eucommia ulmoides. But the removal of the cuticle layer is a technical difficulty now. Cutinase (EC3.1.1.74) is a multifunctional enzyme with a common alpha/beta fold structure belonging to hydroplane that can make a substantial degradation of horny fatty acids. So this study isolated bacteria capable of producing cutinase from the lesion of Eucommia leaves and identified the bacteria. The identification using PCR-RFLP method confirmed that the strain belongs to Rhodotorula mucilaginosa. The fermentation conditions of the strain-producing cutinase were optimized in this study. The finding of cutinase-producing R. mucilaginosa is significant because the yeast is more secure than plant pathogens, being suitable for mass production. Title: Notum Is Required for Neural and Head Induction via Wnt Deacylation, Oxidation, and Inactivation Zhang X, Cheong SM, Amado NG, Reis AH, MacDonald BT, Zebisch M, Jones EY, Abreu JG, He X Ref: Dev Cell, 32:719, 2015 : PubMed ESTHER: Zhang_2015_Dev.Cell_32_719 PubMedSearch: Zhang 2015 Dev.Cell 32 719 PubMedID: 25771893 Abstract Secreted Wnt morphogens are essential for embryogenesis and homeostasis and require a lipid/palmitoleoylate modification for receptor binding and activity. Notum is a secreted Wnt antagonist that belongs to the alpha/beta hydrolase superfamily, but its mechanism of action and roles in vertebrate embryogenesis are not fully understood. Here, we report that Notum hydrolyzes the Wnt palmitoleoylate adduct extracellularly, resulting in inactivated Wnt proteins that form oxidized oligomers incapable of receptor binding. Thus, Notum is a Wnt deacylase, and palmitoleoylation is obligatory for the Wnt structure that maintains its active monomeric conformation. Notum is expressed in naive ectoderm and neural plate in Xenopus and is required for neural and head induction. These findings suggest that Notum is a prerequisite for the "default" neural fate and that distinct mechanisms of Wnt inactivation by the Tiki protease in the Organizer and the Notum deacylase in presumptive neuroectoderm orchestrate vertebrate brain development. Title: Protective effects of low molecular weight chondroitin sulfate on amyloid beta (Abeta)-induced damage in vitro and in vivo Zhang Q, Li J, Liu C, Song C, Li P, Yin F, Xiao Y, Jiang W, Zong A and Wang F <1 more author(s)> Zhang Q, Li J, Liu C, Song C, Li P, Yin F, Xiao Y, Jiang W, Zong A, Zhang X, Wang F (- 1) Ref: Neuroscience, 305:169, 2015 : PubMed ESTHER: Zhang_2015_Neurosci_305_169 PubMedSearch: Zhang 2015 Neurosci 305 169 PubMedID: 26254241 Abstract In the present study, we investigated the effects of low molecular weight chondroitin sulfate (LMWCS) on amyloid beta (Abeta)-induced neurotoxicity in vitro and in vivo. The in vitro results showed that LMWCS blocked Abeta25-35-induced cell viability loss and apoptosis, decreased intracellular calcium concentration, reactive oxygen species (ROS) levels, the mitochondrial membrane potential (MMP) depolarization, and the protein expression of Caspase-3. During in vivo experiments, LMWCS improved the cognitive impairment induced by Abeta1-40, increased the level of choline acetyltransferase (ChAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and decreased the level of malondialdehyde (MDA) and acetylcholinesterase (AChE) in the mouse brain. Moreover, LMWCS decreased the density of pyramidal cells of CA1 regions, and suppressed the protein expression of Bax/Bcl-2 and Caspase-3, -9 in the hippocampus of mice. In conclusion, LMWCS possessed neuroprotective properties against toxic effects induced by Abeta peptides both in vitro and in vivo, which might be related to anti-apoptotic activity. LMWCS might be a useful preventive and therapeutic compound for Alzheimer's disease. Title: Design, synthesis and evaluation of genistein-polyamine conjugates as multi-functional anti-Alzheimer agents Zhang X, Wang J, Hong C, Luo W, Wang C Ref: Acta Pharm Sin B, 5:67, 2015 : PubMed ESTHER: Zhang_2015_Acta.Pharm.Sin.B_5_67 PubMedSearch: Zhang 2015 Acta.Pharm.Sin.B 5 67 PubMedID: 26579427 Abstract A series of genistein-polyamine conjugates (4a-4h) were designed, synthesized and evaluated as multi-functional anti-Alzheimer agents. The results showed that these compounds had significant cholinesterases (ChEs) inhibitory activity. Compound 4b exhibited the strongest inhibition to acetylcholinesterase (AChE) with an IC50 value of 2.75 mumol/L, which was better than that of rivastigmine (5.60 mumol/L). Lineweaver-Burk plot and molecular modeling study showed that compound 4b targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Besides, compound 4b showed potent metal-chelating ability. In addition, it was found that 4a-4h did not affect HepG-2 cell viability at the concentration of 10 mumol/L. Title: Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes Biftu T, Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan Y and Weber AE <19 more author(s)> Biftu T, Sinha-Roy R, Chen P, Qian X, Feng D, Kuethe JT, Scapin G, Gao YD, Yan Y, Krueger D, Bak A, Eiermann G, He J, Cox J, Hicks J, Lyons K, He H, Salituro G, Tong S, Patel S, Doss G, Petrov A, Wu J, Xu SS, Sewall C, Zhang X, Zhang B, Thornberry NA, Weber AE (- 19) Ref: Journal of Medicinal Chemistry, 57:3205, 2014 : PubMed ESTHER: Biftu_2014_J.Med.Chem_57_3205 PubMedSearch: Biftu 2014 J.Med.Chem 57 3205 PubMedID: 24660890 Gene_locus related to this paper: human-DPP4 Inhibitor(s) related to this paper: Omarigliptin Abstract In our effort to discover DPP-4 inhibitors with added benefits over currently commercially available DPP-4 inhibitors, MK-3102 (omarigliptin), was identified as a potent and selective dipeptidyl peptidase 4 (DPP-4) inhibitor with an excellent pharmacokinetic profile amenable for once-weekly human dosing and selected as a clinical development candidate. This manuscript summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and human efficacy data for omarigliptin, which is currently in phase 3 clinical development. Title: A novel esterase from a marine metagenomic library exhibiting salt tolerance ability Fang Z, Li J, Wang Q, Fang W, Peng H, Zhang X, Xiao Y Ref: J Microbiol Biotechnol, 24:771, 2014 : PubMed ESTHER: Fang_2014_J.Microbiol.Biotechnol_24_771 PubMedSearch: Fang 2014 J.Microbiol.Biotechnol 24 771 PubMedID: 24633233 Gene_locus related to this paper: 9bact-j9vdv8 Abstract A putative lipolytic enzyme gene, named as est9x, was obtained from a marine microbial metagenome of the South China Sea. Sequence analysis showed that Est9X shares lower than 27% sequence identities with the characterized lipolytic enzymes, but possesses a catalytic triad highly conserved in lipolytic enzymes of the alpha/beta hydrolase superfamily. By phylogenetic tree construction, Est9X was grouped into a new lipase/esterase family. To understand Est9X protein in depth, it was recombinantly expressed, purified, and biochemically characterized. Within potential hydrolytic activities, only lipase/esterase activity was detected for Est9X, confirming its identity as a lipolytic enzyme. When using p-nitrophenol esters with varying lengths of fatty acid as substrates, Est9X exhibited the highest activity to the C2 substrate, indicating it is an esterase. The optimal activity of Est9X occurred at a temperature of 65 degrees C, and Est9X was pretty stable below the optimum temperature. Distinguished from other salttolerant esterases, Est9X's activity was tolerant to and even promoted by as high as 4 M NaCl. Our results imply that Est9X is a unique esterase and could be a potential candidate for industrial application under extreme conditions. Title: Genome Sequence of the Octopine-Type Agrobacterium tumefaciens Strain Ach5 Henkel CV, den Dulk-Ras A, Zhang X, Hooykaas PJ Ref: Genome Announc, 2:e00225, 2014 : PubMed ESTHER: Henkel_2014_Genome.Announc_2_e00225 PubMedSearch: Henkel 2014 Genome.Announc 2 e00225 PubMedID: 24675863 Gene_locus related to this paper: agrsh-f0lb16 Abstract We have sequenced the complete genome of the plant pathogen Agrobacterium tumefaciens strain LBA4213, a derivative of the wild-type strain A. tumefaciens Ach5 and the ancestor of A. tumefaciens strain LBA4404 used in genetic engineering. The genome consists of a circular chromosome and a linear chromosome, as well as a megaplasmid and a tumor-inducing plasmid. Title: Novel aromatic-polyamine conjugates as cholinesterase inhibitors with notable selectivity toward butyrylcholinesterase Hong C, Luo W, Yao D, Su YB, Zhang X, Tian RG, Wang CJ Ref: Bioorganic & Medicinal Chemistry, 22:3213, 2014 : PubMed ESTHER: Hong_2014_Bioorg.Med.Chem_22_3213 PubMedSearch: Hong 2014 Bioorg.Med.Chem 22 3213 PubMedID: 24794747 Abstract Three types of aromatic-polyamine conjugates (6a-6s) were designed, synthesized and evaluated as potential inhibitors for cholinesterases (ChEs). The results showed that anthraquinone-polyamine conjugates (AQPCs) exhibited the most potent acetylcholinesterase (AChE) inhibitory activity with IC50 values from 1.50 to 11.13 muM. Anthracene-polyamine conjugates (APCs) showed a surprising selectivity (from 76- to 3125-fold) and were most potent at inhibiting butyrylcholinesterase (BChE), with IC50 values from 0.016 to 0.657 muM. A Lineweaver-Burk plot and molecular modeling studies indicated that the representative compounds, 6l and 6k, targeted both the catalytic active site (CAS) and the peripheral anionic site (PAS) of ChEs. Furthermore, APCs did not affect HepG2 cell viability at the concentration of 100 muM. Consequently, these polyamine conjugates could be thoroughly and systematically studied for the treatment of AD. Title: Trajectory and genomic determinants of fungal-pathogen speciation and host adaptation Hu X, Xiao G, Zheng P, Shang Y, Su Y, Zhang X, Liu X, Zhan S, St Leger RJ, Wang C Ref: Proc Natl Acad Sci U S A, 111:16796, 2014 : PubMed ESTHER: Hu_2014_Proc.Natl.Acad.Sci.U.S.A_111_16796 PubMedSearch: Hu 2014 Proc.Natl.Acad.Sci.U.S.A 111 16796 PubMedID: 25368161 Gene_locus related to this paper: metan-a0a086npb7, 9hypo-a0a0b2wj22, 9hypo-a0a0b2wjv9, 9hypo-a0a0b2wph9, 9hypo-a0a0b2wpk8, 9hypo-a0a0b2wpu7, 9hypo-a0a0b2wwt8, 9hypo-a0a0b2wyt3, 9hypo-a0a0b2x1p9, metan-a0a0b4es34, 9hypo-a0a0b4g6h7, 9hypo-a0a0b4gae9, 9hypo-a0a0b4gyw4, 9hypo-a0a0b4gzy5, 9hypo-a0a0b4hfr4, 9hypo-a0a0b4hi37, 9hypo-a0a0b4hin0, 9hypo-a0a0b4fk47, 9hypo-a0a0b4g7m5, 9hypo-a0a0b4i0i8, 9hypo-a0a0b4ie69, 9hypo-a0a0b4if28, 9hypo-a0a0b4h1h6, 9hypo-a0a0b4hlm2, metan-a0a0d9pev7, metas-a0a0b2wy97, metas-a0a0b2wk60, metra-e9ewg3, metaq-pks1, metra-pks2, metmf-pks2, metaf-pks1, metbs-pks2, metas-pks1 Abstract Much remains unknown regarding speciation. Host-pathogen interactions are a major driving force for diversification, but the genomic basis for speciation and host shifting remains unclear. The fungal genus Metarhizium contains species ranging from specialists with very narrow host ranges to generalists that attack a wide range of insects. By genomic analyses of seven species, we demonstrated that generalists evolved from specialists via transitional species with intermediate host ranges and that this shift paralleled insect evolution. We found that specialization was associated with retention of sexuality and rapid evolution of existing protein sequences whereas generalization was associated with protein-family expansion, loss of genome-defense mechanisms, genome restructuring, horizontal gene transfer, and positive selection that accelerated after reinforcement of reproductive isolation. These results advance understanding of speciation and genomic signatures that underlie pathogen adaptation to hosts. Title: Draft Genome Sequences of Psychrobacter Strains JCM 18900, JCM 18901, JCM 18902, and JCM 18903, Isolated Preferentially from Frozen Aquatic Organisms Kudo T, Kidera A, Kida M, Kawauchi A, Shimizu R, Nakahara T, Zhang X, Yamada A, Amano M and Ohkuma M <15 more author(s)> Kudo T, Kidera A, Kida M, Kawauchi A, Shimizu R, Nakahara T, Zhang X, Yamada A, Amano M, Hamada Y, Taniyama S, Arakawa O, Yoshida A, Oshima K, Suda W, Kuwahara H, Nogi Y, Kitamura K, Yuki M, Iida T, Moriya S, Inoue T, Hongoh Y, Hattori M, Ohkuma M (- 15) Ref: Genome Announc, 2:e00280, 2014 : PubMed ESTHER: Kudo_2014_Genome.Announc_2_e00280 PubMedSearch: Kudo 2014 Genome.Announc 2 e00280 PubMedID: 24699965 Gene_locus related to this paper: 9gamm-x0q9t6, 9gamm-x0r0h9, 9gamm-x0rb73, 9gamm-x0qpg3, 9gamm-x0rx94, 9gamm-x0rpe0 Abstract Four Psychrobacter strains, JCM 18900, JCM 18901, JCM 18902, and JCM 18903, related to either Psychrobacter nivimaris or Psychrobacter cibarius, were isolated from frozen marine animals. The genome information of these four strains will be useful for studies of their physiology and adaptation properties to frozen conditions. Title: Draft Genome Sequences of Vibrio sp. Strains Isolated from Tetrodotoxin-Bearing Scavenging Gastropod Kudo T, Kawauchi A, Nakahara T, Zhang X, Taniyama S, Takatani T, Arakawa