Author Report for: Zhang LNo contact information in database for Zhang L
De Gregorio MA, Zengin G, Alp-Turgut FN, Elbasan F, Ozfidan-Konakci C, Arikan B, Yildiztugay E, Zhang L, Lucini L Ref: Plants (Basel), 12:, 2023 : PubMed ESTHER: De Gregorio_2023_Plants.(Basel)_12_ PubMedSearch: De Gregorio 2023 Plants.(Basel) 12 PubMedID: 37176879 Abstract Lettuce (Lactuca sativa L., Asteraceae) is a popular vegetable leafy crop playing a relevant role in human nutrition. Nowadays, novel strategies are required to sustainably support plant growth and elicit the biosynthesis of bioactive molecules with functional roles in crops including lettuce. In this work, the polyphenolic profile of lettuce treated with glutamic acid (GA), humic acid (HA), and their combination (GA + HA) was investigated using an untargeted metabolomics phenolic profiling approach based on high-resolution mass spectrometry. Both aerial and root organ parts were considered, and a broad and diverse phenolic profile could be highlighted. The phenolic profile included flavonoids (anthocyanins, flavones, flavanols, and flavonols), phenolic acids (both hydroxycinnamics and hydroxybenzoics), low molecular weight phenolics (tyrosol equivalents), lignans and stilbenes. Overall, GA and HA treatments significantly modulated the biosynthesis of flavanols, lignans, low molecular weight phenolics, phenolic acids, and stilbene. Thereafter, antioxidant capacity was evaluated in vitro with 2,2-diphenyln-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) assays. In addition, this study examined the inhibitory properties of enzymes, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), tyrosinase, alpha-amylase, and alpha-glucosidase. Compared to individual treatments, the combination of GA + HA showed stronger antioxidant abilities in free radical scavenging and reducing power assays in root samples. Moreover, this combination positively influenced the inhibitory effects of root samples on AChE and BChE and the tyrosinase inhibitory effect of leaf samples. Concerning Pearson's correlations, antioxidant and enzyme inhibition activities were related to phenolic compounds, and lignans in particular correlated with radical scavenging activities. Overall, the tested elicitors could offer promising insights for enhancing the functional properties of lettuce in agricultural treatments. Title: Habitual feeding patterns impact polystyrene microplastic abundance and potential toxicity in edible benthic mollusks Wang S, Zheng L, Shen M, Zhang L, Wu Y, Li G, Guo C, Hu C, Zhang M and Lv L <2 more author(s)> Wang S, Zheng L, Shen M, Zhang L, Wu Y, Li G, Guo C, Hu C, Zhang M, Sui Y, Dong X, Lv L (- 2) Ref: Sci Total Environ, 866:161341, 2023 : PubMed ESTHER: Wang_2023_Sci.Total.Environ_866_161341 PubMedSearch: Wang 2023 Sci.Total.Environ 866 161341 PubMedID: 36603620 Abstract That increasing microplastics (MPs, <5 mm) eventually end up in the sediment which may become a growing menace to diverse benthic lives is worthy of attention. In this experiment, three edible mollusks including one deposit-feeding gastropod (Bullacta exarate) and two filter-feeding bivalves (Cyclina sinensis and Mactra veneriformis) were exposed to polystyrene microplastic (PS-MP) for 7 days and depurated for 3 days. PS-MP numbers in the digestive system and non-digestive system, digestive enzymes, oxidative stress indexes, and a neurotoxicity index of three mollusks were determined at day 0, 3, 7, 8 and 10. After seven-day exposure, the PS-MP were found in all three mollusks' digestive and non-digestive systems. And PS-MP in M. veneriformis (9.57 +/- 2.19 items/individual) was significantly higher than those in C. sinensis (3.00 +/- 2.16 items/individual) and B. exarate (0.83 +/- 1.07 items/individual) at day 7. Three-day depuration could remove most of the PS-MP in the mollusks, and higher PS-MP clearance rates were found in filter-feeding C. sinensis (77.78 %) and M. veneriformis (82.59 %) compared to surface deposit-feeding B. exarate (50.00 %). The digestive enzymes of B. exarate significantly reacted to PS-MP exposure, while oxidative responses were found in C. sinensis. After three-day depuration, the changes of digestive enzymes and the oxidative states were fixed, but neurotoxicity induced by PS-MP was not recoverable. Besides, it is noteworthy that changes of digestive enzymes and acetylcholinesterase are related to feeding patterns. Title: Hesperidin methylchalcone (HMC) hinders amyloid-beta induced Alzheimer's disease by attenuating cholinesterase activity, macromolecular damages, oxidative stress and apoptosis via regulating NF-B and Nrf2/HO-1 pathways Wang Z, Gao C, Zhang L, Sui R Ref: Int J Biol Macromol, :123169, 2023 : PubMed ESTHER: Wang_2023_Int.J.Biol.Macromol__123169 PubMedSearch: Wang 2023 Int.J.Biol.Macromol 123169 PubMedID: 36623626 Abstract Phytocompounds therapy has recently emerged as an effective strategy to treat Alzheimer's disease. Herein, the protective effect of hesperidin methylchalcone (HMC) was evaluated through Alzheimer's disease models of Neuro-2a cells and Wistar rats. The in vitro results showed that HMC possesses significant ability to inhibit the acetylcholinesterase enzyme and exhibiting anti-aggregation and disaggregation properties. Furthermore, HMC could protect the Neuro-2a cells against Abeta-induced neurotoxicity. Simultaneously, HMC treatment significantly improved the cognitive deficits caused by Abeta-peptide on spatial memory in Wistar rats. HMC significantly enhanced the cholinergic effects by inhibiting AChE, BuChE, beta-secretase activity, caspase-3 activity, and attenuating macromolecular damages and apoptosis. Notably, HMC reduced the Abeta-induced oxidative stress by activating the antioxidative defence enzymes. In addition, the HMC treatment suppressed the expression of immunocytokines such as p-NF-kappaB p65, p-IkappaBalpha, induced by Abeta; whereas upregulating Nrf2, HO-1 in brain homogenate. These results suggest that HMC could attenuate Abeta-induced neuroinflammation in brain via suppressing NF-kappaB signalling pathway and activating the Nrf2/HO-1 pathway, thereby improving memory and cognitive impairments in Wistar rats. Overall, the present study reports that HMC can act as a potent candidate with multi-faceted neuroprotective potential against Abeta-induced memory dysfunction in Wistar rats for the treatment of Alzheimer's disease. Title: Antennal transcriptomic analysis of carboxylesterases and glutathione S-transferases associated with odorant degradation in the tea gray geometrid, Ectropis grisescens (Lepidoptera, Geometridae) Zhang F, Chen Y, Zhao X, Guo S, Hong F, Zhi Y, Zhang L, Zhou Z, Zhang Y and Li X <1 more author(s)> Zhang F, Chen Y, Zhao X, Guo S, Hong F, Zhi Y, Zhang L, Zhou Z, Zhang Y, Zhou X, Li X (- 1) Ref: Front Physiol, 14:1183610, 2023 : PubMed ESTHER: Zhang_2023_Front.Physiol_14_1183610 PubMedSearch: Zhang 2023 Front.Physiol 14 1183610 PubMedID: 37082242 Abstract Introduction: Carboxylesterases (CXEs) and glutathione S-transferases (GSTs) can terminate olfactory signals during chemosensation by rapid degradation of odorants in the vicinity of receptors. The tea grey geometrid, Ectropis grisescens (Lepidoptera, Geometridae), one of the most devastating insect herbivores of tea plants in China, relies heavily on plant volatiles to locate the host plants as well as the oviposition sites. However, CXEs and GSTs involved in signal termination and odorant clearance in E. grisescens remains unknown. Methods: In this study, identification and spatial expression profiles of CXEs and GSTs in this major tea pest were investigated by transcriptomics and qRT-PCR, respectively. Results: As a result, we identified 28 CXEs and 16 GSTs from female and male antennal transcriptomes. Phylogenetic analyses clustered these candidates into several clades, among which antennal CXEs, mitochondrial and cytosolic CXEs, and delta group GSTs contained genes commonly associated with odorants degradation. Spatial expression profiles showed that most CXEs (26) were expressed in antennae. In comparison, putative GSTs exhibited a diverse expression pattern across different tissues, with one GST expressed specifically in the male antennae. Disscussion: These combined results suggest that 12 CXEs (EgriCXE1, 2, 4, 6, 8, 18, 20-22, 24, 26, and 29) and 5 GSTs (EgriGST1 and EgriGST delta group) provide a major source of candidate genes for odorants degradation in E. grisescens. Title: Penetrating the Blood-Brain Barrier for Targeted Treatment of Neurotoxicant Poisoning by Nanosustained-Released 2-PAM@VB1-MIL-101-NH(2)(Fe) Zhao D, Liu J, Zhou Y, Zhang L, Zhong Y, Yang Y, Zhao B, Yang M, Wang Y Ref: ACS Appl Mater Interfaces, :, 2023 : PubMed ESTHER: Zhao_2023_ACS.Appl.Mater.Interfaces__ PubMedSearch: Zhao 2023 ACS.Appl.Mater.Interfaces PubMedID: 36867458 Abstract It is very important to establish a sustained-release pralidoxime chloride (2-PAM) drug system with brain targeting function for the treatment of neurotoxicant poisoning. Herein, Vitamin B1 (VB1), also known as thiamine, which can specifically bind to the thiamine transporter on the surface of the blood-brain barrier, was incorporated onto the surface of MIL-101-NH(2)(Fe) nanoparticles with a size of -100 nm. Pralidoxime chloride was further loaded within the interior of the above resulted composite by soaking, and a resulting composite drug (denoted as 2-PAM@VB1-MIL-101-NH(2)(Fe)) with a loading capacity of 14.8% (wt) was obtained. The results showed that the drug release rate of the composite drug was increased in PBS solution with the increase of pH (2-7.4) and a maximum drug release rate of 77.5% at pH 4. Experiments on the treatment of poisoning by gavage with the nerve agent sarin in mice combined with atropine revealed that sustained release of 2-PAM from the composite drug was achieved for more than 72 h. Sustained and stable reactivation of poisoned acetylcholinesterase (AChE) was observed with an enzyme reactivation rate of 42.7% in the ocular blood samples at 72 h. By using both zebrafish brain and mouse brain as models, we found that the composite drug could effectively cross the blood-brain barrier and restore the AChE activity in the brain of poisoned mice. The composite drug is expected to be a stable therapeutic drug with brain targeting and prolonged drug release properties for nerve agent intoxication in the middle and late stages of treatment. Title: New insights into the function of plant tannase with promiscuous acyltransferase activity Chen Y, Jiang C, Yin S, Zhuang J, Zhao Y, Zhang L, Jiang X, Liu Y, Gao L, Xia T Ref: Plant J, :, 2022 : PubMed ESTHER: Chen_2022_Plant.J__ PubMedSearch: Chen 2022 Plant.J PubMedID: 36534122 Gene_locus related to this paper: camsi-CsTA Abstract Plant tannases (TAs) or tannin acyl hydrolases, a class of recently reported carboxylesterase (CXE) in tannin-rich plants, are involved in the degalloylation of two important secondary metabolites: flavan-3-ol gallates and hydrolyzable tannins (HTs). In this paper, we have made a new progress on the function of Camellia sinensis (Cs) TA-it is a hydrolase with promiscuous acyltransferase activity in vitro and in vivo experiments and promotes the synthesis of simple galloyl glucoses and flavan-3-ols gallates in plants. We gained the new understanding to the functions of CsTA through enzyme analysis, protein mass spectrometry identification, metabolic analysis of plants by genetic modification. Firstly, CsTA was proved that it is not only a hydrolase but also an acyltransferase. In the two-step covalent catalytic reaction, when CsTA hydrolyzes the galloylated compounds epigallocatechin-3-gallate (EGCG) or 1,2,3,4,6-penta-O-galloyl-beta-D-glucose (PGG) into their degalloylated forms, a long-lived Ser159-linked galloyl-enzyme covalent intermediate is also formed. Under nucleophilic attack, the galloyl group on the intermediate is transferred to the nucleophilic acyl acceptors (including water, methanol, flavan-3-ols and simple galloyl glucoses). Then, metabolic analysis suggested that transiently overexpression of TAs in young strawberry fruits, young leaves of tea plants and young leaves of Chinese bayberry actually increased the total content of simple galloyl glucoses and flavan-3-ol gallates. Overall, these findings provide new insights into the promiscuous acyltransferase activity of plant tannase. Title: Polar substitutions on the surface of a lipase substantially improve tolerance in organic solvents Davari MD, Cui H, Vedder M, Zhang L, Jaeger KE, Schwaneberg U Ref: ChemSusChem, :, 2022 : PubMed ESTHER: Davari_2022_ChemSusChem__ PubMedSearch: Davari 2022 ChemSusChem PubMedID: 35007408 Abstract Biocatalysis in organic solvents (OSs) enables more efficient routes to the synthesis of various valuable chemicals. However, OSs often reduce enzymatic activity which limits the use enzymes in OSs. Herein, we report a comprehensive understanding of interactions between surface polar substitutions and DMSO by integrating the molecular dynamics (MD) simulations of 45 variants from Bacillus subtilis lipase A (BSLA) and substitution landscape in “BSLA-SSM library. By systematically analyzing 39 structural-, solvation-, and interaction energy-based observables, we discovered hydration shell maintenance, DMSO reduction, and decreased local flexibility simultaneously govern the stability of polar variants in OS. Moreover, the fingerprints of 1644 polar-related variants in three OSs demonstrated substituting aromatic to polar residue(s) hold great potential to highly improve OSs resistance. Hence, surface polar engineering enable to be a powerful and general strategy for generating OS-tolerant lipases and other enzymes, thereby adapting the catalyst to the desired reaction and process with OSs. Title: Flavin-enabled reductive and oxidative epoxide ring opening reactions De BC, Zhang W, Yang C, Mandi A, Huang C, Zhang L, Liu W, Ruszczycky MW, Zhu Y and Zhang C <4 more author(s)> De BC, Zhang W, Yang C, Mandi A, Huang C, Zhang L, Liu W, Ruszczycky MW, Zhu Y, Ma M, Bashiri G, Kurtan T, Liu Hw, Zhang C (- 4) Ref: Nat Commun, 13:4896, 2022 : PubMed ESTHER: De BC#Zhang_2022_Nat.Commun_13_4896 PubMedSearch: De BC#Zhang 2022 Nat.Commun 13 4896 PubMedID: 35986005 Abstract Epoxide ring opening reactions are common and important in both biological processes and synthetic applications and can be catalyzed in a non-redox manner by epoxide hydrolases or reductively by oxidoreductases. Here we report that fluostatins (FSTs), a family of atypical angucyclines with a benzofluorene core, can undergo nonenzyme-catalyzed epoxide ring opening reactions in the presence of flavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide (NADH). The 2,3-epoxide ring in FST C is shown to open reductively via a putative enol intermediate, or oxidatively via a peroxylated intermediate with molecular oxygen as the oxidant. These reactions lead to multiple products with different redox states that possess a single hydroxyl group at C-2, a 2,3-vicinal diol, a contracted five-membered A-ring, or an expanded seven-membered A-ring. Similar reactions also take place in both natural products and other organic compounds harboring an epoxide adjacent to a carbonyl group that is conjugated to an aromatic moiety. Our findings extend the repertoire of known flavin chemistry that may provide new and useful tools for organic synthesis. Title: Improved Aitongxiao prescription (I-ATXP) induces apoptosis, cell cycle arrest and blocks exosomes release in hepatocellular carcinoma (HCC) cells Huang MB, Gao Z, Xia M, Zhao X, Fan X, Lin S, Zhang L, Huang L, Wei A and Leng J <4 more author(s)> Huang MB, Gao Z, Xia M, Zhao X, Fan X, Lin S, Zhang L, Huang L, Wei A, Zhou H, Wu JY, Roth WW, Bond VC, Leng J (- 4) Ref: Int Journal de Physiologie Pathophysiol Pharmacol, 14:90, 2022 : PubMed ESTHER: Huang_2022_Int.J.Physiol.Pathophysiol.Pharmacol_14_90 PubMedSearch: Huang 2022 Int.J.Physiol.Pathophysiol.Pharmacol 14 90 PubMedID: 35619665 Abstract BACKGROUND: Hepatocellular carcinoma (HCC) is the second most common malignancy globally, after lung cancer, accounting for 85-90% of primary liver cancer. Hepatitis B virus (HBV) infection is considered the leading risk factor for HCC development in China. HCC is a highly malignant cancer whose metastasis is primarily influenced by the tumor microenvironment. The role of exosomes in cancer development has become the focus of much research due to the many newly described contents of exosomes, which may contribute to tumorigenesis. However, the possible role exosomes play in the interactions between HCC cells and their surrounding hepatic milieu is mainly unknown. We discovered an Improved Aitongxiao Prescription (I-ATXP): an 80% alcohol extract from a mix of 15 specific plant and animal compounds, which had been shown to have an anticancer effect through inducing apoptosis and cell cycle arrest and blocking exosomes release in HCC cells. However, the anticancer mechanism of I-ATXP on human liver carcinoma is still unclear. OBJECTIVE: Due to its inhibitory effects on chemical carcinogenesis and inflammation, I-ATXP has been proposed as an effective agent for preventing or treating human liver carcinoma. In this study, we aimed to explore the effect of I-ATXP on proliferation, apoptosis, and cell cycles of different HCC cell lines. We investigated the impact of I-ATXP on exosomes' secretion derived from these HCC cells. METHODS: The inhibitory effect of I-ATXP on proliferation and cytotoxicity of HepG2, SMMC7721, HKCL-C3 HCC cell lines, and MIHA immortalized hepatocyte cell line was assessed by CCK-8 assay. The cell cycle distribution and cell apoptosis were determined by flow cytometry using Annexin V-FITC/PI staining. The expression of Alix and CD63 of exosome marker proteins was detected by western blotting. The exosome protein concentration was measured by a fluorescent plate reader. The exosome-specific enzyme activity was measured by acetylcholinesterase (AchE) assay, and exosome morphological characteristics were identified by transmission electron microscopy (TEM). RESULTS: I-ATXP inhibited the growth of HCC cells in a dose and time-dependent manner. Flow cytometry analysis showed that I-ATXP induced G0/G1 phase arrest and cell apoptosis. The I-ATX reduced HepG2, SMMC7721, and HKCI-C HCC cell lines exosomes release and low-dose I-ATXP significantly enhanced the growth inhibition induced by 5-Fu. Western blot analysis shows that after HCC cell lines were treated with various concentrations of I-ATXP (0.125-1 mg/ml) for 24 h, exosomes derived from three different HCC cells expressed exosome-specific proteins Alix and CD63. Compared with the untreated group, with the increment of the concentration of I-ATXP, the expression of exosome-specific proteins Alix and CD63 were reduced. These results suggest that I-ATXP can inhibit the release of exosomes with Alix and CD63 protein from HCC cells. CONCLUSIONS: I-ATXP is a traditional Chinese medicine that acts as an effective agent for preventing or treating human liver carcinoma. (i) I-ATXP can effectively inhibit cell proliferation of different HCC cells in a time and dose-dependent manner. Compared with 5-Fu, I-ATXP exhibited more selective proliferation inhibition in HCC cells, displaying traditional Chinese medicine advantages on tumor therapy and providing the experimental basis for I-ATXP clinical application. (ii) I-ATXP can induce apoptosis and cell cycle arrest in HCC cells. The CCK-8 assay results indicated that I-ATXP could inhibit HCC cell proliferation mediated by apoptosis and cell cycle arrest. (iii) I-ATXP can inhibit both the exosome releases and expression of CD63, and Alix derived from HCC cells, but the exosomes derived from liver cancer cells affect liver cancer cells' biological properties such as proliferation, invasion, and migration. These suggest that I-ATXP may affect HCC cells via regulation of exosomes of HCC cells, further indicating the potential clinical values of I-ATXP for the prevention or treatment of human liver carcinoma. Title: Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis Lang B, Han L, Zeng L, Zhang Q, Chen S, Huang L, Jia Z, Yu Q, Zhang L Ref: BMC Pediatr, 22:295, 2022 : PubMed ESTHER: Lang_2022_BMC.Pediatr_22_295 PubMedSearch: Lang 2022 BMC.Pediatr 22 295 PubMedID: 35590273 Abstract BACKGROUND: A recent survey revealed that extensive off-label use of sugammadex in pediatric anesthesia deserved particular attention. The present study with trial sequential analysis (TSA) aimed to evaluate the effects of sugammadex for antagonizing neuromuscular blockade (NMB) in pediatric patients, and to investigate whether the findings achieved the required information size to draw conclusions. METHODS: PubMed, Embase, Cochrane Library and China National Knowledge Infrastructure (CNKI) were searched from inception to April 2021. All randomized controlled trials used sugammadex as reversal agent in pediatric patients were enrolled. Time from NMB reversal to recovery of the train-of-four ratio (TOFr) to 0.9 and extubation time were considered as co-primary outcomes, and incidences of adverse events were considered as secondary outcomes. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system was used to rate the quality of evidences. RESULTS: Data from 18 studies involving 1,065 pediatric patients were acquired. The results revealed that use of sugammadex was associated with shorter duration from administration of reversal agents to TOFr > 0.9 (MD = -14.42, with 95% CI [-17.08, -11.75]) and shorter interval from reversal from NMB to extubation (MD = -13.98, with 95% CI [-16.70, -11.26]) compared to control groups. TSA also indicated that the current sample sizes were sufficient with unnecessary further trials. Analysis of secondary outcomes indicated that administration of sugammadex was associated with less incidence of postoperative nausea and vomiting (PONV), bradycardia, and dry mouth compared to control groups. CONCLUSION: Considering of satisfactory and rapid neuromuscular blockade reversal with low incidences of adverse events, sugammadex might be considered as the preferred option for children in clinical anesthesia practice compared to acetylcholinesterase inhibitors. However, overall low-quality evidences in present study rated by GRADE system indicated that superiority of sugammadex employed in pediatric patients needs to be confirmed by more studies with high quality and large sample size in future. Title: Identification and expression patterns of candidate carboxylesterases in Carposina sasakii Matsumura (Lepidoptera: Carposinidae), an important pest of fruit trees Li J, Zhang L Ref: Bull Entomol Res, :1, 2022 : PubMed ESTHER: Li_2022_Bull.Entomol.Res__1 PubMedSearch: Li 2022 Bull.Entomol.Res 1 PubMedID: 35670157 Abstract Carposina sasakii Matsumura (Lepidoptera: Carposinidae) is an important pest of fruit trees in a large area of Asia. The adults mainly depend on olfaction to communicate with the environment, but the olfactory mechanism has not been well known. Odorant degrading enzymes (ODEs) are important olfactory proteins, which inactivate and degrade odorants to free odorant receptors for maintaining olfactory sensitivity. Carboxylesterases (CXEs) are considered to be a major group of moth ODEs. In this study, four candidate CXEs (CsasCXE1 ~ CsasCXE4) were identified by using head transcriptomic data from C. sasakii adult females and males. Sequence alignment showed conserved amino acid residues and their variations in C. sasakii CXEs. Phylogenetic analysis indicated the CXEs with the variations cluster well, and each C. sasakii CXE clusters in a clade with some of the other lepidopteran CXEs, with a high enough bootstrap value. Gene expression analysis revealed that CsasCXE2 and CsasCXE3 have similar tissue and sex expression patterns in C. sasakii adults. The two CXEs have relatively high expression levels in the heads and are expressed more abundantly in the female heads than male heads. CsasCXE1 and CsasCXE4 are expressed at higher levels in the male heads than female heads, but not dominantly expressed in the heads among the different tissues. Whether these CXEs function as ODEs remains to be further researched. This study laid the foundation for exploring functions of C. sasakii CXEs. Title: Multiple acetylcholinesterases in Pardosa pseudoannulata brain worked collaboratively to provide protection from organophosphorus insecticides Lin X, Zhang Y, Yang B, Zhang L, Chen Y, Liu Z Ref: Ecotoxicology & Environmental Safety, 248:114301, 2022 : PubMed ESTHER: Lin_2022_Ecotoxicol.Environ.Saf_248_114301 PubMedSearch: Lin 2022 Ecotoxicol.Environ.Saf 248 114301 PubMedID: 36410143 Gene_locus related to this paper: 9arac-KU501290, 9arac-KU501289, 9arac-KU501288, 9arac-KU501287, 9arac-v5qqc6, 9arac-v5qqr1 Abstract Acetylcholinesterase (AChE) is an essential neurotransmitter hydrolase in nervous systems of animals and its number varies among species. So far, five AChEs have been identified in the natural enemy Pardosa pseudoannulata. Here we found that Ppace1, Ppace2 and Ppace5 were highly expressed in the spider brain, among which the mRNA level of Ppace5, but not Ppace1 and Ppace2, could be up-regulated by organophosphorus insecticides at their sublethal concentrations. In spider brain, the treatment by organophosphorus insecticides at the sublethal concentrations could increase total AChE activity, although high concentrations inhibited the activity. The activity that increased from the sublethal concentration pretreatment could compensate for the activity inhibition due to subsequent application of organophosphorus insecticides at lethal concentrations, and consequently reduce the mortality of spiders. PpAChE1 and PpAChE2 were highly sensitive to organophosphorus insecticides, and their activities would be strongly inhibited by the insecticides. In contrast, PpAChE5 displayed relative insensitivity towards organophosphorus insecticides, but with the highest catalytic efficiency for ACh. That meant the up-regulation of Ppace5 under insecticide exposure was important for maintaining AChE activity in spider brain, when PpAChE1 and PpAChE2 were inhibited by organophosphorus insecticides. The study demonstrated that multiple AChEs in the spider brain worked collaboratively, with part members for maintaining AChE activity and other members responding to organophosphorus inhibition, to provide protection from organophosphorus insecticides. In fields, high concentration insecticides are often applied when ineffective controls of insect pests occur due to relative-low concentration of insecticides in last round application. This application pattern of organophosphorus insecticides provides more chances for P. pseudoannulata to survive and controlling insect pests as a natural enemy. Title: Roles of neuroligins in central nervous system development: focus on glial neuroligins and neuron neuroligins Liu X, Hua F, Yang D, Lin Y, Zhang L, Ying J, Sheng H, Wang X Ref: J Transl Med, 20:418, 2022 : PubMed ESTHER: Liu_2022_J.Transl.Med_20_418 PubMedSearch: Liu 2022 J.Transl.Med 20 418 PubMedID: 36088343 Abstract Neuroligins are postsynaptic cell adhesion molecules that are relevant to many neurodevelopmental disorders. They are differentially enriched at the postsynapse and interact with their presynaptic ligands, neurexins, whose differential binding to neuroligins has been shown to regulate synaptogenesis, transmission, and other synaptic properties. The proper functioning of functional networks in the brain depends on the proper connection between neuronal synapses. Impaired synaptogenesis or synaptic transmission results in synaptic dysfunction, and these synaptic pathologies are the basis for many neurodevelopmental disorders. Deletions or mutations in the neuroligins genes have been found in patients with both autism and schizophrenia. It is because of the important role of neuroligins in synaptic connectivity and synaptic dysfunction that studies on neuroligins in the past have mainly focused on their expression in neurons. As studies on the expression of genes specific to various cells of the central nervous system deepened, neuroligins were found to be expressed in non-neuronal cells as well. In the central nervous system, glial cells are the most representative non-neuronal cells, which can also express neuroligins in large amounts, especially astrocytes and oligodendrocytes, and they are involved in the regulation of synaptic function, as are neuronal neuroligins. This review examines the mechanisms of neuron neuroligins and non-neuronal neuroligins in the central nervous system and also discusses the important role of neuroligins in the development of the central nervous system and neurodevelopmental disorders from the perspective of neuronal neuroligins and glial neuroligins. Title: An esterase-activatable curcumin prodrug for tumor-targeting therapy Liu L, Zhang L, Tao M, Wang M, Dong L, Hai Z Ref: Chem Commun (Camb), :, 2022 : PubMed ESTHER: Liu_2022_Chem.Commun.(Camb)__ PubMedSearch: Liu 2022 Chem.Commun.(Camb) PubMedID: 36373630 Abstract A tumor-targeting therapy strategy is urgently needed to increase the accumulation of drugs in tumors and reduce the side effects in normal tissues. Herein, we developed an esterase-activatable curcumin prodrug Cur-RGD for tumor-targeting therapy. Armed with the tumor-targeting RGD peptide and in situ esterase-triggered drug release, this prodrug Cur-RGD can efficiently improve the therapeutic effect of curcumin in tumors. 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: Ancestral sequence reconstruction and spatial structure analysis guided alteration of longer-chain substrate catalysis for Thermomicrobium roseum lipase Ma D, Xin Y, Guo Z, Shi Y, Zhang L, Li Y, Gu Z, Ding Z, Shi G Ref: Enzyme Microb Technol, 156:109989, 2022 : PubMed ESTHER: Ma_2022_Enzyme.Microb.Technol_156_109989 PubMedSearch: Ma 2022 Enzyme.Microb.Technol 156 109989 PubMedID: 35134708 Gene_locus related to this paper: therp-b9l0x7 Abstract Thermomicrobium roseum DSM 5159 lipase (TrLip) is an enzyme with marked thermostability and excellent solvent resistance. However, TrLip reveals relatively high catalytic efficiency on short-chain substrates but poor activity against mid-long or long-chain fatty acids, which would limit its industrial application. In this study, ancestral sequence reconstruction (ASR), a common engineering tool for the evolutionary history of protein families, was employed to identify the natural evolutionary trends within 5 A around the catalytic center. Two mutation libraries were constructed, one for the catalytic center and the other for the pocket flexibility. A total of 69 mutants were expressed and purified in the Escherichia coli expression system to determine the kinetic parameters, and W219G could significantly enhance the catalytic efficiency against substrates with 12-, 16- and 18-carbon side chains. In addition, the double mutant W219G/F265M could further catalyze the breakdown of the above three substrates up to 6.34-, 4.21- and 4.86-folds compared to the wild-type TrLip, while the initial pH and thermostability were maintained. Through bioinformatics analysis, the significantly enhanced catalytic efficiency against longer-side chain substrates should be associated with the reduction of steric hindrance. With the outstanding stability and the promoted activity, TrLip should be of great potential in chemical and food industry. Title: Surface Modification of Magnetic ZIF-90 Nanoparticles Improves the Microenvironment of Immobilized Lipase and Its Application in Esterification Suo H, Geng X, Sun Y, Zhang L, Yang J, Yang F, Yan H, Hu Y, Xu L Ref: Langmuir, :, 2022 : PubMed ESTHER: Suo_2022_Langmuir__ PubMedSearch: Suo 2022 Langmuir PubMedID: 36448653 Abstract Interactions of enzymes with supports significantly affect the activity and stability of immobilized enzymes. Herein, amino-functionalized ionic liquid (IL)-grafted magnetic zeolitic imidazolate framework-90 (MZIF-90) was prepared and used to immobilize porcine pancreatic lipase (PPL). The nanocomposites were fully characterized; meanwhile, the interactions between ILs and ZIF-90 were calculated based on density functional theory. The prepared biocatalyst (PPL-ILs/MZIF-90) had a lipase loading of 178.3 mg/g and hydrolysis activity up to 287.5 U/g. When the biocatalyst was used to synthesize isoamyl acetate, the reaction media, molar ratio of alcohol/acid, temperature, and reaction time were optimized. Under the optimized reaction conditions (in hexane, alcohol/acid = 3:1, under 45 degreesC, reacted for 9 h), the ester yield reached 85.5%. The results of the stability test showed that PPL-ILs/MZIF-90 retained 88.7% of the initial activity after storing for 35 days and 92.5% of the initial activity after reusing for seven cycles for synthesizing isoamyl acetate. Moreover, the secondary structure analysis showed that the synthesized supports protected the active conformation of immobilized lipase, which lead to the enhanced catalytic performance. Additionally, the biocatalyst can be easily separated with a magnet, which facilitated the reusability. This study provides insights regarding the application of metal organic framework composites in the field of enzyme catalysis. Title: Highly stable acetylcholinesterase electrochemical biosensor based on polymerized ionic liquids microgel for pesticides detection Wan Y, Wang H, Zhang L, Chen Y, Li S, Zhou J, Zhang Q, Xia L Ref: Mikrochim Acta, 189:300, 2022 : PubMed ESTHER: Wan_2022_Mikrochim.Acta_189_300 PubMedSearch: Wan 2022 Mikrochim.Acta 189 300 PubMedID: 35904635 Abstract A highly stable electrochemical biosensor for pesticide detection was developed. For the first time polymeric ionic liquids (PILs) were introduced to construct an acetylcholinesterase (AChE) biosensor . AChE was entrapped in PILs microspheres through an emulsion polymerization reaction, where negatively charged Au nanoparticles (Au NPs) can be immobilized by the positively charged PILs, leading to improved catalytic performance. The results suggest that the positively charged PILs not only provide a biocompatible microenvironment around the enzyme molecule, stabilizing its biological activity and preventing its leakage, but also act as a modifiable interface allowing other components with electron transport properties to be loaded onto the polymer substrate, thus providing an efficient electron transport channel for the entrapped enzyme. More notably, when AChE was immobilized in a positively charged environment, the active site is closer to the electrode, promoting faster electron transfer. The detection limits of the constructed electrochemical biosensor AChE@PILs@Au NPs/GCE toward carbaryl and dichlorvos (DDVP) were 5.0 x 10(-2) ng ml(-1) and 3.9 x 10(-2) ng ml(-1), in a wide linear range of 6.3 x 10(-2)-8.8 x 10(2) ng ml(-1) and 1.3 x 10(-1)-1.4 x 10(3) ng ml(-1), respectively. More importantly, the biosensor has high thermal and storage stability, which facilitates rapid field analysis of fruits and vegetables in a variety of climates. In addition, the biosensor reported has good repeatability and selectivity and has high accuracy in the analysis of peaches, tap water, and other types of samples. Title: A Portable Fluorescent Hydrogel-Based Device for On-Site Quantitation of Organophosphorus Pesticides as Low as the Sub-ppb Level Wang T, Zhang L, Xin H Ref: Front Chem, 10:855281, 2022 : PubMed ESTHER: Wang_2022_Front.Chem_10_855281 PubMedSearch: Wang 2022 Front.Chem 10 855281 PubMedID: 35572106 Abstract Portable devices possess powerful application prospects in on-site sensing without the limitation of bulky instruments. Given the relevance of pesticides to food safety, we herein fabricated a robust gold nanocluster (AuNC)-based hydrogel test kit for precisely quantified chlorpyrifos by using a three-dimensional (3D) printed subsidiary device. In this work, the fluorescence of AuNC-based hydrogel could be efficiently quenched by cobalt oxyhydroxide nanoflakes (CoOOH NFs) through the Forster resonance energy transfer effect. Chlorpyrifos as an acetylcholinesterase inhibitor controls the enzymatic hydrolysis reaction and further regulates the production of thiocholine that could decompose CoOOH nanoflakes into Co(2+), resulting in the fluorescence response of AuNC-based hydrogel. By using a homemade subsidiary device and smartphone, the fluorescence color was transformed into digital information, achieving the on-site quantitative detection of chlorpyrifos with the limit of detection of 0.59 ng ml(-1). Owing to specific AuNC signatures and hydrogel encapsulation, the proposed fluorescence hydrogel test kit displayed high sensitivity, good selectivity, and anti-interference capability in a real sample analysis, providing great potential in on-site applications. 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: Identification of Host Molecules Involved in the Proliferation of Nucleopolyhedrovirus in Bombyx mori Xu J, Xie X, Ma Q, Zhang L, Li Y, Chen Y, Li K, Xiao Y, Tettamanti G and Tian L <1 more author(s)> Xu J, Xie X, Ma Q, Zhang L, Li Y, Chen Y, Li K, Xiao Y, Tettamanti G, Xu H, Tian L (- 1) Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: Xu_2022_J.Agric.Food.Chem__ PubMedSearch: Xu 2022 J.Agric.Food.Chem PubMedID: 36321811 Abstract The Bombyx mori nucleopolyhedrovirus (BmNPV), a foodborne infectious virus, is the pathogen causing nuclear polyhedrosis and high lethality in the silkworm. In this study, we characterized the molecules involved in BmNPV-silkworm interaction by RNA sequencing of the fat body isolated from the virus-susceptible strain P50. Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation showed that the upregulated differentially expressed genes (DEGs) were mainly involved in translation, signal transduction, folding, sorting, and degradation, as well as transport and catabolism, while the downregulated DEGs were predominantly enriched in the metabolism of carbohydrates, amino acids, and lipids at 72 h post BmNPV infection. Knockout of the upregulated somatomedin-B and thrombospondin type-1 domain-containing protein, probable allantoicase, trifunctional purine biosynthetic protein adenosine-3, and Psl and pyoverdine operon regulator inhibited the proliferation of BmNPV, while knockout of the downregulated clip domain serine protease 3 and carboxylesterase clade H, member 1 promoted it. The molecules herein identified provide a foundation for developing strategies and designing drugs against BmNPV. Title: Cation-Exchangeable Pralidoxime Chloride@bio-MOF-1 as a Treatment for Nerve Agent Poisoning and Sulfur Mustard Skin Poisoning in Animals Yang Y, Liu J, Liu L, Zhou Y, Zhang L, Zhong Y, Zhao D, Wang Y Ref: ACS Omega, 7:30720, 2022 : PubMed ESTHER: Yang_2022_ACS.Omega_7_30720 PubMedSearch: Yang 2022 ACS.Omega 7 30720 PubMedID: 36092617 Abstract A 2-PAM@bio-MOF-1 composite was prepared by cationic exchange of counter N,N-dimethylammonium cations in the pores of the anionic, biocompatible metal-organic framework (bio-MOF-1) with pralidoxime chloride (2-PAM-Cl) by impregnation. In vitro drug release measurements revealed that the release rate of 2-PAM from 2-PAM@bio-MOF-1 in simulated body fluid (SBF) was more than four-fold higher than that in deionized water, indicating that the presence of endogenous cations in SBF triggered the release of 2-PAM through cation exchange. The release of 2-PAM was rapid within the first 10 h but was much slower over the period of 10-50 h. At room temperature, the maximum release rate of 2-PAM was 88.5% (15 mg of 2-PAM@bio-MOF-1 in 1 mL of SBF), indicating that the drug was efficiently released from the composite MOF in SBF. In simulated gastric fluid, 64.3% of 2-PAM was released from bio-MOF-1 into the simulated gastric fluid after 50h. This suggested that 2-PAM@bio-MOF-1 might be effective for enabling the slow release of 2-PAM in the human body. Indeed, the maximum reactivation rate of acetylcholinesterase in sarin-poisoned mice reached 82.5%. In addition, 2-PAM@bio-MOF-1 demonstrated the ability to adsorb and remove sulfur mustard (HD) in solution and from the skin of guinea pigs. Title: Diagnosis of Alzheimer's Disease and In Situ Biological Imaging via an Activatable Near-Infrared Fluorescence Probe Yang Y, Zhang L, Wang J, Cao Y, Li S, Qin W, Liu Y Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Yang_2022_Anal.Chem__ PubMedSearch: Yang 2022 Anal.Chem PubMedID: 36121878 Abstract Alzheimer's disease (AD) is a common neurodegenerative disease that makes the brain nervous system degenerate rapidly and is accompanied by some special cognitive and behavioral dysfunction. Recently, butyrylcholinesterase (BChE) was reported as an important enzyme, whose activity can provide predictive value for timely discovery and diagnosis of AD. Therefore, it is indispensable to design a detection tool for selective and rapid response toward BChE. In this study, we developed a novel near-infrared fluorescent probe (Chy-1) for the detection of BChE activity. An excellent sensitivity, good biocompatibility, and lower limit of detection (LOD) of 0.12 ng/mL made the probe extremely specific for BChE, which was successfully used in biological imaging. What is more, Chy-1 can not only clearly distinguish tumor from normal cells but also forms a clear boundary between the normal and cancer tissues due to the obvious difference in fluorescence intensity produced via in situ spraying. Most important of all, Chy-1 was also successfully applied to track the BChE activity in AD mouse models. Based on this research, the novel probe may be a powerful tool for clinical diagnosis and therapy of tumor and neurodegenerative diseases. Title: Lipases secreted by a gut bacterium inhibit arbovirus transmission in mosquitoes Yu X, Tong L, Zhang L, Yang Y, Xiao X, Zhu Y, Wang P, Cheng G Ref: PLoS Pathog, 18:e1010552, 2022 : PubMed ESTHER: Yu_2022_PLoS.Pathog_18_e1010552 PubMedSearch: Yu 2022 PLoS.Pathog 18 e1010552 PubMedID: 35679229 Abstract Arboviruses are etiological agents of various severe human diseases that place a tremendous burden on global public health and the economy; compounding this issue is the fact that effective prophylactics and therapeutics are lacking for most arboviruses. Herein, we identified 2 bacterial lipases secreted by a Chromobacterium bacterium isolated from Aedes aegypti midgut, Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with broad-spectrum virucidal activity against mosquito-borne viruses, such as dengue virus (DENV), Zika virus (ZIKV), Japanese encephalitis virus (JEV), yellow fever virus (YFV) and Sindbis virus (SINV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation in the lipase motif of CbAE-1 fully abrogated the virucidal ability. Furthermore, CbAEs also exert lipase-dependent entomopathogenic activity in mosquitoes. The anti-arboviral and entomopathogenic properties of CbAEs render them potential candidates for the development of novel transmission control strategies against vector-borne diseases. Title: Substrate-Binding Mode of a Thermophilic PET Hydrolase and Engineering the Enzyme to Enhance the Hydrolytic Efficacy Zeng W, Li X, Yang Y, Min J, Huang JW, Liu W, Niu D, Yang X, Han X and Guo RT <3 more author(s)> Zeng W, Li X, Yang Y, Min J, Huang JW, Liu W, Niu D, Yang X, Han X, Zhang L, Dai L, Chen CC, Guo RT (- 3) Ref: ACS Catal, 12:3033, 2022 : PubMed ESTHER: Zeng_2022_ACS.Catal_12_3033 PubMedSearch: Zeng 2022 ACS.Catal 12 3033 Gene_locus related to this paper: 9bact-g9by57 Inhibitor(s) related to this paper: MHET Abstract Polyethylene terephthalate (PET) is among the most extensively produced plastics, but huge amounts of PET wastes that have accumulated in the environment have become a serious threat to the ecosystem. Applying PET hydrolytic enzymes to depolymerize PET is an attractive measure to manage PET pollution, and searching for more effective enzymes is a prerequisite to achieve this goal. A thermostable cutinase that originates from the leaf-branch compost termed ICCG is the most effective PET hydrolase reported so far. Here, we illustrated the crystal structure of ICCG in complex with the PET analogue, mono(2-hydroxyethyl)terephthalic acid, to reveal the enzyme-substrate interaction network. Furthermore, we applied structure-based engineering to modify ICCG and screened for variants that exhibit higher efficacy than the parental enzyme. As a result, several variants with the measured melting temperature approaching 99 C and elevated PET hydrolytic activity were obtained. Finally, crystallographic analyses were performed to reveal the structural stabilization effects mediated by the introduced mutations. These results are of importance in the context of understanding the mechanism of action of the thermostable PET hydrolytic enzyme and shall be beneficial to the development of PET biodegradation platforms. Title: Baseline lymphocyte and cholinesterase levels may be the predictors of chronic herbal drug-induced liver injury Zeng Z, Yi W, Dong JP, Chen QQ, Sun FF, Lu HH, Lin YJ, Bi XY, Yang L and Xie Y <3 more author(s)> Zeng Z, Yi W, Dong JP, Chen QQ, Sun FF, Lu HH, Lin YJ, Bi XY, Yang L, Lu Y, Zhang L, Li MH, Xie Y (- 3) Ref: Front Pharmacol, 13:962480, 2022 : PubMed ESTHER: Zeng_2022_Front.Pharmacol_13_962480 PubMedSearch: Zeng 2022 Front.Pharmacol 13 962480 PubMedID: 35991883 Abstract Objective: To investigate the factors influencing the chronicity of drug-induced liver injury (DILI) caused by Chinese herbal medicine. Methods: Patients with DILI diagnosed by using the RUCAM score were enrolled retrospectively. The subjects were patients with DILI induced by taking Chinese herbal medicine and were followed up for 48 weeks. These patients were divided into a cure group and a chronic group. The biochemical indicators were monitored at baseline and every 3 months. Logistic regression was used to analyze the risk factors of DILI chronicity. The ROC (receiver operator characteristic) curve was used to analyze the diagnostic efficiency of each factor. Results: A total of 420 patients with DILI were enrolled; 122 of them were caused by Chinese herbal medicine, 70.5% (86/122) of them were female, chronic group 31.2% (39/122), and cure group 68.0% (83/122); cholinesterase (ChE) in the chronic group was lower than that in the cure group (5467.10 +/- 2010.40 U/L vs. 6248.52 +/- 1901.78 U/L, p = 0.04, t = 2.078). There was no significant difference in the age between cured patients and chronic patients (p = 0.156, Z = -1.417). There was no significant difference between the prognosis of different genders (p = 0.521, Z = -0.639). The logistic regression analysis showed that baseline lymphocyte (OR = 0.429, 95%CI = 0.205-0.898, p = 0.025) and cholinesterase (OR = 0.088, 95%CI = 0.008-0.994, p = 0.049) were independent risk factors of drug-induced chronicity. Conclusion: Baseline lymphocyte and cholinesterase may be the predictive factors for the chronicity of Chinese herbal medicine-induced liver injury. Title: Study on pathological and clinical characteristics of chronic HBV infected patients with HBsAg positive, HBV DNA negative, HBeAg negative Zeng Z, Liu R, Cao W, Yang L, Lin Y, Bi X, Jiang T, Deng W, Wang S and Li M <13 more author(s)> Zeng Z, Liu R, Cao W, Yang L, Lin Y, Bi X, Jiang T, Deng W, Wang S, Lu H, Sun F, Shen G, Chang M, Lu Y, Wu S, Hao H, Xu M, Chen X, Hu L, Zhang L, Wan G, Xie Y, Li M (- 13) Ref: Front Immunol, 13:1113070, 2022 : PubMed ESTHER: Zeng_2022_Front.Immunol_13_1113070 PubMedSearch: Zeng 2022 Front.Immunol 13 1113070 PubMedID: 36685494 Abstract AIMS: Study of clinical characteristics of hepatitis B virus deoxyribonucleic acid (HBV DNA)-negative, hepatitis B surface antigen (HBsAg)-positive, hepatitis B e antigen (HBeAg)-negative patients based on liver histopathology. METHODS: We retrospectively enrolled patients with chronic HBV infection diagnosis at Beijing Ditan Hospital from May 2008 to November 2020. To study the differences between patients with significant hepatic histopathology and those without significant hepatic histopathology. And to study the independent factors of significant hepatic histopathology. RESULTS: 85 HBV DNA-negative and HBeAg-negative patients were 37.90 +/- 10.30 years old, 23.50% of patients with grade of inflammation (G) >1, 35.30% of patients with liver fibrosis stage (S) >1, 44.70% patients were diagnosed with significant hepatic histopathology. Compared to the no significant hepatic histopathology group, another group had older age (41.70 +/- 10.70 vs 34.80 +/- 8.87 years, t=-3.28, P=0.002), higher total bilirubin (TBIL) [14.9(10.3, 22.4) vs 11(8.9, 14.4) micromol/L, z=-2.26, P=0.024], lower cholinesterase (CHE) (t=-2.86, P=0.005, 7388.00 +/- 2156.00 vs 8988.00 +/- 2823.00 U/L) and lower platelet (PLT) (t=2.75, P=0.007, 157.00 +/- 61.40 vs 194.00 +/- 61.00 10^9/L). Abnormal ALT patients are more likely to have significant hepatic histopathology (z=5.44, P=0.020, 66.70% vs 337.50%). G had significant correlation with CHE (P=0.008, r=-0.23), alanine aminotransferase (ALT) (P=0.041, r=0.18), aspartate aminotransferase (AST) (P=0.001, r=0.29). S had significant correlation with TBIL (P = 0.008, r = 0.23), age (P < 0.001, r = 0.32), international normalized ratio (INR) (P = 0.04, r = 0.23), CHE (P < 0.001, r = -0.30), PLT (P < 0.001, r = -0.40) and prothrombin time activity (PTA) (P = 0.046, r = -0.22). Multivariate logistic analysis indicated only age (95%CI=1.014~1.130, OR=1.069, P=0.013) was an impact factor for significant hepatic histopathology. The cutoff point of age was 34.30 years. CONCLUSIONS: A large proportion of chronic HBV infection patients with HBeAg-negative and HBV DNA-negative still have chronic hepatitis. Age is an independent factor for significant hepatic histopathology. Title: Toxicity, Horizontal Transfer, Physiological and Behavioral Effects of Cycloxaprid against Solenopsis invicta (Hymenoptera: Formicidae) Zhang L, Wang L, Chen J, Zhang J, He Y, Lu Y, Cai J, Chen X, Wen X and Wang C <1 more author(s)> Zhang L, Wang L, Chen J, Zhang J, He Y, Lu Y, Cai J, Chen X, Wen X, Xu Z, Wang C (- 1) Ref: Pest Manag Sci, :, 2022 : PubMed ESTHER: Zhang_2022_Pest.Manag.Sci__ PubMedSearch: Zhang 2022 Pest.Manag.Sci PubMedID: 35192738 Abstract BACKGROUND: The red imported fire ant, Solenopsis invicta Buren, is a significant urban, agricultural, and medical pest with a wide distribution in the world. Surface or mound treatment using contact insecticide is one of the main methods to control S. invicta. In the present study, cycloxaprid, a newly-discovered neonicotinoid insecticide, was evaluated for S. invicta control and compared with two referent insecticides, imidacloprid and bifenthrin. RESULTS: Surfaces or sand treated with cycloxaprid, imidacloprid, or bifenthrin caused high mortality of S. invicta workers, and the action of cycloxaprid or imidacloprid was slower than bifenthrin. Like imidacloprid and bifenthrin, cycloxaprid can be horizontally transferred from corpses or live donor ants to recipient ants. In addition, cycloxaprid- or imidacloprid-treated surfaces significantly induced the activities of acetylcholinesterase (AChE) and detoxification enzymes; nevertheless, they had no significant effect on the foraging behaviors of S. invicta workers. Also, sand treated with cycloxaprid or imidacloprid did not negatively affect the digging activities of ants. Interestingly, S. invicta workers excavated significantly more sand containing 0.01 mg/kg cycloxaprid than untreated sand in the no-choice digging bioassays. In addition, extensive nesting activities (sand excavation and stacking) were observed in the flowerpots containing untreated sand or sand treated with cycloxaprid or imidacloprid. On the contrary, bifenthrin significantly reduced the foraging, digging, and nesting activities of S. invicta workers. CONCLUSION: Cycloxaprid is a slow-acting and non-repellent insecticide against S. invicta workers, and its contact and horizontal toxicities are slightly higher than imidacloprid. This article is protected by copyright. All rights reserved. Title: GR24-mediated enhancement of salt tolerance and roles of H(2)O(2) and Ca(2+) in regulating this enhancement in cucumber Zhang XH, Ma C, Zhang L, Su M, Wang J, Zheng S, Zhang TG Ref: J Plant Physiol, 270:153640, 2022 : PubMed ESTHER: Zhang_2022_J.Plant.Physiol_270_153640 PubMedSearch: Zhang 2022 J.Plant.Physiol 270 153640 PubMedID: 35168135 Abstract This study investigated the regulation of the exogenous strigolactone (SL) analog GR24 in enhancing the salt tolerance and the effects of calcium ion (Ca(2+)) and hydrogen peroxide (H(2)O(2)) on GR24's regulation effects in cucumber. The seedlings were sprayed with (1) distilled water (CK), (2) NaCl, (3) GR24, then NaCl, (4) GR24, then H(2)O(2) scavenger, then NaCl, and (5) GR24, then Ca(2+) blocker, then NaCl. The second true leaf was selected for biochemical assays. Under the salt stress, the exogenous GR24 maintained the ion balance, increased the activity of antioxidant enzymes, reduced the membrane lipid peroxidation, and increased the activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX), accompanied by a decrease in relative conductivity, an increase in the proline content, and elevated gene expression levels of antioxidant enzymes, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, calcium-dependent protein kinases (CDPKs), salt overly sensitive SOS1, CBL-interacting protein kinase 2 (CIPK2), and calcineurin B-like protein 3 (CBL3). Such protective effects triggered by GR24 were attenuated or almost abolished by ethylene glycol tetraacetic acid (EGTA), lanthanum chloride (LaCl3, Ca(2+) channel blocker), diphenyleneiodonium (DPI, NADPH oxidase inhibitor), and dimethylthiourea (DMTU, hydroxyl radical scavenger). Our data suggest that exogenous GR24 is highly effective in alleviating salt-induced damages via modulating antioxidant capabilities and improving ionic homeostasis and osmotic balance and that H(2)O(2) and Ca(2+) are required for GR24-mediated enhancement of salt tolerance. Title: Untargeted Phenolic Profiling and Functional Insights of the Aerial Parts and Bulbs of Drimia maritima (L.) Stearn Zhang L, Zengin G, Mahomoodally MF, Yildiztugay E, Jugreet S, Simal-Gandara J, Rouphael Y, Pannico A, Lucini L Ref: Plants (Basel), 11:, 2022 : PubMed ESTHER: Zhang_2022_Plants.(Basel)_11_ PubMedSearch: Zhang 2022 Plants.(Basel) 11 PubMedID: 35270070 Abstract Drimia maritima (L.) Stearn (squill), belonging to the Asparagaceae family, is acknowledged as a medicinally valuable species from the Drimia genera. In this study, water, methanol, and ethyl acetate extracts of D. maritima aerial parts and bulbs were investigated for their polyphenols profile and evaluated for their antioxidant and enzyme inhibition properties. Phenolics were profiled through an untargeted metabolomics approach using an ultra-high pressure liquid chromatograph coupled to quadrupole-time-of-flight mass spectrometry (UHPLC-QTOF-MS). This analysis revealed an enrichment of low molecular weight phenolics and flavonoids in the aerial parts of D. maritima, while lignans mainly characterized bulb extracts. Antioxidant capacity was investigated by different assays, including phosphomolybdenum assays, radical scavenging (DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)), as well as reducing ability (CUPRAC: cupric reducing antioxidant capacity; FRAP: ferric reducing antioxidant power), and metal chelating. In radical scavenging and reducing power assays, the water extract of aerial parts exhibited the strongest ability (DPPH: 36.99 mg trolox equivalent (TE)/g; ABTS: 85.96 mg TE/g; CUPRAC: 87.37 mg TE/g; FRAP: 55.43 mg TE/g). In general, the ethyl acetate extracts from aerial parts and bulbs provided the weakest antioxidant capacity. Concerning enzyme inhibitory activities, the water extracts of the bulb were poorly active, while the ethyl acetate extracts from both plant portions displayed the best alpha-amylase inhibitory abilities. The best acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) abilities were recorded by ethyl acetate extract of aerial parts (2.36 mg galantamine equivalent (GALAE)/g) and bulbs (5.10 mg GALAE/g), respectively. Overall, these results support the medicinal aptitude of D. maritima and its possible use as a natural source of antioxidants and enzyme inhibitors with functional potential. Title: Molecular and Biochemical Analyses of a Novel Trifunctional Endoxylanase/Endoglucanase/Feruloyl Esterase from the Human Colonic Bacterium Bacteroides intestinalis DSM 17393 Zhang R, Lin D, Zhang L, Zhan R, Wang S, Wang K Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: Zhang_2022_J.Agric.Food.Chem__ PubMedSearch: Zhang 2022 J.Agric.Food.Chem PubMedID: 35316064 Gene_locus related to this paper: 9bace-b3c594 Abstract A novel enzyme Bi76 comprising GH10, E_set_Esterase_N, and CE1 modules was identified, with the highest homology (62.9%) with a bifunctional endoxylanase/feruloyl esterase among characterized enzymes. Interestingly, Bi76 hydrolyzed glucan substrates besides xylans and feruloylated substrates, suggesting that it is the first characterized trifunctional endoxylanase/endoglucanase/feruloyl esterase. Analyses of truncation variants revealed that GH10 and E_set_Esterase_N + CE1 modules encoded endoxylanase/endoglucanase and feruloyl esterase activities, respectively. Synergism analyses indicated that endoxylanase, alpha-l-arabinofuranosidase, and feruloyl esterase acted cooperatively in releasing ferulic acid (FA) and xylooligosaccharides from feruloylated arabinoxylan. The interdomain synergism of Bi76 overmatched the intermolecular synergism of TM1 and TM2. Importantly, Bi76 exhibited good capacity in producing FA, releasing 5.20, 4.38, 2.12, 1.35, 0.46, and 0.19 mg/g from corn bran, corn cob, wheat bran, corn stover, rice husk, and rice bran, respectively. This study expands the trifunctional endoxylanase/endoglucanase/feruloyl esterase repertoire and demonstrates the great potential of Bi76 in agricultural residue utilization. Title: A novel indene-chalcone-based fluorescence probe with lysosome-targeting for detection of endogenous carboxylesterases and bioimaging Zhang L, Yan JL, Wang Y, Zhao XL, Wu WN, Fan YC, Xu ZH, Yan LL Ref: Spectrochim Acta A Mol Biomol Spectrosc, 278:121329, 2022 : PubMed ESTHER: Zhang_2022_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_278_121329 PubMedSearch: Zhang 2022 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 278 121329 PubMedID: 35576837 Abstract An indene-chalcone-based fluorescence probe 1 was synthesized and characterized. Under physiological conditions (containing 5% DMSO), probe 1 showed satisfactory stability with a low background signal and recognized carboxylesterases (CEs) based on the catalytic hydrolysis of ester groups, releasing a significant green fluorescence. Probe 1 presents several features including a short response time (within 20 min), low detection limit (1.3 x 10(-4) U/mL) and large stokes shift (over 155 nm). Notably, commercial lysosomal dye co-staining experiments illustrated the lysosomal localization function of 1, with the probe also being used for cell and zebrafish imaging of endogenous CEs. Title: Transcriptomic Identification and Expression Profile Analysis of Odorant-Degrading Enzymes from the Asian Corn Borer Moth, Ostrinia furnacalis Zhang L, Shen Y, Jiang X, Liu S Ref: Insects, 13:, 2022 : PubMed ESTHER: Zhang_2022_Insects_13_ PubMedSearch: Zhang 2022 Insects 13 PubMedID: 36354851 Abstract The Asian corn borer moth Ostrinia furnacalis is an important lepidopteran pest of maize in Asia. Odorant-degrading enzymes (ODEs), including carboxylesterases (CCEs), glutathione S-transferases (GSTs), cytochrome P450s (CYPs), UDP-glycosyltransferases (UGTs), and aldehyde oxidases (AOXs), are responsible for rapid inactivation of odorant signals in the insect antennae. In this study, we performed a transcriptome assembly for the antennae of O. furnacalis to identify putative ODE genes. Transcriptome sequencing revealed 35,056 unigenes, and 21,012 (59.94%) of these were annotated by searching against the reference sequences in the NCBI non-redundant (NR) protein database. For functional classification, these unigenes were subjected to Gene Ontology (GO), Eukaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations. We identified 79 genes encoding putative ODEs: 19 CCEs, 17 GSTs, 24 CYPs, 13 UGTs, and 6 AOXs. BLASTX best hit results indicated that these genes shared quite high amino acid identities with their respective orthologs from other lepidopteran species. Reverse transcription-quantitative PCR showed that OfurCCE2, OfurCCE5, and OfurCCE18 were enriched in male antennae, while OfurCCE7 and OfurCCE10 were enriched in female antennae. OfurCCE14 and OfurCCE15 were expressed at near-equal amounts in the antennae of both sexes. Our findings establish a solid foundation for future studies aimed at understanding the olfactory functions of these genes in O. furnacalis. Title: Biodegradation of Free Gossypol by Helicoverpa armigera Carboxylesterase Expressed in Pichia pastoris Zhang L, Yang X, Huang R, Nie C, Niu J, Chen C, Zhang W Ref: Toxins (Basel), 14:816, 2022 : PubMed ESTHER: Zhang_2022_Toxins.(Basel)_14_816 PubMedSearch: Zhang 2022 Toxins.(Basel) 14 816 PubMedID: 36548713 Abstract Gossypol is a polyphenolic toxic secondary metabolite derived from cotton. Free gossypol in cotton meal is remarkably harmful to animals. Furthermore, microbial degradation of gossypol produces metabolites that reduce feed quality. We adopted an enzymatic method to degrade free gossypol safely and effectively. We cloned the gene cce001a encoding carboxylesterase (CarE) into pPICZalphaA and transformed it into Pichia pastoris GS115. The target protein was successfully obtained, and CarE CCE001a could effectively degrade free gossypol with a degradation rate of 89%. When esterase was added, the exposed toxic groups of gossypol reacted with different amino acids and amines to form bound gossypol, generating substances with (M + H) m/z ratios of 560.15, 600.25, and 713.46. The molecular formula was C(27)H(28)O(13), C(34)H(36)N(2)O(6), and C(47)H(59)N(3)O(3). The observed instability of the hydroxyl groups caused the substitution and shedding of the group, forming a substance with m/z of 488.26 and molecular formula C(31)H(36)O(5). These properties render the CarE CCE001a a valid candidate for the detoxification of cotton meal. Furthermore, the findings help elucidate the degradation process of gossypol in vitro. Title: The Functional Characterization of Carboxylesterases Involved in the Degradation of Volatile Esters Produced in Strawberry Fruits Zhang L, Zhou K, Wang M, Li R, Dai X, Liu Y, Jiang X, Xia T, Gao L Ref: Int J Mol Sci, 24:383, 2022 : PubMed ESTHER: Zhang_2022_Int.J.Mol.Sci_24_383 PubMedSearch: Zhang 2022 Int.J.Mol.Sci 24 383 PubMedID: 36613824 Gene_locus related to this paper: frave-FanCXE17, frave-FanCXE19, frave-FanCXE3, frave-FanCXE2, fraan-FaTA Abstract Volatile ester compounds are important contributors to the flavor of strawberry, which affect consumer preference. Here, the GC-MS results showed that volatile esters are the basic aroma components of strawberry, banana, apple, pear, and peach, and the volatile esters were significantly accumulated with the maturation of strawberry fruits. The main purpose of this study is to discuss the relationship between carboxylesterases (CXEs) and the accumulation of volatile ester components in strawberries. FaCXE2 and FaCXE3 were found to have the activity of hydrolyzing hexyl acetate, Z-3-hexenyl acetate, and E-2-hexenyl acetate to the corresponding alcohols. The enzyme kinetics results showed that FaCXE3 had the higher affinity for hexyl acetate, E-2-hexenyl acetate, and Z-3-hexenyl acetate compared with FaCXE2. The volatile esters were mainly accumulated at the maturity stages in strawberry fruits, less at the early stages, and the least during the following maturation stages. The expression of FaCXE2 gradually increased with fruit ripening and the expression level of FaCXE3 showed a decreasing trend, which suggested the complexity of the true function of CXEs. The transient expression of FaCXE2 and FaCXE3 genes in strawberry fruits resulted in a significantly decreased content of volatile esters, such as Z-3-hexenyl acetate, methyl hexanoate, methyl butyrate, and other volatile esters. Taken together, FaCXE2 and FaCXE3 are indeed involved in the regulation of the synthesis and degradation of strawberry volatile esters. 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: Dual-Modal Nanoscavenger for Detoxification of Organophosphorus Compounds Zou S, Wang B, Wang Q, Liu G, Song J, Zhang F, Li J, Wang F, He Q and Zhang L <1 more author(s)> Zou S, Wang B, Wang Q, Liu G, Song J, Zhang F, Li J, Wang F, He Q, Zhu Y, Zhang L (- 1) Ref: ACS Appl Mater Interfaces, :, 2022 : PubMed ESTHER: Zou_2022_ACS.Appl.Mater.Interfaces__ PubMedSearch: Zou 2022 ACS.Appl.Mater.Interfaces PubMedID: 36089739 Abstract Organophosphorus compounds (OPs) pose great military and civilian hazards. However, therapeutic and prophylactic antidotes against OP poisoning remain challenging. In this study, we first developed a novel nanoscavenger (rOPH/ZIF-8@E-Lipo) against methyl paraoxon (MP) poisoning using enzyme immobilization and erythrocyte-liposome hybrid membrane camouflage techniques. Then, we evaluated the physicochemical characterization, stability, and biocompatibility of the nanoscavengers. Afterward, we examined acetylcholinesterase (AChE) activity, cell viability, and intracellular reactive oxygen species (ROS) to indicate the protective effects of the nanoscavengers in vitro. Following the pharmacokinetic and biodistribution studies, we further evaluated the therapeutic and prophylactic detoxification efficacy of the nanoscavengers against MP in various poisoning settings. Finally, we explored the penetration capacity of the nanoscavengers across the blood-brain barrier (BBB). The present study validated the successful construction of a novel nanoscavenger with excellent stability and biocompatibility. In vitro, the resulting nanoscavenger exhibited a significant protection against MP-induced AChE inactivation, oxidative stress, and cytotoxicity. In vivo, apart from the positive therapeutic effects, the nanoscavengers also exerted significant prophylactic detoxification efficacy against single lethal MP exposure, repeated lethal MP challenges, and sublethal MP poisoning. These excellent detoxification effects of the nanoscavengers against OPs may originate from a dual-mode mechanism of inner recombinant organophosphorus hydrolase (rOPH) and outer erythrocyte membrane-anchored AChE. Finally, in vitro and in vivo studies jointly demonstrated that monosialoganglioside (GM1)-modified rOPH/ZIF-8@E-Lipo could penetrate the BBB with high efficiency. In conclusion, a stable and safe dual-modal nanoscavenger was developed with BBB penetration capability, providing a promising strategy for the treatment and prevention of OP poisoning. Title: Untargeted Phytochemical Profile, Antioxidant Capacity and Enzyme Inhibitory Activity of Cultivated and Wild Lupin Seeds from Tunisia Ben Hassine A, Rocchetti G, Zhang L, Senizza B, Zengin G, Mahomoodally MF, Ben-Attia M, Rouphael Y, Lucini L, El-Bok S Ref: Molecules, 26:, 2021 : PubMed ESTHER: Ben Hassine_2021_Molecules_26_ PubMedSearch: Ben Hassine 2021 Molecules 26 PubMedID: 34200152 Abstract Lupin seeds can represent a valuable source of phenolics and other antioxidant compounds. In this work, a comprehensive analysis of the phytochemical profile was performed on seeds from three Lupinus species, including one cultivar (Lupinus albus) and two wild accessions (Lupinus cossentinii and Lupinus luteus), collected from the northern region of Tunisia. Untargeted metabolomic profiling allowed to identify 249 compounds, with a great abundance of phenolics and alkaloids. In this regard, the species L. cossentinii showed the highest phenolic content, being 6.54 mg/g DW, followed by L. luteus (1.60 mg/g DW) and L. albus (1.14 mg/g DW). The in vitro antioxidant capacity measured by the ABTS assay on seed extracts ranged from 4.67 to 17.58 mg trolox equivalents (TE)/g, recording the highest values for L. albus and the lowest for L. luteus. The DPPH radical scavenging activity ranged from 0.39 to 3.50 mg TE/g. FRAP values varied between 4.11 and 5.75 mg TE/g. CUPRAC values for lupin seeds ranged from 7.20 to 8.95 mg TE/g, recording the highest for L. cossentinii. The results of phosphomolybdenum assay and metal chelation showed similarity between the three species of Lupinus. The acetylcholinesterase (AChE) inhibition activity was detected in each methanolic extract analyzed with similar results. Regarding the butyrylcholinesterase (BChE) enzyme, it was weakly inhibited by the Lupinus extracts; in particular, the highest activity values were recorded for L. albus (1.74 mg GALAE/g). Overall, our results showed that L. cossentinii was the most abundant source of polyphenols, consisting mainly in tyrosol equivalents (5.82 mg/g DW). Finally, significant correlations were outlined between the phenolic compounds and the in vitro biological activity measured, particularly when considering flavones, phenolic acids and lower-molecular-weight phenolics. Title: General features to enhance enzymatic activity of poly(ethylene terephthalate) hydrolysis Chen CC, Han X, Li X, Jiang P, Niu D, Ma L, Liu W, Li S, Qu Y and Chen, CC <8 more author(s)> Chen CC, Han X, Li X, Jiang P, Niu D, Ma L, Liu W, Li S, Qu Y, Hu H, Min J, Yang Y, Zhang L, Zeng W, Huang JW, Dai L, Guo RT, Chen, CC (- 8) Ref: Nature Catalysis, 4:425, 2021 : PubMed ESTHER: Chen_2021_Nat.Catal_4_425 PubMedSearch: Chen 2021 Nat.Catal 4 425 Gene_locus related to this paper: 9burk-a0a1f4jxw8, idesa-peth Abstract Poly(ethylene terephthalate) (PET) is the most abundant polyester plastic and a major contributor to plastic pollution. IsPETase, from the PET-assimilating bacterium Ideonella sakaiensis, is a unique PET-hydrolytic enzyme that shares high sequence identity to canonical cutinases, but shows substrate preference towards PET and exhibits higher PET-hydrolytic activity at ambient temperature. Structural analyses suggest that IsPETase harbours a substrate-binding residue, W185, with a wobbling conformation and a highly flexible W185-locating beta6-beta7 loop. Here, we show that these features result from the presence of S214 and I218 in IsPETase, whose equivalents are strictly His and Phe, respectively, in all other homologous enzymes. We found that mutating His/Phe residues to Ser/Ile could enhance the PET-hydrolytic activity of several IsPETase-like enzymes. In conclusion, the Ser/Ile mutations should provide an important strategy to improve the activity of potential PET-hydrolytic enzymes with properties that may be useful for various applications. Title: Less unfavorable salt-bridges on the enzyme surface results in more organic cosolvent resistance Cui H, Eltoukhy L, Zhang L, Markel U, Jaeger KE, Davari MD, Schwaneberg U Ref: Angew Chem Int Ed Engl, :, 2021 : PubMed ESTHER: Cui_2021_Angew.Chem.Int.Ed.Engl__ PubMedSearch: Cui 2021 Angew.Chem.Int.Ed.Engl PubMedID: 33687787 Gene_locus related to this paper: bacsu-LIPB Abstract Biocatalysis for the synthesis of fine chemicals is highly attractive but usually requires organic (co-)solvents (OSs). However, native enzymes often have low activity and resistance in OSs and at elevated temperatures. Herein, we report a smart salt bridge design strategy for simultaneously improving OS resistance and thermostability of the model enzyme, Bacillus subtilits Lipase A (BSLA). We combined comprehensive experimental studies of 3450 BSLA variants and molecular dynamics simulations of 36 systems. Iterative recombination of four beneficial substitutions yielded superior resistant variants with up to 7.6-fold (D64K/D144K) improved resistance toward three OSs while exhibiting significant thermostability (thermal resistance up to 137-fold, and half-life up to 3.3-fold). Molecular dynamics simulations revealed that locally refined flexibility and strengthened hydration jointly govern the highly increased resistance in OSs and at 50-100 degreesC. The salt bridge redesign provides protein engineers with a powerful and likely general approach to design OSs- and/or thermal-resistant lipases and other alpha/beta-hydrolases. Title: Design, synthesis, and cholinesterase inhibition assay of liquiritigenin derivatives as anti-Alzheimer's activity Guan L, Peng D, Zhang L, Jia J, Jiang H Ref: Bioorganic & Medicinal Chemistry Lett, :128306, 2021 : PubMed ESTHER: Guan_2021_Bioorg.Med.Chem.Lett__128306 PubMedSearch: Guan 2021 Bioorg.Med.Chem.Lett 128306 PubMedID: 34371131 Abstract The marine environment is a rich resource for discovering functional materials, and seaweed is recognized for its potential use in biology and medicine. Liquiritigenin has been isolated and identified from Sargassum pallidum. To find new anti-Alzheimer's activity, we designed and synthesized thirty-two 7-prenyloxy-2,3-dihydroflavanone derivatives (3a-3p) and 5-hydroxy-7-prenyloxy-2,3-dihydro- flavanone derivatives (4a-4p) as cholinesterases inhibitors based on liquiritigenin as the lead compound. Inhibition screening against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) indicated that all synthesized compounds possessed potent AChE inhibitory activity and moderated to weak BuChE inhibitory activity in vitro. Kinetic studies demonstrated that compound 4o inhibited AChE via a dual binding site ability. In addition, all compounds displayed the radical scavenging effects. Finally, the molecular docking simulation of 4o in AChE active site displayed good agreement with the obtained the pharmacological results. Title: Overexpression of serum lncRNA-ABHD11-AS1 as poor prognosis of patients with papillary thyroid carcinoma Hou S, Zhuang YY, Lin QY, Chen Z, Zhao HG, Zhang L, Lin CH Ref: Exp Mol Pathol, 121:104658, 2021 : PubMed ESTHER: Hou_2021_Exp.Mol.Pathol_121_104658 PubMedSearch: Hou 2021 Exp.Mol.Pathol 121 104658 PubMedID: 34102210 Abstract This paper was aimed at exploring the correlation of long non-coding RNA (lncRNA)-ABHD11 Antisense RNA1 (ABHD11-AS1) with the poor prognosis of patients with papillary thyroid carcinoma (PTC) and at investigating its effects on the survival of PTC cells. Serum was respectively collected from 64 PTC patients who were admitted to our hospital (PTC group) and from 50 healthy controls who underwent physical examinations (HC group) both from April 2011 to April 2015. The expression levels of ABHD11-AS1 in the serum were detected, and the values of it for diagnosis and prognosis (5-year follow-ups) were analyzed. The knockdown and overexpression models of ABHD11-AS1 in were constructed to explore the effects of the models on their proliferation, cycles and apoptosis. According to the data, the expression levels of serum ABHD11-AS1 in the PTC patients were remarkably higher than those in the healthy controls, and the area under the curve (AUC) for distinguishing the patients from the controls was 0.920. In the analysis of prognosis, the levels in patients with a poor prognosis were remarkably higher than those in patients with a good prognosis. According to the curves of overall survival rates (OSRs), the high levels of ABHD11-AS1 were remarkably correlated with the poor prognosis (a lower 5-year OSR). COX analysis showed that TNM staging, lymph node metastasis and ABHD11-AS1 were the independent prognostic factors of PTC patients. In the cell experiments, knocking down ABHD11-AS1 remarkably inhibited PTC cells from proliferation, arrested them in G0/G1 phase, and induced their apoptosis, negatively affecting their survival indices. Overexpressing this RNA had positive effects on the survival indices. Taken together, high levels of serum ABHD11-AS1 are related to the poor prognosis of PTC patients, and knocking down its expression can inhibit the survival of PTC cells. Title: Identification of Detoxification Esterase StrH Initiating Strobilurin Fungicides Degradation in Hyphomicrobium sp. DY-1 Jiang W, Gao Q, Zhang L, Liu Y, Zhang M, Ke Z, Zhou Y, Hong Q Ref: Applied Environmental Microbiology, :, 2021 : PubMed ESTHER: Jiang_2021_Appl.Environ.Microbiol__ PubMedSearch: Jiang 2021 Appl.Environ.Microbiol PubMedID: 33741617 Gene_locus related to this paper: hypsm-strH Abstract Strobilurin fungicides are widely used in agricultural production due to their broad-spectrum and fungal mitochondrial inhibitory activities. However, their massive application has detained the growth of eukaryotic algae and increased the collateral damage in freshwater systems, notably the harmful cyanobacterial blooms (HCBs). In this study, a strobilurin fungicide-degrading strain Hyphomicrobium sp. DY-1 was isolated and characterized successfully. Moreover, a novel esterase gene strH responsible for the de-esterification of strobilurin fungicides was cloned, and the enzymatic properties of StrH were studied. For trifloxystrobin, StrH displayed the maximum activity at 50 degreesC and pH 7.0. The catalytic efficiency (k (cat)/K (m)) of StrH for different strobilurin fungicides were 196.32+/-2.30 microM(-1).s(-1) (trifloxystrobin), 4.64+/-0.05 microM(-1).s(-1) (picoxystrobin), 2.94+/-0.02 microM(-1).s(-1) (pyraclostrobin), and (2.41+/-0.19)x10(-2) microM(-1).s(-1) (azoxystrobin). StrH catalyzed the de-esterification of a variety of strobilurin fungicides generating the corresponding parent acid to achieve the detoxification of strobilurin fungicides and relieve strobilurin fungicides growth inhibition on Chlorella This research will provide insight into the microbial remediation of strobilurin fungicides-contaminated environments.IMPORTANCEStrobilurin fungicides have been widely acknowledged as an essential group of pesticides worldwide. So far, their residues and toxic effects on aquatic organisms have been reported in different parts of the world. Microbial degradation could eliminate xenobiotics from the environment. Therefore, the degradation of strobilurin fungicides by microorganisms has also been reported. However, little is known about the involvement of enzyme or gene in strobilurin fungicides degradation. In this study, a novel esterase gene strH responsible for the detoxification of strobilurin fungicides was cloned in the newly isolated strain Hyphomicrobium sp. DY-1. This degradation process detoxifies the strobilurin fungicides and relieves their growth inhibition on Chlorella. Title: A ratiometric fluorescence strategy based on inner filter effect for Cu(2+)-mediated detection of acetylcholinesterase Li Y, Liang H, Lin B, Yu Y, Wang Y, Zhang L, Cao Y, Guo M Ref: Mikrochim Acta, 188:385, 2021 : PubMed ESTHER: Li_2021_Mikrochim.Acta_188_385 PubMedSearch: Li 2021 Mikrochim.Acta 188 385 PubMedID: 34664146 Abstract A novel ratiometric fluorescence strategy for detection of acetylcholestinerase (AChE) is proposed based on carbon nitride quantum dots (g-CNQD) and the complex (PA) formed between phenylboronic acid (PBA) and alizarin red S (ARS). PA showed fluorescence at 598 nm and quenched the fluorescence of g-CNQD at 438 nm. Through UV-visible absorption, fluorescence, and fluorescence lifetime measurements, the quenching effect was demonstrated as inner filter effect (IFE). When Cu(2+) was added, the coordination of ARS and Cu(2+) decreased the fluorescence of PA at 598 nm and recovered that of g-CNQD at 438 nm. In the presence of AChE it catalyzed the hydrolysis of acetylthiocholine (ATCh) to produce thiocholine (TCh) which competed with ARS for binding to Cu(2+); thus, the fluorescence at 598 nm increased and that at 438 nm decreased again. Under the mediation of Cu(2+), the fluorescence ratio F(598)/F(438) of PA-CNQD probe had good linear relationship with AChE concentration in the range 0.5-15 mU/mL with a detection limit of 0.36 mU/mL. The method was successfully applied to the determination of AChE in human serum and the screening of inhibitors. Title: The functional potential of nine Allium species related to their untargeted phytochemical characterization, antioxidant capacity and enzyme inhibitory ability Rocchetti G, Zhang L, Bocchi S, Giuberti G, Ak G, Elbasan F, Yildiztugay E, Ceylan R, Picot-Allain MCN and Zengin G <2 more author(s)> Rocchetti G, Zhang L, Bocchi S, Giuberti G, Ak G, Elbasan F, Yildiztugay E, Ceylan R, Picot-Allain MCN, Mahomoodally MF, Lucini L, Zengin G (- 2) Ref: Food Chem, 368:130782, 2021 : PubMed ESTHER: Rocchetti_2021_Food.Chem_368_130782 PubMedSearch: Rocchetti 2021 Food.Chem 368 130782 PubMedID: 34392121 Abstract In this study, the aerial parts and bulbs of nine Allium species were investigated for their functional phytochemical profile, in vitro antioxidant activities, acetylcholinesterase (AChE), butyrylcholinesterase (BChE), alpha-amylase, alpha-glucosidase, and tyrosinase inhibitory properties. Phenolics, alkaloids, glucosinolates and other sulfur-containing compounds were distinctively profiled in the different species. Maceration in methanol allowed recovering the highest cumulative phenolic content in A. scabrifolium (42.31 mg/g), followed by A. goekyigiti (33.15 mg/g) and A. atroviolaceum (28.35 mg/g). The aerial parts of all Allium species showed high in vitro antioxidant activity whereas methanolic extract of A. cappadocicum bulb showed the highest inhibition against AChE (2.44 mg galantamine equivalent/g) and the water extracts of A. isauricum aerial part were the best BChE inhibitors (4.31 mg galantamine equivalent/g). Bulbs were the richer source of oligosaccharides, and in vitro digestion determined an increase of oligosaccharides bioaccessibility. A promising nutraceutical potential could be highlighted in our understudied Allium species. Title: Metabolomic profiling and biological properties of six Limonium species: novel perspectives for nutraceutical purposes Senizza B, Zhang L, Rocchetti G, Zengin G, Ak G, Yildiztugay E, Elbasan F, Jugreet S, Mahomoodally MF, Lucini L Ref: Food Funct, 12:3443, 2021 : PubMed ESTHER: Senizza_2021_Food.Funct_12_3443 PubMedSearch: Senizza 2021 Food.Funct 12 3443 PubMedID: 33900332 Abstract The genus Limonium includes important halophyte plants containing a variety of bioactive compounds of therapeutic interest. In the present work, the untargeted phytochemical profiles of both aerial part and root extracts from six Limonium species namely, L. bellidifolium, L. globuliferum, L. gmelinii, L. lilacinum, L. sinuatum and L. iconicum from Turkey were determined. Furthermore, several biological activities (in vitro antioxidant and enzyme inhibitory effects) were investigated. Overall, significant amounts of total phenolics (43.64-238.18 mg g-1) and flavonoids (1.61-129.69 mg g-1) were recorded. Particularly, the root extracts of L. gmelinii, L. iconicum and L. globuliferum showed the highest total phenolic content (204.13-238.18 mg g-1), whilst the highest total flavonoid content was recorded in the root extracts of L. gmelinii (129.69 mg g-1). Overall, the tested extracts demonstrated potent radical scavenging activities in both DPPH (2,2- diphenyl-1-picrylhydrazyl) and ABTS (3-ethylbenzothiazoline-6-sulphonic acid) (90.10-507.94 mg g-1 and 163.39-1175.34 mg g-1, respectively). However, the highest scavenging potential (p < 0.05) was displayed by the root extracts of L. iconicum. Conversely, the metal chelating ability assay revealed that L. lilacinum root extract showed the highest activity (21.03 mg g-1). Interestingly, all the extracts were found to be active inhibitors of cholinesterases (AChE (acetylcholinesterase): 4.20-5.11 mg GALAE (galantamine equivalent) per g; BChE (butyrylcholinesterase): 3.89-10.75 mg GALAE per g), amylase (0.52-1.09 mmol ACAE (acarbose equivalent) per g) and tyrosinase (119.41-155.67 mg KAE (kojic acid equivalent) per g), unlike for glucosidase (2.31-2.41 mmol ACAE per g). Taken together, these findings demonstrated a diverse chemical profiles and biological of the extracts, to be potentially considered as phytotherapeutic or functional ingredients due to their antioxidant properties and inhibition of key enzymes involved in several diseases. Title: Late-Stage Modification of Medicine: Pd-Catalyzed Direct Synthesis and Biological Evaluation of N-Aryltacrine Derivatives Wan LX, Zhen YQ, He ZX, Zhang Y, Zhang L, Li X, Gao F, Zhou XL Ref: ACS Omega, 6:9960, 2021 : PubMed ESTHER: Wan_2021_ACS.Omega_6_9960 PubMedSearch: Wan 2021 ACS.Omega 6 9960 PubMedID: 33869976 Abstract A new series of N-aryltacrine derivatives were designed and synthesized as cholinesterase inhibitors by the late-stage modification of tacrine, using the palladium-catalyzed Buchwald-Hartwig cross-coupling reaction. In vitro inhibition assay against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) demonstrated that most of the synthesized compounds had potent AChE inhibitory activity with negative inhibition of BuChE. Among them, N-(4-(trifluoromethyl)phenyl)-tacrine (3g) and N-(4-methoxypyridin-2-yl)-tacrine (3o) showed the most potent activity against AChE (IC(50) values of 1.77 and 1.48 microM, respectively). The anti-AChE activity of 3g and 3o was 3.5 times more than that of tacrine (IC(50) value of 5.16 microM). Compound 3o also displayed anti-BuChE activity with an IC(50) value of 19.00 microM. Cell-based assays against HepG2 and SH-SY5Y cell lines revealed that 3o had significantly lower hepatotoxicity compared to tacrine, with additional neuroprotective activity against H(2)O(2)-induced damage in SH-SY5Y cells. The advantages including synthetic accessibility, high potency, low toxicity, and adjunctive neuroprotective activity make compound 3o a new promising multifunctional candidate for the treatment of Alzheimer's disease. Title: Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (alpha-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities Wang Z, Tu Z, Xie X, Cui H, Kong KW, Zhang L Ref: Foods, 10:, 2021 : PubMed ESTHER: Wang_2021_Foods_10_ PubMedSearch: Wang 2021 Foods 10 PubMedID: 33546380 Abstract This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid-liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 microg GAE/mg DE) and flavonoid content (455.22 microg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful alpha-glucosidase inhibitory ability with the IC(50) value of 190.03 microg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC(50) values of 37.92 and 13.43 microg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent. Title: Influence of seasonal migration on evolution of insecticide resistance in Plutella xylostella Wang M, Zhu B, Zhang L, Xiao Y, Liang P, Wu K Ref: Insect Sci, :, 2021 : PubMed ESTHER: Wang_2021_Insect.Sci__ PubMedSearch: Wang 2021 Insect.Sci PubMedID: 34873833 Abstract The diamondback moth, Plutella xylostella (L.), is one of the most destructive migratory pest species of cruciferous vegetables worldwide and has developed resistance to most of the insecticides used for its control. The migration regularity, migratory behavior, and relationship between flight and reproduction of P. xylostella have been widely reported. However, the effect of migration on insecticide resistance in this pest is still unclear. In this study, the effect of migration on P. xylostella resistance to seven insecticides was investigated using populations across the Bohai Sea that were collected in the early and late seasons during 2017-2019. The bioassay results showed that the early season populations of P. xylostella from South China possessed much higher resistance to insecticides because of intensive insecticide application; alternatively, the late season populations migrated from Northeast China, where the insecticides were only used occasionally, showed much lower insecticide resistance. The genome re-sequencing results revealed that, among the eight mutations involved in insecticide resistance, the frequencies of two acetylcholinesterase mutations (A298S and G324A) responsible for organophosphorus insecticide resistance were significantly decreased in the late season populations. The results indicated that P. xylostella migration between tropical and temperate regions significantly delayed the development of insecticide resistance. These findings illustrated the effect of regional migration on the evolution of insecticide resistance in P. xylostella, and provided foundational information for further research on the relationship between migration and insecticide resistance development in other insects. This article is protected by copyright. All rights reserved. Title: Exposure of Helicoverpa armigera Larvae to Plant Volatile Organic Compounds Induces Cytochrome P450 Monooxygenases and Enhances Larval Tolerance to the Insecticide Methomyl Wu C, Ding C, Chen S, Wu X, Zhang L, Song Y, Li W, Zeng R Ref: Insects, 12:, 2021 : PubMed ESTHER: Wu_2021_Insects_12_ PubMedSearch: Wu 2021 Insects 12 PubMedID: 33808968 Abstract Plants release an array of volatile chemicals into the air to communicate with other organisms in the environment. Insect attack triggers emission of herbivore-induced plant volatiles (HIPVs). How insect herbivores use these odors to plan their detoxification systems is vital for insect adaptation to environmental xenobiotics. Here we show that the larvae of Helicoverpa armigera (Hubner), a broadly polyphagous lepidopteran herbivore, have the capacity to use plant volatiles as cues to upregulate multiple detoxification systems, including cytochrome P450 monooxygenases (P450s), for detoxification of insecticides. Olfactory exposure of the fifth instars to two terpene volatiles limonene and nerolidol, and two green-leaf volatiles 2-heptanone and cis-3-hexenyl acetate significantly reduced larval susceptibility to the insecticide methomyl. However, larval pretreatment with piperonyl butoxide (PBO), a known P450 inhibitor, neutralized the effects of volatile exposure. Furthermore, larval exposure to the four plant volatiles enhanced activities of P450 enzymes in midguts and fatbodies, and upregulated expression of CYP6B2, CYP6B6 and CYP6B7, P450s involved in detoxification of the insecticide. Larval exposure to 2-heptanone and limonene volatiles also enhanced activities of glutathione-s-transferase and carboxylesterase. Our findings suggest that olfactory exposure to HIPVs enhances larval insecticide tolerance via induction of detoxification P450s. Title: Case Report/Case Series: Rare case of anti-LGI1 limbic encephalitis with rapidly progressive dementia, psychiatric symptoms, and frequently seizures: A case report Wu H, Mei F, Liu L, Zhang L, Hao H, Zhang S Ref: Medicine (Baltimore), 100:e26654, 2021 : PubMed ESTHER: Wu_2021_Medicine.