O, Oshima K, Suda W and Ohkuma M <6 more author(s)> Kudo T, Kawauchi A, Nakahara T, Zhang X, Taniyama S, Takatani T, Arakawa O, Oshima K, Suda W, Kitamura K, Iida T, Iino T, Inoue T, Hongoh Y, Hattori M, Ohkuma M (- 6) Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Kudo_2014_Genome.Announc_2_e00623 PubMedSearch: Kudo 2014 Genome.Announc 2 e00623 PubMedID: 24948773 Abstract Vibrio sp. strains JCM 18905 and JCM 19053 were isolated from a tetrodotoxin (TTX)-bearing scavenging gastropod, and Vibrio sp. strain JCM 18904 was isolated from a sea cucumber. All these are closely related to Vibrio alginolyticus. Their comparative genome information is useful for studies of TTX production in bacteria. Title: Draft Genome Sequences of Geomicrobium sp. Strains JCM 19037, JCM 19038, JCM 19039, and JCM 19055, Isolated from Aquatic Samples Kudo T, Nakahara T, Zhang X, Taniyama S, Arakawa O, Murase S, Nakata H, Oshima K, Suda W and Ohkuma M <6 more author(s)> Kudo T, Nakahara T, Zhang X, Taniyama S, Arakawa O, Murase S, Nakata H, Oshima K, Suda W, Kitamura K, Iida T, Oshida Y, Inoue T, Hongoh Y, Hattori M, Ohkuma M (- 6) Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Kudo_2014_Genome.Announc_2_e00622 PubMedSearch: Kudo 2014 Genome.Announc 2 e00622 PubMedID: 24948772 Gene_locus related to this paper: 9bacl-a0a061nv39, 9bacl-a0a061nsm4, 9bacl-a0a061ndf6, 9bacl-a0a061nlu5, 9bacl-a0a061ntb4, 9bacl-a0a061nnc9, 9bacl-a0a061pf66 Abstract Haloalkaliphilic strains JCM 19037, JCM 19038, JCM 19039, and JCM 19055, closely related to Geomicrobium sediminis, were isolated from aquatic samples, and their draft genome sequences were determined. The genome information of these four strains will be useful for studies of their physiology and ecology. Title: Draft Genome Sequences of Cyclodextrin-Producing Alkaliphilic Bacillus Strains JCM 19045, JCM 19046, and JCM 19047 Kudo T, Sakamoto K, Akinaga M, Kawauchi A, Nakahara T, Zhang X, Yamada A, Oshima K, Suda W and Ohkuma M <10 more author(s)> Kudo T, Sakamoto K, Akinaga M, Kawauchi A, Nakahara T, Zhang X, Yamada A, Oshima K, Suda W, Kuwahara H, Nakamura N, Nogi Y, Kitamura K, Yuki M, Iida T, Moriya S, Inoue T, Hongoh Y, Hattori M, Ohkuma M (- 10) Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Kudo_2014_Genome.Announc_2_e00211 PubMedSearch: Kudo 2014 Genome.Announc 2 e00211 PubMedID: 24652985 Gene_locus related to this paper: 9baci-a0a060lzd7, 9baci-w7yjr4, 9baci-w7zpe5, 9baci-w8a608, 9baci-w7zad0 Abstract Bacillus strains JCM 19045, JCM 19046, and JCM 19047 are alkaliphiles that produce beta-cyclodextrin from starch. They are related to Bacillus xiaoxiensis and Bacillus lehensis. The genome information for these three strains will be useful for studies of the physiological role of cyclodextrin and cyclodextrin production. Title: Comparative genomics and transcriptomics analyses reveal divergent lifestyle features of nematode endoparasitic fungus Hirsutella minnesotensis Lai Y, Liu K, Zhang X, Li K, Wang N, Shu C, Wu Y, Wang C, Bushley KE and Liu X <1 more author(s)> Lai Y, Liu K, Zhang X, Li K, Wang N, Shu C, Wu Y, Wang C, Bushley KE, Xiang M, Liu X (- 1) Ref: Genome Biol Evol, 6:3077, 2014 : PubMed ESTHER: Lai_2014_Genome.Biol.Evol_6_3077 PubMedSearch: Lai 2014 Genome.Biol.Evol 6 3077 PubMedID: 25359922 Gene_locus related to this paper: 9hypo-a0a0f7zjg7, 9hypo-a0a0f7zm48, 9hypo-a0a0f7zrk5, 9hypo-a0a0f7ztt4, 9hypo-a0a0f7ztz3, 9hypo-a0a0f7zun4, 9hypo-a0a0f7zus6, 9hypo-a0a0f7zx75, 9hypo-a0a0f7zy63, 9hypo-a0a0f8a122, 9hypo-a0a0f8a341, 9hypo-a0a0f8a483, 9hypo-a0a0f8a644, 9hypo-a0a0f8a655, 9hypo-a0a0f8a6k2, 9hypo-a0a0f7zgk0, 9hypo-a0a0f7zy10, 9hypo-a0a0f7zmp5 Abstract Hirsutella minnesotensis [Ophiocordycipitaceae (Hypocreales, Ascomycota)] is a dominant endoparasitic fungus by using conidia that adhere to and penetrate the secondary stage juveniles of soybean cyst nematode. Its genome was de novo sequenced and compared with five entomopathogenic fungi in the Hypocreales and three nematode-trapping fungi in the Orbiliales (Ascomycota). The genome of H. minnesotensis is 51.4 Mb and encodes 12,702 genes enriched with transposable elements up to 32%. Phylogenomic analysis revealed that H. minnesotensis was diverged from entomopathogenic fungi in Hypocreales. Genome of H. minnesotensis is similar to those of entomopathogenic fungi to have fewer genes encoding lectins for adhesion and glycoside hydrolases for cellulose degradation, but is different from those of nematode-trapping fungi to possess more genes for protein degradation, signal transduction, and secondary metabolism. Those results indicate that H. minnesotensis has evolved different mechanism for nematode endoparasitism compared with nematode-trapping fungi. Transcriptomics analyses for the time-scale parasitism revealed the upregulations of lectins, secreted proteases and the genes for biosynthesis of secondary metabolites that could be putatively involved in host surface adhesion, cuticle degradation, and host manipulation. Genome and transcriptome analyses provided comprehensive understanding of the evolution and lifestyle of nematode endoparasitism. Title: Opposite effects of gene deficiency and pharmacological inhibition of soluble epoxide hydrolase on cardiac fibrosis Li L, Li N, Pang W, Zhang X, Hammock BD, Ai D, Zhu Y Ref: PLoS ONE, 9:e94092, 2014 : PubMed ESTHER: Li_2014_PLoS.One_9_e94092 PubMedSearch: Li 2014 PLoS.One 9 e94092 PubMedID: 24718617 Abstract Arachidonic acid-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; manipulation of their levels is a potentially useful pharmacological strategy. EETs are hydrolyzed by soluble epoxide hydrolase (sEH) to form the corresponding diols, thus altering and reducing the activity of these oxylipins. To better understand the phenotypic impact of sEH disruption, we compared the effect of EPHX2 gene knockout (EPHX2-/-) and sEH inhibition in mouse models. Measurement of plasma oxylipin profiles confirmed that the ratio of EETs/DHETs was increased in EPHX2-/- and sEH-inhibited mice. However, plasma concentrations of 9, 11, 15, 19-HETE were elevated in EPHX2-/- but not sEH-inhibited mice. Next, we investigated the role of this difference in cardiac dysfunction induced by Angiotensin II (AngII). Both EPHX2 gene deletion and inhibition protected against AngII-induced cardiac hypertrophy. Interestingly, cardiac dysfunction was attenuated by sEH inhibition rather than gene deletion. Histochemical staining revealed that compared with pharmacological inhibition, EPHX2 deletion aggravated AngII-induced myocardial fibrosis; the mRNA levels of fibrotic-related genes were increased. Furthermore, cardiac inflammatory response was greater in EPHX2-/- than sEH-inhibited mice with AngII treatment, as evidenced by increased macrophage infiltration and expression of MCP-1 and IL-6. In vitro, AngII-upregulated MCP-1 and IL-6 expression was significantly attenuated by sEH inhibition but promoted by EPHX2 deletion in cardiofibroblasts. Thus, compared with pharmacological inhibition of sEH, EPHX2 deletion caused the shift in arachidonic acid metabolism, which may led to pathological cardiac remodeling, especially cardiac fibrosis. Title: Territrem and Butyrolactone Derivatives from a Marine-Derived Fungus Aspergillus Terreus Nong X, Wang Y, Zhang X, Zhou M, Xu X, Qi S Ref: Mar Drugs, 12:6113, 2014 : PubMed ESTHER: Nong_2014_Mar.Drugs_12_6113 PubMedSearch: Nong 2014 Mar.Drugs 12 6113 PubMedID: 25522319 Abstract Seventeen lactones including eight territrem derivatives (1-8) and nine butyrolactone derivatives (9-17) were isolated from a marine-derived fungus Aspergillus terreus SCSGAF0162 under solid-state fermentation of rice. Compounds 1-3 and 9-10 were new, and their structures were elucidated by spectroscopic analysis. The acetylcholinesterase inhibitory activity and antiviral activity of compounds 1-17 were evaluated. Among them, compounds 1 and 2 showed strong inhibitory activity against acetylcholinesterase with IC50 values of 4.2 +/- 0.6, 4.5 +/- 0.6 nM, respectively. This is the first time it has been reported that 3, 6, 10, 12 had evident antiviral activity towards HSV-1 with IC50 values of 16.4 +/- 0.6, 6.34 +/- 0.4, 21.8 +/- 0.8 and 28.9 +/- 0.8 mug.mL-1, respectively. Antifouling bioassay tests showed that compounds 1, 11, 12, 15 had potent antifouling activity with EC50 values of 12.9 +/- 0.5, 22.1 +/- 0.8, 7.4 +/- 0.6, 16.1 +/- 0.6 mug.mL-1 toward barnacle Balanus amphitrite larvae, respectively. Title: AChE inhibition: One dominant factor for swimming behavior changes of Daphnia magna under DDVP exposure Ren Z, Zhang X, Wang X, Qi P, Zhang B, Zeng Y, Fu R, Miao M Ref: Chemosphere, 120C:252, 2014 : PubMed ESTHER: Ren_2014_Chemosphere_120C_252 PubMedSearch: Ren 2014 Chemosphere 120C 252 PubMedID: 25112705 Abstract As a key enzyme that hydrolyzes the neurotransmitter acetylcholine in cholinergic synapses of both vertebrates and invertebrates, acetylcholinesterase (AChE) is strongly inhibited by organophosphates. AChE inhibition may induce the decrease of swimming ability. According to previous research, swimming behavior of different aquatic organisms could be affected by different chemicals, and there is a shortage of research on direct correlation analysis between swimming behavior and biochemical indicators. Therefore, swimming behavior and whole-body AChE activity of Daphnia magna under dichlorvos (DDVP) exposure were identified in order to clarify the relationship between behavioral responses and AChE inhibition in this study. In the beginning, AChE activity was similar in all treatments with the control. During all exposures, the tendency of AChE activity inhibition was the same as the behavioral responses of D. magna. The AChE activity of individuals without movement would decrease to about zero in several minutes. The correlation analysis between swimming behavior of D. magna and AChE activity showed that the stepwise behavioral response was mainly decided by AChE activity. All of these results suggested that the toxicity characteristics of DDVP as an inhibitor of AChE on the swimming behavior of organisms were the same, and the AChE activity inhibition could induce loss of the nerve conduction ability, causing hyperactivity, loss of coordination, convulsions, paralysis and other kinds of behavioral changes, which was illustrated by the stepwise behavioral responses under different environmental stresses. Title: Genome of the human hookworm Necator americanus Tang YT, Gao X, Rosa BA, Abubucker S, Hallsworth-Pepin K, Martin J, Tyagi R, Heizer E, Zhang X and Mitreva M <19 more author(s)> Tang YT, Gao X, Rosa BA, Abubucker S, Hallsworth-Pepin K, Martin J, Tyagi R, Heizer E, Zhang X, Bhonagiri-Palsikar V, Minx P, Warren WC, Wang Q, Zhan B, Hotez PJ, Sternberg PW, Dougall A, Gaze ST, Mulvenna J, Sotillo J, Ranganathan S, Rabelo EM, Wilson RK, Felgner PL, Bethony J, Hawdon JM, Gasser RB, Loukas A, Mitreva M (- 19) Ref: Nat Genet, 46:261, 2014 : PubMed ESTHER: Tang_2014_Nat.Genet_46_261 PubMedSearch: Tang 2014 Nat.Genet 46 261 PubMedID: 24441737 Gene_locus related to this paper: necam-w2tsu7 Abstract The hookworm Necator americanus is the predominant soil-transmitted human parasite. Adult worms feed on blood in the small intestine, causing iron-deficiency anemia, malnutrition, growth and development stunting in children, and severe morbidity and mortality during pregnancy in women. We report sequencing and assembly of the N. americanus genome (244 Mb, 19,151 genes). Characterization of this first hookworm genome sequence identified genes orchestrating the hookworm's invasion of the human host, genes involved in blood feeding and development, and genes encoding proteins that represent new potential drug targets against hookworms. N. americanus has undergone a considerable and unique expansion of immunomodulator proteins, some of which we highlight as potential treatments against inflammatory diseases. We also used a protein microarray to demonstrate a postgenomic application of the hookworm genome sequence. This genome provides an invaluable resource to boost ongoing efforts toward fundamental and applied postgenomic research, including the development of new methods to control hookworm and human immunological diseases. Title: Genome sequencing of the high oil crop sesame provides insight into oil biosynthesis Wang L, Yu S, Tong C, Zhao Y, Liu Y, Song C, Zhang Y, Zhang X, Wang Y and Varshney RK <12 more author(s)> Wang L, Yu S, Tong C, Zhao Y, Liu Y, Song C, Zhang Y, Zhang X, Wang Y, Hua W, Li D, Li F, Yu J, Xu C, Han X, Huang S, Tai S, Wang J, Xu X, Li Y, Liu S, Varshney RK (- 12) Ref: Genome Biol, 15:R39, 2014 : PubMed ESTHER: Wang_2014_Genome.Biol_15_R39 PubMedSearch: Wang 2014 Genome.Biol 15 R39 PubMedID: 24576357 Gene_locus related to this paper: sesin-a0a6i9snr9 Abstract BACKGROUND: Sesame, Sesamum indicum L., is considered the queen of oilseeds for its high oil content and