(Baltimore)_100_e26654 PubMedSearch: Wu 2021 Medicine.(Baltimore) 100 e26654 PubMedID: 34398024 Abstract RATIONALE: Anti leucine-rich glioma inactivated 1 (LGI1) limbic encephalitis (LE) is rare autoimmune encephalitis, characterized by acute or subacute cognitive impairment, faciobrachial dystonic seizures, mental disorders, and refractory hyponatremia. As a type of treatable rapidly progressive dementia with a good prognosis, early, and accurate diagnosis is essential. We present a case of anti-LGI1 LE who was initially misdiagnosed with Alzheimer disease because his clinical manifestations were similar to Alzheimer disease. PATIENT CONCERNS: A male patient presenting with rapidly progressive dementia, faciobrachial dystonic seizures, psychiatric disturbance, and refractory hyponatremia was admitted. The scores of Mini-Mental State Examination, Montreal Cognitive Assessment, and Neuropsychiatric Inventory were 19/30, 16/30, and 91/144, respectively. Brain magnetic resonance images indicated moderate atrophy of the hippocampus and abnormally hyperintensities in the left medial temporal and hippocampus. DIAGNOSIS: The patient was diagnosed with anti-LGI1 LE based on the presence of LGI-1 antibodies in the cerebrospinal fluid and serum and clinical manifestations. INTERVENTIONS: Patient was treated with glucocorticoid against LGI1, antiepileptic drug, cholinesterase inhibitors, and other adjuvant therapy. OUTCOMES: The patient showed marked improvement on immunotherapy. Clinical symptoms were disappeared and the LGI-1 antibodies in cerebrospinal fluid and serum were both negative at the time of discharge. CONCLUSIONS: Recognition of the specific symptoms and LGI-1 antibody test will be helpful for the early diagnosis, prompt immunotherapy, and good prognosis. This case raises the awareness that rapidly progressive dementia with frequent seizures could be caused by immunoreactions. Title: Genome-wide analysis of the serine carboxypeptidase-like protein family in Triticum aestivum reveals TaSCPL184-6D is involved in abiotic stress response Xu X, Zhang L, Zhao W, Fu L, Han Y, Wang K, Yan L, Li Y, Zhang XH, Min DH Ref: BMC Genomics, 22:350, 2021 : PubMed ESTHER: Xu_2021_BMC.Genomics_22_350 PubMedSearch: Xu 2021 BMC.Genomics 22 350 PubMedID: 33992092 Abstract BACKGROUND: The serine carboxypeptidase-like protein (SCPL) family plays a vital role in stress response, growth, development and pathogen defense. However, the identification and functional analysis of SCPL gene family members have not yet been performed in wheat. RESULTS: In this study, we identified a total of 210 candidate genes encoding SCPL proteins in wheat. According to their structural characteristics, it is possible to divide these members into three subfamilies: CPI, CPII and CPIII. We uncovered a total of 209 TaSCPL genes unevenly distributed across 21 wheat chromosomes, of which 65.7% are present in triads. Gene duplication analysis showed that ~ 10.5% and ~ 64.8% of the TaSCPL genes are derived from tandem and segmental duplication events, respectively. Moreover, the Ka/Ks ratios between duplicated TaSCPL gene pairs were lower than 0.6, which suggests the action of strong purifying selection. Gene structure analysis showed that most of the TaSCPL genes contain multiple introns and that the motifs present in each subfamily are relatively conserved. Our analysis on cis-acting elements showed that the promoter sequences of TaSCPL genes are enriched in drought-, ABA- and MeJA-responsive elements. In addition, we studied the expression profiles of TaSCPL genes in different tissues at different developmental stages. We then evaluated the expression levels of four TaSCPL genes by qRT-PCR, and selected TaSCPL184-6D for further downstream analysis. The results showed an enhanced drought and salt tolerance among TaSCPL184-6D transgenic Arabidopsis plants, and that the overexpression of the gene increased proline and decreased malondialdehyde levels, which might help plants adapting to adverse environments. Our results provide comprehensive analyses of wheat SCPL genes that might work as a reference for future studies aimed at improving drought and salt tolerance in wheat. CONCLUSIONS: We conducte a comprehensive bioinformatic analysis of the TaSCPL gene family in wheat, which revealing the potential roles of TaSCPL genes in abiotic stress. Our analysis also provides useful resources for improving the resistance of wheat. Title: Twin drug design, synthesis and evaluation of diosgenin derivatives as multitargeted agents for the treatment of vascular dementia Yang GX, Sun JM, Zheng LL, Zhang L, Li J, Gan HX, Huang Y, Huang J, Diao XX and Ma L <2 more author(s)> Yang GX, Sun JM, Zheng LL, Zhang L, Li J, Gan HX, Huang Y, Huang J, Diao XX, Tang Y, Wang R, Ma L (- 2) Ref: Bioorganic & Medicinal Chemistry, 37:116109, 2021 : PubMed ESTHER: Yang_2021_Bioorg.Med.Chem_37_116109 PubMedSearch: Yang 2021 Bioorg.Med.Chem 37 116109 PubMedID: 33780813 Abstract A novel series of multitargeted molecules were designed and synthesized by combining the pharmacological role of cholinesterase inhibitor and antioxidant of steroid as potential ligands for the treatment of Vascular Dementia (VD). The oxygen-glucose deprivation (OGD) model was used to evaluate these molecules, among which the most potent compound ML5 showed the highest activity. Firstly, ML5 showed appropriate inhibition of cholinesterases (ChEs) at orally 15 mg/kg in vivo. The further test revealed that ML5 promoted the nuclear translocation of Nrf2. Furthermore, ML5 has significant neuroprotective effect in vivo model of bilateral common carotid artery occlusion (BCCAO), significantly increasing the expression of Nrf2 protein in the cerebral cortex. In the molecular docking research, we predicted the ML5 combined with hAChE and Keap1. Finally, compound ML5 displayed normal oral absorption and it was nontoxic at 500 mg/kg, po, dose. We can draw the conclusion that ML5 could be considered as a new potential compound for VD treatment. 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: Reversal of motor-skill transfer impairment by trihexyphenidyl and reduction of dorsolateral striatal cholinergic interneurons in Dyt1 GAG knock-in mice Yokoi F, Dang MT, Zhang L, Dexter KM, Efimenko I, Krishnaswamy S, Villanueva M, Misztal CI, Gerard M and Li Y <1 more author(s)> Yokoi F, Dang MT, Zhang L, Dexter KM, Efimenko I, Krishnaswamy S, Villanueva M, Misztal CI, Gerard M, Lynch P, Li Y (- 1) Ref: IBRO Neurosci Rep, 11:1, 2021 : PubMed ESTHER: Yokoi_2021_IBRO.Neurosci.Rep_11_1 PubMedSearch: Yokoi 2021 IBRO.Neurosci.Rep 11 1 PubMedID: 34189496 Abstract DYT-TOR1A or DYT1 early-onset generalized dystonia is an inherited movement disorder characterized by sustained muscle contractions causing twisting, repetitive movements, or abnormal postures. The majority of the DYT1 dystonia patients have a trinucleotide GAG deletion in DYT1/TOR1A. Trihexyphenidyl (THP), an antagonist for excitatory muscarinic acetylcholine receptor M1, is commonly used to treat dystonia. Dyt1 heterozygous deltaGAG knock-in (KI) mice, which have the corresponding mutation, exhibit impaired motor-skill transfer. Here, the effect of THP injection during the treadmill training period on the motor-skill transfer to the accelerated rotarod performance was examined. THP treatment reversed the motor-skill transfer impairment in Dyt1 KI mice. Immunohistochemistry showed that Dyt1 KI mice had a significant reduction of the dorsolateral striatal cholinergic interneurons. In contrast, Western blot analysis showed no significant alteration in the expression levels of the striatal enzymes and transporters involved in the acetylcholine metabolism. The results suggest a functional alteration of the cholinergic system underlying the impairment of motor-skill transfer and the pathogenesis of DYT1 dystonia. Training with THP in a motor task may improve another motor skill performance in DYT1 dystonia. Title: Functional Characterization and Crystal Structure of the Bifunctional Thioesterase Catalyzing Epimerization and Cyclization in Skyllamycin Biosynthesis Yu J, Juan S, Chi C, Liu T, Geng T, Cai Z, Dong W, Shi C, Ma X and Ma M <6 more author(s)> Yu J, Juan S, Chi C, Liu T, Geng T, Cai Z, Dong W, Shi C, Ma X, Zhang Z, Xing B, Jin H, Zhang L, Dong S, Yang D, Ma M (- 6) Ref: ACS Catal, 11:11733, 2021 : PubMed ESTHER: Yu_2021_ACS.Catalysis_11_11733 PubMedSearch: Yu 2021 ACS.Catalysis 11 11733 Gene_locus related to this paper: strsq-a0a1j0r317 Abstract The d-amino acid residues are hallmark building blocks of nonribosomal peptides. Here, we report the bifunctional thioesterase domain (TE domain) Skyxy-TE that catalyzes both epimerization and cyclization in skyllamycin biosynthesis. Skyxy-TE specifically catalyzes the epimerization of the C-terminal l-amino acid residue of the linear substrate, then catalyzes regioselective intramolecular cyclization. The crystal structure of Skyxy-TE was solved at 2.25 and site-directed mutagenesis was performed, revealing key residues involved in the epimerization and cyclization. This study expands the understanding of the versatile TE domains and facilitates chemoenzymatic synthesis or combinatorial biosynthesis in the future. Title: Clinical Evaluation and Test of a Modified Lp-PLA2 Kit in Diagnosing Atherosclerosis Yuan L, Hou L, Zhang L, Qin Z, Yu C Ref: Clin Lab, 67:, 2021 : PubMed ESTHER: Yuan_2021_Clin.Lab_67_ PubMedSearch: Yuan 2021 Clin.Lab 67 PubMedID: 34383412 Abstract BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2) has been identified as an inflammatory marker tightly correlated with the onset of atherosclerosis. Although several methodologies have been developed to detect Lp-PLA2, including enzyme-linked immunosorbent assay, Lp-PLA2 detection is still time- and resource-consuming with poor antiinterference ability and low sensitivity. Thus, it is urgent to explore new methodology for Lp-PLA2 detection. METHODS: In the current study, we evaluated the clinical performance of a modified Lp-PLA2 quantitative assay kit based on magnetic particle chemiluminescence, and analyzed the levels of Lp-PLA2 in atherosclerosis patients using this kit. RESULTS: Our results showed that the magnetic particle chemiluminescence method could effectively dissociate Lp-PLA2 from lipoprotein and finish the test within 20 minutes with high accuracy and good repeatability, as demonstrated by the results of linear measurement range, precision, and recovery rate. Furthermore, our preliminary data revealed that serum Lp-PLA2 levels were correlated to the presence and degree of atherosclerotic plaques. CONCLUSIONS: Lp-PLA2 could be helpful in diagnosing atherosclerosis. Title: Combined effects of polyethylene and organic contaminant on zebrafish (Danio rerio): Accumulation of 9-Nitroanthracene, biomarkers and intestinal microbiota Zhang J, Meng H, Kong X, Cheng X, Ma T, He H, Du W, Yang S, Li S, Zhang L Ref: Environ Pollut, 277:116767, 2021 : PubMed ESTHER: Zhang_2021_Environ.Pollut_277_116767 PubMedSearch: Zhang 2021 Environ.Pollut 277 116767 PubMedID: 33640823 Abstract Microplastics, as emerging pollutant, are predicted to act as carriers for organic pollutants, but the carrier role and bio-toxic effects with other pollutants in environments are poorly acknowledged. In this study, both the single and combined effects of polyethylene (PE, 10 and 40 mg/L) with the particle size of 100-150 microm and 9-Nitroanthracene (9-NAnt, 5 and 500 microg/L) on zebrafish (Danio rerio) had been investigated. The results illustrated that PE could be as 9-NAnt carrier to enter into zebrafish body, but significantly reduced the bioaccumulation of 9-NAnt, due to the occurrence of adsorption interactions between the simultaneous presence of both PE and 9-NAnt. After 4 days, the enzymes activity of cytochrome P4501A, acetylcholinesterase (AChE), superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), and the abundance of malondialdehyde (MDA), lipid peroxide (LPO) responded strongly to low-dose PE exposure (10 mg/L). After 7 days exposure to PE-9-NAnt (40 mg/L), the P4501A activity increased significantly, but the activities of AChE and LDH were inhibited clearly, causing certain neurotoxicity and disorders of energy metabolism to zebrafish. The analysis of integrated biomarker response index (IBR) suggested that PE had greater bio-toxicity to zebrafish in all exposure groups after short-term exposure, but the PE-9-NAnt complex showed greater bio-toxicity after 7 days, which indicated that complex exposure of PE-9-NAnt had a delayed effect on the bio-toxicity of zebrafish. Furthermore, analysis of the intestinal microbiota exhibited that under the conditions of the exposure group with 9-NAnt, the relative abundance of the five dominant bacterial phyla (Proteobacteria, Firmicutes, Fusobacteriota, Bacteroidota and Verrucomicrobiota) changed greatly. Overall, this study confirmed that PE could carry 9-NAnt into fish causing bioaccumulation, but in the case of coexisting exposures, PE reduced 9-NAnt bioaccumulation, suggesting that microplastics with other emerging pollutants in chronic toxicity are probably next objects in future works. Title: Smart nanozyme of silver hexacyanoferrate with versatile bio-regulated activities for probing different targets Zhang L, Zhang Q, Liu Q, Wu X, Dong Y, Wang GL Ref: Talanta, 228:122268, 2021 : PubMed ESTHER: Zhang_2021_Talanta_228_122268 PubMedSearch: Zhang 2021 Talanta 228 122268 PubMedID: 33773716 Abstract Smart nanozymes that can be facile and rapidly produced, while with efficiently bio-regulated activity, are attractive for biosensing applications. Herein, a smart nanozyme, silver hexacyanoferrate (Ag(4)[Fe(CN)(6)]), was constructed in situ via the rapid, direct reaction between silver(I) and K(4)[Fe(CN)(6)]. And the activity of the nanozyme can be rationally modulated by different enzymatic reactions including the glucose oxidase (GOx, taken as a model oxidoreductase), alkaline phosphatase (ALP), and acetylcholinesterase (AChE). On the basis of which, a multiple function platform for the highly sensitive detection of glucose, ALP and AChE were developed through colorimetry. Corresponding detection limits for the above three targets were found to be as low as 0.32 microM, 3.3 U/L and 0.083 U/L (S/N = 3), respectively. The present study provides a novel nanozyme that can be produced in situ, which rules out the harsh, cumbersome, and time-consuming synthesis/purification procedures. In addition, it establishes a multiple function platform for the amplified detection of versatile targets by the aid of the developed nanozyme, whose detection has the advantages of low cost, ease-of-use, high sensitivity, and good selectivity. Title: UHPLC-QTOF-MS based metabolomics and biological activities of different parts of Eriobotrya japonica Zhang L, Saber FR, Rocchetti G, Zengin G, Hashem MM, Lucini L Ref: Food Res Int, 143:110242, 2021 : PubMed ESTHER: Zhang_2021_Food.Res.Int_143_110242 PubMedSearch: Zhang 2021 Food.Res.Int 143 110242 PubMedID: 33992354 Abstract Eriobotrya japonica, commonly known as loquat, has been used traditionally for the treatment of different diseases. Herein, untargeted profiling based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) was used to depict the phytochemical profile of loquat roots, leaves, stems, seeds, and fruits. This allowed the tentative annotation of 349 compounds, representing different phytochemical classes that included flavonoids, phenolic acids, lignans, stilbenes, and terpenoids. Among others, low molecular weight phenolics (tyrosol derivatives) and terpenoids were the most abundant phytochemicals. After that, in vitro antioxidant and enzyme inhibition assays were applied to investigate the biological activity of the different organs of Eriobotrya japonica. Roots of E. japonica exhibited the highest antioxidant capacity, showing 181.88, 275.48, 325.18, 169.74 mg Trolox equivalent (TE)/g in DPPH, ABTS, CUPRAC, and FRAP assays, respectively. Furthermore, the root extract of E. japonica strongly inhibited butyryl cholinesterase (3.64 mg galantamine equivalent (GALAE)/g), whereas leaves, stems, seeds, and fruits showed comparable inhibition of both acetyl and butyryl cholinesterases. All the investigated organs of E. japonica exhibited in vitro tyrosinase inhibition (57.27-71.61 mg Kojic Acid Equivalent (KAE)/g). Our findings suggest a potential food and pharmaceutical exploitation of different organs of E. japonica (mainly roots) in terms of enrichment with health-promoting phenolics and triterpenes. Title: The UHPLC-QTOF-MS Phenolic Profiling and Activity of Cydonia oblonga Mill. Reveals a Promising Nutraceutical Potential Zhang L, Rocchetti G, Zengin G, Ak G, Saber FR, Montesano D, Lucini L Ref: Foods, 10:, 2021 : PubMed ESTHER: Zhang_2021_Foods_10_ PubMedSearch: Zhang 2021 Foods 10 PubMedID: 34071443 Abstract Cydonia oblonga Mill., normally known as the quince fruit, has been widely used in agro-food industries mainly to produce jams and jellies. However, other parts of the plants are still underutilized and not completely assessed for their nutraceutical profile. Therefore, in this work, the polyphenolic profile of C. oblonga was investigated using an untargeted metabolomics approach based on high-resolution mass spectrometry. Several compounds were identified in the different parts of the plants, including flavonoids (i.e., anthocyanins, flavones, flavan-3-ols, and flavonols), phenolic acids (both hydroxycinnamics and hydroxybenzoics), low-molecular-weight phenolics (tyrosol equivalents), lignans, and stilbenes. Overall, C. oblonga leaves showed the highest in vitro antioxidant potential, as revealed by 2,2-difenil-1-picrylhydrazyl (DPPH), 2,2'-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), ferric reducing antioxidant power (FRAP), and cupric ion reducing antioxidant capacity (CUPRAC) assays, being 189.5, 285.6, 158.9, and 348.8 mg Trolox Equivalent/g, respectively. The enzymes acetyl- and butyryl-cholinesterases were both inhibited by the different plant parts of C. oblonga, with stems showing the higher inhibitory potential. Interestingly, the fruit extracts were the only parts inhibiting the alpha-glucosidase, with a value of 1.36 mmol acarbose equivalents (ACAE)/g. On the other hand, strong tyrosinase inhibition was found for stems and leaves, being 72.11 and 68.32 mg Kojic acid Equivalent/g, respectively. Finally, a high number of significant (0.05 < p < 0.01) correlations were outlined between phenolics (mainly anthocyanins, flava-3-ols, and tyrosol equivalents) and the different biological assays. Taken together, our findings suggest a potential exploitation of C. oblonga leaves and stems for the food, pharmaceutical, and cosmetic industries. Title: A near-infrared light triggered fluormetric biosensor for sensitive detection of acetylcholinesterase activity based on NaErF(4): 0.5 % Ho(3+)@NaYF(4) upconversion nano-probe Zhao X, Zhang L, Yan X, Lu Y, Pan J, Zhang M, Wang C, Suo H, Jia X and Lu G <1 more author(s)> Zhao X, Zhang L, Yan X, Lu Y, Pan J, Zhang M, Wang C, Suo H, Jia X, Liu X, Lu G (- 1) Ref: Talanta, 235:122784, 2021 : PubMed ESTHER: Zhao_2021_Talanta_235_122784 PubMedSearch: Zhao 2021 Talanta 235 122784 PubMedID: 34517642 Abstract Acetylcholinesterase (AChE), as an important neurotransmitter, is widely present in the peripheral and central nervous systems. The aberrant expression of AChE could cause diverse neurodegenerative diseases. Herein, we developed a facile and interference-free fluorimetric biosensing platform for highly sensitive AChE activity determination based on a NaErF(4): 0.5 % Ho(3+)@NaYF(4) nano-probe. This nano-probe exhibits a unique property of emitting bright monochromic red (650 nm) upconversion (UC) emission under multiband (~808, ~980, and ~1530 nm) near-infrared (NIR) excitations. The principle of this detection relies on the quenching of the strong monochromic red UC emission by oxidization products of 3,3',5,5'-tetramethylbenzidine generated through AChE-modulated cascade reactions. This system shows a great sensing performance with a detection limit (LOD) of 0.0019 mU mL(-) (1) for AChE, as well as good specificity and stability. Furthermore, we validated the potential of the nano-probe in biological samples by determination of AChE in whole blood with a LOD of 0.0027 mU mL(-1), indicating the potential application of our proposed platform for monitoring the progression of AChE-related disease. Title: Loading and Sustained Release of Pralidoxime Chloride from Swellable MIL-88B(Fe) and Its Therapeutic Performance on Mice Poisoned by Neurotoxic Agents Zhao D, Liu J, Zhang L, Zhou Y, Zhong Y, Yang Y, Huang C, Wang Y Ref: Inorg Chem, :, 2021 : PubMed ESTHER: Zhao_2021_Inorg.Chem__ PubMedSearch: Zhao 2021 Inorg.Chem PubMedID: 34969248 Abstract Maintaining a long-term continuous and stable reactivator blood concentration to treat organophosphorus nerve agent poisoning using acetylcholinesterase (AChE) reactivator pralidoxime chloride (2-PAM) is very important yet difficult. Because the flexible framework of MIL-88B(Fe) nanoparticles (NPs) can swell in polar solvents, pralidoxime chloride (2-PAM) was loaded in MIL-88B(Fe) NPs (size: ca. 500 nm) by stirring and incubation in deionized water to obtain 2-PAM@MIL-88B(Fe), which had a maximum drug loading capacity of 12.6 wt %. The as-prepared composite was characterized by IR, powder X-ray diffraction (P-XRD), scanning electron microscopy (SEM), -potential, Brunauer-Emmett-Teller (BET), and thermogravimetry/differential thermal analysis (TG/DTA). The results showed that under constant conditions, the maximum drug release rates of 2-PAM@MIL-88B(Fe) in absolute ethanol, phosphate-buffered saline (PBS) solution (pH = 7.4), and PBS solution (pH = 4) at 150 h were 51.7, 80.6, and 67.1%, respectively. This was because the composite showed different swelling behaviors in different solvents. In PBS solution with pH = 2, the 2-PAM@MIL-88B(Fe) framework collapsed after 53 h and released 100% of 2-PAM. For mice after intragastric poisoning with sarin (a neurotoxic agent), an atropine-assisted 2-PAM@MIL-88B(Fe) treatment experiment revealed that 2-PAM@MIL-88B(Fe) continuously released 2-PAM for more than 72 h so that poisoned AChE was continuously and steadily reactivated. The reactivation rate of AChE was 56.7% after 72 h. This composite is expected to provide a prolonged, stable therapeutic drug for the mid- and late-stage treatment of neurotoxic agent poisoning. 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: In vitro gastrointestinal digestibility of phytosterol oleogels: influence of self-assembled microstructures on emulsification efficiency and lipase activity Dong L, Lv M, Gao X, Zhang L, Rogers M, Cao Y, Lan Y Ref: Food Funct, 11:9503, 2020 : PubMed ESTHER: Dong_2020_Food.Funct_11_9503 PubMedSearch: Dong 2020 Food.Funct 11 9503 PubMedID: 32955534 Abstract The objective of this study was to investigate the influence of self-assembled microstructure on lipid digestibility in phytosterol (gamma-oryzanol and beta-sitosterol) oleogels. Different molar ratios of gamma-oryzanol and beta-sitosterol yielded a variety of crystal morphologies; the resulting gels were tested for their lipid emulsification efficiency, release rate of free fatty acids (FFAs) during lipolysis, and their effect on lipase behavior. Results indicated that oleogels were harder to emulsify when compared to oil samples. The emulsification efficiencly was affected by both the gel strength and crystal morphology of the self-assembled structures within phytosterol oleogels. In oil emulsions, intestinal digestion resulted in more extensive lipid droplet coalescence with increased particle size when compared to oleogel emulsions. The FFA release rate suggested that the extent of lipid digestion was correlated to the emulsification efficiency. The interfacial binding of lipase indicated that the amount of lipase adsorption was positively correlated to the interface area created during the emulsification process. Finally, isothermal titration calorimetry results indicated that self-assembled structures within these oleogels physically obstructed the interaction between lipase and lipid. Ultimately, this led to lower reaction rate during gastrointestinal digestion. Collectively, these results may have important implications in designing oleogel systems with controlled lipid digestibility as well as controlling the bioavailability of delivered lipid-soluble bioactive compounds. Title: Amino acid, fatty acid, and carbohydrate metabolomic profiles with ginsenoside-induced insecticidal efficacy against Ostrinia furnacalis (Guenee) Liu S, Wang X, Zhang R, Song M, Zhang N, Li W, Wang Y, Xu Y, Zhang L Ref: J Ginseng Res, 44:544, 2020 : PubMed ESTHER: Liu_2020_J.Ginseng.Res_44_544 PubMedSearch: Liu 2020 J.Ginseng.Res 44 544 PubMedID: 32617034 Abstract Background: Previous studies have shown the insecticidal efficacy of ginsenosides. In the present study, we aimed to investigate the metabolic mechanism related to the inhibitory effect of panaxadiol saponins (PDSs) against the Asian corn borer Ostrinia furnacalis (Guenee). Methods: Third instar larvae of O. furnacalis were fed normal diets with different concentrations of PDSs for 4 days. The consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food were recorded. A targeted gas chromatography-mass spectrometry assay was performed to detect the profiles of amino acids, fatty acids, and carbohydrates in larvae of O. furnacalis. In addition, the activity of detoxification-related enzymes was determined. Results and Conclusions: PDSs decreased the consumption index, relative growth rate, approximate digestibility, and conversion of ingested and digested food in the 3rd instar larvae of O. furnacalis in a dose-dependent manner. PDSs decreased 15 free amino acids, 16 free fatty acids, and 5 carbohydrates and increased the levels of palmitoleic acid, palmitic acid, and 9-octadecenoic acid in the 3rd instar larvae. The activity of detoxification-related enzymes, such as acetylcholinesterase, glutathione S-transferase, cytochrome P450, carboxylesterase, trehalase, acid phosphatase, and alkaline phosphatase, was reduced in a dose-dependent manner in the 3rd instar larvae exposed to PDSs. These data confirmed the inhibitory effect of PDSs against growth, food utilization, and detoxification in the 3rd instar larvae of O. furnacalis and the potential for using PDSs as an efficient tool for insect pest management for O. furnacalis larvae. Title: Embryonic development and oxidative stress effects in the larvae and adult fish livers of zebrafish (Danio rerio) exposed to the strobilurin fungicides, kresoxim-methyl and pyraclostrobin Mao L, Jia W, Zhang L, Zhang Y, Zhu L, Sial MU, Jiang H Ref: Sci Total Environ, 729:139031, 2020 : PubMed ESTHER: Mao_2020_Sci.Total.Environ_729_139031 PubMedSearch: Mao 2020 Sci.Total.Environ 729 139031 PubMedID: 32387777 Abstract Two important strobilurin fungicides, kresoxim-methyl and pyraclostrobin, are widely used globally. Their effects on embryonic development and oxidative stress effects in the larvae and adult fish livers of zebrafish (Danio rerio) were assessed in our study. The hatching, mortality, and teratogenic rates were determined when the eggs of fish were exposed to kresoxim-methyl and pyraclostrobin for 24-144 h postfertilization (hpf). For further study, the effects of kresoxim-methyl and pyraclostrobin on antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD)], detoxification enzymes [carboxylesterase (CarE) and glutathione S-transferase (GST)] and the malondialdehyde (MDA) content of larval zebrafish (96 h) and male or female adult zebrafish livers (up to 28 d) were evaluated for potential toxicity mechanisms. The study of embryonic development revealed that both kresoxim-methyl and pyraclostrobin caused developmental toxicity (hatching inhibition, mortality, and teratogenic rates) increase with significant concentration- and time-dependent responses, and the 144-h median lethal values (LC50) of kresoxim-methyl and pyraclostrobin were 195.0 and 81.3 mug L(-1), respectively. In the larval zebrafish study, both kresoxim-methyl and pyraclostrobin at the highest concentrations (100 mug L(-1) and 15 mug L(-1), respectively) significantly increased the CAT, POD and CarE activities and MDA content compared with those of the control group (P < 0.05). We further found that oxidative stress effects in adult zebrafish livers caused by long-term kresoxim-methyl and pyraclostrobin exposure differed with time and sex. Regarding the residues in natural waters, the potential adverse effects of kresoxim-methyl and pyraclostrobin would be relatively low for adult zebrafish but must not be overlooked for zebrafish embryos/larvae (hatching impairment). Our results from the detoxification enzyme study also initially indicated that adult zebrafish had a greater detoxification ability than larvae and that males had a greater detoxification ability than females. Title: Sequence and annotation of 42 cannabis genomes reveals extensive copy number variation in cannabinoid synthesis and pathogen resistance genes McKernan KJ, Helbert Y, Kane LT, Ebling H, Zhang L, Liu B, Eaton Z, McLaughlin S, Kingan S and Harkins T <5 more author(s)> McKernan KJ, Helbert Y, Kane LT, Ebling H, Zhang L, Liu B, Eaton Z, McLaughlin S, Kingan S, Baybayan P, Concepcion G, Jordan M, Riva A, Barbazuk W, Harkins T (- 5) Ref: Biorxiv, :, 2020 : PubMed ESTHER: Mckernan_2020_bioRxiv__ PubMedSearch: Mckernan 2020 bioRxiv Gene_locus related to this paper: cansa-a0a7j6fzj4 Abstract Cannabis is a diverse and polymorphic species. To better understand cannabinoid synthesis inheritance and its impact on pathogen resistance, we shotgun sequenced and assembled a Cannabis trio (sibling pair and their offspring) utilizing long read single molecule sequencing. This resulted in the most contiguous Cannabis sativa assemblies to date. These reference assemblies were further annotated with full-length male and female mRNA sequencing (Iso-Seq) to help inform isoform complexity, gene model predictions and identification of the Y chromosome. To further annotate the genetic diversity in the species, 40 male, female, and monoecious cannabis and hemp varietals were evaluated for copy number variation (CNV) and RNA expression. This identified multiple CNVs governing cannabinoid expression and 82 genes associated with resistance to Golovinomyces chicoracearum, the causal agent of powdery mildew in cannabis. Results indicated that breeding for plants with low tetrahydrocannabinolic acid (THCA) concentrations may result in deletion of pathogen resistance genes. Low THCA cultivars also have a polymorphism every 51 bases while dispensary grade high THCA cannabis exhibited a variant every 73 bases. A refined genetic map of the variation in cannabis can guide more stable and directed breeding efforts for desired chemotypes and pathogen-resistant cultivars. Title: The Strength of the Nutrient Solution Modulates the Functional Profile of Hydroponically Grown Lettuce in a Genotype-Dependent Manner Senizza B, Zhang L, Miras-Moreno B, Righetti L, Zengin G, Ak G, Bruni R, Lucini L, Sifola MI and Rouphael Y <2 more author(s)> Senizza B, Zhang L, Miras-Moreno B, Righetti L, Zengin G, Ak G, Bruni R, Lucini L, Sifola MI, El-Nakhel C, Corrado G, Rouphael Y (- 2) Ref: Foods, 9:, 2020 : PubMed ESTHER: Senizza_2020_Foods_9_ PubMedSearch: Senizza 2020 Foods 9 PubMedID: 32825768 Abstract Considering that functional components of plant foods are mainly secondary-metabolism products, we investigated the shaping of health-promoting compounds in hydroponically grown butterhead lettuce (Lactuca sativa L. var. capitata) as a function of the strength of the nutrient solution utilized. To this aim, untargeted metabolomics profiling, in vitro antioxidant capacity (total phenolics, 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), cupric reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP) assays), and the inhibition of selected enzyme activities were investigated in two butterhead lettuce cultivars with different pigmentation, i.e., green and red Salanova. Full-strength nutrition, together with half- and quarter-strength solutions of macronutrients, was tested. Our results indicate that by reducing the nutrients strength, we could elicit a distinctive shaping of the phenolic profile of lettuce. It is noteworthy that only specific classes of phenolics (namely, lignans and phenolic acids, followed by flavones and anthocyanins) were modulated by the induction of nutritional eustress (fold-change values in the range between -5 and +11). This indicates that specific responses, rather than a generalized induction of phenolic compounds, could be observed. Nonetheless, a genotype-dependent response could be observed, with the red cultivar being much more responsive to nutritional deprivation than the green Salanova lettuce. Indeed, analysis of variance (ANOVA) confirmed a genotype x nutrition interaction in red Salanova (p < 0.001). As a consequence of the changes in phenolic composition, also the antioxidant capacity (p < 0.001) and amylase inhibition (p < 0.001) properties were affected by the growing conditions. However, the effect on cholinesterase and tyrosinase inhibition was poorly affected by the nutritional strength. Provided that yields are not compromised, the application of a controlled nutritional eustress in hydroponically cultivated lettuce may represent a valuable strategy to produce food with tailored functional features in a sustainable manner. Title: Proteomic Analysis Reveals that EPHX1 Contributes to 5-Fluorouracil Resistance in a Human Hepatocellular Carcinoma Cell Line Sun R, Dong C, Li R, Chu H, Liu J, Hao D, Zhang L, Zhao B, Wang L, Zhang Y Ref: Proteomics Clin Appl, 14:e1900080, 2020 : PubMed ESTHER: Sun_2020_Proteomics.Clin.Appl_14_e1900080 PubMedSearch: Sun 2020 Proteomics.Clin.Appl 14 e1900080 PubMedID: 32067389 Gene_locus related to this paper: human-EPHX1 Abstract PURPOSE: The extensive drug resistance of hepatocellular carcinoma (HCC) has become a major cause of chemotherapy failure. A deeper understanding of the drug resistance mechanism of tumor cells is very significant for improving the clinical prognosis of patients with HCC. EXPERIMENTAL DESIGN: In this study, proteomic studies on the composition of 5-fluorouracil (5-Fu) resistant Bel/5Fu cell line and its parent Bel7402 cell line by using an ionic liquid assisted proteins extraction method with the advantage of extracting plasma membrane proteins to a wider extent are performed. Then the expression level and function of differentially expressed plasma membrane proteins are verified. RESULTS: In total, 25 plasma membrane proteins are shown differentially expressed in Bel/5Fu compared with Bel7402. Western blot analysis results further confirmed that the EPHX1 PLIN2 RAB27B SLC4A2 are upregulated in Bel/5Fu cells in accordance with the proteomics data. Moreover, cell viability assay and clonogenic survival assay results demonstrated that EPHX1 is closely related to the chemoresistance of Bel/5Fu to 5-Fu. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma membrane protein EPHX1 is closely related to the chemotherapy resistance of Bel/5Fu cells and can be used as a new drug target to improve the clinical prognosis of patients with HCC. Title: Adipogenic activity of 2-ethylhexyl diphenyl phosphate via peroxisome proliferator-activated receptor gamma pathway Sun W, Duan X, Chen H, Zhang L, Sun H Ref: Sci Total Environ, 711:134810, 2020 : PubMed ESTHER: Sun_2020_Sci.Total.Environ_711_134810 PubMedSearch: Sun 2020 Sci.Total.Environ 711 134810 PubMedID: 31812418 Inhibitor(s) related to this paper: TPHP, Diphenyl-phosphate, EHDPP Abstract Recent studies have shown that exposure to some organophosphates, such as triphenyl phosphate (TPHP) and diphenyl phosphate (DPHP), can affect adipogenesis in preadipocytes. 2-Ethylhexyl diphenyl phosphate (EHDPP), an organophosphate, is frequently detected in various environmental media. However, there is less information about the toxicity effects and the mechanism by which EHDPP affects preadipocytes. In the present study, we investigated whether EHDPP could induce differentiation in 3T3-L1 preadipocytes through the peroxisome proliferator-activated receptor gamma (PPARgamma) signaling pathway. The fluorescence competitive binding assay and the dual-luciferase reporter gene assay were used to assess the binding affinity and activation of PPARgamma, and the results showed that EHDPP can bind to the ligand binding domain of PPARgamma (PPARgamma-LBD) and activate PPARgamma in vitro. Exposure to EHDPP for 10 days extensively induced adipogenesis in 3T3-L1 preadipocytes as assessed by lipid accumulation and gene expression of adipogenic markers of fatty acid binding protein 4 (FABP4), lipoprotein lipase (Lpl), adiponectin (Adip), and fatty acid synthase (Fasn). Furthermore, the preadipocytes differentiation was blocked by the PPARgamma-specific antagonist GW9662, indicating that the PPARgamma signaling pathway plays an important part in 3T3-L1 cell differentiation induced by EHDPP. Taken together, EHDPP can bind to PPARgamma-LBD, activate PPARgamma receptor, and induce cell differentiation via the PPARgamma signaling pathway in 3T3-L1 preadipocytes. Title: Molecular Basis for the Biosynthesis of an Unusual Chain-Fused Polyketide Gregatin A Wang WG, Wang H, Du LQ, Li M, Chen L, Yu J, Cheng GG, Zhan MT, Hu QF and Matsuda Y <2 more author(s)> Wang WG, Wang H, Du LQ, Li M, Chen L, Yu J, Cheng GG, Zhan MT, Hu QF, Zhang L, Yao M, Matsuda Y (- 2) Ref: Journal of the American Chemical Society, 142:8464, 2020 : PubMed ESTHER: Wang_2020_J.Am.Chem.Soc_142_8464 PubMedSearch: Wang 2020 J.Am.Chem.Soc 142 8464 PubMedID: 32275405 Gene_locus related to this paper: pensq-GrgF Abstract Gregatin A (1) is a fungal polyketide featuring an alkylated furanone core, but the biosynthetic mechanism to furnish the intri-guing molecular skeleton has yet to be elucidated. Herein, we have identified the biosynthetic gene cluster of gregatin A (1) in Penicillium sp. sh18, and investigated the mechanism that produces the intriguing structure of 1 by in vivo and in vitro recon-stitution of its biosynthesis. Our study established the biosynthetic route leading to 1, and illuminated that 1 is generated by the fusion of two different polyketide chains, which are, amazingly, synthesized by a single PKS GrgA with the aid of a trans-acting enoylreductase GrgB. Chain fusion, as well as chain hydrolysis, is catalyzed by an alpha/beta hydrolase GrgF, hybridizing the C11 and C4 carbon chains by Claisen condensation. Finally, structural analysis and mutational experiments using GrgF provided insight into how the enzyme facilitates the unusual chain-fusing reaction. In unraveling a new biosynthetic strategy involving a bifunc-tional PKS and a polyketide fusing enzyme, our study expands our knowledge concerning fungal polyketide biosynthesis. Title: The influence of in vitro gastrointestinal digestion on the Perilla frutescens leaf extract: Changes in the active compounds and bioactivities Wang ZX, Lin QQ, Tu ZC, Zhang L Ref: J Food Biochem, :e13530, 2020 : PubMed ESTHER: Wang_2020_J.Food.Biochem__e13530 PubMedSearch: Wang 2020 J.Food.Biochem e13530 PubMedID: 33084119 Abstract In this study, the influence of in vitro gastrointestinal digestion on the Perilla frutescens leaf extract (PFLE) were measured. Results revealed that total phenolic content (TPC) and total flavonoid content (TFC) were significantly decreased after simulated digestion (ca. 53% of phenolics and 40% of flavonoids). The IC(50) value of DPPH. scavenging activity and ABTS(+) scavenging ability increased by 23% and 56%, respectively, while ferric reducing antioxidant power reduced by 53%. For the inhibition ability on alpha-glucosidase, acetylcholinesterase, and MCF-7 cell proliferation, their IC(50) values increased by 360%, 197%, and 25%, respectively. Three phenolic acids and one flavonoid in PFLE were quantified by high-performance liquid chromatography. Overall, although significant losses of the active components and biological activities occurred during in vitro gastrointestinal digestion, it still showed the potential as an oral agent for treatment and prevention of oxidative stress, cancer, diabetes, and Alzheimer's disease. PRACTICAL APPLICATIONS: As an important annual herbaceous plant with rich biochemical compounds and many biological functions, Perilla frutescens leave is widely used in the food and traditional Chinese medicine. However, the dynamic changes of its active compounds and activities during the digestion process are unclear. In this study, the digestion results in significant loss of the active ingredients and biological activities of P. frutescens leaf extract (PFLE), particularly in the gastric digestion. In addition, PFLE remains to show certain antioxidant activity, alpha-glucosidase inhibitory ability, acetylcholinesterase inhibitory ability, and MCF-7 cell proliferation inhibitory ability after digestion. Therefore, this research might facilitate further research and development of P. frutescens. Title: Short-term exposure to norfloxacin induces oxidative stress, neurotoxicity and microbiota alteration in juvenile large yellow croaker Pseudosciaena crocea Wang X, Hu M, Gu H, Zhang L, Shang Y, Wang T, Zeng J, Ma L, Huang W, Wang Y Ref: Environ Pollut, 267:115397, 2020 : PubMed ESTHER: Wang_2020_Environ.Pollut_267_115397 PubMedSearch: Wang 2020 Environ.Pollut 267 115397 PubMedID: 33254654 Abstract In recent years, antibiotics have been widely detected in coastal waters of China, which raising concerns for coastal biodiversity and aquaculture. This study evaluated the effects of short-term exposure of norfloxacin (NOR) on oxidative stress and intestinal health of the large yellow croaker Pseudosciaena crocea. Juvenile fish were exposed to four concentrations of NOR (0.1, 10, 100 and 1000 g/L) for 14 days. The results showed that NOR inhibited growth and threatened the survival of juveniles. According to the changes of intestinal microbiota, we found that NOR led to a significant decrease in intestinal microbiota diversity, with the decreased relative abundance of Proteobacteria, but the increased Tenericutes. From the perspective of microbial function, NOR inhibited metabolism, cellular defence mechanism and information transduction process. In terms of biochemical indicators, NOR caused an increase in malondialdehyde (MDA) level and inhibited superoxide dismutase (SOD) and acetyl cholinesterase (AChE) activities. Catalase (CAT) activity was activated at low concentration but significantly inhibited at high concentration of NOR. Moreover, there was a high correlation between change in biochemical indicators and change in the microbial community. Overall, environmentally relevant concentrations (0.1 g/L) and high concentrations (10, 100 and 1000 g/L) of NOR have negative effects on the defence function and intestinal health of large yellow croaker juveniles. Title: Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G Ref: Cell Res, 30:269, 2020 : PubMed 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: Effects of Malania oleifera Chun Oil on the Improvement of Learning and Memory Function in Mice Wu R, Zhong S, Ni M, Zhu X, Chen Y, Chen X, Zhang L, Chen J Ref: Evid Based Complement Alternat Med, 2020:8617143, 2020 : PubMed ESTHER: Wu_2020_Evid.Based.Complement.Alternat.Med_2020_8617143 PubMedSearch: Wu 2020 Evid.Based.Complement.Alternat.Med 2020 8617143 PubMedID: 33014116 Abstract BACKGROUND: The fruits of Malania oleifera Chun & S. K. Lee have been highly sought after medically because its seeds have high oil content (>60%), especially the highest known proportion of nervonic acid (>55%). Objective of the Study. The objective was to explore the effects of different doses of Malania oleifera Chun oil (MOC oil) on the learning and memory of mice and to evaluate whether additional DHA algae oil and vitamin E could help MOC oil improve learning and memory and its possible mechanisms. METHODS: After 30 days of oral administration of the relevant agents to mice, behavioral tests were conducted as well as detection of oxidative stress parameters (superoxide dismutase, malondialdehyde, and glutathione peroxidase) and biochemical indicators (acetylcholine, acetyl cholinesterase, and choline acetyltransferase) in the hippocampus. RESULTS: Experimental results demonstrated that MOC oil treatment could markedly improve learning and memory of mouse models in behavioral experiments and increase the activity of GSH-PX in hippocampus and reduce the content of MDA, especially the dose of 46.27 mg/kg. The addition of DHA and VE could better assist MOC oil to improve the learning and memory, and its mechanism may be related to the inhibition of oxidative stress and restrain the activity of AChE and also increase the content of ACh. CONCLUSION: Our results demonstrated that MOC oil treatment could improve learning and memory impairments. Therefore, we suggest that MOC oil is a potentially important resource for the development of nervonic acid products. Title: Design, synthesis and evaluation of diosgenin carbamate derivatives as multitarget anti-Alzheimer's disease agents Yang GX, Huang Y, Zheng LL, Zhang L, Su L, Wu YH, Li J, Zhou LC, Huang J and Ma L <2 more author(s)> Yang GX, Huang Y, Zheng LL, Zhang L, Su L, Wu YH, Li J, Zhou LC, Huang J, Tang Y, Wang R, Ma L (- 2) Ref: Eur Journal of Medicinal Chemistry, 187:111913, 2020 : PubMed ESTHER: Yang_2020_Eur.J.Med.Chem_187_111913 PubMedSearch: Yang 2020 Eur.J.Med.Chem 187 111913 PubMedID: 31837501 Abstract In order to produce an effective and multi-targeted clinical drug that could prevent progressive neurodegeneration, a series of diosgenin carbamate derivatives were designed, synthesized and tested for their anti-inflammatory, antioxidant and anti-Abeta activities. The results demonstrated that compound M15 was the most promising derivative against inflammatory (NO inhibition 22.7 +/- 2.2%,10 muM) and cellular damage induced by H2O2 (SH-SY5Y cell protection = 75.3 +/- 3.4%, 10 muM) or Abeta (astrocytes protection = 70.2 +/- 6.5%, 10 muM). Molecular docking studies revealed the strong binding affinity of M15 to the active site of nNOS, Abeta42 and pro-inflammatory proteins. Western blot demonstrated that M15 decreased IL-1beta, IL-6 and TNF-alpha level, which may contribute to its anti-inflammatory effects. In addition, M15 maintained mitochondrial function as well as cell viability through reducing H2O2-induced ROS production. The results indicated that oral administration of M15 attenuated memory deficits and played a neuroprotective effect on subcutaneous (s.c.) D-gal aging mice. In summary, M15 could be considered as a potential multifunctional neuroprotective agent due to the effects of anti-inflammatory, antioxidant and anti-Abeta activities. Title: A ratiometric fluorescence probe based on graphene quantum dots and o-phenylenediamine for highly sensitive detection of acetylcholinesterase activity Ye M, Lin B, Yu Y, Li H, Wang Y, Zhang L, Cao Y, Guo M Ref: Mikrochim Acta, 187:511, 2020 : PubMed ESTHER: Ye_2020_Mikrochim.Acta_187_511 PubMedSearch: Ye 2020 Mikrochim.Acta 187 511 PubMedID: 32833082 Abstract By using graphene quantum dots (GQDs) and o-phenylenediamine (OPD), a ratiometric fluorescence probe was designed for the highly sensitive and selective detection of AChE. GQDs with strong fluorescence were synthesized by the one-step hydrothermal method. The optimal emission wavelength of GQDs was 450 nm at the excitation wavelength of 375 nm. MnO(2) nanosheets with a wide absorption band of 300-600 nm were prepared at room temperature. Because of the extensive overlap between the absorption spectrum of MnO(2) nanosheets and the excitation and emission spectra of GQDs, the fluorescence of GQDs at 450 nm was efficiently quenched by the inner-filter effect. Meanwhile, due to the peroxidase-like activity of MnO(2) nanosheets, OPD was catalytically oxidized to 2,3-diaminophenazine (oxOPD), a yellow fluorescent substance with a new emission peak at 572 nm. When AChE was present, the substrate acetylthiocholine (ATCh) was hydrolyzed to thiocholine (TCh) that is capable of decomposing MnO(2) nanosheets. Therefore, the quench of GQDs and the oxidation of OPD by MnO(2) nanosheets were suppressed, resulting in the fluorescence recovery of GQDs at 450 nm, while the fluorescence decrease of oxOPD at 572 nm. Utilizing the fluorescence intensity ratio F(450)/F(572) as the signal readout, the ratiometric fluorescence method was established to detect AChE activity. The ratio F(450)/F(572) against the AChE concentration demonstrated two linear relationships in the range 0.1-2.0 and 2.0-4.5 mU mL(-1) with a detection limit of 0.09 mU mL(-1). The method was applied to the detection of positive human serum samples and the analysis of the inhibitor neostigmine. Due to the advantages of high sensitivity, favorable selectivity, and strong anti-interference, the method possesses an application prospect in clinical diagnosis of AChE and the screening of inhibitors. Graphical abstract Schematic presentation of a ratiometric fluorescence method for the detection of acetylcholinesterase (AChE). The fluorescence of graphene quantum dots (GQDs) is quenched and o-phenylenediamine (OPD) is oxidized to generate fluorescent product 2,3-diaminophenazine (oxOPD) by MnO(2) nanosheets. When AChE is present, acetylthiocholine iodide (ATCh) is hydrolyzed to thiocholine (TCh) with reducibility for decomposing MnO(2) nanosheets. Due to the decomposition of MnO(2) nanosheets, the quenching of GQDs and oxidation of OPD are suppressed. The fluorescence of GQDs at 450 nm is enhanced, while the fluorescence of oxOPD at 572 nm is reduced. The fluorescence intensity ratio F(450)/F(572) is used to establish the ratiometric fluorescence method for AChE activity. Title: Complete metabolic study by dibutyl phthalate degrading Pseudomonas sp. DNB-S1 Yu H, Wang L, Lin Y, Liu W, Tuyiringire D, Jiao Y, Zhang L, Meng Q, Zhang Y Ref: Ecotoxicology & Environmental Safety, 194:110378, 2020 : PubMed ESTHER: Yu_2020_Ecotoxicol.Environ.Saf_194_110378 PubMedSearch: Yu 2020 Ecotoxicol.Environ.Saf 194 110378 PubMedID: 32146194 Abstract The primary purpose of this study was to systematically explore the complete metabolic pathway and tolerance mechanism of strain DNB-S1 to dibutyl phthalate (DBP), and the effect of DBP on energy metabolism of DNB-S1. Here, DNB-S1, a strain of Pseudomonas sp. that was highly effective in degrading DBP, was identified, and differentially expressed metabolites and metabolic networks of DBP were studied. The results showed that the differentially expressed metabolites were mainly aromatic compounds and lipid compounds, with only a few toxic intermediate metabolites. It speculated that phthalic acid, salicylic acid, 3-hydroxybenzoate acid, 3-Carboxy-cis, cis-muconate, fumarypyravate were intermediate metabolites of DBP. Their up-regulation indicated that there were two metabolic pathways in the degradation of DBP (protocatechuate pathway and gentisate pathway), which had been verified by peak changes at 290 nm, 320 nm, 330 nm, and 375 nm in the enzymatic method. Also, aspartate, GSH, and other metabolites were up-regulation, indicating that DNB-S1 had a high tolerance to DBP and maintained cell homeostasis, which was also one of the essential reasons to ensure the efficient degradation of DBP. Altogether, this study firstly proposed two pathways to degrade DBP and comprehensively explored the effect of DBP on the metabolic function of DNB-S1, which enriched the study of microbial metabolism of organic pollutants, and which provided a basis for the application of metabolomics. 