quality, and is grown widely in tropical and subtropical areas as an important source of oil and protein. However, the molecular biology of sesame is largely unexplored. RESULTS: Here, we report a high-quality genome sequence of sesame assembled de novo with a contig N50 of 52.2 kb and a scaffold N50 of 2.1 Mb, containing an estimated 27,148 genes. The results reveal novel, independent whole genome duplication and the absence of the Toll/interleukin-1 receptor domain in resistance genes. Candidate genes and oil biosynthetic pathways contributing to high oil content were discovered by comparative genomic and transcriptomic analyses. These revealed the expansion of type 1 lipid transfer genes by tandem duplication, the contraction of lipid degradation genes, and the differential expression of essential genes in the triacylglycerol biosynthesis pathway, particularly in the early stage of seed development. Resequencing data in 29 sesame accessions from 12 countries suggested that the high genetic diversity of lipid-related genes might be associated with the wide variation in oil content. Additionally, the results shed light on the pivotal stage of seed development, oil accumulation and potential key genes for sesamin production, an important pharmacological constituent of sesame. CONCLUSIONS: As an important species from the order Lamiales and a high oil crop, the sesame genome will facilitate future research on the evolution of eudicots, as well as the study of lipid biosynthesis and potential genetic improvement of sesame. Title: Effect of allyl isothiocyanate on ultra-structure and the activities of four enzymes in adult Sitophilus zeamais Wu H, Liu XR, Yu DD, Zhang X, Feng JT Ref: Pesticide Biochemistry and Physiology, 109:12, 2014 : PubMed ESTHER: Wu_2014_Pestic.Biochem.Physiol_109_12 PubMedSearch: Wu 2014 Pestic.Biochem.Physiol 109 12 PubMedID: 24581380 Abstract Rarefaction and vacuolization of the mitochondrial matrix of AITC-treated (allyl isothiocyanate-treated) adult Sitophilus zeamais were evident according to the ultra-structural by TEM. Four important enzymes in adult S. zeamais were further studied after fumigation treatment with allyl isothiocyanate (AITC) extracted from Armoracia rusticana roots and shoots. The enzymes were glutathione S-transferase (GST), catalase (CAT), cytochrome c oxidase, and acetylcholinesterase (AChE). The results indicated that the activities of the four enzymes were strongly time and dose depended. With prolonged exposure time, treatment with 0.74mug/mL AITC inhibited the activities of cytochrome c oxidase, AChE, and CAT, but induced the activity of GST. The activities of cytochrome c oxidase, AChE, and CAT were remarkably induced at a low AITC dosage (0.25mug/mL), but were restrained with increased AITC dosage. The activity of GST was inhibited at a low AITC dosage (0.5mug/mL), but was induced at a high AITC dosage (1.5mug/mL). According to the results of TEM, toxic symptoms and enzymes activities, it suggested that mitochondrial maybe the one site of action of AITC against the adult S. zeamais and it also suggested that cytochrome c oxidase maybe one target protein of AITC against the adult S. zeamais, which need to further confirmed by protein function tested. Title: A natural antisense transcript regulates acetylcholinesterase gene expression via epigenetic modification in Hepatocellular Carcinoma Xi Q, Gao N, Zhang X, Zhang B, Ye W, Wu J Ref: International Journal of Biochemistry & Cell Biology, 55C:242, 2014 : PubMed ESTHER: Xi_2014_Int.J.Biochem.Cell.Biol_55C_242 PubMedSearch: Xi 2014 Int.J.Biochem.Cell.Biol 55C 242 PubMedID: 25240585 Abstract In recent years, widespread antisense transcripts have been identified systematically in mammalian cells and are known to regulate gene expression, although their functional significance remains largely unknown. Previous work has identified that acetylcholinesterase (AChE) is expressed aberrantly in various malignant tumors and function as a tumor growth suppressor. However, the mechanism of AChE gene regulation in tumors remains unclear. In this study, we show that the AChE antisense RNA (AChE-AS) play an important role in AChE expression regulation. An inverse relationship was identified between AChE-AS and AChE expression in hepatocellular carcinoma and hepatoma cells. The silenced AChE-AS corresponds to elevated expression of AChE. Furthermore, we demonstrated that reduced AChE-AS increased H3K4 methylation and decreased H3K9 methylation in the AChE promoter region. As expected, elevated AChE levels induced by inhibition of AChE-AS enhanced anticarcinogen-induced apoptosis. These observations demonstrated that AChE-AS modulates AChE expression and exerts an anti-apoptotic effect through direct repression of AChE expression in HCC cells. Thus, natural antisense RNA may play an important role in AChE regulation via affecting the epigenetic modification in the AChE promoter region. Title: Silencing of an aphid carboxylesterase gene by use of plant-mediated RNAi impairs Sitobion avenae tolerance of Phoxim insecticides Xu L, Duan X, Lv Y, Zhang X, Nie Z, Xie C, Ni Z, Liang R Ref: Transgenic Res, 23:389, 2014 : PubMed ESTHER: Xu_2014_Transgenic.Res_23_389 PubMedSearch: Xu 2014 Transgenic.Res 23 389 PubMedID: 24242160 Abstract RNA interference (RNAi) describes the ability of double-stranded RNA (dsRNA) to inhibit homologous gene expression at the RNA level. Its specificity is sequence-based and depends on the sequence of one strand of the dsRNA corresponding to part or all of a specific gene transcript. In this study we adopted plant-mediated RNAi technology that targets Sitobion avenae (S. avenae) to enable gene silencing in the aphid and to minimize handling of the insects during experiments. S. avenae was selected for this study because it causes serious economic losses to wheat throughout the world. The carboxylesterase (CbE E4) gene in S. avenae was homologously cloned, which increased synthesis of a protein known to be critical to the resistance (tolerance) this species has developed to a wide range of pesticides. A plant RNAi vector was constructed, and transgenic Triticum aesticum (dsCbE1-5 and dsCbE2-2 lines) expressing CbE E4 dsRNA were developed. S. avenae were fed on dsCbE1-5 and dsCbE2-2 lines stably producing the CbE E4 dsRNA. CbE E4 gene expression in S. avenae was reduced by up to 30-60 %. The number of aphids raised on dsCbE1-5 and dsCbE2-2 was lower than the number raised on non-transgenic plants. A solution of CbE E4 enzyme from S. avenae fed on dsCbE1-5 and dsCbE2-2 plants hydrolyzed only up to 20-30 % Phoxim solution within 40 min whereas a solution of the enzyme from CbE E4 fed on control plants hydrolyzed 60 % of Phoxim solution within 40 min. CbE E4 gene silencing was achieved by our wheat-mediated RNAi approach. This plant-mediated RNAi approach for addressing degradation-based pesticide resistance mechanisms in aphids and may prove useful in pest management for diverse agro-ecosystems. Title: Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W and Shi Q <31 more author(s)> You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W, Zhang X, Sun Y, Chen S, Hong W, Li Y, Cheng S, Fan G, Shi C, Liang J, Tom Tang Y, Yang C, Ruan Z, Bai J, Peng C, Mu Q, Lu J, Fan M, Yang S, Huang Z, Jiang X, Fang X, Zhang G, Zhang Y, Polgar G, Yu H, Li J, Liu Z, Ravi V, Coon SL, Yang H, Venkatesh B, Shi Q (- 31) Ref: Nat Commun, 5:5594, 2014 : PubMed ESTHER: You_2014_Nat.Commun_5_5594 PubMedSearch: You 2014 Nat.Commun 5 5594 PubMedID: 25463417 Gene_locus related to this paper: 9gobi-a0a3b4bh68, 9gobi-a0a3b4bmj6, 9gobi-a0a3b4alj9, 9gobi-a0a3b4biy6, 9gobi-a0a3b4ah01, 9gobi-a0a3b3z8m7, 9gobi-a0a3b4aaj5, 9gobi-a0a3b4b6y7 Abstract Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates. Title: Paraoxonase activity and genetic polymorphisms in northern Han Chinese workers exposed to organophosphate pesticides Zhang X, Sui H, Li H, Zheng J, Wang F, Li B, Zhang Y Ref: Exp Biol Med (Maywood), 239:232, 2014 : PubMed ESTHER: Zhang_2014_Exp.Biol.Med.(Maywood)_239_232 PubMedSearch: Zhang 2014 Exp.Biol.Med.(Maywood) 239 232 PubMedID: 24326413 Abstract Paraoxonase (PON1) is one of the major players in the detoxification of organophosphates (OPs). This study presents our investigation into the effect of OPs on serum PON1 activity and the distribution of common PON1 polymorphisms in Han Chinese workers with repeated high exposure to OP pesticides, and the factors modulating PON1 activity. In all, 400 participants, including 180 workers exposed to OP pesticides occupationally, and 220 controls were investigated. Serum PON1 and cholinesterase (ChE) activity were measured, and genotyping was done using polymerase chain reaction-restriction fragment length polymorphism. The association between PON1 activity and PON1 polymorphisms, and the influencing factors of PON1 activity, were analyzed. The results revealed that repeated OP exposures significantly decreased serum PON1 and ChE activity (P < 0.05), although the exposed workers did not complain of health problems. Higher L and R allele frequencies for the L55M and Q192R polymorphisms of PON1 were observed. PON1 polymorphisms (especially the Q192R polymorphism) and pesticide exposures significantly affected serum PON1 activity in the study population. Therefore, the results of this investigation indicate PON1 polymorphisms and pesticide exposures may be important risk predictors for OP poisoning in the Han Chinese population, who display very high frequencies of the M allele and R allele for PON1 polymorphisms at the positions 55 and 192, respectively. Title: Hsa-miR-132 Regulates Apoptosis in Non-Small Cell Lung Cancer Independent of Acetylcholinesterase Zhang B, Lu L, Zhang X, Ye W, Wu J, Xi Q Ref: Journal of Molecular Neuroscience, 53:335, 2014 : PubMed ESTHER: Zhang_2014_J.Mol.Neurosci_53_335 PubMedSearch: Zhang 2014 J.Mol.Neurosci 53 335 PubMedID: 24158730 Abstract MiR-132 is enriched in the central nerve system and is thought to be involved in neuronal development, maturation and function, and to be associated with several neurological disorders including Alzheimer's disease. In addition to its documented neuronal functions, an emerging role for miR-132 in tumorigenesis has been suggested. Recently, hsa-miR-132 was shown to be modulated in different tumor types. However, its role in non-small cell lung cancer (NSCLC) remains unclear. Here, we show that hsa-miR-132 can initiate apoptosis in NSCLC cells to dramatically attenuate tumor formation in nude mice independent of its effect on the proliferation/apoptosis-associated gene, acetylcholinesterase (AChE). Interestingly, hsa-miR-132 has no pro-apoptotic effect in normal pulmonary trachea epithelium. Taken together, these results suggest that hsa-miR-132 represses NSCLC growth by inducing apoptosis independent of AChE. Title: Complete Genome Sequence of Neisseria meningitidis Serogroup A Strain NMA510612, Isolated from a Patient with Bacterial Meningitis in China Zhang Y, Yang J, Xu L, Zhu Y, Liu B, Shao Z, Zhang X, Jin Q Ref: Genome Announc, 2:e00360, 2014 : PubMed ESTHER: Zhang_2014_Genome.Announc_2_e00360 PubMedSearch: Zhang 2014 Genome.Announc 2 e00360 PubMedID: 24812217 Gene_locus related to this paper: neime-r0tza2 Abstract Serogroup A meningococcal strains have been involved in several pandemics and a series of epidemics worldwide in the past. Determination of the genome sequence of the prevalent genotype strain will help us understand the genetic background of the evolutionary and epidemiological properties of these bacteria. We sequenced the complete genome of Neisseria meningitidis NMA510612, a clinical isolate from a patient with meningococcal meningitis. Title: Complete Genome Sequence of Staphylococcus aureus XN108, an ST239-MRSA-SCCmec III Strain with Intermediate Vancomycin Resistance Isolated in Mainland China Zhang X, Xu X, Yuan W, Hu Q, Shang W, Hu X, Tong Y, Rao X Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Zhang_2014_Genome.Announc_2_e00449 PubMedSearch: Zhang 2014 Genome.Announc 2 e00449 PubMedID: 25059856 Abstract ST239-MRSA-SCCmec III (ST239, sequence type 239; MRSA, methicillin-resistant Staphylococcus aureus; SCCmec III, staphylococcal cassette chromosome mec type III) is the most predominant clone of hospital-acquired methicillin-resistant S. aureus in mainland China. We report here the complete genome sequence of XN108, the first vancomycin-intermediate S. aureus strain isolated from a steam-burned patient with a wound infection. Title: A new rhesus macaque assembly and annotation for next-generation sequencing analyses Zimin AV, Cornish AS, Maudhoo MD, Gibbs RM, Zhang X, Pandey S, Meehan DT, Wipfler K, Bosinger SE and Norgren RB, Jr. <9 more author(s)> Zimin AV, Cornish AS, Maudhoo MD, Gibbs RM, Zhang X, Pandey S, Meehan DT, Wipfler K, Bosinger SE, Johnson ZP, Tharp GK, Marcais G, Roberts M, Ferguson B, Fox HS, Treangen T, Salzberg SL, Yorke JA, Norgren RB, Jr. (- 9) Ref: Biol Direct, 9:20, 2014 : PubMed ESTHER: Zimin_2014_Biol.Direct_9_20 PubMedSearch: Zimin 2014 Biol.Direct 9 20 PubMedID: 25319552 Gene_locus related to this paper: macmu-g7n4x3, macmu-h9er02, macmu-h9fud6, macmu-f6qwx1, macmu-i2cyv7, macmu-h9zaw9, macmu-i0fgb6, macmu-i2cu80, macmu-f7h550, macmu-f7gkb9 Abstract BACKGROUND: The rhesus macaque (Macaca mulatta) is a key species for advancing biomedical research. Like all draft mammalian genomes, the draft rhesus assembly (rheMac2) has gaps, sequencing errors and misassemblies that have prevented automated annotation pipelines from functioning correctly. Another rhesus macaque assembly, CR_1.0, is also available but is substantially more fragmented than rheMac2 with smaller contigs and scaffolds. Annotations for these two assemblies are limited in completeness and accuracy. High quality assembly and annotation files are required for a wide range of studies including expression, genetic and evolutionary analyses. Title: Genome sequence of the date palm Phoenix dactylifera L Al-Mssallem IS, Hu S, Zhang X, Lin Q, Liu W, Tan J, Yu X, Liu J, Pan L and Yu J <34 more author(s)> Al-Mssallem IS, Hu S, Zhang X, Lin Q, Liu W, Tan J, Yu X, Liu J, Pan L, Zhang T, Yin Y, Xin C, Wu H, Zhang G, Ba Abdullah MM, Huang D, Fang Y, Alnakhli YO, Jia S, Yin A, Alhuzimi EM, Alsaihati BA, Al-Owayyed SA, Zhao D, Zhang S, Al-Otaibi NA, Sun G, Majrashi MA, Li F, Tala, Wang J, Yun Q, Alnassar NA, Wang L, Yang M, Al-Jelaify RF, Liu K, Gao S, Chen K, Alkhaldi SR, Liu G, Zhang M, Guo H, Yu J (- 34) Ref: Nat Commun, 4:2274, 2013 : PubMed ESTHER: Al-Mssallem_2013_Nat.Commun_4_2274 PubMedSearch: Al-Mssallem 2013 Nat.Commun 4 2274 PubMedID: 23917264 Gene_locus related to this paper: phodc-a0a2h3y3d5, phodc-a0a2h3z529, phodc-a0a2h3y147, phodc-a0a2h3xrz4, phodc-a0a3q0ic37, phodc-a0a2h3yxf0, phodc-a0a2h3zh01, phodc-a0a3q0hs32 Abstract Date palm (Phoenix dactylifera L.) is a cultivated woody plant species with agricultural and economic importance. Here we report a genome assembly for an elite variety (Khalas), which is 605.4 Mb in size and covers >90% of the genome (~671 Mb) and >96% of its genes (~41,660 genes). Genomic sequence analysis demonstrates that P. dactylifera experienced a clear genome-wide duplication after either ancient whole genome duplications or massive segmental duplications. Genetic diversity analysis indicates that its stress resistance and sugar metabolism-related genes tend to be enriched in the chromosomal regions where the density of single-nucleotide polymorphisms is relatively low. Using transcriptomic data, we also illustrate the date palm's unique sugar metabolism that underlies fruit development and ripening. Our large-scale genomic and transcriptomic data pave the way for further genomic studies not only on P. dactylifera but also other Arecaceae plants. Title: Whole-genome sequencing of Oryza brachyantha reveals mechanisms underlying Oryza genome evolution Chen J, Huang Q, Gao D, Wang J, Lang Y, Liu T, Li B, Bai Z, Luis Goicoechea J and Chen M <30 more author(s)> Chen J, Huang Q, Gao D, Wang J, Lang Y, Liu T, Li B, Bai Z, Luis Goicoechea J, Liang C, Chen C, Zhang W, Sun S, Liao Y, Zhang X, Yang L, Song C, Wang M, Shi J, Liu G, Liu J, Zhou H, Zhou W, Yu Q, An N, Chen Y, Cai Q, Wang B, Liu B, Min J, Huang Y, Wu H, Li Z, Zhang Y, Yin Y, Song W, Jiang J, Jackson SA, Wing RA, Chen M (- 30) Ref: Nat Commun, 4:1595, 2013 : PubMed ESTHER: Chen_2013_Nat.Commun_4_1595 PubMedSearch: Chen 2013 Nat.Commun 4 1595 PubMedID: 23481403 Gene_locus related to this paper: orysa-Q6ZDG3, orysa-q6h415, orysj-q6yse8, orysa-q33aq0, orybr-j3l7k2, orybr-j3m138, orybr-j3l6m8, orybr-j3m3b3, orybr-j3l8d1, orybr-j3kza5, orybr-j3mnb5, orybr-j3n4p4, orybr-j3lg73, orybr-j3l342, orybr-j3msi2, orybr-j3nb83, orybr-j3mpc5 Abstract The wild species of the genus Oryza contain a largely untapped reservoir of agronomically important genes for rice improvement. Here we report the 261-Mb de novo assembled genome sequence of Oryza brachyantha. Low activity of long-terminal repeat retrotransposons and massive internal deletions of ancient long-terminal repeat elements lead to the compact genome of Oryza brachyantha. We model 32,038 protein-coding genes in the Oryza brachyantha genome, of which only 70% are located in collinear positions in comparison with the rice genome. Analysing breakpoints of non-collinear genes suggests that double-strand break repair through non-homologous end joining has an important role in gene movement and erosion of collinearity in the Oryza genomes. Transition of euchromatin to heterochromatin in the rice genome is accompanied by segmental and tandem duplications, further expanded by transposable element insertions. The high-quality reference genome sequence of Oryza brachyantha provides an important resource for functional and evolutionary studies in the genus Oryza. Title: Genomics-driven discovery of the pneumocandin biosynthetic gene cluster in the fungus Glarea lozoyensis Chen L, Yue Q, Zhang X, Xiang M, Wang C, Li S, Che Y, Ortiz-Lopez FJ, Bills GF and An Z <1 more author(s)> Chen L, Yue Q, Zhang X, Xiang M, Wang C, Li S, Che Y, Ortiz-Lopez FJ, Bills GF, Liu X, An Z (- 1) Ref: BMC Genomics, 14:339, 2013 : PubMed ESTHER: Chen_2013_BMC.Genomics_14_339 PubMedSearch: Chen 2013 BMC.Genomics 14 339 PubMedID: 23688303 Gene_locus related to this paper: glal2-s3cg73, glal2-s3d2r4, glal2-s3dmm6, glal2-s3e306, glal2-s3dl45, glal2-s3d1r9, glal2-s3e4a7, glal2-s3ddr1, glal2-s3ctz6, glal2-s3dy35, glal2-s3dws5, glal2-s3df31, glal2-s3d7q5, glal2-s3cwz5, glal2-s3dcn7, glal2-s3dhj7, glal2-s3dm96, glal2-s3d6q1, glal2-s3cv25, glal2-s3e8v9, glal2-s3crh2, glal2-s3dde8, glal2-s3cxt6, glal2-s3da89, glal2-s3ckn8, glal2-s3d4y3, glal2-s3ddw6, glal2-s3dk02, glal2-s3d048 Abstract BACKGROUND: The antifungal therapy caspofungin is a semi-synthetic derivative of pneumocandin B0, a lipohexapeptide produced by the fungus Glarea lozoyensis, and was the first member of the echinocandin class approved for human therapy. The nonribosomal peptide synthetase (NRPS)-polyketide synthases (PKS) gene cluster responsible for pneumocandin biosynthesis from G. lozoyensis has not been elucidated to date. In this study, we report the elucidation of the pneumocandin biosynthetic gene cluster by whole genome sequencing of the G. lozoyensis wild-type strain ATCC 20868. Title: Genome survey uncovers the secrets of sex and lifestyle in caterpillar fungus. Hu X, Zhang Y, Xiao G, Zheng P, Xia Y, Zhang X, St Leger R.J, Liu X, Wang C Ref: Chin Sci Bull, 58:2846, 2013 : PubMed ESTHER: Hu_2013_Chin.Sci.Bull_58_2846 PubMedSearch: Hu 2013 Chin.Sci.Bull 58 2846 Gene_locus related to this paper: ophsc-t5ap86, ophsc-t5abc7, ophsc-t5acw5, ophsc-t5ajn1, ophsc-t5aqy1 Abstract The caterpillar fungus Ophiocordyceps sinensis (best known as Cordyceps sinensis) mummifies ghost moth larvae exclusively in Tibetan Plateau alpine ecosystems. Touted as -YHimalayan Viagra, the fungus is highly prized due to its medical benefits and dwindling supplies. Attempts to culture the sexual fruiting-body have failed and the huge market demand has led to severe devastation of local ecosystems and to the fungus heading towards extinction. By genome sequencing, we establish that unlike related insect pathogens O. sinensis contains two compatible mating-type genes in its genome and is self-fertile, i.e. homothallic. However, sexual processes are only initiated under native environmental conditions. O. sinensis resembles biotrophic plant pathogens in having a genome shaped by retrotransposon-driven expansions. The resulting changes in gene content suggest that O. sinensis has a biphasic pathogenic mechanism beginning with stealth pathogenesis in early host instars. O. sinensis is the first psychrophilic fungus sequenced and is adapted to extreme cold with putative antifreeze proteins and mechanisms for increasing lipid accumulation and fatty acid unsaturation. We hypothesize that for the inbreeding O. sinensis the massive proliferation of retrotransposons provides a tradeoff between the advantages of increased genetic variation independent of sexual recombination and deletion of genes dispensable for its specialized pathogenic lifestyle. Title: Seasonally variable intestinal metagenomes of the red palm weevil (Rhynchophorus ferrugineus) Jia S, Zhang X, Zhang G, Yin A, Zhang S, Li F, Wang L, Zhao D, Yun Q and Yu J <7 more author(s)> Jia S, Zhang X, Zhang G, Yin A, Zhang S, Li F, Wang L, Zhao D, Yun Q, Tala, Wang J, Sun G, Baabdullah M, Yu X, Hu S, Al-Mssallem IS, Yu J (- 7) Ref: Environ Microbiol, 15:3020, 2013 : PubMed ESTHER: Jia_2013_Environ.Microbiol_15_3020 PubMedSearch: Jia 2013 Environ.Microbiol 15 3020 PubMedID: 24102776 Abstract The intestinal microbes residing in the red palm weevil (RPW, Rhynchophorus ferrugineus) larva consume tender interior fibrous tissues of date palm trunks. The understanding of such microbiota at molecular level provides vital clues for the biological control of this devastating pest. Using pyrosequencing and shotgun strategy, we first study taxonomic profiles of the microbiota sampled at different months (March, July and November), and then confirm the impact of high-temperature stress on the microbial populations based on data from 16S rRNA amplicons using both field and laboratory samples. We further identify Klebsiella pneumoniae in November and Lactococcus lactis in July as the dominant species of the microbiota. We find that the RPW gut microbiota degrades polysaccharides and sucrose with hydrolases and that different active bacterial species in November and July are responsible for the symbiotic relationship between the microbiota and the host. Our results provide vital information for pest control and cellulolytic bacterial species characterization. Title: Draft Genome Sequence of the Cellulolytic, Mesophilic, Anaerobic Bacterium Clostridium termitidis Strain CT1112 (DSM 5398) Lal S, Ramachandran U, Zhang X, Munir R, Sparling R, Levin DB Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Lal_2013_Genome.Announc_1_E00281 PubMedSearch: Lal 2013 Genome.Announc 1 E00281 PubMedID: 23704187 Gene_locus related to this paper: 9clot-s0fuv1 Abstract Here, we report the draft genome sequence of Clostridium termitidis strain CT1112 (DSM 5398), a mesophilic, cellulolytic bacterium that can utilize a variety of sugars, as well as pure cellulose, as a sole carbon source; it also synthesizes fermentation end products with potential industrial applications. Title: Draft Genome Sequence of the Hydrogen- and Ethanol-Producing Bacterium Clostridium intestinale Strain URNW Lal S, Ramachandran U, Zhang X, Sparling R, Levin DB Ref: Genome Announc, 1:e00871, 2013 : PubMed ESTHER: Lal_2013_Genome.Announc_1_e00871 PubMedSearch: Lal 2013 Genome.Announc 1 e00871 PubMedID: 24136853 Gene_locus related to this paper: 9clot-u2n0g1 Abstract Here, we report the draft genome sequence of Clostridium intestinale strain URNW, which can convert biomass to useful products such as biofuels (hydrogen or ethanol) and other soluble end products. Title: Association of LIPC and advanced age-related macular degeneration Lee J, Zeng J, Hughes G, Chen Y, Grob S, Zhao L, Lee C, Krupa M, Quach J and Zhang K <10 more author(s)> Lee J, Zeng J, Hughes G, Chen Y, Grob S, Zhao L, Lee C, Krupa M, Quach J, Luo J, Wei X, Zhang X, Zhu J, Duan Y, Ferreyra H, Goldbaum M, Haw W, Shaw PX, Tang L, Zhang K (- 10) Ref: Eye (Lond), 27:265, 2013 : PubMed ESTHER: Lee_2013_Eye.(Lond)_27_265 PubMedSearch: Lee 2013 Eye.