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: Tuning Butyrylcholinesterase Inactivation and Reactivation by Polymer-Based Protein Engineering Zhang L, Baker SL, Murata H, Harris N, Ji W, Amitai G, Matyjaszewski K, Russell AJ Ref: Adv Sci (Weinh), 7:1901904, 2020 : PubMed ESTHER: Zhang_2020_Adv.Sci.(Weinh)_7_1901904 PubMedSearch: Zhang 2020 Adv.Sci.(Weinh) 7 1901904 PubMedID: 31921563 Abstract Organophosphate nerve agents rapidly inhibit cholinesterases thereby destroying the ability to sustain life. Strong nucleophiles, such as oximes, have been used as therapeutic reactivators of cholinesterase-organophosphate complexes, but suffer from short half-lives and limited efficacy across the broad spectrum of organophosphate nerve agents. Cholinesterases have been used as long-lived therapeutic bioscavengers for unreacted organophosphates with limited success because they react with organophosphate nerve agents with one-to-one stoichiometries. The chemical power of nucleophilic reactivators is coupled to long-lived bioscavengers by designing and synthesizing cholinesterase-polymer-oxime conjugates using atom transfer radical polymerization and azide-alkyne "click" chemistry. Detailed kinetic studies show that butyrylcholinesterase-polymer-oxime activity is dependent on the electrostatic properties of the polymers and the amount of oxime within the conjugate. The covalent coupling of oxime-containing polymers to the surface of butyrylcholinesterase slows the rate of inactivation of paraoxon, a model nerve agent. Furthermore, when the enzyme is covalently inhibited by paraoxon, the covalently attached oxime induced inter- and intramolecular reactivation. Intramolecular reactivation will open the door to the generation of a new class of nerve agent scavengers that couple the speed and selectivity of biology to the ruggedness and simplicity of synthetic chemicals. Title: Molluscicidal activity of fatty acids in the kernel of Chimonanthus praecox cv. Luteus against the golden apple snail Pomacea canaliculata Zhang L, Zou Z Ref: Pestic Biochem Physiol, 167:104620, 2020 : PubMed ESTHER: Zhang_2020_Pestic.Biochem.Physiol_167_104620 PubMedSearch: Zhang 2020 Pestic.Biochem.Physiol 167 104620 PubMedID: 32527423 Abstract The fatty acid composition of the kernel of Chimonanthus praecox cv. Luteus (FKC) was analyzed by gas chromatography-mass spectrometry (GC-MS), its ability to kill Pomacea canaliculata was detected, and the degree of damage and physiological and biochemical effects of an FKC soaking treatment on the hepatopancreas tissue of P. canaliculata were evaluated. In total, 16 fatty acids were detected in FKC, among which 13 were qualitatively identified; octadecadienoic acid (56.76%) and palmitic acid (17.03%) had the highest contents. After 48 h of treatment with FKC, the hepatopancreas of P. canaliculata had a large area of necrosis. The contents of soluble sugar, soluble protein, and albumin (Alb) in the hepatopancreas of P. canaliculata decreased with increasing FKC concentration. The content of malondialdehyde (MDA) and the activities of cereal third transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (AKP), and acetylcholinesterase (AChE) increased with increasing FKC concentration. The results showed that FKC has an obvious negative effect on the hepatopancreas cell structure and physiological function of P. canaliculata, i.e., has strong molluscicidal activity. Title: Total flavonoids of Selaginella pulvinata alleviates cognitive impairment in mice Zhang L, Zhang Y, Hou Y, Li H, Li C, Xin J, Zhou N, Li Q, Song Y, Zhang Z Ref: Biomed Rep, 13:8, 2020 : PubMed ESTHER: Zhang_2020_Biomed.Rep_13_8 PubMedSearch: Zhang 2020 Biomed.Rep 13 8 PubMedID: 32607237 Abstract Cognitive impairment (CI) refers to dysfunctional cognition, which encompasses a spectrum of disorders, ranging from mild cognitive impairment to dementia. Any factor that results in cortical damage may cause CI. Total flavonoids of Selaginella pulvinata (TFSP), have shown promising antioxidant and protective effects in animal models. In the present study, mice were intraperitoneally treated with scopolamine, sodium nitrite or 45% ethanol to induce memory impairment, and the effects were assessed using a step-down test. After performing the behavioural test, hippocampal sections were collected for anatomical analysis, and the brain and serum levels of memory-related molecules were evaluated. The results showed that TFSP improved memory in a mouse model of CI significantly. Serum data were consistent with the behavioural results: TFSP increased blood acetylcholine levels through modulation of the acetylcholinesterase and choline acetyltransferase levels. It also ameliorated oxidative stress in neurons, increasing superoxide dismutase, glutathione peroxidase and inhibiting nitric oxide synthase levels in the brain. These results suggest that TFSP may exhibit potential as a clinical treatment for neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, and senile dementia. Title: Mutation of an atypical oxirane oxyanion hole improves regioselectivity of the alpha/beta-fold epoxide hydrolase Alp1U Zhang L, De BC, Zhang W, Mandi A, Fang Z, Yang C, Zhu Y, Kurtan T, Zhang C Ref: Journal of Biological Chemistry, 295:16987, 2020 : PubMed ESTHER: Zhang_2020_J.Biol.Chem_295_16987 PubMedSearch: Zhang 2020 J.Biol.Chem 295 16987 PubMedID: 33004437 Gene_locus related to this paper: stram-q1rqu8 Abstract Epoxide hydrolases (EHs) have been characterized and engineered as biocatalysts that convert epoxides to valuable chiral vicinal diol precursors of drugs and bioactive compounds. Nonetheless, the regioselectivity control of the epoxide ring opening by EHs remains challenging. Alp1U is an alpha/beta-fold EH that exhibits poor regioselectivity in the epoxide hydrolysis of fluostatin C (1), and produces a pair of stereoisomers. Herein, we established the absolute configuration of the two stereoisomeric products and determined the crystal structure of Alp1U. A W186/W187/Y247 oxirane oxygen hole was identified in Alp1U that replaced the canonical Tyr/Tyr pair in alpha/beta-EHs. Mutation of residues in the atypical oxirane oxygen hole of Alp1U improved the regioselectivity for epoxide hydrolysis on 1. The single site Y247F mutation led to highly regioselective (98%) attack at C-3 of 1, while the double mutation W187F/Y247F resulted in regioselective (94%) nucleophilic attack at C-2. Furthermore, single crystal X-ray structures of the two regioselective Alp1U variants in complex with 1 were determined. These findings allowed insights into the reaction details of Alp1U, and provided a new approach for engineering regioselective epoxide hydrolases. Title: Pharmacological effects of harmine and its derivatives: a review Zhang L, Li D, Yu S Ref: Arch Pharm Res, 43:1259, 2020 : PubMed ESTHER: Zhang_2020_Arch.Pharm.Res_43_1259 PubMedSearch: Zhang 2020 Arch.Pharm.Res 43 1259 PubMedID: 33206346 Inhibitor(s) related to this paper: Harmine Abstract Harmine is isolated from the seeds of the medicinal plant, Peganum harmala L., and has been used for thousands of years in the Middle East and China. Harmine has many pharmacological activities including anti-inflammatory, neuroprotective, antidiabetic, and antitumor activities. Moreover, harmine exhibits insecticidal, antiviral, and antibacterial effects. Harmine derivatives exhibit pharmacological effects similar to those of harmine, but with better antitumor activity and low neurotoxicity. Many studies have been conducted on the pharmacological activities of harmine and harmine derivatives. This article reviews the pharmacological effects and associated mechanisms of harmine. In addition, the structure-activity relationship of harmine derivatives has been summarized. Title: Catalytic Detoxification of Organophosphorus Nerve Agents by Butyrylcholinesterase-Polymer-Oxime Bioscavengers Zhang L, Murata H, Amitai G, Smith PN, Matyjaszewski K, Russell AJ Ref: Biomacromolecules, 21:3867, 2020 : PubMed ESTHER: Zhang_2020_Biomacromolecules_21_3867 PubMedSearch: Zhang 2020 Biomacromolecules 21 3867 PubMedID: 32786529 Abstract Organophosphorus nerve agents (OPNAs), used in chemical warfare, irreversibly inhibit essential cholinesterases (ChEs) in the cholinergic neurotransmission system. Several potent nucleophilic oximes have been approved for the treatment of acute poisoning by OPNAs, but they are rapidly cleared from blood circulation. Butyrylcholinesterase (BChE) stoichiometrically binds nerve agents, but because the molecular weight of a nerve agent is about 500-fold less than the enzyme, the bioscavenger has had limited utility. We synthesized BChE-polymer-oxime conjugates using atom transfer radical polymerization (ATRP) and azide-alkyne "click" chemistry. The activity of the BChE-polymer-oxime conjugates was dependent on the degree of oxime loading within the copolymer side chains. The covalent modification of oxime-containing copolymers prolonged the activity of BChE in the presence of the VX- and cyclosarin-fluorogenic analogues EMP-MeCyC and CMP-MeCyC, respectively. After complete inactivation by VX and cyclosarin fluorogenic analogues, the conjugates demonstrated efficient self-reactivation of up to 80% within 3-6 h. Repeated inhibition and high-level self-reactivation assays revealed that the BChE-polymer-oxime conjugates were excellent reactivators of OPNA-inhibited BChE. Recurring self-reactivation of BChE-polymer-oxime conjugates following repeated BChE inhibition by fluorogenic OPNAs (Flu-OPNAs) opens the door to developing the next generation of nerve agent "catalytic" bioscavengers. Title: Metal-Organic Frameworks Conjugated Lipase with Enhanced Bio-catalytic Activity and Stability Zou B, Zhang L, Xia J, Wang P, Yan Y, Wang X, Adesanya IO Ref: Appl Biochem Biotechnol, :, 2020 : PubMed ESTHER: Zou_2020_Appl.Biochem.Biotechnol__ PubMedSearch: Zou 2020 Appl.Biochem.Biotechnol PubMedID: 32323142 Abstract Covalent immobilization of lipase onto a solid carrier is an effective way to enhance stability. Immobilization inhibits the activity of lipase due to decreased flexibility of enzyme structure via the covalent bond. In this study, monomer of the metal-organic frameworks (MOFs) material ZIF-8 (2-methyl imidazole-4-carboxylic acid) was innovatively used as a chemical modifier of Candida nrugosa lipase (CRL). The circular dichroism spectra results show that the CRL molecule was altered by chemical modification and thus its catalytic activity was 1.3 times higher than that of the free CRL. The modified CRL molecule was further immobilized in the "skeleton" of ZIF-8 through the monomer while in situ forming the cell skeleton of the MOFs, which prevent the active center from being destroyed. The results show that conjugation of chemical modification and immobilized enzymes ensure that there was no obvious reduction in the activity of CRL after immobilization and the stability of CRL was improved. Especially, the organic solvent stability of the modified immobilization CRL in isopropanol was significantly improved and retained more than 148% of its activity. Title: Enhancing bio-catalytic activity and stability of lipase nanogel by functional ionic liquids modification Zou B, Yan Y, Xia J, Zhang L, Adesanya IO Ref: Colloids Surf B Biointerfaces, 195:111275, 2020 : PubMed ESTHER: Zou_2020_Colloids.Surf.B.Biointerfaces_195_111275 PubMedSearch: Zou 2020 Colloids.Surf.B.Biointerfaces 195 111275 PubMedID: 32739774 Abstract A novel integrated lipase nanogel based on functional ionic liquid modification and polymerization immobilization with improved stability was designed. Characterization before and after modification and polymerization was conducted using infrared spectroscopy, Circular dichroism spectroscopy, fluorescence spectroscopy, and scanning electron microscopy. It was shown that the modification of the ionic liquid influenced the catalytic behavior of lipase significantly due to the changed structure and surface properties of lipase. The enzymatic properties, including acid-base stability, thermal stability, organic solvents stability, and storage stability of CRL nanogel, were investigated in the p-nitrophenyl palmitate hydrolysis reaction (CRL, Lipase from Candida Rugosa). The results indicated that CRL nanogel has a better pH, heat, and organic solvent tolerance after immobilization. After seven weeks of storage, the natural CRL gradually lost its enzymatic activity, and only 17.5+/-1.7 % of the catalytic activity remained, the residual activity of CRL nanogel was 97.3+/-1.8 %. It was indicated that the novel CRL nanogel was an excellent biocatalyst. Title: Ester-Producing Mechanism of Ethanol O-acyltransferase EHT1 Gene in Pichia pastoris from Shanxi Aged Vinegar Chen J, Nan R, Wang R, Zhang L, Shi J Ref: Biomed Res Int, 2019:4862647, 2019 : PubMed ESTHER: Chen_2019_Biomed.Res.Int_2019_4862647 PubMedSearch: Chen 2019 Biomed.Res.Int 2019 4862647 PubMedID: 30719444 Gene_locus related to this paper: kompc-f2qms6 Abstract The ethanol O-acyltransferase EHT1 is an important element of key signaling pathways and is widely expressed in yeast strains. In this study, we investigated the expression of EHT1 in the overexpression lines or knockout system of Pichia pastoris using qRT-PCR and western blotting. The amount of total protein was determined using the Bradford method; the esterase activity was determined using p-nitrophenyl acetate as a substrate, and the production of volatile fatty acids in wild-type, knockout, and over-expression systems was detected using SPME GC-MS. The esterase activity of EHT1-knockout P. pastoris was significantly lower than that in wild type (P<0.01), and the activities of esterase in three EHT1-overexpressing strains-OE-1, OE-2, and OE-3-were significantly higher than those in wild type (P<0.01). In the EHT1-knockout strain products, the contents of nine volatile fatty acids were significantly lower than those in wild type (P<0.01), and the relative percentages of three fatty acids, methyl nonanoate, methyl decanoate, and ethyl caprate, were significantly lower than those in the other six species in the wild-type and knockout groups (P<0.05). The nine volatile fatty acids in the fermentation products of the overexpressed EHT1 gene were significantly higher than those in the wild-type group (P<0.01). The relative percentages of the three fatty acid esters, methyl nonanoate, methyl caprate, and ethyl caprate, were significantly higher than those in the other six species (P<0.05). EHT1 plays an important regulatory role in esterase activity and the production of medium-chain volatile fatty acids. Title: Cell-Membrane-Cloaked Oil Nanosponges Enable Dual-Modal Detoxification Chen Y, Zhang Y, Zhuang J, Lee JH, Wang L, Fang RH, Gao W, Zhang L Ref: ACS Nano, 13:7209, 2019 : PubMed ESTHER: Chen_2019_ACS.Nano_13_7209 PubMedSearch: Chen 2019 ACS.Nano 13 7209 PubMedID: 31117372 Abstract The lack of pharmaceutical antidotes for deadly toxicants has motivated tremendous research interests in seeking synthetic nanoscavengers to absorb and neutralize harmful biological or chemical agents. Herein, we report a cell-membrane-cloaked oil nanosponge formulation capable of dual-modal detoxification. The biomimetic oil nanosponge consists of an olive oil nanodroplet wrapped by a red blood cell membrane. In such a construct, the oil core can nonspecifically soak up toxicants through physical partition and the cell membrane shell can specifically absorb and neutralize toxicants through biological binding. The dual-modal detoxification capability of the oil nanosponges was validated using three distinct organophosphates (OPs), including paraoxon, diisopropyl fluorophosphate, and dichlorvos. By inhibiting acetylcholinesterase, OPs cause the accumulation of acetylcholine, which leads to neuromuscular disorders and even death. In mouse models of OP poisoning, the oil nanosponges reduced clinical signs of OP intoxication, lowered OP concentration in tissues, and greatly enhanced mouse survival in both the therapeutic regimen and the prophylactic regimen. Overall, oil nanosponges combine the merits of both cell membrane and oil nanodroplets for safe and effective detoxification, which also serve as a prototype of multimodal detoxification platforms. Title: Tempol Attenuates Neuropathic Pain by Inhibiting Nitric Oxide Production Jia D, Wang H, Han B, Zhang L, Guo J Ref: Anal Cell Pathol (Amst), 2019:8253850, 2019 : PubMed ESTHER: Jia_2019_Anal.Cell.Pathol.(Amst)_2019_8253850 PubMedSearch: Jia 2019 Anal.Cell.Pathol.(Amst) 2019 8253850 PubMedID: 31223559 Abstract Background: Neuropathic pain not only affects individual life quality but also increases economic burden for the society. Treatment to alleviate neuropathic pain is required. Methodology: Fifty rats were randomly assigned into sham, spinal nerve ligation, and three treatment groups with different doses of Tempol (100, 200, and 300 mg/kg, respectively), with 10 rats in each group. A neuropathic pain model was created with spinal nerve L5 and L6 ligation. Mechanical allodynia and thermal hyperalgesia were tested preoperatively (day 0) and postoperatively (days 1, 3, 5, and 7). Spinal cord levels of nitric oxide, as well as activities of nitric oxide synthase and acetylcholinesterase, were tested in postoperative day 7. Results: Compared with rats in the spinal nerve ligation group, rats in Tempol treatment groups had decreased responses to mechanical pain and cold plate stimulations. A high dose of Tempol produced more attenuating effects. The level of nitric oxide and activity of nitric oxide synthase were also decreased with Tempol treatments, whereas no significant changes were observed in the activity of acetylcholinesterase. Conclusions: Tempol attenuated an experimental rat model with neuropathic pain by inhibiting nitric oxide production. Title: Single intranasal immunization with chimpanzee adenovirus-based vaccine induces sustained and protective immunity against MERS-CoV infection Jia W, Channappanavar R, Zhang C, Li M, Zhou H, Zhang S, Zhou P, Xu J, Shan S and Zhang L <5 more author(s)> Jia W, Channappanavar R, Zhang C, Li M, Zhou H, Zhang S, Zhou P, Xu J, Shan S, Shi X, Wang X, Zhao J, Zhou D, Perlman S, Zhang L (- 5) Ref: Emerg Microbes Infect, 8:760, 2019 : PubMed ESTHER: Jia_2019_Emerg.Microbes.Infect_8_760 PubMedSearch: Jia 2019 Emerg.Microbes.Infect 8 760 PubMedID: 31130102 Abstract The recently identified Middle East Respiratory Syndrome Coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no approved prophylactic and therapeutic interventions are currently available. The MERS-CoV envelope spike protein serves as a crucial target for neutralizing antibodies and vaccine development, as it plays a critical role in mediating viral entry through interactions with the cellular receptor, dipeptidyl peptidase 4 (DPP4). Here, we constructed a recombinant rare serotype of the chimpanzee adenovirus 68 (AdC68) that expresses full-length MERS-CoV S protein (AdC68-S). Single intranasal immunization with AdC68-S induced robust and sustained neutralizing antibody and T cell responses in BALB/c mice. In a human DPP4 knock-in (hDPP4-KI) mouse model, it completely protected against lethal challenge with a mouse-adapted MERS-CoV (MERS-CoV-MA). Passive transfer of immune sera to naive hDPP4-KI mice also provided survival advantages from lethal MERS-CoV-MA challenge. Analysis of sera absorption and isolated monoclonal antibodies from immunized mice demonstrated that the potent and broad neutralizing activity was largely attributed to antibodies targeting the receptor binding domain (RBD) of the S protein. These results show that AdC68-S can induce protective immune responses in mice and represent a promising candidate for further development against MERS-CoV infection in both dromedaries and humans. Title: The adverse effect of TCIPP and TCEP on neurodevelopment of zebrafish embryos/larvae Li R, Wang H, Mi C, Feng C, Zhang L, Yang L, Zhou B Ref: Chemosphere, 220:811, 2019 : PubMed ESTHER: Li_2019_Chemosphere_220_811 PubMedSearch: Li 2019 Chemosphere 220 811 PubMedID: 30612050 Abstract Tris (1-chloro-2-propyl) phosphate (TCIPP) and tris (2-chloroethyl)phosphate (TCEP) are two widely used chlorinated organophosphate flame retardants (ClOPFRs), and have been frequently detected in various environmental media. Concern is now growing whether TCIPP and TCEP can cause neurotoxicity since they have similar chemical structure with organophosphorus pesticide. Therefore, in this study, zebrafish embryos (2-120h post-fertilization [hpf]) were exposed to TCIPP or TCEP (0, 100, 500 or 2500mug/L) or a model neurotoxicant, chlorpyrifos (CPF, 100mug/L) to investigate the adverse effects and possible mechanisms of TCIPP and TCEP on neurodevelopment. Our results showed that CPF exposure resulted in developmental toxicity including decreased hatching, survival rates and increased malformation rates (e.g., spinal curvature) as well as behavior changes such as decreased locomotive activity in dark stimulation. In contrast, TCIPP and TCEP showed no significant effects on developmental parameters, but caused similar effects on locomotive activity at high concentration, indicating that although not as potent as CPF, TCIPP and TCEP may still cause adverse effects on neurodevelopment. Furthermore, our results suggest that TCIPP and TCEP showed no effects on acetylcholine content or AChE activity, which were considered as the main targets of CPF. However, TCIPP and TCEP exposure can significantly down-regulate the expression of selected genes and proteins related to neurodevelopment (e.g., mbp, syn2a, and alpha1-tubulin) similar as CPF did. Besides that, TCIPP and TCEP can also affect the transcription of shha and gap43, which were not affected by CPF, pointing out a complex mechanism underlying TCIPP and TCEP's neurodevelopmental toxicity. Overall, our results demonstrated that TCEP and TCIPP may have adverse effect on the neurodevelopment of zebrafish embryos/larvae, but the underlying mechanism is not via the inhibition of acetyl cholinesterase activity. Title: Macrophage ABHD5 Suppresses NFkappaB-Dependent Matrix Metalloproteinase Expression and Cancer Metastasis Shang S, Ji X, Zhang L, Chen J, Li C, Shi R, Xiang W, Kang X, Zhang D and Miao H <6 more author(s)> Shang S, Ji X, Zhang L, Chen J, Li C, Shi R, Xiang W, Kang X, Zhang D, Yang F, Dai R, Chen P, Chen S, Chen Y, Li Y, Miao H (- 6) Ref: Cancer Research, 79:5513, 2019 : PubMed ESTHER: Shang_2019_Cancer.Res_79_5513 PubMedSearch: Shang 2019 Cancer.Res 79 5513 PubMedID: 31439546 Gene_locus related to this paper: human-ABHD5 Abstract Metabolic reprogramming in tumor-associated macrophages (TAM) is associated with cancer development, however, the role of macrophage triglyceride metabolism in cancer metastasis is unclear. Here, we showed that TAMs exhibited heterogeneous expression of abhydrolase domain containing 5 (ABHD5), an activator of triglyceride hydrolysis, with migratory TAMs expressing lower levels of ABHD5 compared with the nonmigratory TAMs. ABHD5 expression in macrophages inhibited cancer cell migration in vitro in xenograft models and in genetic cancer models. The effects of macrophage ABHD5 on cancer cell migration were dissociated from its metabolic function as neither triglycerides nor ABHD5-regulated metabolites from macrophages affected cancer cell migration. Instead, ABHD5 deficiency in migrating macrophages promoted NFkappaB p65-dependent production of matrix metalloproteinases (MMP). ABHD5 expression negatively correlated with MMP expression in TAMs and was associated with better survival in patients with colorectal cancer. Taken together, our findings show that macrophage ABHD5 suppresses NFkappaB-dependent MMP production and cancer metastasis and may serve as a prognostic marker in colorectal cancer. SIGNIFICANCE: These findings highlight the mechanism by which reduced expression of the metabolic enzyme ABHD5 in macrophages promotes cancer metastasis.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/21/5513/F1.large.jpg. Title: Analysis of the SNP rs3747333 and rs3747334 in NLGN4X gene in autism spectrum disorder: a meta-analysis Sun H, Yang Y, Zhang L, Wu H, Zhang H, Li H Ref: Ann Gen Psychiatry, 18:6, 2019 : PubMed ESTHER: Sun_2019_Ann.Gen.Psychiatry_18_6 PubMedSearch: Sun 2019 Ann.Gen.Psychiatry 18 6 PubMedID: 31139237 Gene_locus related to this paper: human-NLGN4X Abstract Background: The SNP rs3747333 and rs3747334 in Neuroligin 4X (NLGN4X) gene have been demonstrated to be associated with the susceptibility to Autism spectrum disorder (ASDs; MIM 209850), but the results are inconsistent. Therefore, a meta-analysis of eligible studies reporting the association between rs3747333 and rs3747334 and ASD was carried out to enhance the reliability of published results. Methods: A systematic literature search was performed using PubMed, Web of Science, Cochrane Library to search English articles concerning the relation between rs3747333, rs3747334 and ASD up to Sep. 21th, 2017. Summary odds ratios (OR) and 95% confidence interval (CI) were used to evaluate the risk of rs3747333, rs3747334 in the ASD. The heterogeneity and publication bias of the eligible studies were also evaluated. Results: Six eligible studies involving 1284 subjects (735 patients and 549 healthy controls) were included in this meta-analysis. Overall, the results indicated that there was no significant risk elevation between rs3747333, rs3747334 variants and ASD (OR = 0.39, 95% CI 0.10-1.60). Furthermore, sensitivity analysis and publication bias analysis confirmed this result. Conclusions: In conclusion, our meta-analysis suggests that the rs3747333, rs3747334 in NLGN4X gene are not frequent causes of ASD. Title: Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation Tian C, Qiang X, Song Q, Cao Z, Ye C, He Y, Deng Y, Zhang L Ref: Bioorg Chem, :103477, 2019 : PubMed ESTHER: Tian_2019_Bioorg.Chem__103477 PubMedSearch: Tian 2019 Bioorg.Chem 103477 PubMedID: 31818478 Abstract The complex pathogenesis of Alzheimer's disease (AD) calls for multitarget approach for disease management. Herein, a series of novel flurbiprofen-chalcone hybrid Mannich base derivatives were designed and synthesized. The biological screening results indicated that most of the derivatives exhibited potent multi-target effects involved in AD. In particular, compound 6c bearing a pyrrolidine group showed the highest activities against self- and Cu(2+)-induced Abeta1-42 aggregation (70.65% and 54.89% at 25.0 microM, respectively), highly selective inhibition towards AChE and MAO-B (IC50 = 7.15 muM and 0.43 muM respectively), good antioxidant ability and metal-chelating property. Moreover, 6c displayed excellent anti-neuroinflammatory activity and appropriate BBB permeability in vitro. These outstanding results qualified compound 6c as a promising multifunctional agent for further development of disease-modifying treatment of AD. Title: Chemical composition and biological activities of an essential oil from the aerial parts of Artemisia Gmelinii weber ex Stechm Xu Q, Zhang L, Yu S, Xia G, Zhu J, Zang H Ref: Nat Prod Res, :1, 2019 : PubMed ESTHER: Xu_2019_Nat.Prod.Res__1 PubMedSearch: Xu 2019 Nat.Prod.Res 1 PubMedID: 31177847 Abstract The aerial parts of Artemisia gmelinii Weber ex Stechm were collected from the northeast of China. The essential oil was obtained by hydrodistillation and analysed by GC-MS. A set of 66 compounds were identified representing 99.1% of the oil composition. The major compounds in the oil were cyclobutaneethanol, endo-borneol, germacrene D, eucalyptol, selin-6-en-4alpha-ol, bisabolone oxide A, caryophyllene and terpinen-4-ol. Moreover, the essential oil was evaluated for its antioxidant, antidiabetic, and anticholinesterase activities in vitro. Additionally, the antioxidant potential of the oil was evaluated using DPPH and ABTS assays. The oil showed good antidiabetic activity with an IC50 of 63.2 microg/mL, which was similar to that of the positive control acarbose, and weak anticholinesterase activities. These findings demonstrated that the essential oil of Artemisia gmelinii may be a good natural antidiabetic. Title: Retinoic Acid Induces Differentiation of Mouse F9 Embryonic Carcinoma Cell by Modulating the miR-485 Targeting of Abhd2 Yu M, Zhang L, Liu Y, Liu D, Guo Z Ref: Int J Mol Sci, 20:, 2019 : PubMed ESTHER: Yu_2019_Int.J.Mol.Sci_20_ PubMedSearch: Yu 2019 Int.J.Mol.Sci 20 PubMedID: 31035455 Gene_locus related to this paper: human-ABHD2 Abstract Retinoic acid (RA) plays a key role in pluripotent cell differentiation. In F9 embryonic carcinoma cells, RA can induce differentiation towards somatic lineages via the Ras-extracellular signal-regulated kinase (Ras/Erk) pathway, but the mechanism through which it induces the Erk1/2 phosphorylation is unclear. Here, we show that miR-485 is a positive regulator that targets alpha/beta-hydrolase domain-containing protein 2 (Abhd2), which can result in Erk1/2 phosphorylation and triggers differentiation. RA up-regulates miR-485 and concurrently down-regulates Abhd2. We verified that Abhd2 is targeted by miR-485 and they both can influence the phosphorylation of Erk1/2. In summary, RA can mediate cell differentiation by phosphorylating Erk1/2 via miR-485 and Abhd2. Title: Efficacy and outcomes of lipid resuscitation on organophosphate poisoning patients: A systematic review and meta-analysis Yu S, Zhang L, Gao Y, Walline J, Lu X, Ma Y, Zhu H, Yu X, Li Y Ref: Am J Emerg Med, 37:1611, 2019 : PubMed ESTHER: Yu_2019_Am.J.Emerg.Med_37_1611 PubMedSearch: Yu 2019 Am.J.Emerg.Med 37 1611 PubMedID: 30527914 Abstract OBJECTIVE: Organophosphate (OP) pesticides are still widely available in developing countries, leading to numerous accidental or suicidal poisonings every year. Lipid emulsion treatments are commonly used in resuscitating OP poisoning patients but few studies regarding their use have been reported. Our meta-analysis aimed to analyze the efficacy and outcomes of lipid resuscitation on OP poisoning patients. METHODS: A systematic search for associated studies was conducted in Pubmed, EMBASE, MEDLINE, the Cochrane Library and the Chinese National Knowledge Infrastructure. Collected data was pooled using Revman v5.3. Outcomes included prognosis (cured vs. mortality rates), hepatic function (serum ALT, AST, Total Bilirubin (TBIL) level), serum acetylcholinesterase (AchE) level and respiratory function (rate of respiratory muscular paralysis). RESULTS: Seven randomized controlled studies consisting of 630 patients meeting inclusion criteria were identified. Lipid emulsion helped to improve the cure rate [OR=2.54, 95% CI (1.33, 4.86), p=0.005] and lower the mortality rate [OR=0.31, 95% CI (0.13, 0.74), p=0.009]. Serum ALT, AST and TBIL in patients undergoing lipid resuscitation were lower than those in the control groups [ALT, SMD=-1.52, 95% CI (-2.64, 0.40), p=0.008; AST, SMD=-1.66, 95% CI (-3.15, 0.16), p=0.03; TBIL, SMD=-1.26, 95% CI (-2.32, 0.20), p=0.02]. Serum AchE level were increased in patients treated with lipid emulsion [SMD=2.15, 95% CI (1.60, 2.71), p<0.00001]. Rate of respiratory muscular paralysis was lower in patients undergoing lipid resuscitation than those in the control groups [OR=0.19, 95% CI (0.05, 0.71), p=0.01]. CONCLUSION: Based on our meta-analysis of included RCT reports, lipid resuscitation seems likely to help improve prognosis and liver function of OP poisoning patients. However, larger multi-center RCTs are still recommended. Title: Bioaccumulation, behavior changes and physiological disruptions with gender-dependent in lizards (Eremias argus) after exposure to glufosinate-ammonium and l-glufosinate-ammonium Zhang L, Chen L, Meng Z, Zhang W, Xu X, Wang Z, Qin Y, Deng Y, Liu R and Diao J <1 more author(s)> Zhang L, Chen L, Meng Z, Zhang W, Xu X, Wang Z, Qin Y, Deng Y, Liu R, Zhou Z, Diao J (- 1) Ref: Chemosphere, 226:817, 2019 : PubMed ESTHER: Zhang_2019_Chemosphere_226_817 PubMedSearch: Zhang 2019 Chemosphere 226 817 PubMedID: 30965253 Abstract Reptiles, the most diverse taxon of terrestrial vertebrates, might be particularly vulnerable to soil pollution. Reptiles especially lizards have been rarely evaluated in ecotoxicological studies, and there is a very limited report for effects of soil pesticide contaminants on lizards. In this study, male and female lizards (Eremias argus) were exposed to Glufosinate-ammonium (GLA) and l- Glufosinate-ammonium (L-GLA) for 60 days. Slower sprint speed, higher frequency of turning back and reduced brain index were observed in treatment groups. The accumulation of GLA in the brain of lizard was higher than that of L-GLA. Moreover, the activities of neurotoxicity-related enzymes and biomarkers of oxidative stress were also investigated. In summary, the neurotoxic effects of lizards have been observed after exposure to GLA and L-GLA. Based on the result of the Integrated Biomarker Response (IBR), males were more sensitive to contaminants than females. On the other hand, the neurotoxic pathways by GLA and L-GLA triggered were slightly different: GLA mainly acted on glutamine synthetase (GS), acetylcholinesterase (AchE) and Catalase (CAT) and L-GLA aimed at AchE, Na(+)/K(+)-ATPase, Superoxide dismutase (SOD) and Malondialdehyde (MDA). In summary, the accumulation of GLA and L-GLA in lizard's brain induced neurotoxicity by altering the levels of enzymes related to nervous system and antioxidant activity and further resulted in the decrease of brain index and locomotor performance. Title: Excipient-free nanodispersion of 7-ethyl-10-hydroxycamptothecin exerts potent therapeutic effects against pancreatic cancer cell lines and patient-derived xenografts Zhang L, Zhou J, Yan Y, Zhou X, Zhou Q, Du R, Hu S, Ge W, Huang Y and Wang W <5 more author(s)> Zhang L, Zhou J, Yan Y, Zhou X, Zhou Q, Du R, Hu S, Ge W, Huang Y, Xu H, Kong Y, Zheng H, Ding Y, Shen Y, Wang W (- 5) Ref: Cancer Letters, 465:36, 2019 : PubMed ESTHER: Zhang_2019_Cancer.Lett_465_36 PubMedSearch: Zhang 2019 Cancer.Lett 465 36 PubMedID: 31479691 Abstract Irinotecan (CPT-11) is an anti-tumor drug and formulated as nanomedicines to reduce side effects and improve efficacy. In vivo, CPT-11 must be hydrolyzed by carboxylesterase to its active form 7-ethyl-10-hydroxycamptothecin (SN-38) to exert anti-tumor activity, but the lack of this enzyme in humans causes inefficient generation of SN-38. Thus, direct delivery of SN-38, not relying on carboxylesterase, will potentially achieve higher efficacy. However, it is difficult to effectively formulate SN-38 using current excipients due to its hydrophobicity and tendency to crystallize. Herein, we report the nanodispersion of SN-38 with its amphiphilic prodrug, CPT-11, as an effective treatment for pancreatic cancer (PC). SN-38 and CPT-11 formed stable nanoparticles without any other excipients, and showed potent cytotoxicity against PC cells in vitro, slowed tumor growth in vivo, namely subcutaneously and orthotopically xenografted mice, with minimal adverse effects, and prolonged their overall survival. Even in clinically-relevant patient-derived xenograft (PDX) models, the nanodispersion showed greater anti-tumor efficacy than CPT-11. Importantly, the nanodispersion directly released SN-38, resulting in carboxylesterase-independent anti-tumor activity, in contrast to carboxylesterase-dependent CPT-11. These characteristics may enable the excipient-free nanodispersion to exert potent therapeutic effects in patients. Title: Identification and Development of an Irreversible Monoacylglycerol Lipase (MAGL) Positron Emission Tomography (PET) Radioligand with High Specificity Zhang L, Butler CR, Maresca KP, Takano A, Nag S, Jia Z, Arakawa R, Piro JR, Samad T and Halldin C <8 more author(s)> Zhang L, Butler CR, Maresca KP, Takano A, Nag S, Jia Z, Arakawa R, Piro JR, Samad T, Smith DL, Nason DM, O'Neil S, McAllister L, Schildknegt K, Trapa P, McCarthy TJ, Villalobos A, Halldin C (- 8) Ref: Journal of Medicinal Chemistry, 62:8532, 2019 : PubMed ESTHER: Zhang_2019_J.Med.Chem_62_8532 PubMedSearch: Zhang 2019 J.Med.Chem 62 8532 PubMedID: 31483137 Abstract Monoacylglycerol lipase (MAGL), a serine hydrolase extensively expressed throughout the brain, serves as a key gatekeeper regulating the tone of endocannabinoid signaling. Preclinically, inhibition of MAGL is known to provide therapeutic benefits for a number of neurological disorders. The availability of a MAGL-specific positron emission tomography (PET) ligand would considerably facilitate the development and clinical characterization of MAGL inhibitors via noninvasive and quantitative PET imaging. Herein, we report the identification of the potent and selective irreversible MAGL inhibitor 7 (PF-06809247) as a suitable radioligand lead, which upon radiolabeling was found to exhibit a high level of MAGL specificity; this enabled cross-species measurement of MAGL brain expression (Bmax), assessment of in vivo binding in the rat, and nonhuman primate PET imaging. Title: Bio-/Nanoimmobilization Platform Based on Bioinspired Fibrin-Bone@Polydopamine-Shell Adhesive Composites for Biosensing Zhang L, Liu Z, Zha S, Liu G, Zhu W, Xie Q, Li Y, Ying Y, Fu Y Ref: ACS Appl Mater Interfaces, 11:47311, 2019 : PubMed ESTHER: Zhang_2019_ACS.Appl.Mater.Interfaces_11_47311 PubMedSearch: Zhang 2019 ACS.Appl.Mater.Interfaces 11 47311 PubMedID: 31742992 Abstract Inspired by blood coagulation and mussel adhesion, we report novel adhesive fibrin-bone@polydopamine (PDA)-shell composite matrix as highly efficient immobilization platform for biomacromolecules and nanomaterials. Fibrin, as a bioglue, and PDA, as a chemical adhesive, are integrated in a one-pot simultaneous polymerization consisting of biopolymerization of fibrinogen and chemical polymerization of dopamine. Fibrin fibers act as adhesive bones to construct scaffold, while PDA coat on the scaffold to form adhesive shell, generating 3D porous composite matrix with unique bone@shell structure. Two types of enzymes (glucose oxidase and acetylcholinesterase) and Au nanoparticles were adopted as respective model biomolecules and nanomaterials to investigate the immobilization capability of the matrix. The bionanocomposites showed high efficiency in capturing nanoparticles and enzymes, as well as significant mass-transfer and biocatalysis efficiencies. Therefore, the bionanocomposites exhibited significant potential in biosensing of glucose and paraoxon with limits of detection down to 5.2 muM and 4 ppt, respectively. The biological-chemical-combined polymerization strategy and composite platform with high immobilization capacity and mass-transfer efficiency open up a novel way for the preparation of high-performance bionanocomposites for various applications, in particular, biosensing. Title: Structural definition of a neutralization epitope on the N-terminal domain of MERS-CoV spike glycoprotein Zhou H, Chen Y, Zhang S, Niu P, Qin K, Jia W, Huang B, Lan J, Zhang L and Wang X <1 more author(s)> Zhou H, Chen Y, Zhang S, Niu P, Qin K, Jia W, Huang B, Lan J, Zhang L, Tan W, Wang X (- 1) Ref: Nat Commun, 10:3068, 2019 : PubMed ESTHER: Zhou_2019_Nat.Commun_10_3068 PubMedSearch: Zhou 2019 Nat.Commun 10 3068 PubMedID: 31296843 Abstract Most neutralizing antibodies against Middle East respiratory syndrome coronavirus (MERS-CoV) target the receptor-binding domain (RBD) of the spike glycoprotein and block its binding to the cellular receptor dipeptidyl peptidase 4 (DPP4). The epitopes and mechanisms of mAbs targeting non-RBD regions have not been well characterized yet. Here we report the monoclonal antibody 7D10 that binds to the N-terminal domain (NTD) of the spike glycoprotein and inhibits the cell entry of MERS-CoV with high potency. Structure determination and mutagenesis experiments reveal the epitope and critical residues on the NTD for 7D10 binding and neutralization. Further experiments indicate that the neutralization by 7D10 is not solely dependent on the inhibition of DPP4 binding, but also acts after viral cell attachment, inhibiting the pre-fusion to post-fusion conformational change of the spike. These properties give 7D10 a wide neutralization breadth and help explain its synergistic effects with several RBD-targeting antibodies. Title: Design, synthesis and biological evaluation of novel copper-chelating acetylcholinesterase inhibitors with pyridine N-benzylpiperidine fragments Zhou Y, Sun W, Peng J, Yan H, Zhang L, Liu X, Zuo Z Ref: Bioorg Chem, 93:103322, 2019 : PubMed ESTHER: Zhou_2019_Bioorg.Chem_93_103322 PubMedSearch: Zhou 2019 Bioorg.Chem 93 103322 PubMedID: 31585263 Abstract Cholinergic depletion is the direct cause of disability and dementia among AD patients. AChE is a classical and key target of cholinergic disorders. Some new inhibitors of AChE combining pyridine, acylhydrazone and N-benzylpiperidine fragments were developed in this work. The hit structure was optimized to yield the compound 21 with an IC50 value of 6.62nM against AChE, while almost no inhibitory effect against BChE. ADMET predictions and PAMPA permeability evaluation showed good drug-like property. The higher activity with an intermediate alkyl chain substitution indicates a new binding mode of inhibitor with AChE. This finding provides new insights into the binding mechanism and is helpful for discovery of novel high-activity AChE inhibitors. Title: Inhibiting Abeta toxicity in Alzheimer's disease by a pyridine amine derivative Zhu Z, Yang T, Zhang L, Liu L, Yin E, Zhang C, Guo Z, Xu C, Wang X Ref: Eur Journal of Medicinal Chemistry, 168:330, 2019 : PubMed ESTHER: Zhu_2019_Eur.J.Med.Chem_168_330 PubMedSearch: Zhu 2019 Eur.J.Med.Chem 168 330 PubMedID: 30826509 Abstract Alzheimer's disease (AD) is a neurodegenerative disorder with no radical therapy. Aggregation of amyloid beta-peptide (Abeta) induced by various factors is associated with pathogenesis of AD. A pyridine amine derivative, 3-bis(pyridin-2-ylmethyl)aminomethyl-5-hydroxybenzyltriphenylphosphonium bromide (PAT), is synthesized. The inhibition of self- and metal-induced Abeta aggregation by PAT is confirmed by thioflavine T fluorescence, circular dichroism spectroscopy, and TEM. Western blot, RT-PCR and fluorescence imaging indicate that PAT can alleviate the Abeta-induced paralysis, reduce the production of ROS, and protect the mitochondrial function in transgenic C. elegans. Genetic analyses indicate that heat shock protein is involved in the alleviation of Abeta toxicity. PAT also inhibits the activity of acetylcholinesterase in C. elegans. Morris water maze test shows that the memory and cognitive ability of APP/PS1 AD model mice are significantly improved by PAT. Both in vitro and in vivo studies demonstrate that PAT is effective in counteracting Abeta toxicity and ameliorating cognitive functions in AD mice, and therefore a potential lead compound of anti-AD drugs. Title: Effects of two strobilurins (azoxystrobin and picoxystrobin) on embryonic development and enzyme activities in juveniles and adult fish livers of zebrafish (Danio rerio) Jia W, Mao L, Zhang L, Zhang Y, Jiang H Ref: Chemosphere, 207:573, 2018 : PubMed ESTHER: Jia_2018_Chemosphere_207_573 PubMedSearch: Jia 2018 Chemosphere 207 573 PubMedID: 29843034 Abstract Azoxystrobin and picoxystrobin are two primary strobilurin fungicides used worldwide. This study was conducted to test their effects on embryonic development and the activity of several enzyme in the zebrafish (Danio rerio). After fish eggs were separately exposed to azoxystrobin and picoxystrobin from 24 to 144h post fertilization (hpf), the mortality, hatching, and teratogenetic rates were measured. Additionally, effects of azoxystrobin and picoxystrobin on activities of three important antioxidant enzymes [catalase (CAT), superoxide dismutase (SOD) and peroxidase (POD)] and two primary detoxification enzymes [carboxylesterase (CarE) and glutathione S-transferase (GST)] and malondialdehyde (MDA) content in zebrafish larvae (96h) and livers of adult zebrafish of both sexes were also assessed for potential toxicity mechanisms. Based on the embryonic development test results, the mortality, hatching, and teratogenetic rates of eggs treated with azoxystrobin and picoxystrobin all showed significant dose- and time-dependent effects, and the 144-h LC50 values of azoxystrobin and picoxystrobin were 1174.9 and 213.8mugL(-1), respectively. In the larval zebrafish (96h) test, activities of CAT, POD, CarE, and GST and MDA content in azoxystrobin and picoxystrobin-treated zebrafish larvae increased significantly with concentrations of the pesticides compared with those in the control. We further revealed that azoxystrobin and picoxystrobin exposure both caused significant oxidative stress in adult fish livers and the changes differed between the sexes. Our results indicated that picoxystrobin led to higher embryonic development toxicity and oxidative stress than azoxystrobin in zebrafish and the male zebrafish liver had stronger ability to detoxify than that of the females. Title: Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding Lau SKP, Zhang L, Luk HKH, Xiong L, Peng X, Li KSM, He X, Zhao PS, Fan RYY and Woo PCY <11 more author(s)> Lau SKP, Zhang L, Luk HKH, Xiong L, Peng X, Li KSM, He X, Zhao PS, Fan RYY, Wong ACP, Ahmed SS, Cai JP, Chan JFW, Sun Y, Jin D, Chen H, Lau TCK, Kok RKH, Li W, Yuen KY, Woo PCY (- 11) Ref: J Infect Dis, 218:197, 2018 : PubMed ESTHER: Lau_2018_J.Infect.Dis_218_197 PubMedSearch: Lau 2018 J.Infect.Dis 218 197 PubMedID: 29346682 Abstract Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4. Title: A protective role of autophagy in TDCIPP-induced developmental neurotoxicity in zebrafish larvae Li R, Zhang L, Shi Q, Guo Y, Zhang W, Zhou B Ref: Aquat Toxicol, 199:46, 2018 : PubMed ESTHER: Li_2018_Aquat.Toxicol_199_46 PubMedSearch: Li 2018 Aquat.Toxicol 199 46 PubMedID: 29605586 Abstract Tris (1, 3-dichloro-2-propyl) phosphate (TDCIPP), an extensively used organophosphorus flame retardant, is frequently detected in various environmental media and biota, and has been demonstrated as neurotoxic. Autophagy has been proposed as a protective mechanism against toxicant-induced neurotoxicity. The purpose of the present study was to investigate the effect of TDCIPP exposure on autophagy, and its role in TDCIPP-induced developmental neurotoxicity. Zebrafish embryos (2-120h post-fertilization [hpf]) were exposed to TDCIPP (0, 5, 50 and 500mug/l) and a model neurotoxic chemical, chlorpyrifos (CPF, 100mug/l). The developmental endpoints, locomotive behavior, cholinesterase activities, gene and protein expression related to neurodevelopment and autophagy were measured in the larvae. Our results demonstrate that exposure to TDCIPP (500mug/l) and CPF causes developmental toxicity, including reduced hatching and survival rates and increased malformation rate (e.g., spinal curvature), as well as altered locomotor behavior. The expression of selected neurodevelopmental gene and protein markers (e.g., mbp, syn2a, and alpha1-tubulin) was significantly down-regulated in CPF and TDCIPP exposed zebrafish larvae. Treatment with CPF significantly inhibits AChE and BChE, while TDCIPP (0-500mug/l) exerts no effects on these enzymes. Furthermore, the conversion of microtubule-associated protein I (LC3 I) to LC3 II was significantly increased in TDCIPP exposed zebrafish larvae. In addition, exposure to TDCIPP also activates transcription of several critical genes in autophagy (e.g. Becn1, atg3, atg5, map1lc3b and sqstm1). To further investigate the role of autophagy in TDCIPP induced developmental neurotoxicity, an autophagy inducer (rapamycin, Rapa, 1nM) and inhibitor (chloroquine, CQ, 1muM) were used. The results demonstrate that the hatching rate, survival rate, and the expression of mbp and small a, Cyrillic1-tubulin proteins were all significantly increased in larvae treated with TDCIPP (500mug/l) and Rapa compared to TDCIPP alone. In contrast, co-treatment with the autophagy inhibitor CQ results in exacerbated neurodevelopmental toxicity. Taken together, our results confirm that exposure to TDCIPP induces autophagy, which plays a protective role in TDCIPP-induced developmental neurotoxicity in zebrafish embryos and larvae. Title: The Expression Pattern of PLIN2 in Differentiated Adipocytes from Qinchuan Cattle Analysis of Its Protein Structure and Interaction with CGI-58 Li P, Wang Y, Zhang L, Ning Y, Zan L Ref: Int J Mol Sci, 19:, 2018 : PubMed ESTHER: Li_2018_Int.J.Mol.Sci_19_ PubMedSearch: Li 2018 Int.J.Mol.Sci 19 PubMedID: 29723991 Abstract PLIN2 (Perilipin-2) is a protein that can anchor on the membrane of lipid droplets (LDs), playing a vital role in the early formation of LDs and in the regulation of LD metabolism in many types of cells. However, little research has been conducted in cattle adipocytes. In the present study, we found that the expression of PLIN2 mRNA peaks at Day 2 during cattle adipocyte differentiation (p < 0.01), but PLIN2 protein levels maintain high abundance until Day 4 and then decrease sharply. We first built an interaction model using PyMOL. The results of a pull-down assay indicated that bovine PLIN2 and CGI-58 (ABHD5, α/β hydrolase domain-containing protein 5) had an interaction relationship. Furthermore, Bimolecular Fluorescence Complementation-Flow Cytometry (BiFC-FC) was used to explore the function of the PLIN2-CGI-58 interaction. Interestingly, we found that different combined models had different levels of fluorescence intensity; specifically, PLIN2-VN173+CGI-58-VC155 expressed in bovine adipocytes exhibited the highest level of fluorescence intensity. Our findings elucidate the PLIN2 expression pattern in cattle adipocytes, the protein structure and the function of protein(-)protein interactions (PPI) as well as highlight the characteristics of bovine PLIN2 during the early formation and accumulation of lipid droplets. Title: Food up-take and reproduction performance of Daphnia magna under the exposure of Bisphenols Liu Y, Yan Z, Zhang L, Deng Z, Yuan J, Zhang S, Chen J, Guo R Ref: Ecotoxicology & Environmental Safety, 170:47, 2018 : PubMed ESTHER: Liu_2018_Ecotoxicol.Environ.Saf_170_47 PubMedSearch: Liu 2018 Ecotoxicol.Environ.Saf 170 47 PubMedID: 30522006 Abstract Because the application of Bisphenol A (BPA) was restricted, many substitutes, such as Bisphenol F (BPF) and Bisphenol S (BPS), were developed as BPA substitutes. Therefore, environmental impacts of BPA and its substitutes on aquatic organisms should be concerned, especially their combined toxicity. In this study, the impacts of BPA, BPF, BPS and their mixture on the feeding behavior, reproduction and physiological function of daphnids were synthetically evaluated, involving the duration and mode of exposure. In short-term exposure tests, feeding rates of D. magna decreased after exposure to BPA, BPF, BPS and their mixture, while the inhibition reversed into stimulation in the recovery period. It may benefit from overcompensation of D. magna. In long-term exposure tests, the inhibition effect on the reproduction and growth of the exposed D. magna was difficult to recover, and only some experimental groups have a certain recovery. In conclusion, environmental risk of BPA, BPF, BPS and their mixture on the behavior of D. magna increased with prolonged exposure time. Moreover, relative activities of trypsin, amylase (AMS), acetylcholinesterase (AChE), carbonic anhydrase (CA), glutathione peroxidase (GPx) and super oxidase dimutase (SOD) of the exposed daphnids decreased in most treatment groups, indicating the disorder of digestive, nervous and antioxidative system of D. magna. Interestingly, inhibition of enzymes activities decreased with the increase of the exposure time, which implied the tolerance may be occurred. Title: The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis Shen Q, Zhang L, Liao Z, Wang S, Yan T, Shi P, Liu M, Fu X, Pan Q and Tang K <15 more author(s)> Shen Q, Zhang L, Liao Z, Wang S, Yan T, Shi P, Liu M, Fu X, Pan Q, Wang Y, Lv Z, Lu X, Zhang F, Jiang W, Ma Y, Chen M, Hao X, Li L, Tang Y, Lv G, Zhou Y, Sun X, Brodelius PE, Rose JKC, Tang K (- 15) Ref: Mol Plant, 11:776, 2018 : PubMed ESTHER: Shen_2018_Mol.Plant_11_776 PubMedSearch: Shen 2018 Mol.Plant 11 776 PubMedID: 29703587 Gene_locus related to this paper: artan-a0a2u1ns65, artan-a0a2u1nuf0, artan-a0a2u1pw87, artan-a0a2u1ql98, artan-a0a2u1n9p7.2, artan-a0a2u1ky94, artan-a0a2u1pvq0, artan-a0a2u1q8x4, artan-a0a2u1mtd1, artan-a0a2u1l9j8, artan-a0a2u1lak5, artan-a0a2u1lfl1, artan-a0a2u1lzs1, artan-a0a2u1m5v6, artan-a0a2u1n4s5, artan-a0a2u1qgg7 Abstract Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin. Title: Dual-Channel Enzymatic Inhibition Measurement (DEIM) Coupling Isotope Substrate via Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry Tao M, Zhang L, Guo Y Ref: J Am Soc Mass Spectrom, 29:2427, 2018 : PubMed ESTHER: Tao_2018_J.Am.Soc.Mass.Spectrom_29_2427 PubMedSearch: Tao 2018 J.Am.Soc.Mass.Spectrom 29 2427 PubMedID: 30159674 Abstract A novel dual-channel enzymatic inhibition measurement (DEIM) method was developed to improve the repeatability with light/heavy isotope substrates, producing reliable relative standard deviations (< 3%) by employing acetylcholinesterase (AChE) as the model enzyme. The matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) was adapted for enzyme-inhibited method due to its good salt-tolerance and high throughput; meanwhile, dual-channel enzymatic reactions were performed to improve the repeatability of each well. The acetylcholinesterase inhibition measurement was conducted by mixing the quenched enzyme reaction solution of blank group (with heavy isotope as substrate) and experimental group (with light isotope as substrate), of which the inhibition rate might be affected by isotope effects. Hence, inverse study and Km measurement were implemented to validate the method. The inverse study shows similar inhibition rate (68.9 and 70.3%) and the Km of isotope substrates are analogous (0.139 and 0.135 mM), which demonstrated that the novel method is feasible to AChE inhibition measurement. Finally, the method was applied to herb extracts, half of which exhibit inhibition to AChE. The precise dual-channel enzymatic inhibition measurement (DEIM) method could be regarded as a promising approach to potential enzyme inhibitor screening. Graphical Abstract . Title: Genomic Analysis of Microbulbifer sp. Strain A4B-17 and the Characterization of Its Metabolic Pathways for 4-Hydroxybenzoic Acid Synthesis Tian J, Zhu L, Wang W, Zhang L, Li Z, Zhao Q, Xing K, Feng Z, Peng X Ref: Front Microbiol, 9:3115, 2018 : PubMed ESTHER: Tian_2018_Front.Microbiol_9_3115 PubMedSearch: Tian 2018 Front.Microbiol 9 3115 PubMedID: 30619190 Abstract The marine bacterium Microbulbifer sp. A4B-17 produces secondary metabolites such as 4-hydroxybenzoic acid (4HBA) and esters of 4HBA (parabens). 4HBA is a useful material in the synthesis of the liquid crystal. Parabens are man-made compounds that have been extensively used since the 1920s in the cosmetic, pharmaceutical, and food industries for their effective antimicrobial activity. In this study, we completed the sequencing and annotation of the A4B-17 strain genome and found all genes for glucose utilization and 4HBA biosynthesis. Strain A4B-17 uses the Embden-Meyerhof-Parnas (EMP), hexose monophosphate (HMP), and Entner-Doudoroff (ED) pathways to utilize glucose. Other sugars such as fructose, sucrose, xylose, arabinose, galactose, mannitol, and glycerol supported cell growth and 4HBA synthesis. Reverse transcriptional analysis confirmed that the key genes involved in the glucose metabolism were functional. Paraben concentrations were proportionally increased by adding alcohols to the culture medium, indicating that strain A4B-17 synthesizes the 4HBA and the alcohols separately and an esterification reaction between them is responsible for the paraben synthesis. A gene that codes for a carboxylesterase was proposed to catalyze this reaction. The temperature and NaCl concentration for optimal growth were determined to be 35 degrees C and 22.8 g/L. Title: Comparative genomic analysis of the Lipase3 gene family in five plant species reveals distinct evolutionary origins Wang D, Zhang L, Hu J, Gao D, Liu X, Sha Y Ref: Genetica, 146:179, 2018 : PubMed ESTHER: Wang_2018_Genetica_146_179 PubMedSearch: Wang 2018 Genetica 146 179 PubMedID: 29468429 Abstract Lipases are physiologically important and ubiquitous enzymes that share a conserved domain and are classified into eight different families based on their amino acid sequences and fundamental biological properties. The Lipase3 family of lipases was reported to possess a canonical fold typical of alpha/beta hydrolases and a typical catalytic triad, suggesting a distinct evolutionary origin for this family. Genes in the Lipase3 family do not have the same functions, but maintain the conserved Lipase3 domain. There have been extensive studies of Lipase3 structures and functions, but little is known about their evolutionary histories. In this study, all lipases within five plant species were identified, and their phylogenetic relationships and genetic properties were analyzed and used to group them into distinct evolutionary families. Each identified lipase family contained at least one dicot and monocot Lipase3 protein, indicating that the gene family was established before the split of dicots and monocots. Similar intron/exon numbers and predicted protein sequence lengths were found within individual groups. Twenty-four tandem Lipase3 gene duplications were identified, implying that the distinctive function of Lipase3 genes appears to be a consequence of translocation and neofunctionalization after gene duplication. The functional genes EDS1, PAD4, and SAG101 that are reportedly involved in pathogen response were all located in the same group. The nucleotide diversity (Dxy) and the ratio of nonsynonymous to synonymous nucleotide substitutions rates (Ka/Ks) of the three genes were significantly greater than the average across the genomes. We further observed evidence for selection maintaining diversity on three genes in the Toll-Interleukin-1 receptor type of nucleotide binding/leucine-rich repeat immune receptor (TIR-NBS LRR) immunity-response signaling pathway, indicating that they could be vulnerable to pathogen effectors. Title: Comparative transcriptomic profiling of peripheral efferent and afferent nerve fibres at different developmental stages in mice Wang H, Zhou Y, Cong M, Zhang L, Gu X, Tang X Ref: Sci Rep, 8:11990, 2018 : PubMed ESTHER: Wang_2018_Sci.Rep_8_11990 PubMedSearch: Wang 2018 Sci.Rep 8 11990 PubMedID: 30097601 Abstract Peripheral nerve injury impairs motor and sensory function in humans, and its functional recovery largely depends on the axonal outgrowth required for the accurate reinnervation of appropriate targets. To better understand how motor and sensory nerve fibres select their terminal pathways, an unbiased cDNA microarray analysis was conducted to examine differential gene expression patterns in peripheral efferent and afferent fibres at different developmental stages in mice. Gene ontology (GO) and Kyoto Enrichment of Genes and Genomes (KEGG) analyses revealed common and distinct features of enrichment for differentially expressed genes during motor and sensory nerve fibre development. Ingenuity Pathway Analysis (IPA) further indicated that the key differentially expressed genes were associated with trans-synaptic neurexin-neuroligin signalling components and a variety of gamma-aminobutyric acid (GABA) receptors. The aim of this study was to generate a framework of gene networks regulated during motor and sensory neuron differentiation/maturation. These data may provide new clues regarding the underlying cellular and molecular mechanisms that determine the intrinsic capacity of neurons to regenerate after peripheral nerve injury. Our findings may thus facilitate further development of a potential intervention to manipulate the therapeutic efficiency of peripheral nerve repair in the clinic. Title: Development and validation of a novel score for fibrosis staging in patients with chronic hepatitis B Wu D, Rao Q, Chen W, Ji F, Xie Z, Huang K, Chen E, Zhao Y, Ouyang X and Li L <5 more author(s)> Wu D, Rao Q, Chen W, Ji F, Xie Z, Huang K, Chen E, Zhao Y, Ouyang X, Zhang S, Jiang Z, Zhang L, Xu L, Gao H, Li L (- 5) Ref: Liver Int, 38:1930, 2018 : PubMed ESTHER: Wu_2018_Liver.Int_38_1930 PubMedSearch: Wu 2018 Liver.Int 38 1930 PubMedID: 29654711 Abstract BACKGROUND & AIMS: Non-invasive assessment methods for liver fibrosis are urgently needed. The present study aimed to develop a novel diagnostic model for fibrosis staging in patients with chronic hepatitis B. METHODS: A cross-sectional set of 417 chronic hepatitis B patients who underwent liver biopsy was enrolled and the METAVIR score was adopted as the reference of fibrosis staging. RESULTS: Among thyroid hormones, only the level of free tetraiodothyronine (FT4) decreased gradually with the METAVIR fibrosis score (P < .001). FibroStage, a novel diagnosis model that incorporates data on FT4, platelets, cholinesterase, gamma-glutamyl transpeptidase, and age, was developed using the deriving set (n = 219). For the diagnosis of significant fibrosis, the FibroStage model had a significantly higher area under the receiver operating curve than did the FibroIndex, Forn, and Lok models (all of P < .01) and tended to better than the fibrosis-4 (P = .0791) but comparable with the aspartate transaminase-to-platelet ratio index model (P = .1694). For the diagnosis of advanced fibrosis, FibroStage had a higher area under the receiver operating curve than did the aspartate transaminase-to-platelet ratio index, FibroIndex, Forn, and Lok models (all of P < .05) and had a comparable area under the receiver operating curve with the fibrosis-4 model (P = .2109). For the diagnosis of cirrhosis, the area under the receiver operating curve of FibroStage was higher than those of the aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, and Lok (all of P < .05) models and was comparable with Forn (P = .1649). These results was validated by a validation set (n = 198). CONCLUSION: FT4 may be an indicator for fibrosis staging in chronic hepatitis B patients. FibroStage is a better model than aspartate transaminase-to-platelet ratio index, fibrosis-4, FibroIndex, Forn, and Lok for the comprehensively diagnosis of significant and advanced fibrosis and cirrhosis. Title: Sublethal or not? Responses of multiple biomarkers in Daphnia magna to single and joint effects of BDE-47 and BDE-209 Xiong Q, Shi Y, Lu Y, Pan K, Dakhil MA, Zhang L, Xiao Y Ref: Ecotoxicology & Environmental Safety, 164:164, 2018 : PubMed ESTHER: Xiong_2018_Ecotoxicol.Environ.Saf_164_164 PubMedSearch: Xiong 2018 Ecotoxicol.Environ.Saf 164 164 PubMedID: 30107326 Abstract Polybrominated diphenyl ethers (PBDEs) are extremely incessant anthropogenic contaminants found in the environment, with dreadful risk to aquatic ecosystems. However, there is a limited amount of data concerning their impacts on freshwater organisms. 2,2',3,3',4,4',5,5',6,6'-decabromodiphenyl ether (BDE-209) and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) are significant components of total PBDEs in water. The sublethal effects of BDE-47, BDE-209 and their binary mixtures on the aquatic organism Daphnia magna were investigated in acute and chronic exposure experiments. Immobilization and heartbeat were studied in daphnids after 48h of exposure. Mortality rate, breed number, Cholinesterase (ChE), Glutathione S-transferases (GST) and Catalase (CAT) activities were evaluated after 21 days of exposure. The results showed that at 100 and 200mug/L concentration of BDE-47, immobilization rate of daphnids were inhibited by 44.0+/-16.7% and 88.0+/-10.9%, respectively. The binary mixture of BDE-47 and BDE-209 had uncongenial effects on immobilization of D. magna under acute toxicity test. BDE-209 significantly increased the heartbeat rate of daphnids, which increased even further when combined with BDE-47. After 21 days of exposure, daphnids exposed to single BDE-47 were physiologically altered. The combination of BDE-47 with BDE-209 significantly decreased the mortality rate of daphnids. Irrespective of the concentration, higher numbers of offsprings were produced in the mixtures compared to BDE-47 treatment alone. ChE activities significantly (p<0.05) decreased at concentrations of 2 and 4mug/L in single BDE-47 treatment, while GST activity significantly (p<0.05) decreased at 0.5mug/L. CAT activities significantly increased with BDE-47 treatments in all the tested concentrations (p<0.05). The mixtures significantly affect ChE (p<0.05), GST (p<0.05) and CAT activities (p<0.05). The results illustrated that the toxicity of the mixture of PBDE congeners exposed to aquatic organisms may have antagonistic effects. The 21 days chronic test in this study suggests that acute toxicity tests, i.e. 48-h tests, using Daphnia may lead to underestimation of risks associated with PBDEs, especially, BDE-209. Hence, there is a necessity to re-examine PBDE congeners' environmental risk in aquatic organisms. Title: Enhanced lincomycin production by co-overexpression of metK1 and metK2 in Streptomyces lincolnensis Xu Y, Tan G, Ke M, Li J, Tang Y, Meng S, Niu J, Wang Y, Liu R and Zhang B <3 more author(s)> Xu Y, Tan G, Ke M, Li J, Tang Y, Meng S, Niu J, Wang Y, Liu R, Wu H, Bai L, Zhang L, Zhang B (- 3) Ref: J Ind Microbiol Biotechnol, 45:345, 2018 : PubMed ESTHER: Xu_2018_J.Ind.Microbiol.Biotechnol_45_345 PubMedSearch: Xu 2018 J.Ind.Microbiol.Biotechnol 45 345 PubMedID: 29574602 Gene_locus related to this paper: strln-a0a1b1ma73, strln-a0a1b1m575 Abstract Streptomyces lincolnensis is generally utilized for the production of lincomycin A (Lin-A), a clinically useful antibiotic to treat Gram-positive bacterial infections. Three methylation steps, catalyzed by three different S-adenosylmethionine (SAM)-dependent methyltransferases, are required in the biosynthesis of Lin-A, and thus highlight the significance of methyl group supply in lincomycin production. In this study, we demonstrate that externally supplemented SAM cannot be taken in by cells and therefore does not enhance Lin-A production. Furthermore, bioinformatics and in vitro enzymatic assays revealed there exist two SAM synthetase homologs, MetK1 (SLCG_1651) and MetK2 (SLCG_3830) in S. lincolnensis that could convert L-methionine into SAM in the presence of ATP. Even though we attempted to inactivate metK1 and metK2, only metK2 was deleted in S. lincolnensis LCGL, named as DeltametK2. Following a reduction of the intracellular SAM concentration, DeltametK2 mutant exhibited a significant decrease of Lin-A in comparison to its parental strain. Individual overexpression of metK1 or metK2 in S. lincolnensis LCGL either elevated the amount of intracellular SAM, concomitant with 15% and 22% increase in Lin-A production, respectively. qRT-PCR assays showed that overexpression of either metK1 or metK2 increased the transcription of lincomycin biosynthetic genes lmbA and lmbR, and regulatory gene lmbU, indicating SAM may also function as a transcriptional activator. When metK1 and metK2 were co-expressed, Lin-A production was increased by 27% in LCGL, while by 17% in a high-yield strain LA219X. Title: Study of the interactions of forsythiaside and rutin with acetylcholinesterase (AChE) Yan X, Chen T, Zhang L, Du H Ref: Int J Biol Macromol, 119:1344, 2018 : PubMed ESTHER: Yan_2018_Int.J.Biol.Macromol_119_1344 PubMedSearch: Yan 2018 Int.J.Biol.Macromol 119 1344 PubMedID: 30048725 Abstract Acetylcholinesterase (AChE) inhibitors have been considered as candidates for the treatment of Alzheimer's disease (AD) and have been utilized in clinical trials. In the present study, the interactions of forsythiaside and rutin with AChE have been investigated, after discovering the inhibitory AChE activity of the two compounds. Forsythiaside and rutin both can bind to AChE to form forsythiaside-AChE and rutin-AChE complex, and thus quench the intrinsic fluorescence of AChE. The quenching mechanism, the binding sites, the binding forces, the binding constants and the energy transfer involved were studied in details. Forsythiaside and rutin show some properties in common, including the stoichiometric binding ratio of 1:1 with AChE and the full quenching of AChE fluorescence. At the same time, the two compounds distinctly present some different characters, for example, the binding constant of rutin is less than that of forsythiaside, and the interaction force and the affinity between forsythiaside and AChE are much bigger than that of rutin. Spectroscopy data and docking analysis powerfully support the findings that forsythiaside inhibit AChE activity more strongly than rutin. The current study will provide the better understanding on the nature of the possible interactions between forsythiaside and rutin with AChE. Title: Insights into the effect and interaction mechanism of bisphenol S on lipids hydrolysis in sludge through multi-spectra, thermodynamics, and molecule docking analysis Yang H, Zhang L, Hou G, Liu C Ref: Environ Sci Pollut Res Int, 25:7834, 2018 : PubMed ESTHER: Yang_2018_Environ.Sci.Pollut.Res.Int_25_7834 PubMedSearch: Yang 2018 Environ.Sci.Pollut.Res.Int 25 7834 PubMedID: 29297162 Abstract As an alternative to bisphenol A, bisphenol S (BPS) is widely used in industrial production and daily life, which is then discharged into sewage treatment plants and accumulates in sludge. In this research, impact and interaction mechanism of BPS on lipids hydrolysis in sludge is studied from the respect of soluble organic matter and volatile organic fatty acids (VFAs). Multi-spectra, thermodynamics, molecule docking, and enzyme activity assay are applied to elucidate the effect mechanism of BPS on lipids hydrolysis. Results show that lipids hydrolysis is restrained due to the denaturation of lipase with BPS exposure. The interaction mechanism is involved in hydrophobic bond and hydrogen bond interaction in the activity region of lipase. This interaction not only results in an unfolding skeleton structure of lipase and a less hydrophobic microenvironment of tyrosine and tryptophan residues but also leads to fluorophore static quenching with the formation of lipase-BPS complex. The experimental results and the combined research methods not only contribute to the development of novel technique for sludge treatment containing micropollutant but also profit to clarify the interaction mechanism between other micropollutant and enzymes. Title: Crius: A novel fragment-based algorithm of de novo substrate prediction for enzymes Yao Z, Jiang S, Zhang L, Gao B, He X, Zhang JZH, Wei D Ref: Protein Science, 27:1526, 2018 : PubMed ESTHER: Yao_2018_Protein.Sci_27_1526 PubMedSearch: Yao 2018 Protein.Sci 27 1526 PubMedID: 29722450 Abstract The study of enzyme substrate specificity is vital for developing potential applications of enzymes. However, the routine experimental procedures require lot of resources in the discovery of novel substrates. This article reports an in silico structure-based algorithm called Crius, which predicts substrates for enzyme. The results of this fragment-based algorithm show good agreements between the simulated and experimental substrate specificities, using a lipase from Candida antarctica (CALB), a nitrilase from Cyanobacterium syechocystis sp. PCC6803 (Nit6803), and an aldo-keto reductase from Gluconobacter oxydans (Gox0644). This opens new prospects of developing computer algorithms that can effectively predict substrates for an enzyme. Title: Identification of Human Acetylcholinesterase Inhibitors from the Constituents of EGb761 by Modeling Docking and Molecular Dynamics Simulations Zhang L, Li D, Cao F, Xiao W, Zhao L, Ding G, Wang ZZ Ref: Comb Chem High Throughput Screen, 21:41, 2018 : PubMed ESTHER: Zhang_2018_Comb.Chem.High.Throughput.Screen_21_41 PubMedSearch: Zhang 2018 Comb.Chem.High.Throughput.Screen 21 41 PubMedID: 29173156 Abstract AIM AND OBJECTIVE: EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial role in the treatment of multiple diseases, particularly Alzheimer's disease (AD). Identification of natural acetylcholinesterase (AChE) inhibitors from EGb761 would provide a novel therapeutic approach against the Alzheimer's disease. MATERIAL AND METHOD: A series of 21 kinds of promising EGb761 compounds were selected, and subsequently evaluated for their potential ability to bind AChE enzyme by molecular docking and a deep analysis of protein surface pocket features. RESULTS: Docking results indicated that these compounds can bind tightly with the active site of human AChE, with favorable distinct interactions around several important residues Asp74, Leu289, Phe295, Ser293, Tyr341, Trp286 and Val294 in the active pocket. Most EGB761 compounds could form the hydrogen bond interactions with the negatively charged Asp74 and Phe295 residues. Among these compounds, diosmetin is the one with the best-predicted docking score while three key hydrogen bonds can be formed between small molecule and corresponding residues of the binding site. Besides, other three compounds luteolin, apigenin, and isorhamnetin have better predicted docking scores towards AChE than other serine proteases, i.e. Elastase, Tryptase, Factor XA, exhibiting specificity for AChE inhibition. The RMSD and MM-GBSA results from molecular dymamic simulations indicated that the docking pose of diosmetin-AChE complex displayed highly stable, which can be used for validating the accuracy of molecular docking study. Subsequently, the AChE inhibitory activities of these compounds were evaluated by the Ellman's colorimetric method. CONCLUSION: The obtained results revealed that all the four compounds exhibited modest AChE inhibitory activity, among which Diosmetin manifested remarkable anti-AChE activity, comparable with the reference compound, Physostigmine. It can be deduced that these EGB761 compounds can be regarded as a promising starting point for developing AChE inhibitors against AD. Title: Structural Definition of a Unique Neutralization Epitope on the Receptor-Binding Domain of MERS-CoV Spike Glycoprotein Zhang S, Zhou P, Wang P, Li Y, Jiang L, Jia W, Wang H, Fan A, Wang D and Zhang L <5 more author(s)> Zhang S, Zhou P, Wang P, Li Y, Jiang L, Jia W, Wang H, Fan A, Wang D, Shi X, Fang X, Hammel M, Wang S, Wang X, Zhang L (- 5) Ref: Cell Rep, 24:441, 2018 : PubMed ESTHER: Zhang_2018_Cell.Rep_24_441 PubMedSearch: Zhang 2018 Cell.Rep 24 441 PubMedID: 29996104 Abstract The major mechanism of antibody-mediated neutralization of the Middle East respiratory syndrome coronavirus (MERS-CoV) involves competition with the cellular receptor dipeptidyl peptidase 4 (DPP4) for binding to the receptor-binding domain (RBD) of the spike (S) glycoprotein. Here, we report a unique epitope and unusual neutralizing mechanism of the isolated human antibody MERS-4. Structurally, MERS-4 approached the RBD from the outside of the RBD-DPP4 binding interface. Such binding resulted in the folding of the beta5-beta6 loop toward a shallow groove on the RBD interface critical for accommodating DPP4. The key residues for binding are identified through site-directed mutagenesis. Structural modeling revealed that MERS-4 binds to RBD only in the "up" position in the S trimer. Furthermore, MERS-4 demonstrated synergy with several reported antibodies. These results indicate that MERS-4 neutralizes MERS-CoV by indirect rather than direct competition with DPP4. This mechanism provides a valuable addition for the combined use of antibodies against MERS-CoV infection. Title: Benzo(a)pyrene inhibits the accumulation and toxicity of cadmium in subcellular fractions of Eisenia fetida Zhang L, Zhou L, Han L, Zhao C, Norton JM, Li H, Hu F, Xu L Ref: Chemosphere, 219:740, 2018 : PubMed ESTHER: Zhang_2018_Chemosphere_219_740 PubMedSearch: Zhang 2018 Chemosphere 219 740 PubMedID: 30557731 Abstract Cadmium (Cd) and benzo [a]pyrene (BaP) often co-occur in the environment, and the critical body residue of organisms is used as an indicator of the toxic effects of contaminants. However, little is known about their distributions and toxicities when pollution of Cd and BaP are combined. Semi-static solution culture experiment was used to study the impacts of BaP on the subcellular distribution of the toxic metal Cd in the earthworm Eisenia fetida. We explored the mechanisms by which this organism responds to combined exposure to these pollutants by measuring the protein content of each of three subcellular fractions, as well as acetylcholinesterase (AChE) and glutathione S-transferase (GST) activities. The subcellular partitioning of Cd was heterogeneous and Cd mainly accumulated in the cytosolic fraction (Fraction C), which was previously reported to be involved in metal immobilization. In Fraction C, Cd accumulation was correlated with the external concentration to which the earthworm had been exposed; however, in the presence of BaP, Cd accumulation was inhibited and plateaued at high external Cd concentrations. A principal component analysis revealed that this decreased Cd accumulation might be caused by increases in GST activity, which likely increased the excretion of Cd. BaP was also found to stimulate protein biosynthesis and upregulate AChE and GST activities in the debris fraction (Fraction E), indicating other potential detoxification mechanisms in this fraction. Granule fraction (Fraction D) had a lower protein content, AChE and GST activities than the other subcellular fractions, supporting previous findings that Fraction D is largely inert. 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: Preclinical profile of a dopamine D1 potentiator suggests therapeutic utility in neurological and psychiatric disorders Bruns RF, Mitchell SN, Wafford KA, Harper AJ, Shanks EA, Carter G, O'Neill MJ, Murray TK, Eastwood BJ and Svensson KA <17 more author(s)> Bruns RF, Mitchell SN, Wafford KA, Harper AJ, Shanks EA, Carter G, O'Neill MJ, Murray TK, Eastwood BJ, Schaus JM, Beck JP, Hao J, Witkin JM, Li X, Chernet E, Katner JS, Wang H, Ryder JW, Masquelin ME, Thompson LK, Love PL, Maren DL, Falcone JF, Menezes MM, Zhang L, Yang CR, Svensson KA (- 17) Ref: Neuropharmacology, 128:351, 2017 : PubMed ESTHER: Bruns_2017_Neuropharmacol_128_351 PubMedSearch: Bruns 2017 Neuropharmacol 128 351 PubMedID: 29102759 Abstract DETQ, an allosteric potentiator of the dopamine D1 receptor, was tested in therapeutic models that were known to respond to D1 agonists. Because of a species difference in affinity for DETQ, all rodent experiments used transgenic mice expressing the human D1 receptor (hD1 mice). When given alone, DETQ reversed the locomotor depression caused by a low dose of reserpine. DETQ also acted synergistically with L-DOPA to reverse the strong hypokinesia seen with a higher dose of reserpine. These results indicate potential as both monotherapy and adjunct treatment in Parkinson's disease. DETQ markedly increased release of both acetylcholine and histamine in the prefrontal cortex, and increased levels of histamine metabolites in the striatum. In the hippocampus, the combination of DETQ and the cholinesterase inhibitor rivastigmine increased ACh to a greater degree than either agent alone. DETQ also increased phosphorylation of the AMPA receptor (GluR1) and the transcription factor CREB in the striatum, consistent with enhanced synaptic plasticity. In the Y-maze, DETQ increased arm entries but (unlike a D1 agonist) did not reduce spontaneous alternation between arms at high doses. DETQ enhanced wakefulness in EEG studies in hD1 mice and decreased immobility in the forced-swim test, a model for antidepressant-like activity. In rhesus monkeys, DETQ increased spontaneous eye-blink rate, a measure that is known to be depressed in Parkinson's disease. Together, these results provide support for potential utility of D1 potentiators in the treatment of several neuropsychiatric disorders, including Parkinson's disease, Alzheimer's disease, cognitive impairment in schizophrenia, and major depressive disorder. Title: Nine Different Chemical Species and Action Mechanisms of Pancreatic Lipase Ligands Screened Out from Forsythia suspensa Leaves All at One Time Chen T, Li Y, Zhang L Ref: Molecules, 22:E795, 2017 : PubMed ESTHER: Chen_2017_Molecules_22_E795 PubMedSearch: Chen 2017 Molecules 22 E795 PubMedID: 28498356 Abstract It is difficult to screen out as many active components as possible from natural plants all at one time. In this study, subfractions of Forsythia suspensa leaves were firstly prepared; then, their inhibitive abilities on pancreatic lipase were tested; finally, the highest inhibiting subfraction was screened by self-made immobilized pancreatic lipase. Results showed that nine ligands, including eight inhibitors and one promotor, were screened out all at one time. They were three flavonoids (rutin, IC50: 149 +/- 6.0 mumol/L; hesperidin, 52.4 mumol/L; kaempferol-3-O-rutinoside, isolated from F. suspensa leaves for the first time, IC50 notably reached 2.9 +/- 0.5 mumol/L), two polyphenols (chlorogenic acid, 3150 +/- 120 mumol/L; caffeic acid, 1394 +/- 52 mumol/L), two lignans (phillyrin, promoter; arctigenin, 2129 +/- 10.5 mumol/L), and two phenethyl alcohol (forsythiaside A, 2155 +/- 8.5 mumol/L; its isomer). Their action mechanisms included competitive inhibition, competitive promotion, noncompetitive inhibition, and uncompetitive inhibition. In sum, using the appropriate methods, more active ingredients can be simply and quickly screened out all at one time from a complex natural product system. In addition, F. suspensa leaves contain numerous inhibitors of pancreatic lipase. Title: Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita Cui R, Zhang L, Chen Y, Huang W, Fan C, Wu Q, Peng D, da Silva W, Sun X Ref: Experimental Parasitology, 176:75, 2017 : PubMed ESTHER: Cui_2017_Exp.Parasitol_176_75 PubMedSearch: Cui 2017 Exp.Parasitol 176 75 PubMedID: 28238686 Gene_locus related to this paper: melin-ACHE1, melin-ACHE2, melic-a0a0m5m7r8 Abstract The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant. Title: Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells Fu G, Dai J, Zhang D, Zhu L, Tang X, Zhang L, Zhou T, Duan P, Quan C and Shi Y <2 more author(s)> Fu G, Dai J, Zhang D, Zhu L, Tang X, Zhang L, Zhou T, Duan P, Quan C, Zhang Z, Song S, Shi Y (- 2) Ref: Environ Toxicol, 32:1055, 2017 : PubMed ESTHER: Fu_2017_Environ.Toxicol_32_1055 PubMedSearch: Fu 2017 Environ.Toxicol 32 1055 PubMedID: 27416487 Abstract Di(2-ethylhexyl) phthalate (DEHP), a plasticizer of synthetic polymers, is a well-known endocrine disrupting chemical (EDC) and reproductive toxicant. Addressing the unclear mechanism of DEHP-induced reproductive dysfunction, this study used GC-2spd cells to investigate the molecular mechanism involved in the DEHP-induced toxicity in the male reproductive system. The results indicated that the apoptotic cell death was significantly induced by DEHP exposure over 100 muM. Furthermore, DEHP treatment could induce oxidative stress in GC-2spd cells involving in the decrease of superoxide dismutase (SOD) activity (200 muM) and glutathione peroxidase (GSH-Px) activity (50 and 100 muM). In addition, DEHP induction also caused the elevated ratios of Bax/Bcl-2, release of cytochrome c and decomposition of procaspase-3 and procaspase-9 in GC-2spd cells. Taken together, our work provided the evidence that DEHP exposure might induce apoptosis of GC-2spd cells via mitochondria pathway mediated by oxidative stress. Title: Planarian cholinesterase: in vitro characterization of an evolutionarily ancient enzyme to study organophosphorus pesticide toxicity and reactivation Hagstrom D, Hirokawa H, Zhang L, Radic Z, Taylor P, Collins ES Ref: Archives of Toxicology, 91:2837, 2016 : PubMed ESTHER: Hagstrom_2017_Arch.Toxicol_91_2837 PubMedSearch: Hagstrom 2017 Arch.Toxicol 91 2837 PubMedID: 27990564 Gene_locus related to this paper: dugja-CHE1, dugja-CHE2 Abstract The freshwater planarian Dugesia japonica has recently emerged as an animal model for developmental neurotoxicology and found to be sensitive to organophosphorus (OP) pesticides. While previous activity staining of D. japonica, which possess a discrete cholinergic nervous system, has shown acylthiocholine catalysis, it is unknown whether this is accomplished through an acetylcholinesterase (AChE), butyrylcholinesterase (BChE), or a hybrid esterase and how OP exposure affects esterase activity. Here, we show that the majority of D. japonica cholinesterase (DjChE) activity departs from conventional AChE and BChE classifications. Inhibition by classic protonable amine and quaternary reversible inhibitors (ethopropazine, donepezil, tacrine, edrophonium, BW284c51, propidium) shows that DjChE is far less sensitive to these inhibitors than human AChE, suggesting discrete differences in active center and peripheral site recognition and structures. Additionally, we find that different OPs (chlorpyrifos oxon, paraoxon, dichlorvos, diazinon oxon, malaoxon) and carbamylating agents (carbaryl, neostigmine, physostigmine, pyridostigmine) differentially inhibit DjChE activity in vitro. DjChE was most sensitive to diazinon oxon and neostigmine and least sensitive to malaoxon and carbaryl. Diazinon oxon-inhibited DjChE could be reactivated by the quaternary oxime, pralidoxime (2-PAM), and the zwitterionic oxime, RS194B, with RS194B being significantly more potent. Sodium fluoride (NaF) reactivates OP-DjChE faster than 2-PAM. As one of the most ancient true cholinesterases, DjChE provides insight into the evolution of a hybrid enzyme before the separation into distinct AChE and BChE enzymes found in higher vertebrates. The sensitivity of DjChE to OPs and capacity for reactivation validate the use of planarians for OP toxicology studies. Title: Fatal poisoning by terbufos following occupational exposure Liang Y, Tong F, Zhang L, Li W, Huang W, Zhou Y Ref: Clinical Toxicology (Phila), :1, 2017 : PubMed ESTHER: Liang_2017_Clin.Toxicol.