(Lond) 27 265 PubMedID: 23348725 Abstract PURPOSE: To determine whether there is an association between hepatic lipase (LIPC) and age-related macular degeneration (AMD) in two independent Caucasian cohorts. Title: Heteroaromatic and aniline derivatives of piperidines as potent ligands for vesicular acetylcholine transporter Li J, Zhang X, Zhang Z, Padakanti PK, Jin H, Cui J, Li A, Zeng D, Rath NP and Tu Z <3 more author(s)> Li J, Zhang X, Zhang Z, Padakanti PK, Jin H, Cui J, Li A, Zeng D, Rath NP, Flores H, Perlmutter JS, Parsons SM, Tu Z (- 3) Ref: Journal of Medicinal Chemistry, 56:6216, 2013 : PubMed ESTHER: Li_2013_J.Med.Chem_56_6216 PubMedSearch: Li 2013 J.Med.Chem 56 6216 PubMedID: 23802889 Abstract To identify suitable lipophilic compounds having high potency and selectivity for vesicular acetylcholine transporter (VAChT), a heteroaromatic ring or a phenyl group was introduced into the carbonyl-containing scaffold for VAChT ligands. Twenty new compounds with ALogD values between 0.53 and 3.2 were synthesized, and their in vitro binding affinities were assayed. Six of them (19a, 19e, 19g, 19k, and 24a-b) displayed high affinity for VAChT (Ki = 0.93-18 nM for racemates) and moderate to high selectivity for VAChT over sigma1 and sigma2 receptors (Ki = 44-4400-fold). These compounds have a methyl or a fluoro substitution that provides the position for incorporating PET radioisotopes C-11 or F-18. Compound (-)-[(11)C]24b (Ki = 0.78 nM for VAChT, 1200-fold over sigma receptors) was successfully synthesized and evaluated in vivo in rats and nonhuman primates. The data revealed that (-)-[(11)C]24b has highest binding in striatum and has favorable pharmacokinetics in the brain. Title: Drosophila Neuroligin 4 Regulates Sleep through Modulating GABA Transmission Li Y, Zhou Z, Zhang X, Tong H, Li P, Zhang ZC, Jia Z, Xie W, Han J Ref: Journal of Neuroscience, 33:15545, 2013 : PubMed ESTHER: Li_2013_J.Neurosci_33_15545 PubMedSearch: Li 2013 J.Neurosci 33 15545 PubMedID: 24068821 Gene_locus related to this paper: drome-b6idz4 Abstract Sleep is an essential and evolutionarily conserved behavior that is closely related to synaptic function. However, whether neuroligins (Nlgs), which are cell adhesion molecules involved in synapse formation and synaptic transmission, are involved in sleep is not clear. Here, we show that Drosophila Nlg4 (DNlg4) is highly expressed in large ventral lateral clock neurons (l-LNvs) and that l-LNv-derived DNlg4 is essential for sleep regulation. GABA transmission is impaired in mutant l-LNv, and sleep defects in dnlg4 mutant flies can be rescued by genetic manipulation of GABA transmission. Furthermore, dnlg4 mutant flies exhibit a severe reduction in GABAA receptor RDL clustering, and DNlg4 associates with RDLs in vivo. These results demonstrate that DNlg4 regulates sleep through modulating GABA transmission in l-LNvs, which provides the first known link between a synaptic adhesion molecule and sleep in Drosophila. Title: Organophosphate and pyrethroid hydrolase activities of mutant Esterases from the cotton bollworm Helicoverpa armigera Li Y, Farnsworth CA, Coppin CW, Teese MG, Liu JW, Scott C, Zhang X, Russell RJ, Oakeshott JG Ref: PLoS ONE, 8:e77685, 2013 : PubMed ESTHER: Li_2013_PLoS.One_8_e77685 PubMedSearch: Li 2013 PLoS.One 8 e77685 PubMedID: 24204917 Abstract Two mutations have been found in five closely related insect esterases (from four higher Diptera and a hymenopteran) which each confer organophosphate (OP) hydrolase activity on the enzyme and OP resistance on the insect. One mutation converts a Glycine to an Aspartate, and the other converts a Tryptophan to a Leucine in the enzymes' active site. One of the dipteran enzymes with the Leucine mutation also shows enhanced activity against pyrethroids. Introduction of the two mutations in vitro into eight esterases from six other widely separated insect groups has also been reported to increase substantially the OP hydrolase activity of most of them. These data suggest that the two mutations could contribute to OP, and possibly pyrethroid, resistance in a variety of insects. We therefore introduced them in vitro into eight Helicoverpa armigera esterases from a clade that has already been implicated in OP and pyrethroid resistance. We found that they do not generally enhance either OP or pyrethroid hydrolysis in these esterases but the Aspartate mutation did increase OP hydrolysis in one enzyme by about 14 fold and the Leucine mutation caused a 4-6 fold increase in activity (more in one case) of another three against some of the most insecticidal isomers of fenvalerate and cypermethrin. The Aspartate enzyme and one of the Leucine enzymes occur in regions of the H. armigera esterase isozyme profile that have been previously implicated in OP and pyrethroid resistance, respectively. Title: Draft genome of the wheat A-genome progenitor Triticum urartu Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L and Zhang A <39 more author(s)> Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L, Tao Y, Gao C, Wu H, Li Y, Cui Y, Guo X, Zheng S, Wang B, Yu K, Liang Q, Yang W, Lou X, Chen J, Feng M, Jian J, Zhang X, Luo G, Jiang Y, Liu J, Wang Z, Sha Y, Zhang B, Tang D, Shen Q, Xue P, Zou S, Wang X, Liu X, Wang F, Yang Y, An X, Dong Z, Zhang K, Luo MC, Dvorak J, Tong Y, Yang H, Li Z, Wang D, Zhang A (- 39) Ref: Nature, 496:87, 2013 : PubMed ESTHER: Ling_2013_Nature_496_87 PubMedSearch: Ling 2013 Nature 496 87 PubMedID: 23535596 Gene_locus related to this paper: triua-m8a764, triua-m8ag96, triua-m7zp69, wheat-w5d1z6, wheat-w5d232, wheat-w5bnf5, triua-t1nm05, wheat-w5cae4, triua-m7ytf7, wheat-w5f1j8, triua-m8ad49, wheat-a0a077s1q2, wheat-a0a3b6c2m6, triua-m7zi26, wheat-a0a3b6at77 Abstract Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat. Title: Acetylcholinesterase immobilized capillary reactors coupled to protein coated magnetic beads: A new tool for plant extract ligand screening Lourenco Vanzolini K, Jiang Z, Zhang X, Curcino Vieira LC, Goncalvez Correa A, Lucia Cardoso C, Bezerra Cass Q, Moaddel R Ref: Talanta, 116:647, 2013 : PubMed ESTHER: Lourenco_2013_Talanta_116_647 PubMedSearch: Lourenco 2013 Talanta 116 647 PubMedID: 24148457 Abstract The use of immobilized capillary enzyme reactors (ICERs) and enzymes coated to magnetic beads ((NT or CT)-MB) for ligand screening has been adopted as a new technique of high throughput screening (HTS). In this work the selected target was the enzyme acetylcholinesterase (AChE), which acts on the central nervous system and is a validated target for the treatment of Alzheimer's disease, as well as for new insecticides. A new approach for the screening of plant extracts was developed based on the ligand fishing experiments and zonal chromatography. For that, the magnetic beads were used for the ligand fishing experiments and capillary bioreactors for the activity assays. The latter was employed also under non-linear conditions to determine the affinity constants of known ligands, for the first time, as well as for the active fished ligand. Title: Synaptic acetylcholinesterase targeted by microRNA-212 functions as a tumor suppressor in non-small cell lung cancer Lu L, Zhang X, Zhang B, Wu J Ref: International Journal of Biochemistry & Cell Biology, 45:2530, 2013 : PubMed ESTHER: Lu_2013_Int.J.Biochem.Cell.Biol_45_2530 PubMedSearch: Lu 2013 Int.J.Biochem.Cell.Biol 45 2530 PubMedID: 23974008 Abstract Acetylcholinesterase expression is modulated in various types of tumor, which suggests it is associated with tumor development; however, the mechanism of acetylcholinesterase gene regulation in tumors remains unclear. Here, we report that acetylcholinesterase is aberrantly expressed in non-small cell lung cancer and is an evolutionarily conserved functional target of miR-212. Acetylcholinesterase expression was negatively regulated by miR-212 in vitro and was inversely correlated with miR-212 expression in vivo. In addition, acetylcholinesterase levels were increased, and miR-212 levels decreased, in non-small cell lung cancer cells during cisplatin-induced apoptosis. We further determined that acetylcholinesterase acted as a pro-apoptotic gene in non-small cell lung cells; and attenuated the growth of xenografts in nude mice when upregulated. In contrast, elevated miR-212 levels preserved the protective effect of acetylcholinesterase silencing by RNA interference against cisplatin-induced apoptosis, whereas restoration of miR-212-resistant synaptic acetylcholinesterase expression inhibited the miR-212 anti-apoptotic function. The results demonstrated that miR-212 exerted an anti-apoptotic effect through direct repression of synaptic acetylcholinesterase expression in non-small cell lung cancer cells. Taken together, our study revealed that synaptic acetylcholinesterase may be a tumor suppressor and is modulated by miR-212 in non-small cell lung cancer. Title: In vitro and in vivo characterization of a novel soluble epoxide hydrolase inhibitor Podolin PL, Bolognese BJ, Foley JF, Long E, 3rd, Peck B, Umbrecht S, Zhang X, Zhu P, Schwartz B and Callahan JF <16 more author(s)> Podolin PL, Bolognese BJ, Foley JF, Long E, 3rd, Peck B, Umbrecht S, Zhang X, Zhu P, Schwartz B, Xie W, Quinn C, Qi H, Sweitzer S, Chen S, Galop M, Ding Y, Belyanskaya SL, Israel DI, Morgan BA, Behm DJ, Marino JP, Jr., Kurali E, Barnette MS, Mayer RJ, Booth-Genthe CL, Callahan JF (- 16) Ref: Prostaglandins Other Lipid Mediat, 104-105:25, 2013 : PubMed ESTHER: Podolin_2013_Prostaglandins.Other.Lipid.Mediat_104-105_25 PubMedSearch: Podolin 2013 Prostaglandins.Other.Lipid.Mediat 104-105 25 PubMedID: 23434473 Inhibitor(s) related to this paper: GSK2256294A Abstract Soluble epoxide hydrolase (sEH, EPHX2) metabolizes eicosanoid epoxides, including epoxyeicosatrienoic acids (EETs) to the corresponding dihydroxyeicosatrienoic acids (DHETs), and leukotoxin (LTX) to leukotoxin diol (LTX diol). EETs, endothelium-derived hyperpolarizing factors, exhibit potentially beneficial properties, including anti-inflammatory effects and vasodilation. A novel, potent, selective inhibitor of recombinant human, rat and mouse sEH, GSK2256294A, exhibited potent cell-based activity, a concentration-dependent inhibition of the conversion of 14,15-EET to 14,15-DHET in human, rat and mouse whole blood in vitro, and a dose-dependent increase in the LTX/LTX diol ratio in rat plasma following oral administration. Mice receiving 10 days of cigarette smoke exposure concomitant with oral administration of GSK2256294A exhibited significant, dose-dependent reductions in pulmonary leukocytes and keratinocyte chemoattractant (KC, CXCL1) levels. Mice receiving oral administration of GSK2256294A following 10 days of cigarette smoke exposure exhibited significant reductions in pulmonary leukocytes compared to vehicle-treated mice. These data indicate that GSK2256294A attenuates cigarette smoke-induced inflammation by both inhibiting its initiation and/or maintenance and promoting its resolution. Collectively, these data indicate that GSK2256294A would be an appropriate agent to evaluate the role of sEH in clinical studies, for example in diseases where cigarette smoke is a risk factor, such as chronic obstructive pulmonary disease (COPD) and cardiovascular disease. Title: Pan genome of the phytoplankton Emiliania underpins its global distribution Read BA, Kegel J, Klute MJ, Kuo A, Lefebvre SC, Maumus F, Mayer C, Miller J, Monier A and Grigoriev IV <27 more author(s)> Read BA, Kegel J, Klute MJ, Kuo A, Lefebvre SC, Maumus F, Mayer C, Miller J, Monier A, Salamov A, Young J, Aguilar M, Claverie JM, Frickenhaus S, Gonzalez K, Herman EK, Lin YC, Napier J, Ogata H, Sarno AF, Shmutz J, Schroeder D, de Vargas C, Verret F, von Dassow P, Valentin K, Van de Peer Y, Wheeler G, Dacks JB, Delwiche CF, Dyhrman ST, Glockner G, John U, Richards T, Worden AZ, Zhang X, Grigoriev IV (- 27) Ref: Nature, 499:209, 2013 : PubMed ESTHER: Read_2013_Nature_499_209 PubMedSearch: Read 2013 Nature 499 209 PubMedID: 23760476 Abstract Coccolithophores have influenced the global climate for over 200 million years. These marine phytoplankton can account for 20 per cent of total carbon fixation in some systems. They form blooms that can occupy hundreds of thousands of square kilometres and are distinguished by their elegantly sculpted calcium carbonate exoskeletons (coccoliths), rendering them visible from space. Although coccolithophores export carbon in the form of organic matter and calcite to the sea floor, they also release CO2 in the calcification process. Hence, they have a complex influence on the carbon cycle, driving either CO2 production or uptake, sequestration and export to the deep ocean. Here we report the first haptophyte reference genome, from the coccolithophore Emiliania huxleyi strain CCMP1516, and sequences from 13 additional isolates. Our analyses reveal a pan genome (core genes plus genes distributed variably between strains) probably supported by an atypical complement of repetitive sequence in the genome. Comparisons across strains demonstrate that E. huxleyi, which has long been considered a single species, harbours extensive genome variability reflected in different metabolic repertoires. Genome variability within this species complex seems to underpin its capacity both to thrive in habitats ranging from the equator to the subarctic and to form large-scale episodic blooms under a wide variety of environmental conditions. Title: Draft Genome Sequence of Medium-Chain-Length Polyhydroxyalkanoate-Producing Pseudomonas putida Strain LS46 Sharma PK, Fu J, Zhang X, Fristensky BW, Davenport K, Chain PS, Sparling R, Levin DB Ref: Genome Announc, 1:e0015113, 2013 : PubMed ESTHER: Sharma_2013_Genome.Announc_1_e0015113 PubMedSearch: Sharma 2013 Genome.Announc 1 e0015113 PubMedID: 23599293 Gene_locus related to this paper: psepu-PIP, psepu-PP1500, psepu-PP4249, psepu-q9wwz4 Abstract We describe the draft genome sequence of Pseudomonas putida strain LS46, a novel isolate that synthesizes medium-chain-length polyhydroxyalkanoates. The draft genome of P. putida LS46 consists of approximately 5.86 million bp, with a G+C content of 61.69%. A total of 5,316 annotated genes and 5,219 coding sequences (CDS) were identified. Title: Heterologous expression and characterization of a malathion-hydrolyzing carboxylesterase from a thermophilic bacterium, Alicyclobacillus tengchongensis Xie Z, Xu B, Ding J, Liu L, Zhang X, Li J, Huang Z Ref: Biotechnol Lett, 35:1283, 2013 : PubMed ESTHER: Xie_2013_Biotechnol.Lett_35_1283 PubMedSearch: Xie 2013 Biotechnol.Lett 35 1283 PubMedID: 23801110 Gene_locus related to this paper: 9bacl-j9e7t9 Abstract A carboxylesterase gene from thermophilic bacterium, Alicyclobacillus tengchongensis, was cloned and expressed in Escherichia coli BL21 (DE3). The gene coded for a 513 amino acid protein with a calculated molecular mass of 57.82 kDa. The deduced amino acid sequence had structural features highly conserved among serine hydrolases, including Ser204, Glu325, and His415 as a catalytic triad, as well as type-B carboxylesterase serine active site (FGGDPENITIGGQSAG) and type-B carboxylesterase signature 2 (EDCLYLNIWTP). The purified enzyme exhibited optimum activity with beta-naphthyl acetate at 60 degrees C and pH 7 as well as stability at 25 degrees C and pH 7. One unit of the enzyme hydrolyzed 5 mg malathion l(-1) by 50 % within 25 min and 89 % within 100 min. The enzyme strongly degraded malathion and has a potential use for the detoxification of malathion residues. Title: Preparation, characterization of Fe(3)O(4) at TiO(2) magnetic nanoparticles and their application for immunoassay of biomarker of exposure to organophosphorus pesticides Zhang X, Wang H, Yang C, Du D, Lin Y Ref: Biosensors & Bioelectronics, 41:669, 2013 : PubMed ESTHER: Zhang_2013_Biosens.Bioelectron_41_669 PubMedSearch: Zhang 2013 Biosens.Bioelectron 41 669 PubMedID: 23122753 Abstract Novel Fe(3)O(4) at TiO(2) magnetic nanoparticles were prepared and developed for a new nanoparticle-based immunosensor for electrochemical quantification of organophosphorylated butyrylcholinesterase (BChE) in plasma, a specific biomarker of exposure to organophosphorus (OP) agents. The Fe(3)O(4) at TiO(2) nanoparticles were synthesized by hydrolysis of tetrabutyltitanate on the surface of Fe(3)O(4) magnetic nanospheres, and characterized by attenuated total reflection Fourier-transform infrared spectra, transmission electron microscope and X-ray diffraction. The functional Fe(3)O(4) at TiO(2) nanoparticles were performed as capture antibody to selectively enrich phosphorylated moiety instead of phosphoserine antibody in the traditional sandwich immunoassays. The secondary recognition was performed by quantum dots (QDs)-tagged anti-BChE antibody (QDs-anti-BChE). With the help of a magnet, the resulting sandwich-like complex, Fe(3)O(4) at TiO(2)/OP-BChE/QDs-anti-BChE, was easily isolated from sample solutions and the released cadmium ions were detected on a disposable screen-printed electrode (SPE). The binding affinities were investigated by both surface plasmon resonance (SPR) and square wave voltammetry (SWV). This method not only avoids the drawback of unavailability of commercial OP-specific antibody but also amplifies detection signal by QDs-tags together with easy separation of samples by magnetic forces. The proposed immunosensor yields a linear response over a broad OP-BChE concentrations range from 0.02 to 10nM, with detection limit of 0.01nM. Moreover, the disposable nanoparticle-based immunosensor has been validated with human plasma samples. It offers a new method for rapid, sensitive, selective and inexpensive screening/evaluating exposure to OP pesticides and nerve agents. Title: Acetylcholinesterase deficiency decreases apoptosis in dopaminergic neurons in the neurotoxin model of Parkinson's disease Zhang X, Lu L, Liu S, Ye W, Wu J Ref: International Journal of Biochemistry & Cell Biology, 45:265, 2013 : PubMed ESTHER: Zhang_2013_Int.J.Biochem.Cell.Biol_45_265 PubMedSearch: Zhang 2013 Int.J.Biochem.Cell.Biol 45 265 PubMedID: 23201480 Abstract The apoptosis pathway has been proposed to be involved in causing neuronal cell death in the pathogenesis of Parkinson's disease. However, the details of this pathway are poorly understood. Previous research has shown increased acetylcholinesterase expression during apoptosis in various cell types, which suggests that acetylcholinesterase has a potential role in neuronal cell death. In this study, we found that acetylcholinesterase protein expression increased and caspase-3 was activated in PC12 cells treated with 1-methyl-4-phenylpyridinium. Furthermore, the genetic or pharmacological inhibition of acetylcholinesterase was shown to protect PC12 cells from MPP+ induced apoptotic cell death. To study the function of acetylcholinesterase as a mechanism of neuronal cell death in vivo, we subsequently established a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Parkinson's disease mouse model utilizing acetylcholinesterase-deficient mice. Studies in these mice revealed reduced dopaminergic neuron loss and lower expression levels of apoptotic proteins in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated heterozygous mice compared to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated wild-type mice. We conclude that it is highly probable that acetylcholinesterase is involved in the pathogenesis of the neurotoxin model of Parkinson's disease via apoptosis. Specifically, a deficiency or inhibition of acetylcholinesterase can decrease apoptosis and protect dopaminergic neurons in the neurotoxin model of Parkinson's disease. Title: Epimediphine, a novel alkaloid from Epimedium koreanum inhibits acetylcholinesterase Zhang X, Oh M, Kim S, Kim J, Kim H, Houghton PJ, Whang W Ref: Nat Prod Res, 27:1067, 2013 : PubMed ESTHER: Zhang_2013_Nat.Prod.Res_27_1067 PubMedSearch: Zhang 2013 Nat.Prod.Res 27 1067 PubMedID: 22823459 Abstract A novel aporphine alkaloid was isolated from the leaves of Epimedium koreanum Nakai during activity-guided fractionation in search of compounds with an anticholinesterase activity. The structure of the new compound was assigned as 1,10-methoxy-7-hydroxy-aporphine (1), which we have named epimediphine. Unambiguous (1)H-NMR and (13)C-NMR data for epimediphine are described. Epimediphine inhibited an acetylcholinesterase (AchE) activity in a dose-dependent manner with an IC50 value of 3.1 microM. Meanwhile, tacrine, dehydroevodiamine and physostigmine, which are therapeutic drugs or candidates for AD, exhibited an anti-AchE activity with IC50 values of 0.4, 37.9 and 0.12 microM, respectively. Title: Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X and Meng J <2 more author(s)> Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X, Allard M, Brown E, Meng J (- 2) Ref: Genome Announc, 1:E00213, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00213 PubMedSearch: Zhang 2013 Genome.Announc 1 E00213 PubMedID: 23661485 Gene_locus related to this paper: salty-STY1441 Abstract Salmonellosis contributes significantly to the public health burden globally. Salmonella enterica serotype Newport is among Salmonella serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four S. Newport strains isolated from humans in China. Title: First report of a sequence type 239 vancomycin-intermediate Staphylococcus aureus isolate in Mainland China Zhang X, Hu Q, Yuan W, Shang W, Cheng H, Yuan J, Zhu J, Hu Z, Li S and Rao X <2 more author(s)> Zhang X, Hu Q, Yuan W, Shang W, Cheng H, Yuan J, Zhu J, Hu Z, Li S, Chen W, Hu X, Rao X (- 2) Ref: Diagn Microbiol Infect Dis, 77:64, 2013 : PubMed ESTHER: Zhang_2013_Diagn.Microbiol.Infect.Dis_77_64 PubMedSearch: Zhang 2013 Diagn.Microbiol.Infect.Dis 77 64 PubMedID: 23876353 Abstract Methicillin-resistant Staphylococcus aureus (MRSA) is an important pathogen that causes a wide range of both hospital- and community-acquired infections. The high prevalence of MRSA and the extensive use of vancomycin in Mainland China may lead to the emergence of vancomycin-intermediate S. aureus (VISA) isolates. In this case, we report a VISA isolate from a 34-year-old male patient with steam burn. The isolate was determined to be sequence type 239 staphylococcal cassette chromosome mec type III, the most prevalent MRSA clone in Mainland China. Title: Solvent-free enzymatic synthesis of 1, 3-diacylglycerols by direct esterification of glycerol with saturated fatty acids Zhong N, Gui Z, Xu L, Huang J, Hu K, Gao Y, Zhang X, Xu Z, Su J, Li B Ref: Lipids Health Dis, 12:65, 2013 : PubMed ESTHER: Zhong_2013_Lipids.Health.Dis_12_65 PubMedSearch: Zhong 2013 Lipids.Health.Dis 12 65 PubMedID: 23656739 Abstract BACKGROUND: Pure 1, 3-diacylglycerols (1, 3-DAG) have been considered to be significant surfactants in food, cosmetics and pharmaceutical industries, as well as the effect on obesity prevention. METHODS: In this study, a vacuum-driven air bubbling operation mode was developed and evaluated for the enzymatic synthesis of 1, 3-DAG of saturated fatty acids, by direct esterification of glycerol with fatty acids in a solvent-free system. The employed vacuum-driven air bubbling operation mode was comparable to vacuum-driven N2 bubbling protocol, in terms of lauric acid conversion and 1, 3-dilaurin content. RESULTS: Some operation parameters were optimized, and 95.3% of lauric acid conversion and 80.3% of 1, 3-dilaurin content was obtained after 3-h reaction at 50 degC, with 5 wt% of Lipozyme RM IM (based on reactants) amount. Of the lipases studied, both Lipozyme RM IM and Novozym 435 exhibited good performance in terms of lauric acid conversion. Lipozyme TL IM, however, showed low activity. Lipozyme RM IM showed good operational stability in this operation protocol, 80.2% of the original catalytic activity remained after 10 consecutive batch applications. Some other 1, 3-DAG were prepared and high content was obtained after purification: 98.5% for 1, 3-dicaprylin, 99.2% for 1, 3-dicaprin, 99.1% for 1, 3-dilaurin, 99.5 for 1, 3-dipalmitin and 99.4% for 1, 3-disterin. CONCLUSION: The established vacuum-driven air bubbling operation protocol had been demonstrated to be a simple-operating, cost-effective, application practical and efficient methodology for 1, 3-DAG preparation. Title: D14-SCFD3-dependent degradation of D53 regulates strigolactone signalling Zhou F, Lin Q, Zhu L, Ren Y, Zhou K, Shabek N, Wu F, Mao H, Dong W and Wan J <24 more author(s)> Zhou F, Lin Q, Zhu L, Ren Y, Zhou K, Shabek N, Wu F, Mao H, Dong W, Gan L, Ma W, Gao H, Chen J, Yang C, Wang D, Tan J, Zhang X, Guo X, Wang J, Jiang L, Liu X, Chen W, Chu J, Yan C, Ueno K, Ito S, Asami T, Cheng Z, Lei C, Zhai H, Wu C, Wang H, Zheng N, Wan J (- 24) Ref: Nature, 504:406, 2013 : PubMed ESTHER: Zhou_2013_Nature_504_406 PubMedSearch: Zhou 2013 Nature 504 406 PubMedID: 24336215 Abstract Strigolactones (SLs), a newly discovered class of carotenoid-derived phytohormones, are essential for developmental processes that shape plant architecture and interactions with parasitic weeds and symbiotic arbuscular mycorrhizal fungi. Despite the rapid progress in elucidating the SL biosynthetic pathway, the perception and signalling mechanisms of SL remain poorly understood. Here we show that DWARF 53 (D53) acts as a repressor of SL signalling and that SLs induce its degradation. We find that the rice (Oryza sativa) d53 mutant, which produces an exaggerated number of tillers compared to wild-type plants, is caused by a gain-of-function mutation and is insensitive to exogenous SL treatment. The D53 gene product shares predicted features with the class I Clp ATPase proteins and can form a complex with the alpha/beta hydrolase protein DWARF 14 (D14) and the F-box protein DWARF 3 (D3), two previously identified signalling components potentially responsible for SL perception. We demonstrate that, in a D14- and D3-dependent manner, SLs induce D53 degradation by the proteasome and abrogate its activity in promoting axillary bud outgrowth. Our combined genetic and biochemical data reveal that D53 acts as a repressor of the SL signalling pathway, whose hormone-induced degradation represents a key molecular link between SL perception and responses. Title: The key role of a non-active-site residue Met148 on the catalytic efficiency of meta-cleavage product hydrolase BphD Zhou H, Qu Y, Kong C, Shen E, Wang J, Zhang X, Ma Q, Zhou J Ref: Applied Microbiology & Biotechnology, 97:10399, 2013 : PubMed ESTHER: Zhou_2013_Appl.Microbiol.Biotechnol_97_10399 PubMedSearch: Zhou 2013 Appl.Microbiol.Biotechnol 97 10399 PubMedID: 23494625 Abstract meta-Cleavage product (MCP) hydrolases (EC 3.7.1.9) can catalyze a specific C-C bond fission during the microbial aerobic degradation of aromatics. The previous studies on structure-function relationship of MCP hydrolases mainly focus on the active site residues by site-directed mutagenesis. However, the information about the role of the non-active-site residues is still unclear. In this study, a non-active-site residue Met148 of MCP hydrolase BphD was selected as the mutagenesis site according to the sequence alignments, structure superimpose and the tunnel analysis, which underwent the saturation mutagenesis resulting 19 mutants. The catalytic efficiencies of the mutants on 6-oxo-6-phenylhexa-2,4-dienoic acid (HOPDA) were all decreased compared with the wild-type one except for the M148D mutant. Especially, the M148P mutant exhibited 290-fold lower k cat/K m than that of the wild-type BphD. Transient kinetic analyses of M148P showed the reciprocal relaxation time corresponded to C-C bond cleavage and product release steps (9.6 s(-1)) was 4.08-fold lower than BphD WT (39.2 s(-1)). Tunnel cluster analysis of BphD WT, M148P and M148W demonstrated that only the bulky Trp148 could block tunnel T2 in the BphD WT, but it exhibited slight effects on the catalytic efficiency (0.94-fold of BphD WT). Therefore, product release was not the main reason for the efficiency decrease of M148P. On the other hand, molecular dynamics simulations on the BphD WT and BphD M148P in complex with HOPDA indicated that the dramatic decrease of the catalytic efficiencies of BphD M148P should be due to the unproductive binding of HOPDA. The study demonstrated the catalytic efficiency of MCP hydrolase can be engineered by modification of non-active site residue. Title: Identification and characterization of novel esterases from a deep-sea sediment metagenome Jiang X, Xu X, Huo Y, Wu Y, Zhu X, Zhang X, Wu M Ref: Arch Microbiol, 194:207, 2012 : PubMed ESTHER: Jiang_2012_Arch.Microbiol_194_207 PubMedSearch: Jiang 2012 Arch.Microbiol 194 207 PubMedID: 21861153 Gene_locus related to this paper: 9bact-H6BDX1, 9bact-h6bdx2 Abstract A deep-sea sediment metagenomic library was constructed and screened for lipolytic enzymes by activity-based approach. Nine novel lipolytic enzymes were identified, and the amino acid sequences shared 56% to 84% identity to other lipolytic enzymes in the database. Phylogenetic analysis showed that these enzymes belonged to family IV lipolytic enzymes. One of the lipolytic enzymes, Est6, was successfully cloned and expressed in Escherichia coli Rosetta in a soluble form. The recombinant protein was purified by Ni-nitrilotriacetic affinity chromatography column and characterized using p-nitrophenyl esters with various chain lengths. The est6 gene consisted of 909 bp that encoded 302 amino acid residues. Est6 was most similar to a lipolytic enzyme from uncultured bacterium (ACL67845, 61% identity) isolated from the South China Sea marine sediment metagenome. The characterization of Est6 revealed that it was a cold-active esterase and exhibited the highest activity toward p-nitrophenyl butyrate (C4) at 20 degrees C and pH 7.5. Title: Cloning, expression and characterization of a halotolerant esterase from a marine bacterium Pelagibacterium halotolerans B2T Jiang X, Huo Y, Cheng H, Zhang X, Zhu X, Wu M Ref: Extremophiles, 16:427, 2012 : PubMed ESTHER: Jiang_2012_Extremophiles_16_427 PubMedSearch: Jiang 2012 Extremophiles 16 427 PubMedID: 22481638 Gene_locus related to this paper: pelhb-g4rec9 Abstract An esterase PE10 (279 aa) from Pelagibacterium halotolerans B2(T) was cloned and overexpressed in Escherichia coli Rosetta in a soluble form. The deduced protein was 29.91 kDa and the phylogenetic analysis of the deduced amino acids sequence showed it represented a new family of lipolytic enzymes. The recombinant protein was purified by Ni-NTA affinity chromatography column and the characterization showed its optimal temperature and pH were 45 degrees C and pH 7.5, respectively. Substrate specificity study showed PE10 preferred short chain p-nitrophenyl esters and exhibited maximum activity toward p-nitrophenyl acetate. In addition, PE10 was a halotolerant esterase as it was still active under 4 M NaCl. Three-dimensional modeling of PE10 suggested that the high negative electrostatic potential on the surface may relevant to its tolerance to high salt environment. With this halotolerance property, PE10 could be a candidate for industrial use. Title: Genome organization, phylogenies, expression patterns, and three-dimensional protein models of two acetylcholinesterase genes from the red flour beetle Lu Y, Pang YP, Park Y, Gao X, Yao J, Zhang X, Zhu KY Ref: PLoS ONE, 7:e32288, 2012 : PubMed ESTHER: Lu_2012_PLoS.One_7_e32288 PubMedSearch: Lu 2012 PLoS.One 7 e32288 PubMedID: 22359679 Abstract Since the report of a paralogous acetylcholinesterase (AChE, EC3.1.1.7) gene in the greenbug (Schizaphis graminum) in 2002, two different AChE genes (Ace1 and Ace2) have been identified in each of at least 27 insect species. However, the gene models of Ace1 and Ace2, and their molecular properties have not yet been comprehensively analyzed in any insect species. In this study, we sequenced the full-length cDNAs, computationally predicted the corresponding three-dimensional protein models, and profiled developmental stage and tissue-specific expression patterns of two Ace genes from the red flour beetle (Tribolium castaneum; TcAce1 and TcAce2), a globally distributed major pest of stored grain products and an emerging model organism. TcAce1 and TcAce2 encode 648 and 604 amino acid residues, respectively, and have conserved motifs including a choline-binding site, a catalytic triad, and an acyl pocket. Phylogenetic analysis show that both TcAce genes are grouped into two insect Ace clusters and TcAce1 is completely diverged from TcAce2, suggesting that these two genes evolve from their corresponding Ace gene lineages in insect species. In addition, TcAce1 is located on chromosome 5, whereas TcAce2 is located on chromosome 2. Reverse transcription polymerase chain reaction (PCR) and quantitative real-time PCR analyses indicate that both genes are virtually transcribed in all the developmental stages and predominately expressed in the insect brain. Our computational analyses suggest that the TcAce1 protein is a robust acetylcholine (ACh) hydrolase and has susceptibility to sulfhydryl agents whereas the TcAce2 protein is not a catalytically efficient ACh hydrolase. Title: Cholinergic and non-cholinergic functions of two acetylcholinesterase genes revealed by gene-silencing in Tribolium castaneum Lu Y, Park Y, Gao X, Zhang X, Yao J, Pang YP, Jiang H, Zhu KY Ref: Sci Rep, 2:288, 2012 : PubMed ESTHER: Lu_2012_Sci.Rep_2_288 PubMedSearch: Lu 2012 Sci.Rep 2 288 PubMedID: 22371826 Abstract We compared biological functions of two acetylcholinesterase genes (TcAce1 and TcAce2) in Tribolium castaneum, a globally distributed major pest of stored grain products and an emerging model organism, by using RNA interference. Although both genes expressed at all developmental stages and mainly in the brain, the transcript level of TcAce1 was 1.2- to 8.7-fold higher than that of TcAce2, depending on developmental stages. Silencing TcAce1 in 20-day larvae led to 100% mortality within two weeks after eclosion and increased larval susceptibilities to anticholinesterase insecticides. In contrast, silencing TcAce2 did not show insect mortality and significantly affect insecticide susceptibility, but delayed insect development and reduced female egg-laying and egg hatching. These results demonstrate for the first time that TcAce1 plays a major role in cholinergic functions and is the target of anticholinesterase insecticides, whereas TcAce2 plays an important, non-cholinergic role in female reproduction, embryo development, and growth of offspring. Title: Acetylcholinesterase blocks cleavage of APP by gamma-secretase in 293 cells and mouse brain Niu X, Zhang X, Xie J Ref: Mol Neurodegener, 7 Suppl 1:S11, 2012 : PubMed Title: Comparative genomics of the classical Bordetella subspecies: the evolution and exchange of virulence-associated diversity amongst closely related pathogens Park J, Zhang Y, Buboltz AM, Zhang X, Schuster SC, Ahuja U, Liu M, Miller JF, Sebaihia M and Harvill ET <2 more author(s)> Park J, Zhang Y, Buboltz AM, Zhang X, Schuster SC, Ahuja U, Liu M, Miller JF, Sebaihia M, Bentley SD, Parkhill J, Harvill ET (- 2) Ref: BMC Genomics, 13:545, 2012 : PubMed ESTHER: Park_2012_BMC.Genomics_13_545 PubMedSearch: Park 2012 BMC.Genomics 13 545 PubMedID: 23051057 Gene_locus related to this paper: borbr-BB0273 Abstract BACKGROUND: The classical Bordetella subspecies are phylogenetically closely related, yet differ in some of the most interesting and important characteristics of pathogens, such as host range, virulence and persistence. The compelling picture from previous comparisons of the three sequenced genomes was of genome degradation, with substantial loss of genome content (up to 24%) associated with adaptation to humans. Title: Synthesis and evaluation of in vitro bioactivity for vesicular acetylcholine transporter inhibitors containing two carbonyl groups Tu Z, Wang W, Cui J, Zhang X, Lu X, Xu J, Parsons SM Ref: Bioorganic & Medicinal Chemistry, 20:4422, 2012 : PubMed ESTHER: Tu_2012_Bioorg.Med.Chem_20_4422 PubMedSearch: Tu 2012 Bioorg.Med.Chem 20 4422 PubMedID: 22739089 Abstract To identify selective high-affinity ligands for the vesicular acetylcholine transporter (VAChT), we have incorporated a carbonyl group into the structures of trozamicol and prezamicol scaffolds, and also converted the secondary amines of the piperidines of trozamicols and prezamicols into amides. Of 18 new racemic compounds, 4 compounds displayed high affinity for VAChT (K(i)=10-20 nM) and greater than 300-fold selectivity for VAChT over sigma(1) and sigma(2) receptors, namely (4-(4-fluorobenzoyl)-4'-hydroxy-[1,3'-bipiperidin]-1'-yl)(3-methylthiophen-2-yl)m ethanone oxalate (9g) (K(i-VAChT)=11.4 nM, VAChT/sigma(1)=1063, VAChT/sigma(2)=370), (1'-benzoyl-4'-hydroxy-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)methanone oxalate (10c) (K(i-VAChT)=15.4 nM, VAChT/sigma(1)=374, VAChT/sigma(2)=315), (4'-hydroxy-1'-(thiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)me thanone oxalate (10e) (K(i-VAChT)=19.0 nM, VAChT/sigma(1)=1787, VAChT/sigma(2)=335), and (4'-hydroxy-1'-(3-methylthiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyp henyl)methanone oxalate (10g) (K(i-VAChT)=10.2 nM, VAChT/sigma(1)=1500, VAChT/sigma(2)=2030). These four compounds can be radiosynthesized with C-11 or F-18 to validate their possibilities of serving as PET probes for quantifying the levels of VAChT in vivo. Title: Novel pyrrolopyrimidine analogues as potent dipeptidyl peptidase IV inhibitors based on pharmacokinetic property-driven optimization Xie H, Zeng L, Zeng S, Lu X, Zhang G, Zhao X, Cheng N, Tu Z, Li Z and Hu W <5 more author(s)> Xie H, Zeng L, Zeng S, Lu X, Zhang G, Zhao X, Cheng N, Tu Z, Li Z, Xu H, Yang L, Zhang X, Huang M, Zhao J, Hu W (- 5) Ref: Eur Journal of Medicinal Chemistry, 52:205, 2012 : PubMed ESTHER: Xie_2012_Eur.J.Med.Chem_52_205 PubMedSearch: Xie 2012 Eur.J.Med.Chem 52 205 PubMedID: 22475866 Inhibitor(s) related to this paper: Alogliptin Abstract We previously reported a highly potent DPP-IV inhibitor 6 with low in vivo efficacy. While trying to maintain consistent in vitro and in vivo biological activity, we initiated a pharmacokinetic property-driven optimization to improve the metabolic stability and permeability of inhibitor 6. A simple scaffold replacement of thienopyrimidine with pyrrolopyrimidine (21a) led to significantly improved metabolic stability (4% vs. 65% remaining). Further modification of the pyrrolopyrimidine scaffold to produce compound 21j resulted in much better oral bioavailability than 6. Importantly, compound 21j exhibits greater in vivo efficacy than does 6 and Alogliptin and is worthy of further development. Title: Acetylcholinesterase responsive polymeric supra-amphiphiles for controlled self-assembly and disassembly Xing Y, Wang C, Han P, Wang Z, Zhang X Ref: Langmuir, 28:6032, 2012 : PubMed ESTHER: Xing_2012_Langmuir_28_6032 PubMedSearch: Xing 2012 Langmuir 28 6032 PubMedID: 22404254 Abstract We have fabricated enzyme responsive polymeric supra-amphiphiles by mixing a block copolymer of poly(ethylene glycol)-block-poly(acrylic acid) with myristoylcholine chloride in water. The polymeric supra-amphiphiles self-assemble into spherical aggregates with sizes varying from about 40 to 150 nm. Moreover, the spherical aggregates can be disassembled triggered by acetylcholinesterase, an enzyme which can cut off the ester linkage of myristoylcholine chloride. Nile red can be loaded into the spherical aggregates and released in several hours upon the treatment of acetylcholinesterase. The releasing rate is rather fast considering that it takes more than 150 h for Nile red to diffuse out of the spherical aggregates without addition of acetylcholinesterase. It is anticipated that the new enzyme responsive polymeric supra-amphiphile may be explored as a carrier for drug delivery. Title: An aporphine alkaloid from Nelumbo nucifera as an acetylcholinesterase inhibitor and the primary investigation for structure-activity correlations Yang ZD, Zhang X, Du J, Ma ZJ, Guo F, Li S, Yao XJ Ref: Nat Prod Res, 26:387, 2012 : PubMed ESTHER: Yang_2012_Nat.Prod.Res_26_387 PubMedSearch: Yang 2012 Nat.Prod.Res 26 387 PubMedID: 21732870 Abstract N-methylasimilobine (1), a new-found strong acetylcholinesterase (AChE) inhibitor, along with two weakly active aporphine alkaloids, nuciferine (2) and nornuciferine (3) were separated from Nelumbo nucifera. N-methylasimilobine (1) inhibited 50% of AChE activity at the concentrations of 1.5 +/- 0.2 microg mL(-1) when the standard IC(50) value of Physostigmine was 0.013 +/- 0.002 microg mL(-1). The mode of AChE inhibition by 1 was reversible and non-competitive. In addition, molecular modelling was performed to explore the binding mode of inhibitor 1 at the active site of AChE. Title: Acetylcholinesterase is associated with apoptosis in beta cells and contributes to insulin-dependent diabetes mellitus pathogenesis Zhang B, Yang L, Yu L, Lin B, Hou Y, Wu J, Huang Q, Han Y, Guo L and Zhang X <2 more author(s)> Zhang B, Yang L, Yu L, Lin B, Hou Y, Wu J, Huang Q, Han Y, Guo L, Ouyang Q, Lu L, Zhang X (- 2) Ref: Acta Biochim Biophys Sin (Shanghai), 44:207, 2012 : PubMed ESTHER: Zhang_2012_Acta.Biochim.Biophys.Sin.