(Phila)__1 PubMedSearch: Liang 2017 Clin.Toxicol.(Phila) 1 PubMedID: 28681657 Abstract CONTEXT: Terbufos (TBF) is a class Ia (extremely hazardous) organophosphate pesticide (OP) and its distribution in industrialized countries has been severely restricted. Thus, acute occupational poisoning is rather uncommon. However, it still occurs in rural areas of some developing countries, where the sale of TBF is not controlled and its use is thus not properly regulated. We report a case of a 43-year-old female farmer who died after applying TBF granules. CASE: The patient died within 3 h after applying 20 bags of 5% TBF granules (900 g per bag). Investigation showed that her personal protective equipment (PPE) did not provide effective protection against dermal and inhalational exposure. Postmortem analysis revealed extremely low red blood cell acetylcholinesterase activity. Toxicological analysis of TBF showed 1.45 x 10-2 mug/ml in the heart blood and 0.17 mug/g in the liver. DISCUSSIONS: This patient died as a result of toxicity from dermal and inhalational exposure to TBF. Over-application, improper equipment, inadequate and defective PPE, and lack of hygienic precautions were all contributing factors. Title: Post-exposure treatment with the oxime RS194B rapidly reverses early and advanced symptoms in macaques exposed to sarin vapor Rosenberg YJ, Mao L, Jiang X, Lees J, Zhang L, Radic Z, Taylor P Ref: Chemico-Biological Interactions, 274:50, 2017 : PubMed ESTHER: Rosenberg_2017_Chem.Biol.Interact_274_50 PubMedSearch: Rosenberg 2017 Chem.Biol.Interact 274 50 PubMedID: 28693885 Abstract Organophosphate (OP) nerve agents and pesticides trigger a common mechanism of neurotoxicity resulting from critical targeting and inhibition of acetylcholinesterases (AChE) in central and peripheral synapses in the cholinergic nervous system. Therapeutic countermeasures have thus focused on either administering an oxime post-exposure, that can rapidly reactivate OP-inhibited AChE, or by preventing OP poisoning through administering pre-exposure treatments that scavenge OPs before they inhibit their physiological AChE targets. While several pyridinium aldoxime antidotes are currently approved, their utility is impaired due to their inability to cross the blood-brain barrier (BBB) efficiently. The present study utilized a macaque (Ma) model to demonstrate the efficacy of a novel zwitterionic and centrally acting oxime RS194B to reactivate sarin- and paraoxon-inhibited macaque AChE and butyrylcholinesterase (BChE) in vitro and to further assess the capacity of RS194B to effect a reversal of clinical symptoms following sarin inhalation in vivo. In vitro, oxime reactivation of MaAChE and MaBChE was shown to be comparable to their human orthologs, while the macaque studies indicated that IM administration of 62.5 mg/kg of RS194B and 0.28 mg/kg atropine after continuous exposure to 49.6 mug/kg sarin vapor, rapidly reactivated the inhibited AChE and BChE in blood and reversed both early and advanced clinical symptoms of sarin-induced toxicity following pulmonary exposure within 1 h. The rapid cessation of autonomic and central symptoms, including convulsions, observed in macaques bodes well for the use of RS194B as an intra- or post-exposure human treatment and validates the macaque model in generating efficacy and toxicology data required for approval under the FDA Animal rule. Title: Scallop genome provides insights into evolution of bilaterian karyotype and development Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B and Bao Z <42 more author(s)> Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B, Zhang L, Hu X, Sun X, Wang J, Zhao C, Wang Y, Wang D, Huang X, Wang R, Lv J, Li Y, Zhang Z, Liu B, Lu W, Hui Y, Liang J, Zhou Z, Hou R, Li X, Liu Y, Li H, Ning X, Lin Y, Zhao L, Xing Q, Dou J, Mao J, Guo H, Dou H, Li T, Mu C, Jiang W, Fu Q, Fu X, Miao Y, Liu J, Yu Q, Li R, Liao H, Kong Y, Jiang Z, Chourrout D, Bao Z (- 42) Ref: Nat Ecol Evol, 1:120, 2017 : PubMed ESTHER: Wang_2017_Nat.Ecol.Evol_1_120 PubMedSearch: Wang 2017 Nat.Ecol.Evol 1 120 PubMedID: 28812685 Gene_locus related to this paper: mizye-a0a210qls6, mizye-a0a210qis3, mizye-a0a210qg00, mizye-a0a210ped6, mizye-a0a210q4h5, mizye-a0a210q4h9, mizye-a0a210q4j1, mizye-a0a210qf86, mizye-a0a210q332, mizye-a0a210pqn0, mizye-a0a210q7t5, mizye-a0a210pij5, mizye-a0a210qyk8, mizye-a0a210pwl7, mizye-a0a210q8u5, mizye-a0a210r5n9, mizye-a0a210qbv2, mizye-a0a210pu25, mizye-a0a210pek1, mizye-a0a210pul3, mizye-a0a210pum3, mizye-a0a210ptr6, mizye-a0a210ptq5, mizye-a0a210ptc4.1, mizye-a0a210ptc4.2, mizye-a0a210ptv1, mizye-a0a210ptv7, mizye-a0a210qgl6, mizye-a0a210qg90, mizye-a0a210ptq0, mizye-a0a210qg72, mizye-a0a210ptb1, mizye-a0a210pjd3, mizye-a0a210qg92, mizye-a0a210q8v2, mizye-a0a210qg93, mizye-a0a210q160.1, mizye-a0a210q160.2, mizye-a0a210qes4, mizye-a0a210pk25, mizye-a0a210q1b8, mizye-a0a210q110, mizye-a0a210r503, mizye-P021348901.1, mizye-P021348901.2 Abstract Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology. 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: Protective effects of Forsythoside A on amyloid beta-induced apoptosis in PC12 cells by downregulating acetylcholinesterase Yan X, Chen T, Zhang L, Du H Ref: European Journal of Pharmacology, 810:141, 2017 : PubMed ESTHER: Yan_2017_Eur.J.Pharmacol_810_141 PubMedSearch: Yan 2017 Eur.J.Pharmacol 810 141 PubMedID: 28687196 Abstract Increasing the acetylcholine level and fighting the neuroinflammation has always been taken as a treatment strategy for Alzheimer's disease (AD). Forsythoside A is a major component in Forsythia suspensa (Thunb.) Vahl (F. suspensa, Lianqiao in Chinese) that has been traditionally used as Chinese herbal medicine to treat the inflammation in China. This study examined the inhibitory acetylcholinesterase activities of Forsythoside A at chemical and biological level. Forsythoside A inhibited acetylcholinesterase in a mixed type of inhibition, with Ki of 47.68muM. Docking analysis strongly supported these findings. In PC12 cells Forsythoside A increased cell viability and suppressed acetylcholinesterase increased by Abeta25-35, thus alleviated the corresponding apoptosis. Taken together, these results suggest that Forsythoside A has the protective effects on Abeta25-35-induced apoptosis in PC12 cells by downregulating acetylcholinesterase, making it a potential functional food ingredient or drug candidate for the treatment of AD. Title: N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2 Yang X, Zhu F, Yu C, Lu J, Zhang L, Lv Y, Sun J, Zheng M Ref: Oncotarget, 8:47709, 2017 : PubMed ESTHER: Yang_2017_Oncotarget_8_47709 PubMedSearch: Yang 2017 Oncotarget 8 47709 PubMedID: 28537875 Gene_locus related to this paper: human-NDRG1 Abstract N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Calpha (PKCalpha), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug. 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: Control of secondary cell wall patterning involves xylan deacetylation by a GDSL esterase Zhang B, Zhang L, Li F, Zhang D, Liu X, Wang H, Xu Z, Chu C, Zhou Y Ref: Nat Plants, 3:17017, 2017 : PubMed ESTHER: Zhang_2017_Nat.Plants_3_17017 PubMedSearch: Zhang 2017 Nat.Plants 3 17017 PubMedID: 28260782 Abstract O-acetylation, a ubiquitous modification of cell wall polymers, has striking impacts on plant growth and biomass utilization and needs to be tightly controlled. However, the mechanisms that underpin the control of cell wall acetylation remain elusive. Here, we show a rice brittle leaf sheath1 (bs1) mutant, which contains a lesion in a Golgi-localized GDSL esterase that deacetylates the prominent hemicellulose xylan. Cell wall composition, detailed xylan structure characterization and enzyme kinetics and activity assays on acetylated sugars and xylooligosaccharides demonstrate that BS1 is an esterase that cleaves acetyl moieties from the xylan backbone at O-2 and O-3 positions of xylopyranosyl residues. BS1 thus plays an important role in the maintenance of proper acetylation level on the xylan backbone, which is crucial for secondary wall formation and patterning. Our findings outline a mechanism for how plants modulate wall acetylation and endow a plethora of uncharacterized GDSL esterases with surmisable activities. Title: The Relation Between Lipase Thermostability and Dynamics of Hydrogen Bond and Hydrogen Bond Network Based on Long Time Molecular Dynamics Simulation Zhang L, Ding Y Ref: Protein Pept Lett, 24:643, 2017 : PubMed ESTHER: Zhang_2017_Protein.Pept.Lett_24_643 PubMedSearch: Zhang 2017 Protein.Pept.Lett 24 643 PubMedID: 28464764 Abstract BACKGROUND: Compared with the wild type of lipase (WTL), mutant lipase 6B has twelve mutations (A15S, F17S, A20E, N89Y, G111D, L114P, A132D, M134E, M137P, I157M, S163P, N166Y). The melting temperature of 6B (78.2 degrees C) is much higher than that of WTL (56 degrees C). Hydrogen bond (HB) play an important role in stabilizing the protein. It is important to analyze how mutations affect hydrogen bond and hydrogen bond network and explain how hydrogen bond and hydrogen bond network affect lipase thermostability by the change of the intensity of HB and HB networks with temperature changing. OBJECTIVE: Study the dynamics of HB and HB networks to find that how HBs and HB networks change over time and over temperature in WTL and 6B. METHOD: Long time MD simulations of WTL and 6B are carried out to analyze how mutations affect hydrogen bond and hydrogen bond network. All proteins were simulated at 300K, 325K, 350K, 375K, 400K for 300ns respectively. The definition of HB is that the distance between acceptor and donor is smaller than a cutoff 3.0 A and the angle between Donor-H and H-Acceptor is larger than 120o. If two or more HBs connect together, they formed HB network. In the network, residues that formed HB represent nodes, the HB interactions between residues represent edges. The persistence value of HB is computed by . RESULTS: The persistence values of HBs formed by mutations A15S, A20E, G111D, M137P, N166Y are significantly different from that of WTL. HB Glu20-Ser24, Asp111-Asp144, Leu160-Tyr166 and Lys170-Tyr166 are important to stabilize 6B. In addition, the HB networks dynamics show that there are three HB networks are more stable in mutants than that in WTL. The first HB network makes beta3, beta5, loop and 310-helix closely connect with each other at mutants. The second HB network increases the rigidity of the loop, alphaC, beta3 and beta5. The third HB network enhances the interaction between loops, alphaB and alphaC. CONCLUSION: The higher HB persistence value generally means that the HB is more stable. These mutations directly improve the stability of these HBs referring to their persistence values, which show that mutations strengthen the ability of HBs to withstand high temperature and then stabilize the secondary structure. It is thus clear that the mutations change the stability of HBs and the HB networks, which are responsible for increasing protein thermostability. 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: Matsutakone and Matsutoic Acid, Two (Nor)steroids with Unusual Skeletons from the Edible Mushroom Tricholoma matsutake Zhao ZZ, Chen HP, Wu B, Zhang L, Li ZH, Feng T, Liu JK Ref: J Org Chem, 82:7974, 2017 : PubMed ESTHER: Zhao_2017_J.Org.Chem_82_7974 PubMedSearch: Zhao 2017 J.Org.Chem 82 7974 PubMedID: 28691489 Abstract Matsutakone (1), a novel sterol with an unprecedented polycyclic ring system, together with a new norsteroid matsutoic acid (2) were isolated from the fruiting bodies of Tricholoma matsutake. Their structures and absolute configurations were assigned by extensive spectroscopic analyses and computational methods. Bioassay results showed that compounds 1 and 2 exhibited inhibitory activities against acetylcholinesterase (IC50 20.9 muM for 1). Title: Novel Natural Oximes and Oxime Esters with a Vibralactone Backbone from the Basidiomycete Boreostereum vibrans Chen HP, Zhao ZZ, Li ZH, Dong ZJ, Wei K, Bai X, Zhang L, Wen CN, Feng T, Liu JK Ref: ChemistryOpen, 5:142, 2016 : PubMed ESTHER: Chen_2016_ChemistryOpen_5_142 PubMedSearch: Chen 2016 ChemistryOpen 5 142 PubMedID: 27308232 Inhibitor(s) related to this paper: Vibralactone Abstract A variety of novel natural products with significant bioactivities are produced by the basidiomycete Boreostereum vibrans. In the present study, we describe 16 novel natural oximes and oxime esters with a vibralactone backbone, vibralactoximes, which were isolated from the scale-up fermentation broth of B. vibrans. Their structures were determined through extensive spectroscopic analyses. These compounds represent the first oxime esters from nature. The hypothetical biosynthetic pathway of these compounds was also proposed. Seven compounds exhibited significant pancreatic lipase inhibitory activity, while ten compounds exhibited cytotoxicities against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, and SW480), with IC50 values comparable with those of cisplatin. Title: Development of a neuroprotective potential algorithm for medicinal plants Liu W, Ma H, DaSilva NA, Rose KN, Johnson SL, Zhang L, Wan C, Dain JA, Seeram NP Ref: Neurochem Int, 100:164, 2016 : PubMed ESTHER: Liu_2016_Neurochem.Int_100_164 PubMedSearch: Liu 2016 Neurochem.Int 100 164 PubMedID: 27693453 Abstract Medicinal plants are promising candidates for Alzheimer's disease (AD) research but there is lack of systematic algorithms and procedures to guide their selection and evaluation. Herein, we developed a Neuroprotective Potential Algorithm (NPA) by evaluating twenty-three standardized and chemically characterized Ayurvedic medicinal plant extracts in a panel of bioassays targeting oxidative stress, carbonyl stress, protein glycation, amyloid beta (Abeta) fibrillation, acetylcholinesterase (AChE) inhibition, and neuroinflammation. The twenty-three herbal extracts were initially evaluated for: 1) total polyphenol content (Folin-Ciocalteu assay), 2) free radical scavenging capacity (DPPH assay), 3) ferric reducing antioxidant power (FRAP assay), 4) reactive carbonyl species scavenging capacity (methylglyoxal trapping assay), 5) anti-glycative effects (BSA-fructose, and BSA-methylglyoxal assays) and, 6) anti-Abeta fibrillation effects (thioflavin-T assay). Based on assigned index scores from the initial screening, twelve extracts with a cumulative NPA score >/=40 were selected for further evaluation for their: 1) inhibitory effects on AChE activity, 2) in vitro anti-inflammatory effects on murine BV-2 microglial cells (Griess assay measuring levels of lipopolysaccharide-induced nitric oxide species), and 3) in vivo neuroprotective effects on Caenorhabditis elegans post induction of Abeta1-42 induced neurotoxicity and paralysis. Among these, four extracts had a cumulative NPA score >/=60 including Phyllanthus emblica (amla; Indian gooseberry), Mucuna pruriens (velvet bean), Punica granatum (pomegranate) and Curcuma longa (turmeric; curcumin). These extracts also showed protective effects on H2O2 induced cytotoxicity in differentiated cholinergic human neuronal SH-SY5Y and murine BV-2 microglial cells and reduced tau protein levels in the SH-SY5Y neuronal cells. While published animal data support the neuroprotective effects of several of these Ayurvedic medicinal plant extracts, some remain unexplored for their anti-AD potential. Therefore, the NPA may be utilized, in part, as a strategy to help guide the selection of promising medicinal plant candidates for future AD-based research using animal models. Title: Activation of mTOR signaling mediates the increased expression of AChE in high glucose condition: in vitro and in vivo evidences Liu YW, Zhang L, Li Y, Cheng YQ, Zhu X, Zhang F, Yin XX Ref: Molecular Neurobiology, 53:4972, 2016 : PubMed ESTHER: Liu_2016_Mol.Neurobiol_53_4972 PubMedSearch: Liu 2016 Mol.Neurobiol 53 4972 PubMedID: 26374551 Abstract Acetylcholinesterase (AChE) is impaired in brain of diabetic animals, which may be one of the reasons for diabetes-associated cognitive decline. However, the mechanism is still unknown. The present study was designed to investigate whether the increased expression of AChE in central neurons under high glucose (HG) condition was due to activation of mammalian target of rapamycin (mTOR) signaling. It was found that more production of reactive oxygen species, and higher levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE were detected in HT-22 cells in HG group than normal glucose group after culture for 24 h, which were all attenuated by an antioxidant N-acetyl-L-cysteine. A PI3K inhibitor LY294002 significantly decreased the levels of phospho-Akt, phospho-mTOR, phospho-p70S6K, and AChE protein expression in HG-cultured HT-22 cells, and an mTOR inhibitor rapamycin markedly reduced the levels of phospho-mTOR, phospho-p70S6K, and AChE expression. Furthermore, compared with normal rats, diabetic rats showed remarkable increases in levels of AChE activity and expression, malondialdehyde, phospho-mTOR, phospho-p70S6K, and a significant decrease in total superoxide dismutase activity in both hippocampus and cerebral cortex. However, much lower levels of phospho-mTOR, phospho-p70S6K, and AChE expression occurred in both brain regions of diabetic rats treated with rapamycin when compared with untreated ones. These results indicated that mTOR signaling was activated through the activation of PI3K/Akt pathway mediated by oxidative stress in HG-cultured HT-22 cells and diabetic rat brains, which contributed to the elevated protein expression of AChE in central neurons under the condition of HG. Title: Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors Si W, Zhang T, Zhang L, Mei X, Dong M, Zhang K, Ning J Ref: Bioorganic & Medicinal Chemistry Lett, 26:2380, 2016 : PubMed ESTHER: Si_2016_Bioorg.Med.Chem.Lett_26_2380 PubMedSearch: Si 2016 Bioorg.Med.Chem.Lett 26 2380 PubMedID: 27017111 Abstract A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44nM and 13.58nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study. Title: Display of fungal hydrophobin on the Pichia pastoris cell surface and its influence on Candida antarctica lipase B Wang P, He J, Sun Y, Reynolds M, Zhang L, Han S, Liang S, Sui H, Lin Y Ref: Applied Microbiology & Biotechnology, 100:5883, 2016 : PubMed ESTHER: Wang_2016_Appl.Microbiol.Biotechnol_100_5883 PubMedSearch: Wang 2016 Appl.Microbiol.Biotechnol 100 5883 PubMedID: 26969039 Abstract To modify the Pichia pastoris cell surface, two classes of hydrophobins, SC3 from Schizophyllum commune and HFBI from Trichoderma reesei, were separately displayed on the cell wall. There was an observable increase in the hydrophobicity of recombinant strains. Candida antarctica lipase B (CALB) was then co-displayed on the modified cells, generating strains GS115/SC3-61/CALB-51 and GS115/HFBI-61/CALB-51. Interestingly, the hydrolytic and synthetic activities of strain GS115/HFBI-61/CALB-51 increased by 37 and 109 %, respectively, but decreased by 26 and 43 %, respectively, in strain GS115/SC3-61/CALB-51 compared with the hydrophobin-minus recombinant strain GS115/CALB-GCW51. The amount of glycerol by-product from the transesterification reaction adsorbed on the cell surface was significantly decreased following hydrophobin modification, removing the glycerol barrier and allowing substrates to access the active sites of lipases. Electron micrographs indicated that the cell wall structures of both recombinant strains appeared altered, including changes to the inner glucan layer and outer mannan layer. These results suggest that the display of hydrophobins can change the surface structure and hydrophobic properties of P. pastoris and affect the catalytic activities of CALB displayed on the surface of P. pastoris cells. Title: Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R and Bavari S <52 more author(s)> Warren TK, Jordan R, Lo MK, Ray AS, Mackman RL, Soloveva V, Siegel D, Perron M, Bannister R, Hui HC, Larson N, Strickley R, Wells J, Stuthman KS, Van Tongeren SA, Garza NL, Donnelly G, Shurtleff AC, Retterer CJ, Gharaibeh D, Zamani R, Kenny T, Eaton BP, Grimes E, Welch LS, Gomba L, Wilhelmsen CL, Nichols DK, Nuss JE, Nagle ER, Kugelman JR, Palacios G, Doerffler E, Neville S, Carra E, Clarke MO, Zhang L, Lew W, Ross B, Wang Q, Chun K, Wolfe L, Babusis D, Park Y, Stray KM, Trancheva I, Feng JY, Barauskas O, Xu Y, Wong P, Braun MR, Flint M, McMullan LK, Chen SS, Fearns R, Swaminathan S, Mayers DL, Spiropoulou CF, Lee WA, Nichol ST, Cihlar T, Bavari S (- 52) Ref: Nature, 531:381, 2016 : PubMed ESTHER: Warren_2016_Nature_531_381 PubMedSearch: Warren 2016 Nature 531 381 PubMedID: 26934220 Inhibitor(s) related to this paper: Remdesivir Abstract The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the potential for wider medical use. GS-5734 is amenable to large-scale manufacturing, and clinical studies investigating the drug safety and pharmacokinetics are ongoing. Title: A Semiautomated Structure-Based Method To Predict Substrates of Enzymes via Molecular Docking: A Case Study with Candida antarctica Lipase B Yao Z, Zhang L, Gao B, Cui D, Wang F, He X, Zhang JZ, Wei D Ref: J Chem Inf Model, 56:1979, 2016 : PubMed ESTHER: Yao_2016_J.Chem.Inf.Model_56_1979 PubMedSearch: Yao 2016 J.Chem.Inf.Model 56 1979 PubMedID: 27529495 Abstract The discovery of unique substrates is important for developing potential applications of enzymes. However, the experimental procedures for substrate identification are laborious, time-consuming, and expensive. Although in silico structure-based approaches show great promise, recent extensive studies have shown that these approaches remain a formidable challenge for current biocomputational methodologies. Here we present an open-source, extensible, and flexible software platform for predicting enzyme substrates called THEMIS, which performs in silico virtual screening for potential catalytic targets of an enzyme on the basis of the enzyme's catalysis mechanism. On the basis of a generalized transition state theory of enzyme catalysis, we introduce a modified docking procedure called "mechanism-based restricted docking" (MBRD) for novel substrate recognition from molecular docking. Comprising a series of utilities written in C/Python, THEMIS automatically executes parallel-computing MBRD tasks and evaluates the results with various molecular mechanics (MM) criteria such as energy, distance, angle, and dihedral angle to help identify desired substrates. Exhaustive sampling and statistical measures were used to improve the robustness and reproducibility of the method. We used Candida antarctica lipase B (CALB) as a test system to demonstrate the effectiveness of our computational prediction of (non)substrates. A novel MM score function for CALB substrate identification derived from the near-attack conformation was used to evaluate the possibility of chemical transformation. A highly positive rate of 93.4% was achieved from a CALB substrate library with 61 known substrates and 35 nonsubstrates, and the screening rate has reached 103 compounds/day (96 CPU cores, 100 samples/compound). The performance shows that the present method is perhaps the first reported scheme to meet the requirement for practical applicability to enzyme studies. An additional study was performed to validate the universality of our method. In this verification we employed two distinct enzymes, nitrilase Nit6803 and SDR Gox2181, where the correct rates of both enzymes exceeded 90%. The source code used will be released under the GNU General Public License (GPLv3) and will be free to download. We believe that the present method will provide new insights into enzyme research and accelerate the development of novel enzyme applications. Title: Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography Zha X, Lamba D, Zhang L, Lou Y, Xu C, Kang D, Chen L, Xu Y, De Simone A and Bartolini M <6 more author(s)> Zha X, Lamba D, Zhang L, Lou Y, Xu C, Kang D, Chen L, Xu Y, De Simone A, Samez S, Pesaresi A, Stojan J, Lopez MG, Egea J, Andrisano V, Bartolini M (- 6) Ref: Journal of Medicinal Chemistry, 59:114, 2016 : PubMed ESTHER: Zha_2016_J.Med.Chem_59_114 PubMedSearch: Zha 2016 J.Med.Chem 59 114 PubMedID: 26632651 Gene_locus related to this paper: torca-ACHE Inhibitor(s) related to this paper: Tacrine-Benzofuran Abstract Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and beta-amyloid self-aggregation. Selected compounds displayed significant inhibition of human beta-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both beta-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 muM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity. Title: Respiratory toxicity of cyanobacterial aphantoxins from Aphanizomenon flos-aquae DC-1 in the zebrafish gill Zhang L, Liu SY, Zhang J, Zhang JK, Hu CX, Liu YD Ref: Aquat Toxicol, 176:106, 2016 : PubMed ESTHER: Zhang_2016_Aquat.Toxicol_176_106 PubMedSearch: Zhang 2016 Aquat.Toxicol 176 106 PubMedID: 27130970 Abstract Aphantoxins from Aphanizomenon flos-aquae are frequently identified in eutrophic waterbodies worldwide. These toxins severely endanger environmental safety and human health due to the production of paralytic shellfish poisons (PSPs). Although the molecular mechanisms of aphantoxin neurotoxicity have been studied, many questions remain to be resolved such as in vivo alterations in branchial histology and neurotransmitter inactivation induced by these neurotoxins. Aphantoxins extracted from a naturally isolated strain of A. flos-aquae DC-1 were determined by high performance liquid chromatography. The basic components of the isolated aphantoxins identified were gonyautoxin 1 (GTX1), gonyautoxin 5 (GTX5), and neosaxitoxin (neoSTX), which comprised 34.04, 21.28, and 12.77% of the total, respectively. Zebrafish (Danio rerio) was administrated 5.3 or 7.61mg STX equivalents (eq)/kg (low and high doses, respectively) of the A. flos-aquae DC-1 aphantoxins by intraperitoneal injection. Histological alterations and changes in neurotransmitter inactivation in the gills of zebrafish were investigated for 24h following exposure. Aphantoxin exposure significantly increased the activities of gill alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and resulted in histological alterations in the gills during the first 12h of exposure, indicating the induction of functional and structural damage. Gill acetylcholinesterase (AChE) and monoamine oxidase (MAO) activities were inhibited significantly, suggesting an alteration of neurotransmitter inactivation in zebrafish gills. The observed alterations in gill structure and function followed a time- and dose-dependent pattern. The results demonstrate that aphantoxins or PSPs lead to structural damage and altered function in the gills of zebrafish, including changes in histological structure and increases in the activities of AST and ALT. The inhibition of the activities of AChE and MAO suggest that aphantoxins or PSPs could induce respiratory toxicity in the zebrafish gill. Furthermore, these parameters may be used as bioindicators for investigating aphantoxin exposure and cyanobacterial blooms in nature. Title: Adhesions of extracellular surface-layer associated proteins in Lactobacillus M5-L and Q8-L Zhang Y, Xiang X, Lu Q, Zhang L, Ma F, Wang L Ref: J Dairy Sci, 99:1011, 2016 : PubMed ESTHER: Zhang_2016_J.Dairy.Sci_99_1011 PubMedSearch: Zhang 2016 J.Dairy.Sci 99 1011 PubMedID: 26709174 Gene_locus related to this paper: lacpl-LP.0796 Abstract Surface-layer associated proteins (SLAP) that envelop Lactobacillus paracasei ssp. paracasei M5-L and Lactobacillus casei Q8-L cell surfaces are involved in the adherence of these strain to the human intestinal cell line HT-29. To further elucidate some of the properties of these proteins, we assessed the yields and expressions of SLAP under different incubation conditions. An efficient and selective extraction of SLAP was obtained when cells of Lactobacillus were treated with 5 M LiCl at 37 degrees C in aerobic conditions. The SLAP of Lactobacillus M5-L and Q8-L in cell extracts were visualized by SDS-PAGE and identified by Western blotting with sulfo-N-hydroxysuccinimide-biotin-labeled HT-29 cells as adhesion proteins. Atomic force microscopy contact imaging revealed that Lactobacillus strains M5-L and Q8-L normally display a smooth, homogeneous surface, whereas the surfaces of M5-L and Q8-L treated with 5 M LiCl were rough and more heterogeneous. Analysis of adhesion forces revealed that the initial adhesion forces of 1.41 and 1.28 nN obtained for normal Lactobacillus M5-L and Q8-L strains, respectively, decreased to 0.70 and 0.48 nN, respectively, following 5 M LiCl treatment. Finally, the dominant 45-kDa protein bands of Lactobacillus Q8-L and Lactobacillus M5-L were identified as elongation factor Tu and surface antigen, respectively, by liquid chromatography-tandem mass spectrometry. Title: Acetylcholinesterase Inhibitors for Alzheimer's Disease Treatment Ameliorate Acetaminophen-Induced Liver Injury in Mice via Central Cholinergic System Regulation Zhang J, Zhang L, Sun X, Yang Y, Kong L, Lu C, Lv G, Wang T, Wang H, Fu F Ref: Journal of Pharmacology & Experimental Therapeutics, 359:374, 2016 : PubMed ESTHER: Zhang_2016_J.Pharmacol.Exp.Ther_359_374 PubMedSearch: Zhang 2016 J.Pharmacol.Exp.Ther 359 374 PubMedID: 27535978 Abstract Acetaminophen (APAP) is widely used as an analgesic and antipyretic agent, but it may induce acute liver injury at high doses. Alzheimer's disease patients, while treated with acetylcholinesterase inhibitor (AChEI), may take APAP when they suffer from cold or pain. It is generally recognized that inhibiting acetylcholinesterase activity may also result in liver injury. To clarify whether AChEI could deteriorate or attenuate APAP hepatotoxicity, the effects of AChEI on APAP hepatotoxicity were investigated. Male C57BL/6J mice were administrated with the muscarinic acetylcholine receptor (mAChR) blocker atropine (Atr), or classic alpha7 nicotine acetylcholine receptor (alpha7nAChR) antagonist methyllycaconitine (MLA) 1 hour before administration of AChEIs-donepezil (4 mg/kg), rivastigmine (2 mg/kg), huperzine A (0.2 mg/kg), or neostigmine (0.15 mg/kg)-followed by APAP (300 mg/kg). Eight hours later, the mice were euthanized for histopathologic examination and biochemical assay. The results demonstrated that the tested AChEIs, excluding neostigmine, could attenuate APAP-induced liver injury, accompanied by reduced reactive oxygen species formation, adenosine triphosphate and cytochrome C loss, c-Jun N-terminal kinase 2 (JNK2) phosphorylation, and cytokines. However, Atr or MLA significantly weakened the protective effect of AChEI by affecting mitochondrial function or JNK2 phosphorylation and inflammation response. These results suggest that central mAChR and alpha7nAChR, which are activated by accumulated acetylcholine resulting from AChEI, were responsible for the protective effect of AChEIs on APAP-induced liver injury. This indicates that Alzheimer's patients treated with AChEI could take APAP, as AChEI is unlikely to deteriorate the hepatotoxicity of APAP. Title: Insights into Adaptations to a Near-Obligate Nematode Endoparasitic Lifestyle from the Finished Genome of Drechmeria coniospora Zhang L, Zhou Z, Guo Q, Fokkens L, Miskei M, Pocsi I, Zhang W, Chen M, Wang L and Lin M <12 more author(s)> Zhang L, Zhou Z, Guo Q, Fokkens L, Miskei M, Pocsi I, Zhang W, Chen M, Wang L, Sun Y, Donzelli BG, Gibson DM, Nelson DR, Luo JG, Rep M, Liu H, Yang S, Wang J, Krasnoff SB, Xu Y, Molnar I, Lin M (- 12) Ref: Sci Rep, 6:23122, 2016 : PubMed ESTHER: Zhang_2016_Sci.Rep_6_23122 PubMedSearch: Zhang 2016 Sci.Rep 6 23122 PubMedID: 26975455 Gene_locus related to this paper: 9hypo-a0a151ga75, 9hypo-a0a151gbh5, 9hypo-a0a151gd50, 9hypo-a0a151ggb9, 9hypo-a0a151gjd5, 9hypo-a0a151gtv2, 9hypo-a0a151gxh2, 9hypo-a0a151gaw8, 9hypo-a0a151gia2 Abstract Nematophagous fungi employ three distinct predatory strategies: nematode trapping, parasitism of females and eggs, and endoparasitism. While endoparasites play key roles in controlling nematode populations in nature, their application for integrated pest management is hindered by the limited understanding of their biology. We present a comparative analysis of a high quality finished genome assembly of Drechmeria coniospora, a model endoparasitic nematophagous fungus, integrated with a transcriptomic study. Adaptation of D. coniospora to its almost completely obligate endoparasitic lifestyle led to the simplification of many orthologous gene families involved in the saprophytic trophic mode, while maintaining orthologs of most known fungal pathogen-host interaction proteins, stress response circuits and putative effectors of the small secreted protein type. The need to adhere to and penetrate the host cuticle led to a selective radiation of surface proteins and hydrolytic enzymes. Although the endoparasite has a simplified secondary metabolome, it produces a novel peptaibiotic family that shows antibacterial, antifungal and nematicidal activities. Our analyses emphasize the basic malleability of the D. coniospora genome: loss of genes advantageous for the saprophytic lifestyle; modulation of elements that its cohort species utilize for entomopathogenesis; and expansion of protein families necessary for the nematode endoparasitic lifestyle. Title: Testosterone Deficiency Induces Changes of the Transcriptomes of Visceral Adipose Tissue in Miniature Pigs Fed a High-Fat and High-Cholesterol Diet Zhang L, Cai Y, Wei S, Ling Y, Zhu L, Li D, Cai Z Ref: Int J Mol Sci, 17:, 2016 : PubMed ESTHER: Zhang_2016_Int.J.Mol.Sci_17_ PubMedSearch: Zhang 2016 Int.J.Mol.Sci 17 PubMedID: 27999286 Abstract Testosterone deficiency causes fat deposition, particularly in visceral fat, and its replacement might reverse fat accumulation, however, the underlying mechanisms of such processes under diet-induced adiposity are largely unknown. To gain insights into the genome-wide role of androgen on visceral adipose tissue (VAT), RNA-Seq was used to investigate testosterone deficiency induced changes of VAT in miniature pigs fed a high-fat and high-cholesterol (HFC) diet among intact male pigs (IM), castrated male pigs (CM), and castrated male pigs with testosterone replacement (CMT) treatments. The results showed that testosterone deficiency significantly increased VAT deposition and serum leptin concentrations. Moreover, a total of 1732 differentially expressed genes (DEGs) were identified between any two groups. Compared with gene expression profiles in IM and CMT pigs, upregulated genes in CM pigs, i.e., LOC100520753 (CD68), LCN2, EMR1, S100A9, NCF1 (p47phox), and LEP, were mainly involved in inflammatory response, oxidation-reduction process, and lipid metabolic process, while downregulated genes in CM pigs, i.e., ABHD5, SPP1, and GAS6, were focused on cell differentiation and cell adhesion. Taken together, our study demonstrates that testosterone deficiency alters the expression of numerous genes involved in key biological processes of VAT accumulation under HFC diet and provides a novel genome-wide view on the role of androgen on VAT deposition under HFC diet, thus improving our understanding of the molecular mechanisms involved in VAT changes induced by testosterone deficiency. Title: Baicalein improves behavioral dysfunction induced by Alzheimer's disease in rats Zhou L, Tan S, Shan YL, Wang YG, Cai W, Huang XH, Liao XY, Li HY, Zhang L and Lu ZQ <1 more author(s)> Zhou L, Tan S, Shan YL, Wang YG, Cai W, Huang XH, Liao XY, Li HY, Zhang L, Zhang BJ, Lu ZQ (- 1) Ref: Neuropsychiatr Dis Treat, 12:3145, 2016 : PubMed ESTHER: Zhou_2016_Neuropsychiatr.Dis.Treat_12_3145 PubMedSearch: Zhou 2016 Neuropsychiatr.Dis.Treat 12 3145 PubMedID: 28003750 Abstract BACKGROUND: Alzheimer's disease (AD) is considered to be a neurodegenerative disorder that is characterized by increased oxidative stress. Medicinal plants, with their antioxidant properties, have been used to cure several human diseases. The aim of the current study was to explore the protective and therapeutic effect of baicalein on AD-induced rats. MATERIALS AND Title: Unraveling adaptation of Pontibacter korlensis to radiation and infertility in desert through complete genome and comparative transcriptomic analysis Dai J, Dai W, Qiu C, Yang Z, Zhang Y, Zhou M, Zhang L, Fang C, Gao Q and Chen X <4 more author(s)> Dai J, Dai W, Qiu C, Yang Z, Zhang Y, Zhou M, Zhang L, Fang C, Gao Q, Yang Q, Li X, Wang Z, Jia Z, Chen X (- 4) Ref: Sci Rep, 5:10929, 2015 : PubMed ESTHER: Dai_2015_Sci.Rep_5_10929 PubMedSearch: Dai 2015 Sci.Rep 5 10929 PubMedID: 26057562 Gene_locus related to this paper: 9bact-a0a0e3zf06, 9bact-a0a0e3zhq7 Abstract The desert is a harsh habitat for flora and microbial life due to its aridness and strong radiation. In this study, we constructed the first complete and deeply annotated genome of the genus Pontibacter (Pontibacter korlensis X14-1(T) = CCTCC AB 206081(T), X14-1). Reconstruction of the sugar metabolism process indicated that strain X14-1 can utilize diverse sugars, including cellulose, starch and sucrose; this result is consistent with previous experiments. Strain X14-1 is also able to resist desiccation and radiation in the desert through well-armed systems related to DNA repair, radical oxygen species (ROS) detoxification and the OstAB and TreYZ pathways for trehalose synthesis. A comparative transcriptomic analysis under gamma radiation revealed that strain X14-1 presents high-efficacy operating responses to radiation, including the robust expression of catalase and the manganese transport protein. Evaluation of 73 novel genes that are differentially expressed showed that some of these genes may contribute to the strain's adaptation to radiation and desiccation through ferric transport and preservation. Title: Alleviating effects of bushen-yizhi formula on ibotenic Acid-induced cholinergic impairments in rat Hou XQ, Zhang L, Yang C, Rong CP, He WQ, Zhang CX, Li S, Su RY, Chang X and Wang Q <3 more author(s)> Hou XQ, Zhang L, Yang C, Rong CP, He WQ, Zhang CX, Li S, Su RY, Chang X, Qin JH, Chen YB, Xian SX, Wang Q (- 3) Ref: Rejuvenation Res, 18:111, 2015 : PubMed ESTHER: Hou_2015_Rejuvenation.Res_18_111 PubMedSearch: Hou 2015 Rejuvenation.Res 18 111 PubMedID: 25482164 Abstract This study explored the curative effect and underlying mechanisms of a traditional Chinese medicine compound prescription, Bushen-Yizhi formula (BSYZ), in ibotenic acid (IBO)-induced rats. Morris water maze and novel object recognition tests showed that BSYZ significantly improved spatial and object memory. Brain immunohistochemistry staining showed that BSYZ significantly up-regulated expression of choline acetyltransferase (ChAT) and nerve growth factor (NGF) in the hippocampus and cortex. The protein tyrosine kinase high-affinity receptor TrkA was slightly increased in the hippocampus and cortex, and significantly enhanced in the nucleus basalis of Meynert (NBM) after BSYZ intervention. The immunoreactivity of the p75 low-affinity receptor in BSYZ-treated rats was significantly strengthened in the cortex. Similar expression trends of nerve growth factor (NGF), TrkA, and p75 mRNA were observed in the hippocampus and cortex. Additionally, BSYZ reversed IBO-induced disorders of acetylcholine (ACh) levels, ChAT, and cholinesterase (ChE) in the cortex, which was consistent with the changes in mRNA levels of ChAT and acetylcholinesterase (AChE). Expression of ChAT and AChE proteins and mRNA in the hippocampus was up-regulated, whereas the apoptosis-relative protein cleaved caspase-3 was decreased after administration of BSYZ. Moreover, changes in cell death were confirmed by histological morphology. Thus, the results indicated that the BSYZ formula could ameliorate memory impairments in IBO-induced rats, and it exerted its therapeutic action probably by modulating cholinergic pathways, NGF signaling, and anti-apoptosis. Overall, it is suggested that the BSYZ formula might be a potential therapeutic approach for the treatment of Alzheimer's disease (AD) and other cholinergic impairment-related diseases. Title: Biphasic photoelectrochemical sensing strategy based on in situ formation of CdS quantum dots for highly sensitive detection of acetylcholinesterase activity and inhibition Hou T, Zhang L, Sun X, Li F Ref: Biosensors & Bioelectronics, 75:359, 2015 : PubMed ESTHER: Hou_2015_Biosens.Bioelectron_75_359 PubMedSearch: Hou 2015 Biosens.Bioelectron 75 359 PubMedID: 26339933 Abstract Herein, we reported a facile and highly sensitive biphasic photoelectrochemical (PEC) sensing strategy based on enzymatic product-mediated in situ formation of CdS quantum dots (QDs), and assayed the activity and inhibition of acetylcholinesterase (AChE) in its optimal state. Upon the hydrolysis of acetylthiocholine catalyzed by AChE, the product thiocholine stabilizes the in situ formation of CdS QDs in homogenous solution. Due to the electrostatic attraction, the resulting tertiary amino group-functionalized CdS QDs are attached to the surface of the negatively charged indium tin oxide (ITO) electrode, generating significant PEC response upon illumination in the presence of electron donors. By taking full advantage of the in situ formation of CdS QDs in homogenous solution, this strategy is capable of detecting AChE activity and inhibition in its optimal state. A directly measured detection limit of 0.01mU/mL for AChE activity is obtained, which is superior to those obtained by some fluorescence methods. The inhibition of AChE activity by aldicarb is successfully detected, and the corresponding IC50 is determined to be 13mug/L. In addition to high sensitivity and good selectivity, this strategy also exhibits additional advantages of simplicity, low cost and easy operation. To the best of our knowledge, the as-proposed strategy is the first example demonstrating the application of CdS QDs formed in situ for biphasic PEC detection of enzyme activity and inhibition. More significantly, it opens up a new horizon for the development of homogenous PEC sensing platforms, and has great potential in probing many other analytes. Title: Association of and with Alzheimer's disease: Meta-analysis based on 56 genetic case-control studies of 12,563 cases and 12,622 controls Ji H, Dai D, Wang Y, Jiang D, Zhou X, Lin P, Ji X, Li J, Zhang Y and Wang Q <5 more author(s)> Ji H, Dai D, Wang Y, Jiang D, Zhou X, Lin P, Ji X, Li J, Zhang Y, Yin H, Chen R, Zhang L, Xu M, Duan S, Wang Q (- 5) Ref: Exp Ther Med, 9:1831, 2015 : PubMed ESTHER: Ji_2015_Exp.Ther.Med_9_1831 PubMedSearch: Ji 2015 Exp.Ther.Med 9 1831 PubMedID: 26136901 Abstract Alzheimer's disease (AD) is a common neurodegenerative disorder that can destroy the memory of sufferers and lead to distress for the individual and society. Brain-derived neurotrophic factor (BDNF) and butyrylcholinesterase (BCHE) are two genes associated with beta-amyloid plaques and neurofibrillary tangles that are two key factors in the pathophysiology of AD. The aim of the current meta-analysis was to evaluate the association between BDNF Val66Met (rs6265), BDNF C270T (rs2030324) and BCHE-K (rs1803274) polymorphisms and AD. A comprehensive meta-analysis was performed using the online database PubMed without a time limitation. A total of 56 articles evaluating 12,563 cases and 12,622 controls were selected for the current meta-analysis. The results showed a moderate association of the BDNF C270T polymorphism with the risk of AD in Asians under a dominant model (P=0.03; odds ratio, 1.88; 95% confidence interval, 1.08-3.27). No other significant association was found during the meta-analysis for the other two polymorphisms (P>0.05). The current meta-analysis suggests that BDNF C270T is a risk factor for AD in Asians. This meta-analysis has been, to the best of our knowledge, the most comprehensive meta-analysis of BDNF Val66Met, BDNF C270T and BCHE-K to date. Title: Complete Genome Sequence of Paenibacillus polymyxa CF05, a Strain of Plant Growth-Promoting Rhizobacterium with Elicitation of Induced Systemic Resistance Lei M, Lu P, Jin L, Wang Y, Qin J, Xu X, Zhang L Ref: Genome Announc, 3:, 2015 : PubMed ESTHER: Lei_2015_Genome.Announc_3_e00198 PubMedSearch: Lei 2015 Genome.Announc 3 e00198 PubMedID: 25883277 Gene_locus related to this paper: paepo-a0a0f6ex20, paepo-a0a0f6em71, paepo-a0a0f6ezz0 Abstract Paenibacillus polymyxa CF05 is a Gram-positive rod-shaped bacterium isolated from the interior of an ancient tree, Cryptomeria fortunei, in China. This bacterium displays potent biocontrol effects against certain soil-borne diseases and the elicitation of induced systemic resistance in tomatoes. Here, we report the complete genome sequence of P. polymyxa CF05. Title: The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis Li D, Huang Q, Lu M, Zhang L, Yang Z, Zong M, Tao L Ref: Chemosphere, 135:387, 2015 : PubMed ESTHER: Li_2015_Chemosphere_135_387 PubMedSearch: Li 2015 Chemosphere 135 387 PubMedID: 26002045 Abstract The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, gammaH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of gammaH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis. Title: Outbred genome sequencing and CRISPR/Cas9 gene editing in butterflies Li X, Fan D, Zhang W, Liu G, Zhang L, Zhao L, Fang X, Chen L, Dong Y and Wang W <14 more author(s)> Li X, Fan D, Zhang W, Liu G, Zhang L, Zhao L, Fang X, Chen L, Dong Y, Chen Y, Ding Y, Zhao R, Feng M, Zhu Y, Feng Y, Jiang X, Zhu D, Xiang H, Feng X, Li S, Wang J, Zhang G, Kronforst MR, Wang W (- 14) Ref: Nat Commun, 6:8212, 2015 : PubMed ESTHER: Li_2015_Nat.Commun_6_8212 PubMedSearch: Li 2015 Nat.Commun 6 8212 PubMedID: 26354079 Gene_locus related to this paper: papxu-a0a194pj15, papxu-a0a194q254, papma-a0a194rdx2, papxu-a0a194q858, papxu-a0a194pyl3, papxu-a0a194q337, papma-a0a194r1p9, papma-a0a194r6h1, papxu-a0a194q1w8, papma-a0a194ql80, papma-a0a0n1ipl3, papma-a0a194qm14 Abstract Butterflies are exceptionally diverse but their potential as an experimental system has been limited by the difficulty of deciphering heterozygous genomes and a lack of genetic manipulation technology. Here we use a hybrid assembly approach to construct high-quality reference genomes for Papilio xuthus (contig and scaffold N50: 492 kb, 3.4 Mb) and Papilio machaon (contig and scaffold N50: 81 kb, 1.15 Mb), highly heterozygous species that differ in host plant affiliations, and adult and larval colour patterns. Integrating comparative genomics and analyses of gene expression yields multiple insights into butterfly evolution, including potential roles of specific genes in recent diversification. To functionally test gene function, we develop an efficient (up to 92.5%) CRISPR/Cas9 gene editing method that yields obvious phenotypes with three genes, Abdominal-B, ebony and frizzled. Our results provide valuable genomic and technological resources for butterflies and unlock their potential as a genetic model system. Title: Detoxification of Organophosphate Poisoning Using Nanoparticle Bioscavengers Pang Z, Hu CM, Fang RH, Luk BT, Gao W, Wang F, Chuluun E, Angsantikul P, Thamphiwatana S and Zhang L <2 more author(s)> Pang Z, Hu CM, Fang RH, Luk BT, Gao W, Wang F, Chuluun E, Angsantikul P, Thamphiwatana S, Lu W, Jiang X, Zhang L (- 2) Ref: ACS Nano, 9:6450, 2015 : PubMed ESTHER: Pang_2015_ACS.Nano_9_6450 PubMedSearch: Pang 2015 ACS.Nano 9 6450 PubMedID: 26053868 Abstract Organophosphate poisoning is highly lethal as organophosphates, which are commonly found in insecticides and nerve agents, cause irreversible phosphorylation and inactivation of acetylcholinesterase (AChE), leading to neuromuscular disorders via accumulation of acetylcholine in the body. Direct interception of organophosphates in the systemic circulation thus provides a desirable strategy in treatment of the condition. Inspired by the presence of AChE on red blood cell (RBC) membranes, we explored a biomimetic nanoparticle consisting of a polymeric core surrounded by RBC membranes to serve as an anti-organophosphate agent. Through in vitro studies, we demonstrated that the biomimetic nanoparticles retain the enzymatic activity of membrane-bound AChE and are able to bind to a model organophosphate, dichlorvos, precluding its inhibitory effect on other enzymatic substrates. In a mouse model of organophosphate poisoning, the nanoparticles were shown to improve the AChE activity in the blood and markedly improved the survival of dichlorvos-challenged mice. Title: Role of Neurexin-1beta and Neuroligin-1 in Cognitive Dysfunction After Subarachnoid Hemorrhage in Rats Shen H, Chen Z, Wang Y, Gao A, Li H, Cui Y, Zhang L, Xu X, Wang Z, Chen G Ref: Stroke, 46:2607, 2015 : PubMed ESTHER: Shen_2015_Stroke_46_2607 PubMedSearch: Shen 2015 Stroke 46 2607 PubMedID: 26219651 Abstract BACKGROUND AND PURPOSE: Neurexin-1beta and neuroligin-1 play an important role in the formation, maintenance, and regulation of synaptic structures. This study is to estimate the potential role of neurexin-1beta and neuroligin-1 in subarachnoid hemorrhage (SAH)-induced cognitive dysfunction. 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: The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y and He Y <14 more author(s)> Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y, Chen M, Xu Y, Jin H, Xiao X, Hu G, Bao F, Hu Y, Wan P, Li L, Deng X, Kuang T, Xiang C, Zhu JK, Oliver MJ, He Y (- 14) Ref: Proc Natl Acad Sci U S A, 112:5833, 2015 : PubMed ESTHER: Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833 PubMedSearch: Xiao 2015 Proc.Natl.Acad.Sci.U.S.A 112 5833 PubMedID: 25902549 Gene_locus related to this paper: 9lami-a0a2z7c6k4, 9lami-a0a2z7bgj4 Abstract "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes. Title: Melatonin attenuates intestinal ischemia--reperfusion-induced lung injury in rats by upregulating N-myc downstream-regulated gene 2 Yang B, Ni YF, Wang WC, Du HY, Zhang H, Zhang L, Zhang WD, Jiang T Ref: J Surg Res, 194:273, 2015 : PubMed ESTHER: Yang_2015_J.Surg.Res_194_273 PubMedSearch: Yang 2015 J.Surg.Res 194 273 PubMedID: 25491174 Abstract BACKGROUND: Successful drug treatment for ischemia--reperfusion-induced lung injury remains a major clinical problem. Melatonin (MT) is a hormone that is principally synthesized in the pineal gland. It has been shown to exhibit a variety of functions including anti-inflammatory and antioxidant effects. Previous reports on N-myc downstream-regulated gene (NDRG)2 have suggested that it is involved in cellular differentiation, development, antiapoptosis, anti-inflammatory cytokine, and antioxidant. The objective of this study was to test whether MT, a novel NDRG2 activator, can protect against intestinal ischemia-reperfusion-induced lung injury (IIRI). MATERIALS AND Title: Fatal diphenidol poisoning: a case report and a retrospective study of 16 cases Zhang L, Ma J, Li S, Xue R, Jin M, Zhou Y Ref: Forensic Science Med Pathol, 11:570, 2015 : PubMed ESTHER: Zhang_2015_Forensic.Sci.Med.Pathol_11_570 PubMedSearch: Zhang 2015 Forensic.Sci.Med.Pathol 11 570 PubMedID: 26481789 Abstract Diphenidol hydrochloride (DPN), a nonphenothiazinic antiemetic agent used primarily in patients with Meniere disease and labyrinthopathies to treat vomiting and vertigo, is considered to be a relatively safe drug. Since it was first approved in the United States in 1967, this drug has been widely used in Latin America and Asia and has contributed to sporadic suicidal and accidental poisonings in mainland China and Taiwan. However, its toxic or lethal concentration ranges have not yet been determined. We report a case of a 23-year-old female who suffered from DPN poisoning that resulted in death. At autopsy, there were no typical pathological findings, except for cerebral edema with high acetylcholinesterase expression. Postmortem analysis of DPN revealed 45 microg/ml in heart blood, 39 microg/ml in femoral vein blood, 141 microg/g in the liver, and 53 mg in the gastric contents. These concentrations indicated that the cause of death was DPN poisoning. The circumstances indicated that the manner of death was suicide. We also present a retrospective study, in which we review and summarize the literature from 1998 to 2014 and describe 16 cases of poisoning, including information from autopsy reports and postmortem drug concentrations. In forensic practice, drug residues at the scene, patients with convulsions and disturbance of consciousness, and rapidly occurring deaths, should draw attention to the possibility of this drug. Toxicological analysis and the exclusion of other diseases may ultimately be used to confirm DPN poisoning. Title: Finding the missing honey bee genes: lessons learned from a genome upgrade Elsik CG, Worley KC, Bennett AK, Beye M, Camara F, Childers CP, de Graaf DC, Debyser G, Deng J and Gibbs RA <38 more author(s)> Elsik CG, Worley KC, Bennett AK, Beye M, Camara F, Childers CP, de Graaf DC, Debyser G, Deng J, Devreese B, Elhaik E, Evans JD, Foster LJ, Graur D, Guigo R, Hoff KJ, Holder ME, Hudson ME, Hunt GJ, Jiang H, Joshi V, Khetani RS, Kosarev P, Kovar CL, Ma J, Maleszka R, Moritz RF, Munoz-Torres MC, Murphy TD, Muzny DM, Newsham IF, Reese JT, Robertson HM, Robinson GE, Rueppell O, Solovyev V, Stanke M, Stolle E, Tsuruda JM, Vaerenbergh MV, Waterhouse RM, Weaver DB, Whitfield CW, Wu Y, Zdobnov EM, Zhang L, Zhu D, Gibbs RA (- 38) Ref: BMC Genomics, 15:86, 2014 : PubMed ESTHER: Elsik_2014_BMC.Genomics_15_86 PubMedSearch: Elsik 2014 BMC.Genomics 15 86 PubMedID: 24479613 Abstract BACKGROUND: The first generation of genome sequence assemblies and annotations have had a significant impact upon our understanding of the biology of the sequenced species, the phylogenetic relationships among species, the study of populations within and across species, and have informed the biology of humans. As only a few Metazoan genomes are approaching finished quality (human, mouse, fly and worm), there is room for improvement of most genome assemblies. The honey bee (Apis mellifera) genome, published in 2006, was noted for its bimodal GC content distribution that affected the quality of the assembly in some regions and for fewer genes in the initial gene set (OGSv1.0) compared to what would be expected based on other sequenced insect genomes. Title: Effects of zinc on CarE activities and its gene transcript level in the English grain aphid, Sitobion avenae Gao HH, Zhao HY, Yang J, Zhang L, Bai XH, Hu ZQ, Hu XS Ref: J Insect Sci, 14:67, 2014 : PubMed ESTHER: Gao_2014_J.Insect.Sci_14_67 PubMedSearch: Gao 2014 J.Insect.Sci 14 67 PubMedID: 25373214 Abstract As a selective stress, heavy metals play an important role in inducing the adaptive adjustments of insects to changing environments. Carboxylesterase (CarE) is one kind of biomarker that could help us to explore the adaptation mechanism of aphids to heavy metal stress. In this study, CarE activity and gene expression level were investigated in English grain aphids, Sitobion avenae (F.) (Hemiptera: Aphididae), exposed to Zn2+ at concentrations of 0, 400, and 1600 mg/kg for 5, 15, 25, and 30 generations. The results showed that the CarE activity was significantly different between different Zn2+ concentrations and different generations. The CarE activity significantly decreased with increasing generations. In the higher generations, the CarE activity was strongly inhibited by the 1600 mg/kg of Zn2+. Realtime quantitative PCR revealed that the CarE gene expression pattern in S. avenae was up-regulated under the condition of 400 mg/kg and 1600 mg/kg of Zn2+, but a significant difference was not found after long-term exposure to high concentrations of Zn2+. It was concluded that CarE could be the sensitive biomarker for S. avenae response to the presence of Zn2+. In order to adapt to heavy metal Zn2+ stress, S. avenae had particular patterns of gene expression under long-term stress. Title: A novel assay for high-throughput screening of anti-Alzheimer's disease drugs to determine their efficacy by real-time monitoring of changes in PC12 cell proliferation Hou XQ, Yan R, Yang C, Zhang L, Su RY, Liu SJ, Zhang SJ, He WQ, Fang SH and Wang Q <3 more author(s)> Hou XQ, Yan R, Yang C, Zhang L, Su RY, Liu SJ, Zhang SJ, He WQ, Fang SH, Cheng SY, Su ZR, Chen YB, Wang Q (- 3) Ref: Int J Mol Med, 33:543, 2014 : PubMed ESTHER: Hou_2014_Int.J.Mol.Med_33_543 PubMedSearch: Hou 2014 Int.J.Mol.Med 33 543 PubMedID: 24378397 Abstract Alzheimer's disease (AD) is a neurodegenerative disease that is characterized by the accumulation of senile plaque and neurofibrilary tangle formation in the brain, including the cerebral cortex and hippocampus. Nowadays, the first-line treatment for AD is the application of acetylcholinesterase inhibitors. However, acetylcholinesterase inhibitors are basically anti-symptomatic for a limited aspect of AD pathology and are associated with serious side-effects. With the advantage of multiple targets, pathways and systems, Chinese herbal compounds hold promising potential for the development of drugs for the treatment of AD. Over the past few years, with the development of Chinese herbal compounds and in vitro pharmacological studies, cell-based disease models are one of the main methods used to screen Chinese herbal compounds for potential efficacy. Testing the efficacy of possible anti-Alzheimer's disease drugs and the development of new drugs are hindered by the lack of objective high-throughput screening methods. Currently, the assessment of the effects of drugs is usually made by MTT assays, involving laborious, subjective, low-throughput methods. Herein, we suggest a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess the effective composition of Chinese herbal compounds by assessing amyloid-beta peptide Abeta1-42-induced apoptosis in PC12 cells. We detected the proliferation and motility of the cells using a fully automated high-throughput and real-time system. We quantitatively assessed cell motility and determined the real-time IC50 values of various anti-AD drugs that intervene in several developmental stages of Abeta1-42-induced apoptosis in PC12 cells, Then, we identified the optimal time phase by curative efficacy. Our data indicate that this technique may aid in the discovery and development of novel anti-Alzheimer's disease drugs. It is possible to utilize a similar technique to measure changes in electrical impedance as cells attach and spread in a culture dish covered with a gold microelectrode array that covers approximately 80% of the area on the bottom of a well. As cells attach and spread on the electrode surface, it leads to an increase in electrical impedance of 9-12. The impedance is displayed as a dimensionless para-meter termed the cell index, which is directly proportional to the total area of tissue culture well that is covered by the cells. Hence, the cell index can be used to monitor cell adhesion, spreading, morphological variation and cell density. Title: Comparative genomic analysis provides insights into the evolution and niche adaptation of marine Magnetospira sp. QH-2 strain Ji B, Zhang SD, Arnoux P, Rouy Z, Alberto F, Philippe N, Murat D, Zhang WJ, Rioux JB and Wu LF <17 more author(s)> Ji B, Zhang SD, Arnoux P, Rouy Z, Alberto F, Philippe N, Murat D, Zhang WJ, Rioux JB, Ginet N, Sabaty M, Mangenot S, Pradel N, Tian J, Yang J, Zhang L, Zhang W, Pan H, Henrissat B, Coutinho PM, Li Y, Xiao T, Medigue C, Barbe V, Pignol D, Talla E, Wu LF (- 17) Ref: Environ Microbiol, 16:525, 2014 : PubMed ESTHER: Ji_2014_Environ.Microbiol_16_525 PubMedSearch: Ji 2014 Environ.Microbiol 16 525 PubMedID: 23841906 Gene_locus related to this paper: 9prot-w6k5m7, 9prot-w6khf2, 9prot-w6kbu9 Abstract Magnetotactic bacteria (MTB) are capable of synthesizing intracellular organelles, the magnetosomes, that are membrane-bounded magnetite or greigite crystals arranged in chains. Although MTB are widely spread in various ecosystems, few axenic cultures are available, and only freshwater Magnetospirillum spp. have been genetically analysed. Here, we present the complete genome sequence of a marine magnetotactic spirillum, Magnetospira sp. QH-2. The high number of repeats and transposable elements account for the differences in QH-2 genome structure compared with other relatives. Gene cluster synteny and gene correlation analyses indicate that the insertion of the magnetosome island in the QH-2 genome occurred after divergence between freshwater and marine magnetospirilla. The presence of a sodium-quinone reductase, sodium transporters and other functional genes are evidence of the adaptive evolution of Magnetospira sp. QH-2 to the marine ecosystem. Genes well conserved among freshwater magnetospirilla for nitrogen fixation and assimilatory nitrate respiration are absent from the QH-2 genome. Unlike freshwater Magnetospirillum spp., marine Magnetospira sp. QH-2 neither has TonB and TonB-dependent receptors nor does it grow on trace amounts of iron. Taken together, our results show a distinct, adaptive evolution of Magnetospira sp. QH-2 to marine sediments in comparison with its closely related freshwater counterparts. Title: Design, synthesis and biological evaluation of 4-fluoropyrrolidine-2-carbonitrile and octahydrocyclopenta[b]pyrrole-2-carbonitrile derivatives as dipeptidyl peptidase IV inhibitors Ji X, Xia C, Wang J, Su M, Zhang L, Dong T, Li Z, Wan X, Li J and Liu H <3 more author(s)> Ji X, Xia C, Wang J, Su M, Zhang L, Dong T, Li Z, Wan X, Li J, Zhao L, Gao Z, Jiang H, Liu H (- 3) Ref: Eur Journal of Medicinal Chemistry, 86:242, 2014 : PubMed ESTHER: Ji_2014_Eur.J.Med.Chem_86_242 PubMedSearch: Ji 2014 Eur.J.Med.Chem 86 242 PubMedID: 25164763 Abstract Based on the previous work in our group and the principle of computer-aided drug design, a series of novel beta-amino pyrrole-2-carbonitrile derivatives was designed and synthesized. Compounds 8l and 9l were efficacious and selective DPP4 inhibitors resulting in decreased blood glucose in vivo. Compound 8l had moderate DPP4 inhibitory activity (IC50 = 0.05 muM) and good oral bioavailability (F = 53.2%). Compound 9l showed excellent DPP4 inhibitory activity (IC50 = 0.01 muM), good selectivity (selective ratio: DPP8/DPP4 = 898.00; DPP9/DPP4 = 566.00) against related peptidases, and good efficacy in an oral glucose tolerance tests in ICR mice and moderate PK profiles (F = 22.8%, t1/2 = 2.74 h). Moreover, compound 9l did not block hERG channel and exhibited no inhibition of liver metabolic enzymes such as CYP2C9. Title: Calsyntenin-3 molecular architecture and interaction with neurexin 1alpha Lu Z, Wang Y, Chen F, Tong H, Reddy MV, Luo L, Seshadrinathan S, Zhang L, Holthauzen LM and Rudenko G <2 more author(s)> Lu Z, Wang Y, Chen F, Tong H, Reddy MV, Luo L, Seshadrinathan S, Zhang L, Holthauzen LM, Craig AM, Ren G, Rudenko G (- 2) Ref: Journal of Biological Chemistry, 289:34530, 2014 : PubMed ESTHER: Lu_2014_J.Biol.Chem_289_34530 PubMedSearch: Lu 2014 J.Biol.Chem 289 34530 PubMedID: 25352602 Abstract Calsyntenin 3 (Cstn3 or Clstn3), a recently identified synaptic organizer, promotes the development of synapses. Cstn3 localizes to the postsynaptic membrane and triggers presynaptic differentiation. Calsyntenin members play an evolutionarily conserved role in memory and learning. Cstn3 was recently shown in cell-based assays to interact with neurexin 1alpha (n1alpha), a synaptic organizer that is implicated in neuropsychiatric disease. Interaction would permit Cstn3 and n1alpha to form a trans-synaptic complex and promote synaptic differentiation. However, it is contentious whether Cstn3 binds n1alpha directly. To understand the structure and function of Cstn3, we determined its architecture by electron microscopy and delineated the interaction between Cstn3 and n1alpha biochemically and biophysically. We show that Cstn3 ectodomains form monomers as well as tetramers that are stabilized by disulfide bonds and Ca(2+), and both are probably flexible in solution. We show further that the extracellular domains of Cstn3 and n1alpha interact directly and that both Cstn3 monomers and tetramers bind n1alpha with nanomolar affinity. The interaction is promoted by Ca(2+) and requires minimally the LNS domain of Cstn3. Furthermore, Cstn3 uses a fundamentally different mechanism to bind n1alpha compared with other neurexin partners, such as the synaptic organizer neuroligin 2, because Cstn3 does not strictly require the sixth LNS domain of n1alpha. Our structural data suggest how Cstn3 as a synaptic organizer on the postsynaptic membrane, particularly in tetrameric form, may assemble radially symmetric trans-synaptic bridges with the presynaptic synaptic organizer n1alpha to recruit and spatially organize proteins into networks essential for synaptic function. Title: Transcriptomic comparison of thiamethoxam-resistance adaptation in resistant and susceptible strains of Aphis gossypii Glover Pan Y, Peng T, Gao X, Zhang L, Yang C, Xi J, Xin X, Bi R, Shang Q Ref: Comparative Biochemistry & Physiology Part D Genomics Proteomics, 13C:10, 2014 : PubMed ESTHER: Pan_2014_Comp.Biochem.Physiol.Part.D.Genomics.Proteomics_13C_10 PubMedSearch: Pan 2014 Comp.Biochem.Physiol.Part.D.Genomics.Proteomics 13C 10 PubMedID: 25528611 Abstract A thiamethoxam-resistant strain of cotton aphid (ThR) strain displayed a 19.35-fold greater resistance to thiamethoxam compared to a susceptible cotton aphid (SS) strain. Solexa sequencing technology was used to investigate differentially expressed genes (DEGs) in cotton aphids in the context of thiamethoxam resistance. A total of 22,569,311 and 21,317,732 clean reads were obtained from the ThR and SS transcriptomes, respectively, and assembled into 35,222 non-redundant (Nr) consensus sequences. The expression of 620 unigenes changed significantly in the ThR libraries compared to the SS strain; 349 genes were up-regulated, and 271 genes were down-regulated (P<=0.001). Expression levels of ribosomal proteins, ATP synthase, cytochrome c oxidase, ecdysteroid UDP-glucosyltransferase and esterase were up-regulated significantly in the ThR strain compared to the SS strain. The genes of cuticle proteins, salivary proteins, and fibroin heavy chain decreased dramatically. One nicotinic acetylcholine receptor (nAChR) alpha subunit was down-regulated in the ThR strain. The expression levels of 10 differentially expressed unigenes were confirmed using real-time RT-PCR, and the observed trends in gene expression matched the Solexa expression profiles. Specific single-nucleotide polymorphisms (SNPs) in nAChRs that cause amino acid substitution were found from the ThR and SS stains respectively. These data illustrate that genetic changes in nAChR genes and up-regulated ribosomal proteins, ecdysteroid UDP-glucosyltransferase, cytochrome c oxidase, esterase and peroxidase may confer the tolerance of resistant cotton aphids to thiamethoxam. Title: Complete Genome Sequence of a Moderately Virulent Aeromonas hydrophila Strain, pc104A, Isolated from Soil of a Catfish Pond in West Alabama Pridgeon JW, Zhang D, Zhang L Ref: Genome Announc, 2:e00554, 2014 : PubMed ESTHER: Pridgeon_2014_Genome.Announc_2_e00554 PubMedSearch: Pridgeon 2014 Genome.Announc 2 e00554 PubMedID: 24903879 Gene_locus related to this paper: aerhh-a0kle4, aerhy-a0a028v5g9 Abstract Aeromonas hydrophila pc104A is a moderately virulent strain isolated from the soil of a catfish pond in west Alabama in 2010. Its full genome is 5,023,829 bp. The availability of this genome will allow comparative genomics to identify the virulence genes that are important for pathogenesis or immunogens for the purpose of vaccine development. Title: Complete Genome Sequence of the Highly Virulent Aeromonas hydrophila AL09-71 Isolated from Diseased Channel Catfish in West Alabama Pridgeon JW, Zhang D, Zhang L Ref: Genome Announc, 2:e00450, 2014 : PubMed ESTHER: Pridgeon_2014_Genome.Announc_2_e00450 PubMedSearch: Pridgeon 2014 Genome.Announc 2 e00450 PubMedID: 24855300 Gene_locus related to this paper: aerhh-a0kle4 Abstract Aeromonas hydrophila AL09-71 was isolated from diseased channel catfish in west Alabama during a 2009 disease outbreak. The full genome of A. hydrophila AL09-71 is 5,023,861 bp. The availability of this genome will allow comparative genomics to identify genes involved in pathogenesis or immunogens for the purpose of vaccine development. Title: Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M and Zhang Z <58 more author(s)> Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M, Luo Y, Yang Y, Wu Z, Mao L, Wu H, Ling-Hu C, Zhou H, Lin H, Gonzalez-Morales S, Trejo-Saavedra DL, Tian H, Tang X, Zhao M, Huang Z, Zhou A, Yao X, Cui J, Li W, Chen Z, Feng Y, Niu Y, Bi S, Yang X, Cai H, Luo X, Montes-Hernandez S, Leyva-Gonzalez MA, Xiong Z, He X, Bai L, Tan S, Liu D, Liu J, Zhang S, Chen M, Zhang L, Zhang Y, Liao W, Wang M, Lv X, Wen B, Liu H, Luan H, Yang S, Wang X, Xu J, Li X, Li S, Wang J, Palloix A, Bosland PW, Li Y, Krogh A, Rivera-Bustamante RF, Herrera-Estrella L, Yin Y, Yu J, Hu K, Zhang Z (- 58) Ref: Proc Natl Acad Sci U S A, 111:5135, 2014 : PubMed ESTHER: Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135 PubMedSearch: Qin 2014 Proc.Natl.Acad.Sci.U.S.A 111 5135 PubMedID: 24591624 Gene_locus related to this paper: capch-q75qh4, capan-a0a1u8fuf5, capan-a0a1u8gmz3, capan-a0a1u8f879, capan-a0a1u8ftr2, capan-a0a1u8g8s6 Abstract As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. Title: Three new vibralactone-related compounds from cultures of Basidiomycete Boreostereum vibrans Wang GQ, Wei K, Zhang L, Li ZH, Wang QA, Liu JK Ref: J Asian Nat Prod Res, 16:447, 2014 : PubMed ESTHER: Wang_2014_J.Asian.Nat.Prod.Res_16_447 PubMedSearch: Wang 2014 J.Asian.Nat.Prod.Res 16 447 PubMedID: 24684503 Inhibitor(s) related to this paper: Vibralactone Abstract Three new compounds, named as vibralactones K-M (1-3), together with vibralactone (4) have been isolated from cultures of the Basidiomycete Boreostereum vibrans. Their structures were determined on the basis of spectroscopic evidences (1D and 2D NMR, HRMS, UV, and IR data), chemical methods and literature data. None of the compounds was cytotoxic against five human cancer cell lines and showed inhibitory activity on the pancreatic lipase. Title: Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients Xu X, Xiong Z, Zhang L, Liu Y, Lu L, Peng Y, Guo H, Zhao J, Xia K, Hu Z Ref: Mol Biol Rep, 41:4133, 2014 : PubMed ESTHER: Xu_2014_Mol.Biol.Rep_41_4133 PubMedSearch: Xu 2014 Mol.Biol.Rep 41 4133 PubMedID: 24570023 Abstract Autism is a neurodevelopmental disorder clinically characterized by impairment of social interaction, deficits in verbal communication, as well as stereotypic and repetitive behaviors. Several studies have implicated that abnormal synaptogenesis was involved in the incidence of autism. Neuroligins are postsynaptic cell adhesion molecules and interacted with neurexins to regulate the fine balance between excitation and inhibition of synapses. Recently, mutation analysis, cellular and mice models hinted neuroligin mutations probably affected synapse maturation and function. In this study, four missense variations [p.G426S (NLGN3), p.G84R (NLGN4X), p.Q162 K (NLGN4X) and p.A283T (NLGN4X)] in four different unrelated patients have been identified by PCR and direct sequencing. These four missense variations were absent in the 453 controls and have not been reported in 1000 Genomes Project. Bioinformatic analysis of the four missense variations revealed that p.G84R and p.A283T were "Probably Damaging". The variations may cause abnormal synaptic homeostasis and therefore trigger the patients more predisposed to autism. By case-control analysis, we identified the common SNPs (rs3747333 and rs3747334) in the NLGN4X gene significantly associated with risk for autism [p = 5.09E-005; OR 4.685 (95% CI 2.073-10.592)]. Our data provided a further evidence for the involvement of NLGN3 and NLGN4X gene in the pathogenesis of autism in Chinese population. Title: A method to rationally increase protein stability based on the charge-charge interaction, with application to lipase LipK107 Zhang L, Tang X, Cui D, Yao Z, Gao B, Jiang S, Yin B, Yuan YA, Wei D Ref: Protein Science, 23:110, 2014 : PubMed ESTHER: Zhang_2014_Protein.Sci_23_110 PubMedSearch: Zhang 2014 Protein.Sci 23 110 PubMedID: 24353171 Gene_locus related to this paper: promi-c2lfd0 Abstract We report a suite of enzyme redesign protocol based on the surface charge-charge interaction calculation, which is potentially applied to improve the stability of an enzyme without compromising its catalytic activity. Together with the experimental validation, we have released a suite of enzyme redesign algorithm Enzyme Thermal Stability System, written based on our model, for open access to meet the needs in wet labs. Lipk107, a lipase of a versatile industrial use, was chosen to test our software. Our calculation determined that four residues, D113, D149, D213, and D253, located on the surface of LipK107 were critical to the stability of the enzyme. The model was validated with mutagenesis at these four residues followed by stability and activity tests. LipK107 mutants D113A and D149K were more resistant to thermal inactivation with approximately 10 degrees C higher half-inactivation temperature than wild-type LipK107. Moreover, mutant D149K exhibited significant retention in residual activity under constant heat, showing a 14-fold increase in the half-inactivation time at 50 degrees C. Activity tests showed that these mutants retained the equal or higher specific activity, among which noteworthy was the mutant D253A with as much as 20% higher activity. We suggest that our protocol could be used as a general guideline to redesign protein enzymes with increased stabilities and enhanced activities. Title: Effects of additives on lipase immobilization in microemulsion-based organogels Zhang WW, Wang N, Zhang L, Wu WX, Hu CL, Yu XQ Ref: Appl Biochem Biotechnol, 172:3128, 2014 : PubMed ESTHER: Zhang_2014_Appl.Biochem.Biotechnol_172_3128 PubMedSearch: Zhang 2014 Appl.Biochem.Biotechnol 172 3128 PubMedID: 24497044 Abstract An inexpensive, facile, and environmentally benign method was developed to improve the activity and stability of Candida rugosa lipase (triacylglycerol acylhydrolase) immobilized on microemulsion-based organogels (CRL MBGs) via the addition of additives during immobilization. The additives used were polyethylene glycol (PEG) or polysaccharides. This study is the first report on the effect of additives in CRL MBGs. Among the tested additives, PEG produced the most improvement in the immobilized CRL, enhancing its stability in organic solvents (specifically polar solvents). The results of circular dichroism and fluorescence spectra experiments indicated that exposure of the acidic CRL to electronegative additives in the buffer, such as polyethylenimine and the electropositive surfactant cetyltrimethylammonium bromide, may change the lipase secondary structure, ultimately causing enzyme inactivation. However, sodium bis(2-ethylhexyl)sulfosuccinate and PEG 2000 had minimal effects on the secondary structure of CRL. The CRL MBGs containing PEG 2000 demonstrated remarkable retention of their catalytic activity during the recycling test. No significant changes in enzymatic activity were observed, even after nine runs, and 90 % of the original yield was maintained after 15 cycles. Title: Short-term effects of Dechlorane Plus on the earthworm Eisenia fetida determined by a systems biology approach Zhang L, Ji F, Li M, Cui Y, Wu B Ref: J Hazard Mater, 273C:239, 2014 : PubMed ESTHER: Zhang_2014_J.Hazard.Mater_273C_239 PubMedSearch: Zhang 2014 J.Hazard.Mater 273C 239 PubMedID: 24751489 Abstract Dechlorane Plus (DP), a chlorinated flame retardant, has been widely detected in environmental matrices, especially in sediment and soil. DP has characteristics similar to persistent organic pollutants. However, no toxicity data of DP on terrestrial invertebrate are available. In this study, earthworms Eisenia fetida were exposed to 0.1, 1, 10, and 50mg/kg DP for 14 days. Lethality, oxidative stress and damage, neurotoxicity, and transcriptomic profiles of E. fetida were assessed on day 7 and day 14 of exposure. Results showed that the acute toxicity of DP was very low. However, DP exposure induced an increase in the oxidative stress markers malonaldehyde (MDA) and 8-Hydroxy-2'-deoxyguanosine (8-OHdG), and altered acetylcholinesterase (AChE) activities. High throughput sequencing-based transcriptomic analysis showed that DP exposure significantly altered gene expression and pathways related to antioxidant enzymes, stress responses, neurological dysfunctions, calcium binding, and signal transduction. The results from different toxicological endpoints indicate that DP toxicity on the earthworm is primarily through oxidative damage and neurotoxicity. Based on these results, we deduce that changes in oxidative stress and neurotoxicity might be the primary mechanisms of DP toxicity. This study provides insight into the toxicological effects of DP on earthworm model, and may be useful for risk assessment of DP on soil ecosystems. Title: Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides and Their Acetylcholinesterase Inhibitory Activity Zhang DB, Chen JJ, Song QY, Zhang L, Gao K Ref: Molecules, 19:9999, 2014 : PubMed ESTHER: Zhang_2014_Molecules_19_9999 PubMedSearch: Zhang 2014 Molecules 19 9999 PubMedID: 25014530 Abstract Four new lycodine-type alkaloids, namely 16-hydroxyhuperzine B (1), N-methyl-11-acetoxyhuperzine B (2), 8,15-dihydrolycoparin A (3) and (7S,12S,13R)-huperzine D-16-O-beta-d-glucopyranoside (4), along with ten known analogues 5-14, were isolated from the whole plant of Lycopodiastrum casuarinoides. The structures of the new compounds were elucidated by means of spectroscopic techniques (IR, MS, NMR, and CD) and chemical methods. Compounds 1 and 2 possessed four connected six-membered rings, while compounds 3 and 4 were piperidine ring cleavage products. In particular, compound 4 was a lycopodium alkaloidal glycoside which is reported for the first time. Among the isolated compounds N-demethylhuperzinine (7), huperzine C (8), huperzine B (9) and lycoparin C (13) possessed significant inhibitory activity against acetylcholinesterase, and the new compound 1 showed moderate inhibitory activity. The structure activity relationships were discussed. Title: Structure, mechanism, and enantioselectivity shifting of lipase LipK107 with a simple way Zhang L, Gao B, Yuan Z, He X, Yuan YA, Zhang JZ, Wei D Ref: Biochimica & Biophysica Acta, 1844:1183, 2014 : PubMed ESTHER: Zhang_2014_Biochim.Biophys.Acta_1844_1183 PubMedSearch: Zhang 2014 Biochim.Biophys.Acta 1844 1183 PubMedID: 24602769 Gene_locus related to this paper: promi-c2lfd0 Abstract Because of the complex mechanisms of enzymatic reactions, no precise and simple method of understanding and controlling the chiral selectivity of enzymes has been developed. However, structure-based rational design is a powerful approach to engineering enzymes with desired catalytic activities. In this work, a simple, structure-based, large-scale in silico design and virtual screening strategy was developed and successfully applied to enzyme engineering. We first performed protein crystallization and X-ray diffraction to determine the structure of lipase LipK107, which is a novel family I.1 lipase displaying activity for both R and S isomers in chiral resolution reactions. The catalytic mechanism of family I.1, which includes LipK107, was ascertained first through comparisons of the sequences and structures of lipases from other families. The binding states of LipK107, including the energy and the conformation of complexes with the R and S enantiomers, have been evaluated by careful biocomputation to figure out the reason for the higher S selectivity. Based on this study, a simple strategy for manipulating the chiral selectivity by modulating a crucial distance in the enzyme-substrate complex and judging virtual mutations in silico is recommended. Then, a novel electrostatic interaction analysis protocol was used to design LipK107 mutants to validate our strategy. Both positive and negative mutations determined using this theoretical protocol have been implemented in wet experiments and were proved to produce the desired enantioselectivity, showing a 176% increase or 50% decrease in enantioselectivity as desired. Because of its accuracy and versatility, the strategy is promising for practical applications. Title: Draft Genome Sequence of Ralstonia pickettii AU12-08, Isolated from an Intravascular Catheter in Australia Zhang L, Morrison M, Rickard CM Ref: Genome Announc, 2:, 2014 : PubMed ESTHER: Zhang_2014_Genome.Announc_2_e00027 PubMedSearch: Zhang 2014 Genome.Announc 2 e00027 PubMedID: 24503988 Gene_locus related to this paper: 9rals-s9rw78, 9rals-s9tfx3, 9rals-s9teu7 Abstract Ralstonia pickettii is a nonfermenting Gram-negative bacillus that creates a significant problem in clinical settings, as it is a widespread cause of nosocomial infections. Here, we report the draft genome sequence of R. pickettii AU12-08, isolated from an intravascular catheter tip. Title: Global analysis of gene expression profiles in physic nut (Jatropha curcas L.) seedlings exposed to salt stress Zhang L, Zhang C, Wu P, Chen Y, Li M, Jiang H, Wu G Ref: PLoS ONE, 9:e97878, 2014 : PubMed ESTHER: Zhang_2014_PLoS.ONE_9_E97878 PubMedSearch: Zhang 2014 PLoS.ONE 9 E97878 PubMedID: 24837971 Gene_locus related to this paper: jatcu-a0a067k7w6, jatcu-a0a067juw0, jatcu-a0a067jz21, jatcu-a0a067jeh8, jatcu-a0a067jvs1, jatcu-a0a067jvz5, jatcu-a0a067jc69, jatcu-a0a067jpe1, jatcu-a0a067jf51, jatcu-a0a067kvu1, jatcu-a0a067kfw0, jatcu-a0a067l7t8, jatcu-a0a067kfv9, jatcu-a0a067kbk6, jatcu-a0a067kqg8, jatcu-a0a067k9z6, jatcu-a0a067k9m8, jatcu-a0a067kc24, jatcu-a0a067jzr6, jatcu-a0a067kjc7, jatcu-a0a067kq44, jatcu-a0a067kwm1, jatcu-a0a067kws6, jatcu-a0a067l048, jatcu-a0a067l054, jatcu-a0a067l7y4, jatcu-a0a067l929, jatcu-a0a067k816 Abstract BACKGROUND: Salt stress interferes with plant growth and production. Plants have evolved a series of molecular and morphological adaptations to cope with this abiotic stress, and overexpression of salt response genes reportedly enhances the productivity of various crops. However, little is known about the salt responsive genes in the energy plant physic nut (Jatropha curcas L.). Thus, excavate salt responsive genes in this plant are informative in uncovering the molecular mechanisms for the salt response in physic nut. METHODOLOGY/PRINCIPAL FINDINGS: We applied next-generation Illumina sequencing technology to analyze global gene expression profiles of physic nut plants (roots and leaves) 2 hours, 2 days and 7 days after the onset of salt stress. A total of 1,504 and 1,115 genes were significantly up and down-regulated in roots and leaves, respectively, under salt stress condition. Gene ontology (GO) analysis of physiological process revealed that, in the physic nut, many "biological processes" were affected by salt stress, particular those categories belong to "metabolic process", such as "primary metabolism process", "cellular metabolism process" and "macromolecule metabolism process". The gene expression profiles indicated that the associated genes were responsible for ABA and ethylene signaling, osmotic regulation, the reactive oxygen species scavenging system and the cell structure in physic nut. CONCLUSIONS/SIGNIFICANCE: The major regulated genes detected in this transcriptomic data were related to trehalose synthesis and cell wall structure modification in roots, while related to raffinose synthesis and reactive oxygen scavenger in leaves. The current study shows a comprehensive gene expression profile of physic nut under salt stress. The differential expression genes detected in this study allows the underling the salt responsive mechanism in physic nut with the aim of improving its salt resistance in the future. Title: Highly sensitive detection of organophosphorus pesticides by acetylcholinesterase-coated thin film bulk acoustic resonator mass-loading sensor Chen D, Wang J, Xu Y, Li D, Zhang L, Li Z Ref: Biosensors & Bioelectronics, 41:163, 2013 : PubMed ESTHER: Chen_2013_Biosens.Bioelectron_41_163 PubMedSearch: Chen 2013 Biosens.Bioelectron 41 163 PubMedID: 23017678 Abstract An acetylcholinesterase-coated thin film bulk acoustic resonator has been developed for the detection of organophosphorus pesticides. The thin film bulk acoustic resonator acts as a robust mass-sensitive transducer for bio-sensing. This device works in thickness shear mode with a resonance at 1.97GHz. The detection is based on the inhibitory effects of organophosphorus compounds on the enzymatic activity of the acetylcholinesterase immobilized on one of the faces of the acoustic resonator. The enzyme reaction in the substrate solution and the inhibitory effect is observed are real time by measuring the frequency shift. The presence of organophosphorus pesticides can be detected from the diminution of the frequency shift compared with the levels found in their absence. The device exhibits linear responses, good reproducibility, simple operation, portability and a low detection limit of 5.3x10(-11)M for paraoxon. The detection results of organophosphorus pesticide residues in practical samples show that the proposed sensor has the feasibility and sensing accuracy comparable to gas chromatography. Title: [Effects of cornel iridoid glycoside on activity of cholinesterases in vitro] Chu SJ, Zhang L, Liu G, Zhou WX, Li L Ref: Zhongguo Zhong Yao Za Zhi, 38:1331, 2013 : PubMed ESTHER: Chu_2013_Zhongguo.Zhong.Yao.Za.Zhi_38_1331 PubMedSearch: Chu 2013 Zhongguo.Zhong.Yao.Za.Zhi 38 1331 PubMedID: 23944063 Abstract The purpose of the present study was to investigate the effects of cornel iridoid glycoside (CIG) on the activity of cholinesterases in vitro, and to investigate the mechanism of CIG's treating Alzheimer's disease (AD). The sources of cholinesterases were prepared from human blood cells, rat brain homogenate and human blood plasma, respectively. The biochemical methods were used to detect the activity of acetylcholine esterase (AChE) and butyryl cholinesterase (BCHE) to investigate the influence of CIG on cholinesterases. The results showed that CIG inhibited the activity of AChE of human blood cells and rat brain homogenate, with the 50% inhibition rate (IC50) of 1.6 g . L-1 and 3.3 g . L-1, respectively; and the inhibition of AChE of CIG is reversible. CIG also inhibited the activity of BCHE of human blood plasma, with the IC50 of 2.9 g . L-1. In conclusion, CIG can inhibit the activity of AChE and BCHE in vitro, which may be one of the mechanisms of CIG to treat AD. Title: A Genetic Screen Identifies Interferon-alpha Effector Genes Required to Suppress Hepatitis C Virus Replication Fusco DN, Brisac C, John SP, Huang YW, Chin CR, Xie T, Zhao H, Jilg N, Zhang L and Brass AL <5 more author(s)> Fusco DN, Brisac C, John SP, Huang YW, Chin CR, Xie T, Zhao H, Jilg N, Zhang L, Chevaliez S, Wambua D, Lin W, Peng L, Chung RT, Brass AL (- 5) Ref: Gastroenterology, 144:1438, 2013 : PubMed ESTHER: Fusco_2013_Gastroenterology_144_1438 PubMedSearch: Fusco 2013 Gastroenterology 144 1438 PubMedID: 23462180 Abstract BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is a leading cause of end-stage liver disease. Interferon-alpha (IFNalpha) is an important component of anti-HCV therapy; it up-regulates transcription of IFN-stimulated genes, many of which have been investigated for their antiviral effects. However, all of the genes required for the antiviral function of IFNalpha (IFN effector genes [IEGs]) are not known. IEGs include not only IFN-stimulated genes, but other nontranscriptionally induced genes that are required for the antiviral effect of IFNalpha. In contrast to candidate approaches based on analyses of messenger RNA (mRNA) expression, identification of IEGs requires a broad functional approach. Title: Genomic and secretomic analyses reveal unique features of the lignocellulolytic enzyme system of Penicillium decumbens Liu G, Zhang L, Wei X, Zou G, Qin Y, Ma L, Li J, Zheng H, Wang S and Qu Y <4 more author(s)> Liu G, Zhang L, Wei X, Zou G, Qin Y, Ma L, Li J, Zheng H, Wang S, Wang C, Xun L, Zhao GP, Zhou Z, Qu Y (- 4) Ref: PLoS ONE, 8:e55185, 2013 : PubMed ESTHER: Liu_2013_PLoS.ONE_8_E55185 PubMedSearch: Liu 2013 PLoS.ONE 8 E55185 PubMedID: 23383313 Gene_locus related to this paper: peno1-s7zjd1, peno1-s8aym9, peno1-s7zcd7, peno1-s8aui7, peno1-s7zba9, peno1-s7z7w2, peno1-s7zkn6, peno1-s8ak78, peno1-s7z721, peno1-s8ajn6, peno1-s7zqw4, peno1-s8bba0, peno1-s8b4w2, peno1-s7zta4, peno1-s8a1h3, peno1-s8aiq5, peno1-s8ba66, peno1-s7zxp5, penox-poxo