(Shanghai)_44_207 PubMedSearch: Zhang 2012 Acta.Biochim.Biophys.Sin.(Shanghai) 44 207 PubMedID: 22236578 Abstract Acetylcholinesterase (AChE) expression is pivotal during apoptosis. Indeed, AChE inhibitors partially protect cells from apoptosis. Insulin-dependent diabetes mellitus (IDDM) is characterized in part by pancreatic beta-cell apoptosis. Here, we investigated the role of AChE in the development of IDDM and analyzed protective effects of AChE inhibitors. Multiple low-dose streptozotocin (MLD-STZ) administration resulted in IDDM in a mouse model. Western blot analysis, cytochemical staining, and immunofluorescence staining were used to detect AChE expression in MIN6 cells, primary beta cells, and apoptotic pancreatic beta cells of MLD-STZ-treated mice. AChE inhibitors were administered intraperitoneally to the MLD-STZ mice for 30 days. Blood glucose, plasma insulin, and creatine levels were measured, and glucose tolerance tests were performed. The effects of AChE inhibitors on MIN6 cells were also evaluated. AChE expression was induced in the apoptotic MIN6 cells and primary beta cells in vitro and pancreatic islets in vivo when treated with STZ. Induction and progressive accumulation of AChE in the pancreatic islets were associated with apoptotic beta cells during IDDM development. The administration of AChE inhibitors effectively decreased hyperglycemia and incidence of diabetes, and restored plasma insulin levels and plasma creatine clearance in the MLD-STZ mice. AChE inhibitors partially protected MIN6 cells from the damage caused by STZ treatment. Induction and accumulation of AChE in pancreatic islets and the protective effects of AChE inhibitors on the onset and development of IDDM indicate a close relationship between AChE and IDDM. Title: Endothelial lipase mediates HDL levels in normal and hyperlipidemic rabbits Zhang J, Yu Y, Nakamura K, Koike T, Waqar AB, Zhang X, Liu E, Nishijima K, Kitajima S and Fan J <9 more author(s)> Zhang J, Yu Y, Nakamura K, Koike T, Waqar AB, Zhang X, Liu E, Nishijima K, Kitajima S, Shiomi M, Qi Z, Yu J, Graham MJ, Crooke RM, Ishida T, Hirata K, Hurt-Camejo E, Chen YE, Fan J (- 9) Ref: J Atheroscler Thromb, 19:213, 2012 : PubMed ESTHER: Zhang_2012_J.Atheroscler.Thromb_19_213 PubMedSearch: Zhang 2012 J.Atheroscler.Thromb 19 213 PubMedID: 22240910 Abstract AIM: Existing evidence suggests that endothelial lipase (EL) plays an important role in high-densitylipoprotein (HDL) metabolism. Because rabbits are a useful animal model for the study of human lipid metabolism and atherosclerosis, we characterized rabbit EL (rEL) expression and investigated its relationship with plasma HDL levels in normal and hyperlipidemic rabbits. METHODS: We cloned the rEL cDNA and analyzed the EL tissue expression using Northern blotting, real-time RT-PCR, Western blotting, and in situ hybridization. We evaluated the effects of rEL antisense on plasma HDL levels. RESULTS: We found that rEL mRNA was highly expressed in cholesterol synthesis-related organs, including the liver, testis, and adrenal along with its expression in the lung, kidney, bone marrow, and small intestine. Interestingly, Watanabe heritable hyperlipidemic (WHHL) rabbits, a model of human familial hypercholesterolemia, had lower plasma levels of HDLs than normal rabbits. The plasma HDL levels in WHHL rabbits were inversely associated with high levels of plasma rEL proteins and hepatic expression of rEL mRNA. Injection of rEL-specific antisense oligonucleotides into rabbits resulted in the elevation of plasma large HDLs. Furthermore, we demonstrated that rEL mRNA was expressed by both endothelial cells and macrophages in the lesions of aortic atherosclerosis of WHHL rabbits. CONCLUSIONS: rEL is expressed in multiple tissues and may have many physiological and pathophysiological functions, such as in the regulation of cholesterol metabolism and atherosclerosis. Our results suggest that EL is an important regulator of plasma HDL levels in rabbits. Title: CutA divalent cation tolerance homolog (Escherichia coli) (CUTA) regulates beta-cleavage of beta-amyloid precursor protein (APP) through interacting with beta-site APP cleaving protein 1 (BACE1) Zhao Y, Wang Y, Hu J, Zhang X, Zhang YW Ref: Journal of Biological Chemistry, 287:11141, 2012 : PubMed ESTHER: Zhao_2012_J.Biol.Chem_287_11141 PubMedSearch: Zhao 2012 J.Biol.Chem 287 11141 PubMedID: 22351782 Abstract Accumulation of the neurotoxic beta-amyloid (Abeta) peptide in the brain is central to the pathogenesis of Alzheimer disease. Abeta is derived from the beta-amyloid precursor protein (APP) through sequential cleavages by beta- and gamma-secretases, and the production of Abeta is greatly affected by the subcellular localization of these factors. CUTA, the mammalian CutA divalent cation tolerance homolog (E. coli), has been proposed to mediate acetylcholinesterase activity and copper homeostasis, which are important in Alzheimer disease pathology. However, the exact function of CUTA remains largely unclear. Here we show that human CUTA has several variants that differ in their N-terminal length and are separated as heavy (H) and light (L) components. The H component has the longest N terminus and is membrane-associated, whereas the L component is N-terminally truncated at various sites and localized in the cytosol. Importantly, we demonstrate that the H component of CUTA interacts through its N terminus with the transmembrane domain of beta-site APP cleaving enzyme 1 (BACE1), the putative beta-secretase, mainly in the Golgi/trans-Golgi network. Overexpression and RNA interference knockdown of CUTA can reduce and increase BACE1-mediated APP processing/Abeta secretion, respectively. RNA interference of CUTA decelerates intracellular trafficking of BACE1 from the Golgi/trans-Golgi network to the cell surface and reduces the steady-state level of cell surface BACE1. Our results identify the H component of CUTA as a novel BACE1-interacting protein that mediates the intracellular trafficking of BACE1 and the processing of APP to Abeta. Title: Lipase-coated K2SO4 micro-crystals: preparation, characterization, and application in biodiesel production using various oil feedstocks Zheng J, Xu L, Liu Y, Zhang X, Yan Y Ref: Bioresour Technol, 110:224, 2012 : PubMed ESTHER: Zheng_2012_Bioresour.Technol_110_224 PubMedSearch: Zheng 2012 Bioresour.Technol 110 224 PubMedID: 22330591 Abstract This study investigated the preparation and characteristics of protein-coated microcrystals (PCMCs) from Pseudomonas cepacia lipase (PS) and K(2)SO(4), and their application in biodiesel synthesis, via single factorial experiments and response surface methodology (RSM), the optimized PCMC-PS exhibited high activity and stability; the optimal temperature was 60 degrees C (which gave 99.83% conversion), although fairly high activity was exhibited after incubation at different temperatures (25-70 degrees C). The organic solvents stability of the PCMC-PS was improved, and it significantly reduced ethanol toxicity. Circular dichroism (CD) analysis revealed the correlation between the conformation and the enzyme activity. The morphology of the PCMC-PS was also confirmed via scanning electron microscopy (SEM). When catalyzed by PCMC-PS, above 83% biodiesel yield was obtained for most of the seven oils tested. The PCMC-PS (washed with hexane) activity remained relatively stable after eight batch reactions, with only a 15.73% reduction in the conversion (from 99.02% to 83.29%). Title: Erythrocyte damage of crucian carp (Carassius auratus) caused by microcystin-LR: in vitro study Zhou W, Liang H, Zhang X Ref: Fish Physiol Biochem, 38:849, 2012 : PubMed ESTHER: Zhou_2012_Fish.Physiol.Biochem_38_849 PubMedSearch: Zhou 2012 Fish.Physiol.Biochem 38 849 PubMedID: 22286870 Abstract Fish suffer from anemia and hypovolemic hypotensive shock after in vivo exposure with microcystins.However except for in vivo causes for anemia and hypotension an in vitro study of fish erythrocytes exposed to MC is necessary For a better understanding of hematology toxicity of MC the main aim of the present study was to investigate the toxic effects of microcystin on fish erythrocytes in vitro Crucian carp erythrocytes were incubated in vitro with microcystin-LR MC-LR at doses of 0 1 10 100 and 1,000 nM.The level of lipid peroxidate significantly increased in MC-LR treatment groups Glutathione decreased after exposure to MC-LR The activities of antioxidative enzymes including superoxide dismutase catalase,glutathione peroxidase and glutathione-S-transferase,were significantly increased after exposure with MC-LR.The hemolysis was significantly increased while the activities of acetylcholinesterase Na-K-ATPase and Ca2+-Mg2+-ATPase were significantly decreased In addition pathological alterations in agglomerated and jagged erythrocytes were observed in blood smears The findings indicate that damages to erythrocytes should also be responsible for anemia and hypotensive shock or even death. Title: Interkingdom gene transfer may contribute to the evolution of phytopathogenicity in botrytis cinerea Zhu B, Zhou Q, Xie G, Zhang G, Zhang X, Wang Y, Sun G, Li B, Jin G Ref: Evol Bioinform Online, 8:105, 2012 : PubMed ESTHER: Zhu_2012_Evol.Bioinform.Online_8_105 PubMedSearch: Zhu 2012 Evol.Bioinform.Online 8 105 PubMedID: 22346340 Abstract The ascomycete Botrytis cinerea is a phytopathogenic fungus infecting and causing significant yield losses in a number of crops. The genome of B. cinerea has been fully sequenced while the importance of horizontal gene transfer (HGT) to extend the host range in plant pathogenic fungi has been recently appreciated. However, recent data confirm that the B. cinerea fungus shares conserved virulence factors with other fungal plant pathogens with narrow host range. Therefore, interkingdom HGT may contribute to the evolution of phytopathogenicity in B. cinerea. In this study, a stringent genome comparison pipeline was used to identify potential genes that have been obtained by B. cinerea but not by other fungi through interkingdom HGT. This search led to the identification of four genes: a UDP-glucosyltransferase (UGT), a lipoprotein and two alpha/beta hydrolase fold proteins. Phylogenetic analysis of the four genes suggests that B. cinerea acquired UGT from plants and the other 3 genes from bacteria. Based on the known gene functions and literature searching, a correlation between gene acquision and the evolution of pathogenicity in B. cinerea can be postulated. Title: The DPP-4 inhibitor vildagliptin increases pancreatic beta cell mass in neonatal rats Duttaroy A, Voelker F, Merriam K, Zhang X, Ren X, Subramanian K, Hughes TE, Burkey BF Ref: European Journal of Pharmacology, 650:703, 2011 : PubMed ESTHER: Duttaroy_2011_Eur.J.Pharmacol_650_703 PubMedSearch: Duttaroy 2011 Eur.J.Pharmacol 650 703 PubMedID: 21070766 Abstract The present study addressed the effect of the dipeptidyl peptidase-4 (DPP-4) inhibitor vildagliptin ((1-[[(3-hydroxy-1-adamantyl) amino] acetyl]-2-cyano-(S)-pyrrolidine), LAF237) on pancreatic beta cell mass in neonatal rats. Newborn rats were treated orally with vildagliptin (60 mg/kg) or vehicle once daily for 19 days starting from postnatal day 2. Pancreatic immunohistochemistry and morphometric analysis were performed to evaluate changes in beta cell mass, cell apoptosis (Apoptag stain) and replication (5'-Bromo-2'-deoxyuridine (BrdU)-incorporation) on days 7, 21, and 33. On day 7, an eight-fold increase in BrdU-positive pancreatic beta cells and a 71% decrease in Apoptag-positive cells were observed. On day 21, vildagliptin produced a two-fold increase in pancreatic beta cell mass compared to placebo (0.06+/-0.01 mg vs 0.11+/-0.02 |