Abstract Many Penicillium species could produce extracellular enzyme systems with good lignocellulose hydrolysis performance. However, these species and their enzyme systems are still poorly understood and explored due to the lacking of genetic information. Here, we present the genomic and secretomic analyses of Penicillium decumbens that has been used in industrial production of lignocellulolytic enzymes in China for more than fifteen years. Comparative genomics analysis with the phylogenetically most similar species Penicillium chrysogenum revealed that P. decumbens has evolved with more genes involved in plant cell wall degradation, but fewer genes in cellular metabolism and regulation. Compared with the widely used cellulase producer Trichoderma reesei, P. decumbens has a lignocellulolytic enzyme system with more diverse components, particularly for cellulose binding domain-containing proteins and hemicellulases. Further, proteomic analysis of secretomes revealed that P. decumbens produced significantly more lignocellulolytic enzymes in the medium with cellulose-wheat bran as the carbon source than with glucose. The results expand our knowledge on the genetic information of lignocellulolytic enzyme systems in Penicillium species, and will facilitate rational strain improvement for the production of highly efficient enzyme systems used in lignocellulose utilization from Penicillium species. Title: The Specific alpha-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development Pettem KL, Yokomaku D, Luo L, Linhoff MW, Prasad T, Connor SA, Siddiqui TJ, Kawabe H, Chen F and Craig AM <4 more author(s)> Pettem KL, Yokomaku D, Luo L, Linhoff MW, Prasad T, Connor SA, Siddiqui TJ, Kawabe H, Chen F, Zhang L, Rudenko G, Wang YT, Brose N, Craig AM (- 4) Ref: Neuron, 80:113, 2013 : PubMed ESTHER: Pettem_2013_Neuron_80_113 PubMedSearch: Pettem 2013 Neuron 80 113 PubMedID: 24094106 Abstract Perturbations of cell surface synapse-organizing proteins, particularly alpha-neurexins, contribute to neurodevelopmental and psychiatric disorders. From an unbiased screen, we identify calsyntenin-3 (alcadein-beta) as a synapse-organizing protein unique in binding and recruiting alpha-neurexins, but not beta-neurexins. Calsyntenin-3 is present in many pyramidal neurons throughout cortex and hippocampus but is most highly expressed in interneurons. The transmembrane form of calsyntenin-3 can trigger excitatory and inhibitory presynapse differentiation in contacting axons. However, calsyntenin-3-shed ectodomain, which represents about half the calsyntenin-3 pool in brain, suppresses the ability of multiple alpha-neurexin partners including neuroligin 2 and LRRTM2 to induce presynapse differentiation. Clstn3-/- mice show reductions in excitatory and inhibitory synapse density by confocal and electron microscopy and corresponding deficits in synaptic transmission. These results identify calsyntenin-3 as an alpha-neurexin-specific binding partner required for normal functional GABAergic and glutamatergic synapse development. Title: An unexpected role of neuroligin-2 in regulating KCC2 and GABA functional switch Sun C, Zhang L, Chen G Ref: Mol Brain, 6:23, 2013 : PubMed ESTHER: Sun_2013_Mol.Brain_6_23 PubMedSearch: Sun 2013 Mol.Brain 6 23 PubMedID: 23663753 Abstract BACKGROUND: GABAA receptors are ligand-gated Cl- channels, and the intracellular Cl- concentration governs whether GABA function is excitatory or inhibitory. During early brain development, GABA undergoes functional switch from excitation to inhibition: GABA depolarizes immature neurons but hyperpolarizes mature neurons due to a developmental decrease of intracellular Cl- concentration. This GABA functional switch is mainly mediated by the up-regulation of KCC2, a potassium-chloride cotransporter that pumps Cl- outside neurons. However, the upstream factor that regulates KCC2 expression is unclear. Title: ContigScape: a Cytoscape plugin facilitating microbial genome gap closing Tang B, Wang Q, Yang M, Xie F, Zhu Y, Zhuo Y, Wang S, Gao H, Ding X and Zheng H <2 more author(s)> Tang B, Wang Q, Yang M, Xie F, Zhu Y, Zhuo Y, Wang S, Gao H, Ding X, Zhang L, Zhao G, Zheng H (- 2) Ref: BMC Genomics, 14:289, 2013 : PubMed ESTHER: Tang_2013_BMC.Genomics_14_289 PubMedSearch: Tang 2013 BMC.Genomics 14 289 PubMedID: 23627759 Gene_locus related to this paper: myctu-cut3, myctu-cutas1, myctu-cutas2, myctu-Rv0160c, myctu-Rv1069c, myctu-RV1215C, myctu-Rv2045c, myctu-RV3452, myctu-Rv3802c, amyor-r4tdn6, amyor-r4sys4, amyor-r4svp2, amyor-r4t193, amyor-r4t8c7, amyor-r4t8w6, amyor-r4t1x8, amyor-r4stv4, amyor-r4t7z6, 9pseu-r4sx12 Abstract BACKGROUND: With the emergence of next-generation sequencing, the availability of prokaryotic genome sequences is expanding rapidly. A total of 5,276 genomes have been released since 2008, yet only 1,692 genomes were complete. The final phase of microbial genome sequencing, particularly gap closing, is frequently the rate-limiting step either because of complex genomic structures that cause sequence bias even with high genomic coverage, or the presence of repeat sequences that may cause gaps in assembly. Title: Structure of MERS-CoV spike receptor-binding domain complexed with human receptor DPP4 Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, Guo D, Fu L, Cui Y and Wang X <4 more author(s)> Wang N, Shi X, Jiang L, Zhang S, Wang D, Tong P, Guo D, Fu L, Cui Y, Liu X, Arledge KC, Chen YH, Zhang L, Wang X (- 4) Ref: Cell Res, 23:986, 2013 : PubMed ESTHER: Wang_2013_Cell.Res_23_986 PubMedSearch: Wang 2013 Cell.Res 23 986 PubMedID: 23835475 Gene_locus related to this paper: human-DPP4 Abstract The spike glycoprotein (S) of recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) targets the cellular receptor, dipeptidyl peptidase 4 (DPP4). Sequence comparison and modeling analysis have revealed a putative receptor-binding domain (RBD) on the viral spike, which mediates this interaction. We report the 3.0 A-resolution crystal structure of MERS-CoV RBD bound to the extracellular domain of human DPP4. Our results show that MERS-CoV RBD consists of a core and a receptor-binding subdomain. The receptor-binding subdomain interacts with DPP4 beta-propeller but not its intrinsic hydrolase domain. MERS-CoV RBD and related SARS-CoV RBD share a high degree of structural similarity in their core subdomains, but are notably divergent in the receptor-binding subdomain. Mutagenesis studies have identified several key residues in the receptor-binding subdomain that are critical for viral binding to DPP4 and entry into the target cell. The atomic details at the interface between MERS-CoV RBD and DPP4 provide structural understanding of the virus and receptor interaction, which can guide development of therapeutics and vaccines against MERS-CoV infection. Title: A novel approach to medical countermeasures against organophosphorus compound toxicity Wang T, Wang Y, Zhang L, Han B, Wang H, Li Y, Fu F Ref: Biomed Rep, 1:901, 2013 : PubMed ESTHER: Wang_2013_Biomed.Rep_1_901 PubMedSearch: Wang 2013 Biomed.Rep 1 901 PubMedID: 24649050 Abstract The toxicity of organophosphorus compounds (OPs) results primarily from the irreversible inhibition of acetylcholinesterase (AChE). Huperzine A (HupA) is a reversible inhibitor of AChE and HupA sustained-release microspheres (HSMs) steadily release HupA, resulting in the continual inhibition of AChE activity for 14 days in mice. The present study aimed to investigate the preventive effects of HSMs on the toxicity of methyl parathion (MP). The mice were pretreated with HSMs followed by MP exposure. Subsequently, the median lethal dose (LD50) and survival of the mice were determined. A histopathological examination of the brain, liver, lungs, heart, kidneys and intercostal muscles was also performed. The results revealed that the LD50 was 51.4 mg/kg in the control group and 70.0, 67.5, 63.4 and 53.5 mg/kg at 2 h, 5, 10 and 15 days after pretreatment with HSMs, respectively. Pretreatment with HSMs at 2 h, 5 days and 10 days prior to an acute challenge with 1.2 x LD50 MP was sufficient to counteract the lethality and acute toxicity of MP. HSM pretreatment also attenuated the pulmonary edema induced by MP. The results demonstrated that pretreatment with HSMs may be an effective method to counteract MP poisoning. To the best of our knowledge, the present study was the first to demonstrate that pretreatment with an AChE reversible inhibitor sustained-release agent may be a novel approach to effective protection against OP toxicity. Title: Microsomal epoxide hydrolase (EPHX1) polymorphisms are associated with aberrant promoter methylation of ERCC3 and hematotoxicity in benzene-exposed workers Xing C, Chen Q, Li G, Zhang L, Zheng M, Zou Z, Hou L, Wang QF, Liu X, Guo X Ref: Environmental & Molecular Mutagenesis, 54:397, 2013 : PubMed ESTHER: Xing_2013_Environ.Mol.Mutagen_54_397 PubMedSearch: Xing 2013 Environ.Mol.Mutagen 54 397 PubMedID: 23797950 Abstract Benzene is an important industrial chemical and widespread environmental pollutant known to induce leukemia and other blood disorders. To be carcinogenic, benzene must be metabolized to produce toxic metabolites. To investigate whether single nucleotide polymorphisms (SNPs) in the metabolic enzyme genes are associated with benzene-induced alterations in DNA methylation and hematotoxicity, we genotyped four commonly studied SNPs in three metabolic enzymes genes CYP1A1, EPHX1 and NQO1; and analyzed promoter DNA methylation status in 11 genes which have been reported to be associated with benzene-induced hematotoxicity (BLM, CYP1A1, EPHX1, ERCC3, NQO1, NUDT1, p15, p16, RAD51, TP53 and WRAP53) in 77 benzene-exposed workers and 25 unexposed controls in China. ERCC3, a DNA repair gene, showed a small but statistically significant increase of promoter DNA methylation in the exposed group compared with the unexposed group (mean +/- SD: 4.73 +/- 3.46% vs. 3.63 +/- 1.96%, P = 0.048). We also observed that an increased number of C allele for rs1051740 in EPHX1 was associated with decreased ERCC3 methylation levels in benzene-exposed workers (P(trend) = 0.001), but not in unexposed controls (P(trend) = 0.379). Interestingly, another EPHX1 SNP (rs2234922) was associated with lower white blood cell (WBC) counts (P(trend) = 0.044) in benzene-exposed workers. These associations remained the same when ERCC3 promoter methylation and WBCs were dichotomized according to the 90th percentile (>/=6%) of methylation levels in controls and a leucopenia cutoff (<4 x 10(9) /L), respectively. Our findings suggest that benzene exposure may be associated with hypermethylation in ERCC3, and that genetic variants in EPHX1 may play an important role in epigenetic changes and hematotoxicity among benzene-exposed workers. Title: Characterization of streptonigrin biosynthesis reveals a cryptic carboxyl methylation and an unusual oxidative cleavage of a N-C bond Xu F, Kong D, He X, Zhang Z, Han M, Xie X, Wang P, Cheng H, Tao M and Lin S <2 more author(s)> Xu F, Kong D, He X, Zhang Z, Han M, Xie X, Wang P, Cheng H, Tao M, Zhang L, Deng Z, Lin S (- 2) Ref: Journal of the American Chemical Society, 135:1739, 2013 : PubMed ESTHER: Xu_2013_J.Am.Chem.Soc_135_1739 PubMedSearch: Xu 2013 J.Am.Chem.Soc 135 1739 PubMedID: 23301954 Gene_locus related to this paper: 9actn-l7pij2 Abstract Streptonigrin (STN, 1) is a highly functionalized aminoquinone alkaloid with broad and potent antitumor activity. Here, we reported the biosynthetic gene cluster of STN identified by genome scanning of a STN producer Streptomyces flocculus CGMCC4.1223. This cluster consists of 48 genes determined by a series of gene inactivations. On the basis of the structures of intermediates and shunt products accumulated from five specific gene inactivation mutants and feeding experiments, the biosynthetic pathway was proposed, and the sequence of tailoring steps was preliminarily determined. In this pathway, a cryptic methylation of lavendamycin was genetically and biochemically characterized to be catalyzed by a leucine carboxyl methyltransferase StnF2. A [2Fe-2S](2+) cluster-containing aromatic ring dioxygenase StnB1/B2 system was biochemically characterized to catalyze a regiospecific cleavage of the N-C8' bond of the indole ring of the methyl ester of lavendamycin. This work provides opportunities to illuminate the enzymology of novel reactions involved in this pathway and to create, using genetic and chemo-enzymatic methods, new streptonigrinoid analogues as potential therapeutic agents. Title: The effects of huperzine A on gastrointestinal acetylcholinesterase activity and motility after single and multiple dosing in mice Zhang L, Song Y, Lu C, Zhang J, Yuan J, Wang T, Fu F Ref: Exp Ther Med, 5:793, 2013 : PubMed ESTHER: Zhang_2013_Exp.Ther.Med_5_793 PubMedSearch: Zhang 2013 Exp.Ther.Med 5 793 PubMedID: 23403922 Abstract The acetylcholinesterase inhibitor (AChEI), huperzine A has been used in the treatment of the cognitive deterioration associated with Alzheimer's disease (AD). However, the side-effects of huperzine A associated with increased cholinergic activity, particularly in the gastrointestinal system, are evident. It is not yet known how quickly these side-effects become tolerated; this information would provide guidance to doctors on how to use huperzine A so as to attenuate the adverse events. The present study aimed to observe the effects of huperzine A on gastrointestinal motility and acetylcholinesterase (AChE) activity in mice. After oral administration of huperzine A with single and multiple dosing, the gastrointestinal motility and AChE activity of the mice were examined. The results revealed that, following a single dose of huperzine A, the AChE activity in the stomach and duodenum were significantly inhibited and the gastrointestinal motility was significantly increased. However, following multiple doses (7 or 28 doses, one dose per day), no significant changes in the AChE activity and gastrointestinal motility were identified. These findings indicate that the gastrointestinal adverse effects of huperzine A may be well-tolerated relatively quickly and do not recur. Additionally, it suggests that patients with AD are likely to have minimal gastrointestinal side-effects after taking multiple doses of huperzine A. Title: [Effects of Shenwu capsule on learning-memory ability and cholinergic function of brain in AD-like rat model induced by chronic infusion of sodium azide by minipump] Zhang L, Zhang RY, Li YL, Ye CF, Li L Ref: Zhongguo Zhong Yao Za Zhi, 38:1300, 2013 : PubMed ESTHER: Zhang_2013_Zhongguo.Zhong.Yao.Za.Zhi_38_1300 PubMedSearch: Zhang 2013 Zhongguo.Zhong.Yao.Za.Zhi 38 1300 PubMedID: 23944056 Abstract Because of the proposed importance of mitochondrial cytochrome C oxidase (COX) decrease in Alzheimer's disease (AD) , the protective effect of Shenwu capsule on mitochondrial deficiency model rats and its pharmacological mechanism were investigated in present study. Rats were administered with azide at 1 mg . kg-1 . h-1 subcutaneously via an Alzet minipump for 30 days. Tweny-four hours after the operation, the rats were administered intragastrically by Shenwu capsule with the dose of 0. 45, 0. 9 and 1. 8 g . kg-1 . d-1 for one month. Then learning-memory ability was determined by the watermaze test and passive avoidance tests. The activity of choline-acetyl-transfertase(ChAT) and acetylcholinesterase (AChE) in hippocampus and cortex of rats were measured by radiochemical method and hydroxylamine colorimetry separately. M-cholinergic receptor binding ability (M-binding) was assayed by radio binding. Chronic infusion of sodium azide via minipump induced learning-memory deficiency of rats. Both ChAT activity and M-binding decreased in hippocampus and cortex of model rats, however, the activity of AChE increased in hippocampus and was not affected at the cortex. As the result, the cholinergic function of the brain decreased in model rats. Shenwu capsule significantly improved learning and memory ability and the mechanism may be related with the improved cholinergic function in model brain: ChAT activity and M-binding significantly increased in Shenwu treated groups compared with model group; and the increased activity of AChE in hippocampus returned to normal. Mitochondria, especially mitochondrial cytochrome C oxidase, may play the key role in the early event of AD. Chronic, partial in vivo inhibition of mitochondrial cytochrome C oxidase in rats provides a suitable model mimicking several aspects of AD. Shenwu capsule indicate effectiveness in AD-like mitochondrial deficiency model rats, so it would be applied in the treatment of AD. Title: Genome Sequence of Stenotrophomonas maltophilia Strain AU12-09, Isolated from an Intravascular Catheter Zhang L, Morrison M, P OC, Evans P, Rickard CM Ref: Genome Announc, 1:e00195, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00195 PubMedSearch: Zhang 2013 Genome.Announc 1 E00195 PubMedID: 23640378 Gene_locus related to this paper: stema-t5kff6 Abstract Stenotrophomonas maltophilia is an opportunistic nosocomial pathogen that is characterized by its high-level intrinsic resistance to a variety of antibiotics and its ability to form biofilms. Here, we report the draft genome sequence of Stenotrophomonas maltophilia AU12-09, isolated from an intravascular catheter tip. Title: The genome of the hydatid tapeworm Echinococcus granulosus Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y and Wang S <21 more author(s)> Zheng H, Zhang W, Zhang L, Zhang Z, Li J, Lu G, Zhu Y, Wang Y, Huang Y, Liu J, Kang H, Chen J, Wang L, Chen A, Yu S, Gao Z, Jin L, Gu W, Wang Z, Zhao L, Shi B, Wen H, Lin R, Jones MK, Brejova B, Vinar T, Zhao G, McManus DP, Chen Z, Zhou Y, Wang S (- 21) Ref: Nat Genet, 45:1168, 2013 : PubMed ESTHER: Zheng_2013_Nat.Genet_45_1168 PubMedSearch: Zheng 2013 Nat.Genet 45 1168 PubMedID: 24013640 Gene_locus related to this paper: echgr-k4epc5, echmu-u6hbw4, echgr-w6ugl0, echgr-w6u7y4, echgr-w6vaq5, echgr-a0a068wxj3, echgr-a0a068wgw1, echgr-a0a068wl60 Abstract Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavbeta1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control. Title: Biocatalytic Synthesis of Poly(delta-Valerolactone) Using a Thermophilic Esterase from Archaeoglobus fulgidus as Catalyst Cao H, Han H, Li G, Yang J, Zhang L, Yang Y, Fang X, Li Q Ref: Int J Mol Sci, 13:12232, 2012 : PubMed ESTHER: Cao_2012_Int.J.Mol.Sci_13_12232 PubMedSearch: Cao 2012 Int.J.Mol.Sci 13 12232 PubMedID: 23202895 Abstract The ring-opening polymerization of delta-valerolactone catalyzed by a thermophilic esterase from the archaeon Archaeoglobus fulgidus was successfully conducted in organic solvents. The effects of enzyme concentration, temperature, reaction time and reaction medium on monomer conversion and product molecular weight were systematically evaluated. Through the optimization of reaction conditions, poly(delta-valerolactone) was produced in 97% monomer conversion, with a number-average molecular weight of 2225 g/mol, in toluene at 70 degrees C for 72 h. This paper has produced a new biocatalyst for the synthesis of poly(delta-valerolactone), and also deeper insight has been gained into the mechanism of thermophilic esterase-catalyzed ring-opening polymerization. Title: A thin film electro-acoustic enzyme biosensor allowing the detection of trace organophosphorus pesticides Chen D, Wang J, Xu Y, Zhang L Ref: Analytical Biochemistry, 429:42, 2012 : PubMed ESTHER: Chen_2012_Anal.Biochem_429_42 PubMedSearch: Chen 2012 Anal.Biochem 429 42 PubMedID: 22796536 Abstract We report an analytical method using a thin film electro-acoustic resonator for the detection of organophosphorus pesticides The acetylcholinesterase AChE enzyme was immobilized on the surface of the resonator In the presence of organophosphorus compounds the degree of inhibitory effect of organophosphorus compounds on the AChE activity and the concentration of pesticides were detected in real time by measuring the frequency shift of the resonator The proposed device has a remarkably low detection limit of 1.8x10(-11)M and obvious advantages such as small size simple operation and integrated circuit compatibility providing a promising tool for pesticide analysis. Title: Catalytic characteristics of plant-esterase from wheat flour Hou CJ, He K, Yang LM, Huo DQ, Yang M, Huang S, Zhang L, Shen CH Ref: World J Microbiol Biotechnol, 28:541, 2012 : PubMed ESTHER: Hou_2012_World.J.Microbiol.Biotechnol_28_541 PubMedSearch: Hou 2012 World.J.Microbiol.Biotechnol 28 541 PubMedID: 22806849 Abstract A plant-esterase extracted from wheat flour and purified with a PEG1000/NaH(2)PO(4) aqueous two-phase system was characterized for its catalytic characteristics. The optimal condition for plant-esterase to catalyze 1-naphthyl acetate was at 30 degrees C, pH 6.5. It kept stability at 20 degrees C during 120 min and at pH 5.5 during 60 h. The effects of metal ions, chemical modification reagents and pesticides on plant-esterase activity were investigated. It was found that Ba(2+) and Pb(2+) at concentrations of 20 mM significantly inhibited the activity of plant-esterase while Mg(2+), Ca(2+) and Fe(2+) at the same concentration enhanced the enzyme activity. Chemical modification reagents significantly influenced the activity of plant-esterase. Particularly, PMSF (4.5 mM) and N-bromosuccinimide (11 mM) inhibited by 5.40-19.87% of the enzyme activity. It is implied that serine and tryptophan are related to the enzyme activity. Plant-esterase were displayed concentration-dependent inhibition by dichlorvos, carbofuran and carbendazim (IC50 = 0.31-63.12 ppm). All these results indicated that catalytic efficiency of plant-esterase strongly depends on reaction conditions, activity effectors and amino acid residues at the active site. It makes meaningful guidance on further design of sensing material in monitoring pesticides. Title: Protective effects of nizofenone administration on the cognitive impairments induced by chronic restraint stress in mice Liu Y, Zhuang X, Gou L, Ling X, Tian X, Liu L, Zheng Y, Zhang L, Yin X Ref: Pharmacol Biochem Behav, 103:474, 2012 : PubMed ESTHER: Liu_2012_Pharmacol.Biochem.Behav_103_474 PubMedSearch: Liu 2012 Pharmacol.Biochem.Behav 103 474 PubMedID: 23026061 Abstract The present study was aimed to investigate the effects of nizofenone administration on the chronic restraint stress-induced cognitive impairments in mice. Adult male mice were randomized into five groups: control group, nizofenone control group, chronic restraint stress group, and nizofenone treatment groups (3.0mg/kg and 9.0mg/kg). The changes of cognitive performances were examined by Morris water maze (MWM), open field and step-through tests. Our results showed that the cognitive performances in CRS group were markedly deteriorated, accompanied by noticeable alterations in oxidative parameters, acetylcholinesterase activity and catecholamines levels in the hippocampus and the prefrontal cortex. These changes could be reversed by nizofenone treatment. Moreover, CRS group showed higher corticosterone levels and lower catecholamines levels in the serum, which were reversed in the nizofenone treatment groups. Collectively, the present results suggested the potential of nizofenone in attenuating the CRS-induced cognitive impairments. Title: Intranasal administration of TAT-haFGF(14-154) attenuates disease progression in a mouse model of Alzheimer's disease Lou G, Zhang Q, Xiao F, Xiang Q, Su Z, Zhang L, Yang P, Yang Y, Zheng Q, Huang Y Ref: Neuroscience, 223:225, 2012 : PubMed ESTHER: Lou_2012_Neurosci_223_225 PubMedSearch: Lou 2012 Neurosci 223 225 PubMedID: 22885230 Abstract Human acidic fibroblast growth factor (haFGF), a neurotrophin-like growth factor in the brain, plays important roles in the development, differentiation and regeneration of brain neurons, which makes it potential to treat Alzheimer's disease (AD). In this study, haFGF(14-154) and TAT-haFGF(14-154) (haFGF(14-154) fused with the cell-penetrating peptide transactivator of transcription protein transduction domain (TAT-PTD)) were intranasally administrated for 5 weeks to investigate the effects on senescence-accelerated mouse prone-8 (SAMP8) mice (a mouse model of AD). Results showed that TAT-PTD could increase the concentration of haFGF in the brain significantly, and TAT-haFGF(14-154) was more effective than haFGF(14-154) in the same dosage (300 ug/kg). Importantly, TAT-haFGF(14-154) improved the learning and memory abilities of SAMP8 mice in the behavioral test, and promoted the function of cholinergic system by measuring the relevant biomarkers (acetylcholine (ACh) level, acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities). TAT-haFGF(14-154) also significantly reduced beta-amyloid protein(1-42) (Abeta(1-42)) deposits as well as the levels of Abeta soluble forms in the mice brains and prevented the neurons from apoptosis. Besides, the oxidative stress impairment in the brain and serum was also ameliorated. The results suggest that TAT-haFGF(14-154) could attenuate the disease progression of SAMP8 AD mice, and the mechanism is related to the regulation of neurons microenvironment including neurotransmitters, Abeta pathology and oxidative stress. Title: Repeated polyploidization of Gossypium genomes and the evolution of spinnable cotton fibres Paterson AH, Wendel JF, Gundlach H, Guo H, Jenkins J, Jin D, Llewellyn D, Showmaker KC, Shu S and Schmutz J <64 more author(s)> Paterson AH, Wendel JF, Gundlach H, Guo H, Jenkins J, Jin D, Llewellyn D, Showmaker KC, Shu S, Udall J, Yoo MJ, Byers R, Chen W, Doron-Faigenboim A, Duke MV, Gong L, Grimwood J, Grover C, Grupp K, Hu G, Lee TH, Li J, Lin L, Liu T, Marler BS, Page JT, Roberts AW, Romanel E, Sanders WS, Szadkowski E, Tan X, Tang H, Xu C, Wang J, Wang Z, Zhang D, Zhang L, Ashrafi H, Bedon F, Bowers JE, Brubaker CL, Chee PW, Das S, Gingle AR, Haigler CH, Harker D, Hoffmann LV, Hovav R, Jones DC, Lemke C, Mansoor S, ur Rahman M, Rainville LN, Rambani A, Reddy UK, Rong JK, Saranga Y, Scheffler BE, Scheffler JA, Stelly DM, Triplett BA, Van Deynze A, Vaslin MF, Waghmare VN, Walford SA, Wright RJ, Zaki EA, Zhang T, Dennis ES, Mayer KF, Peterson DG, Rokhsar DS, Wang X, Schmutz J (- 64) Ref: Nature, 492:423, 2012 : PubMed ESTHER: Paterson_2012_Nature_492_423 PubMedSearch: Paterson 2012 Nature 492 423 PubMedID: 23257886 Gene_locus related to this paper: gosra-a0a0d2qg22, gosra-a0a0d2w3z1, gosra-a0a0d2uuz7, gosra-a0a0d2rxs2, gosra-a0a0d2sdk0, gosra-a0a0d2tng2, gosra-a0a0d2twz7, gosra-a0a0d2vdc5, gosra-a0a0d2vj24, gosra-a0a0d2sr31, goshi-a0a1u8knd1, goshi-a0a1u8nhw9, goshi-a0a1u8kis4, gosra-a0a0d2pul0, gosra-a0a0d2p3f2, gosra-a0a0d2ril5, gosra-a0a0d2s7d5, gosra-a0a0d2t9b3, gosra-a0a0d2tw88, gosra-a0a0d2umz5, gosra-a0a0d2pzd7 Abstract Polyploidy often confers emergent properties, such as the higher fibre productivity and quality of tetraploid cottons than diploid cottons bred for the same environments. Here we show that an abrupt five- to sixfold ploidy increase approximately 60 million years (Myr) ago, and allopolyploidy reuniting divergent Gossypium genomes approximately 1-2 Myr ago, conferred about 30-36-fold duplication of ancestral angiosperm (flowering plant) genes in elite cottons (Gossypium hirsutum and Gossypium barbadense), genetic complexity equalled only by Brassica among sequenced angiosperms. Nascent fibre evolution, before allopolyploidy, is elucidated by comparison of spinnable-fibred Gossypium herbaceum A and non-spinnable Gossypium longicalyx F genomes to one another and the outgroup D genome of non-spinnable Gossypium raimondii. The sequence of a G. hirsutum A(t)D(t) (in which 't' indicates tetraploid) cultivar reveals many non-reciprocal DNA exchanges between subgenomes that may have contributed to phenotypic innovation and/or other emergent properties such as ecological adaptation by polyploids. Most DNA-level novelty in G. hirsutum recombines alleles from the D-genome progenitor native to its New World habitat and the Old World A-genome progenitor in which spinnable fibre evolved. Coordinated expression changes in proximal groups of functionally distinct genes, including a nuclear mitochondrial DNA block, may account for clusters of cotton-fibre quantitative trait loci affecting diverse traits. Opportunities abound for dissecting emergent properties of other polyploids, particularly angiosperms, by comparison to diploid progenitors and outgroups. Title: Refinement of structural leads for centrally acting oxime reactivators of phosphylated cholinesterases Radic Z, Sit RK, Kovarik Z, Berend S, Garcia E, Zhang L, Amitai G, Green C, Radic B and Taylor P <2 more author(s)> Radic Z, Sit RK, Kovarik Z, Berend S, Garcia E, Zhang L, Amitai G, Green C, Radic B, Fokin VV, Sharpless KB, Taylor P (- 2) Ref: Journal of Biological Chemistry, 287:11798, 2012 : PubMed ESTHER: Radic_2012_J.Biol.Chem_287_11798 PubMedSearch: Radic 2012 J.Biol.Chem 287 11798 PubMedID: 22343626 Abstract We present a systematic structural optimization of uncharged but ionizable N-substituted 2-hydroxyiminoacetamido alkylamine reactivators of phosphylated human acetylcholinesterase (hAChE) intended to catalyze the hydrolysis of organophosphate (OP)-inhibited hAChE in the CNS. Starting with the initial lead oxime RS41A identified in our earlier study and extending to the azepine analog RS194B, reactivation rates for OP-hAChE conjugates formed by sarin, cyclosarin, VX, paraoxon, and tabun are enhanced severalfold in vitro. To analyze the mechanism of intrinsic reactivation of the OP-AChE conjugate and penetration of the blood-brain barrier, the pH dependence of the oxime and amine ionizing groups of the compounds and their nucleophilic potential were examined by UV-visible spectroscopy, (1)H NMR, and oximolysis rates for acetylthiocholine and phosphoester hydrolysis. Oximolysis rates were compared in solution and on AChE conjugates and analyzed in terms of the ionization states for reactivation of the OP-conjugated AChE. In addition, toxicity and pharmacokinetic studies in mice show significantly improved CNS penetration and retention for RS194B when compared with RS41A. The enhanced intrinsic reactivity against the OP-AChE target combined with favorable pharmacokinetic properties resulted in great improvement of antidotal properties of RS194B compared with RS41A and the standard peripherally active oxime, 2-pyridinealdoxime methiodide. Improvement was particularly noticeable when pretreatment of mice with RS194B before OP exposure was combined with RS194B reactivation therapy after the OP insult. Title: Effect of bis(7)-tacrine on cognition in rats with chronic cerebral ischemia Shu XJ, Liu W, Zhang L, Yang R, Yi HL, Li CL, Ye YJ, Ai YX Ref: Neuroscience Letters, 512:103, 2012 : PubMed ESTHER: Shu_2012_Neurosci.Lett_512_103 PubMedSearch: Shu 2012 Neurosci.Lett 512 103 PubMedID: 22330749 Inhibitor(s) related to this paper: Bis7-tacrine Abstract Bis(7)-tacrine (B7T), a novel dimeric acetyl cholinesterase (AChE) inhibitor, has multiple neuroprotective activities against neuronal damage. However, its therapeutic effects in chronic cerebral ischemia remain unknown. In the present study, adult male Sprague-Dawley rats were subjected with permanent ligation of the bilateral common carotid arteries to investigate the roles of B7T on cognitive function, neuronal apoptosis and neurogenesis in the hippocampus. Results from spatial navigation test showed that chronic cerebral ischemia impaired spatial learning, B7T treatment shorten escape latency of ischemia rats as compared with saline-treated rats. Probe trial test indicated that spatial memory deficit of chronic cerebral ischemic animals was reversed by B7T treatment. Immunohistochemical results showed that B7T reduced neuronal apoptosis in the hippocampal CA1 region as compared with ischemia rats, and B7T treatment increased neurogenesis in the hippocampus. These findings suggest that B7T may exert its neuroprotective effects by inhibiting apoptosis and promoting neurogenesis in 2VO rats. Title: Complete genome sequence of Amycolatopsis mediterranei S699 based on de novo assembly via a combinatorial sequencing strategy Tang B, Zhao W, Zheng H, Zhuo Y, Zhang L, Zhao GP Ref: Journal of Bacteriology, 194:5699, 2012 : PubMed ESTHER: Tang_2012_J.Bacteriol_194_5699 PubMedSearch: Tang 2012 J.Bacteriol 194 5699 PubMedID: 23012281 Gene_locus related to this paper: amymu-d8hpp2, amyms-g0fkj6 Abstract The genome of Amycolatopsis mediterranei S699 was resequenced and assembled de novo. By comparing the sequences of S699 previously released and that of A. mediterranei U32, about 10 kb of major indels was found to differ between the two S699 genomes, and the differences are likely attributable to their different assembly strategies. Title: Protection of salvianolic acid A on rat brain from ischemic damage via soluble epoxide hydrolase inhibition Wang SB, Pang XB, Zhao Y, Wang YH, Zhang L, Yang XY, Fang LH, Du GH Ref: J Asian Nat Prod Res, 14:1084, 2012 : PubMed ESTHER: Wang_2012_J.Asian.Nat.Prod.Res_14_1084 PubMedSearch: Wang 2012 J.Asian.Nat.Prod.Res 14 1084 PubMedID: 23106500 Abstract Epoxyeicosatrienoic acids (EETs) and their regulating enzyme soluble epoxide hydrolase (sEH) have been associated with ischemic stroke. Salvianolic acid A (SAA) is proved to display potent cerebroprotection. However, little information is available about the link between them. This study aimed to investigate whether SAA exhibits its protective effects in rats subjected to middle cerebral artery occlusion (MCAO) through sEH and EETs. The results showed that SAA treatment ameliorated neurological deficits and reduced infarct volume. Notably, the beneficial effects of SAA were attenuated by co-administration of (14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE)), a putative selective EETs antagonist. Furthermore, SAA increased the 14,15-EET levels in the blood and brain of sham and MCAO rats. Assay for hydrolase activity showed that 1 and 3 mg/kg of SAA significantly diminished brain sEH activity of MCAO rats. A fluorescent assay in vitro indicated that SAA could inhibit recombinant human sEH activity in a concentration-dependent manner (IC(50) = 1.62 mumol/l). Immunohistochemical analysis showed that SAA at the doses of 1 and 3 mg/kg significantly decreased sEH protein expression in hippocampus CA1 region of MCAO rats. In conclusion, cerebral protection of SAA is mediated, at least in part, via inhibiting sEH to increase EETs levels. Title: [Screening of endophytic fungi from Huperzia serrata for acetylcholinesterase inhibitory activity and its taxonomic identification] Wang LL, Lv HF, Zhang L, Hua HX, Wang JH, Hu ZB, Li WK Ref: Zhongguo Zhong Yao Za Zhi, 37:3701, 2012 : PubMed ESTHER: Wang_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_3701 PubMedSearch: Wang 2012 Zhongguo.Zhong.Yao.Za.Zhi 37 3701 PubMedID: 23627163 Abstract OBJECTIVE: To screen out fungus strains with acetylcholinesterase inhibitory activity from Huperzia serrata. METHOD: Endophytic fungi fermentation products from 59 H. serrata strains were stained with acetylcholinesterase hydrolyzed alpha-naphthaleneacetic ethyl ester and fast blue B salt, and screened for acetylcholinesterase inhibitory activity with thin-layer chromatography-bioautography. Target strains were classified and identified through the sequence analysis on 18s rDNA and 5.8s rDNA combined with morphological characteristics. RESULT: Fungus strain LQ2F01 from H. serrata showed positive color reaction in the screening for acetylcholinesterase inhibitory activity. The sequence analysis on 18s rDNA and 5.8s rDNA combined with morphological characteristics showed the strain LQ2F01 belonged to Acremonium. CONCLUSION: Endophytic Fungi LQ2F01 from H. serrata shows identical acetylcholinesterase inhibitory activity with the host plant, which is of great significance to the development of natural medicines and the studies on the relationship between the endophytic gungi and the host plant. Title: [Research on quality standards of herbs of Peganum harmala] Wen FF, Zheng LM, Li XJ, Li Y, Zhang L, Cheng XM, Wang CH, Wang ZT Ref: Zhongguo Zhong Yao Za Zhi, 37:2971, 2012 : PubMed ESTHER: Wen_2012_Zhongguo.Zhong.Yao.Za.Zhi_37_2971 PubMedSearch: Wen 2012 Zhongguo.Zhong.Yao.Za.Zhi 37 2971 PubMedID: 23270245 Abstract OBJECTIVE: To establish the quality standards of the herbs of Peganum harmala. METHOD: According to the Chinese Pharmacopoeia (2010 version, volume 1) and its appendix method, the water, total ash, acid insoluble ash, water-soluble extractives, and heavy metal were analyzed for herbs of P. harmala. TLC method was used to separate harmaline, harmine and vasicine from the herb samples by mixture of ethyl acetate-methanol-ammonia (10: 1.5: 0.5) as a developing solvent on high performance silica gel precoated plate (HSGF254) and to identify them inspected under UV 366 nm, visualized by spraying with both Dragendorff reagent, and by bioautographic assay. In the HPLC method, vasicine was separated on a C18 (4.6 mm x 250 mm, 5 microm) column with metnanol-0.1% trifluoroacetic acid (15:85) as the mobile phase and detected at at 280 nm. RESULT: In the TLC procedures, 254 nm fluorescent and bioautographic assay for the detection of acetylcholinesterase inhibitor can be used for the qualitative identification of the active ingredients. For the HPLC quantitation method, the calibration curve of vasicine displayed ideal linearity over the range of 0.7923-792.3 mg x L(-1) with the regression equation of Y = 18,227X - 24.879 (r = 0.9999). The average recovery of vasicine was 101.6% with a RSD of 1.9%. The RSD values of intra-day and inter-day precision were less than 2%. The content of vasicine in 10 batches of herbs of P. harmala fluctuates between 0.23% and 1.47%. CONCLUSION: The results indicated that the limit of vasicine was not lower than 0.6%, and the water, total ash, acid insoluble ash, and water-soluble extractives were not more than 10.0%, 20.0%, 1.7%, and 30.0%, respectively. The heavy metal of plumbum, cadmium, arsenic, mercury, and copper were not more than 5, 3, 2, 2, and 20 mg x kg(-1), respectively. The qualitative and quantitative method established was suitable for the quality evaluation and assessment of herbs of P. harmala. Title: Several genetic polymorphisms interact with overweight/obesity to influence serum lipid levels Yin RX, Wu DF, Miao L, Aung LH, Cao XL, Yan TT, Long XJ, Liu WY, Zhang L, Li M Ref: Cardiovasc Diabetol, 11:123, 2012 : PubMed ESTHER: Yin_2012_Cardiovasc.Diabetol_11_123 PubMedSearch: Yin 2012 Cardiovasc.Diabetol 11 123 PubMedID: 23039238 Abstract BACKGROUND: Information about the interactions of single nucleotide polymorphisms (SNPs) and overweight/obesity on serum lipid profiles is still scarce. The present study was undertaken to detect ten SNPs and their interactions with overweight/obesity on serum lipid levels. Title: The oyster genome reveals stress adaptation and complexity of shell formation Zhang G, Fang X, Guo X, Li L, Luo R, Xu F, Yang P, Zhang L, Wang X and Yin Y <66 more author(s)> Zhang G, Fang X, Guo X, Li L, Luo R, Xu F, Yang P, Zhang L, Wang X, Qi H, Xiong Z, Que H, Xie Y, Holland PW, Paps J, Zhu Y, Wu F, Chen Y, Wang J, Peng C, Meng J, Yang L, Liu J, Wen B, Zhang N, Huang Z, Zhu Q, Feng Y, Mount A, Hedgecock D, Xu Z, Liu Y, Domazet-Loso T, Du Y, Sun X, Zhang S, Liu B, Cheng P, Jiang X, Li J, Fan D, Wang W, Fu W, Wang T, Wang B, Zhang J, Peng Z, Li Y, Li N, Chen M, He Y, Tan F, Song X, Zheng Q, Huang R, Yang H, Du X, Chen L, Yang M, Gaffney PM, Wang S, Luo L, She Z, Ming Y, Huang W, Huang B, Zhang Y, Qu T, Ni P, Miao G, Wang Q, Steinberg CE, Wang H, Qian L, Liu X, Yin Y (- 66) Ref: Nature, 490:49, 2012 : PubMed ESTHER: Zhang_2012_Nature_490_49 PubMedSearch: Zhang 2012 Nature 490 49 PubMedID: 22992520 Gene_locus related to this paper: cragi-k1qzk7, cragi-k1rad0, cragi-k1p6v9, cragi-k1pa46, cragi-k1pga2, cragi-k1pp63, cragi-k1pwa8, cragi-k1q0b1.1, cragi-k1q0b1.2, cragi-k1q1h2, cragi-k1q2z6, cragi-k1qaj8, cragi-k1qaw5, cragi-k1qhl5, cragi-k1qly1, cragi-k1qqb1.1, cragi-k1qqb1.2, cragi-k1qs61, cragi-k1qs99, cragi-k1qwl6, cragi-k1r068, cragi-k1r0n3.1, cragi-k1r0n3.2, cragi-k1r0r4, cragi-k1r1i9, cragi-k1r8q9, cragi-k1rgi1, cragi-k1rig4, cragi-k1s0a7.1, cragi-k1s0a7.2, cragi-k1s0a7.3, cragi-k1q6q0, cragi-k1rru1, cragi-k1qfi4, cragi-k1qvm5, cragi-k1qq58, cragi-k1qdc0, cragi-k1r754, cragi-k1pje5, cragi-k1qca6, cragi-k1qdt5, cragi-k1qkz7, cragi-k1rgd2, cragi-k1puh6, cragi-k1raz4, cragi-k1qqj4, cragi-k1rbs1 Abstract The Pacific oyster Crassostrea gigas belongs to one of the most species-rich but genomically poorly explored phyla, the Mollusca. Here we report the sequencing and assembly of the oyster genome using short reads and a fosmid-pooling strategy, along with transcriptomes of development and stress response and the proteome of the shell. The oyster genome is highly polymorphic and rich in repetitive sequences, with some transposable elements still actively shaping variation. Transcriptome studies reveal an extensive set of genes responding to environmental stress. The expansion of genes coding for heat shock protein 70 and inhibitors of apoptosis is probably central to the oyster's adaptation to sessile life in the highly stressful intertidal zone. Our analyses also show that shell formation in molluscs is more complex than currently understood and involves extensive participation of cells and their exosomes. The oyster genome sequence fills a void in our understanding of the Lophotrochozoa. Title: Genome sequence of Staphylococcus epidermidis strain AU12-03, isolated from an intravascular catheter Zhang L, Morrison M, P OC, Evans P, Rickard CM Ref: Journal of Bacteriology, 194:6639, 2012 : PubMed ESTHER: Zhang_2012_J.Bacteriol_194_6639 PubMedSearch: Zhang 2012 J.Bacteriol 194 6639 PubMedID: 23144393 Gene_locus related to this paper: staep-SERP2035 Abstract In recent years, Staphylococcus epidermidis has become a major nosocomial pathogen and the most common cause of intravascular catheter-related bacteremia, which can increase morbidity and mortality and significantly affect patient recovery. We report a draft genome sequence of Staphylococcus epidermidis AU12-03, isolated from an intravascular catheter tip. Title: Withdrawal from chronic nicotine exposure alters dopamine signaling dynamics in the nucleus accumbens Zhang L, Dong Y, Doyon WM, Dani JA Ref: Biological Psychiatry, 71:184, 2012 : PubMed ESTHER: Zhang_2012_Biol.Psychiatry_71_184 PubMedSearch: Zhang 2012 Biol.Psychiatry 71 184 PubMedID: 21872847 Abstract BACKGROUND: Unaided attempts to quit smoking commonly fail during the first 2 weeks of the nicotine withdrawal syndrome. Alterations in dopamine (DA) signaling correlate with withdrawal from chronic nicotine exposure, but those changes have not been well-characterized. Title: Biosensor based on Prussian blue nanocubes/reduced graphene oxide nanocomposite for detection of organophosphorus pesticides Zhang L, Zhang A, Du D, Lin Y Ref: Nanoscale, 4:4674, 2012 : PubMed ESTHER: Zhang_2012_Nanoscale_4_4674 PubMedSearch: Zhang 2012 Nanoscale 4 4674 PubMedID: 22732870 Abstract We demonstrate a facile procedure to efficiently prepare Prussian blue nanocubes/reduced graphene oxide (PBNCs/rGO) nanocomposite by directly mixing Fe(3+) and [Fe(CN)(6)]((3)-) in the presence of GO in polyethyleneimine aqueous solution, resulting in a novel acetylcholinesterase (AChE) biosensor for detection of organophosphorus pesticides (OPs). The obtained nanocomposite was characterized by X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM) and energy-dispersive X-ray (EDX) microanalysis. It was clearly observed that the nanosheet has been decorated with cubic PB nanoparticles and nearly all the nanoparticles are distributed uniformly only on the surface of the reduced GO. No isolated PB nanoparticles were observed, indicating the strong interaction between PB nanocubes and the reduced GO and the formation of PBNCs/rGO nanocomposite. The obtained PBNCs/rGO based AChE biosensor make the peak potential shift negatively to 220 mV. The over-potential decreases approximately 460 mV compared to that on a bare electrode, suggesting that PBNCs/rGO has a high electrocatalytic activity towards the oxidation of thiocholine. The AChE biosensor shows rapid response and high sensitivity for detection of monocrotophos with a linear range from 1.0 to 600 ng mL(-1) and a detection limit of 0.1 ng mL(-1). These results suggest that the PBNCs/rGO hybrids nanocomposite exhibited high electrocatalytic activity towards the oxidation of thiocholine, which lead to the sensitive detection of OP pesticides. Title: Sequencing the genome of Marssonina brunnea reveals fungus-poplar co-evolution Zhu S, Cao YZ, Jiang C, Tan BY, Wang Z, Feng S, Zhang L, Su XH, Brejova B and Zhou Y <6 more author(s)> Zhu S, Cao YZ, Jiang C, Tan BY, Wang Z, Feng S, Zhang L, Su XH, Brejova B, Vinar T, Xu M, Wang MX, Zhang SG, Huang MR, Wu R, Zhou Y (- 6) Ref: BMC Genomics, 13:382, 2012 : PubMed ESTHER: Zhu_2012_BMC.Genomics_13_382 PubMedSearch: Zhu 2012 BMC.Genomics 13 382 PubMedID: 22876864 Gene_locus related to this paper: marbu-k1wj37, marbu-k1xt94, marbu-k1wdc0, marbu-k1wht2, marbu-k1wj82, marbu-k1wkk6, marbu-k1wnk8, marbu-k1wpc4, marbu-k1wrg1, marbu-k1wsf4, marbu-k1wtx1, marbu-k1x087, marbu-k1x383, marbu-k1x3g3, marbu-k1x464, marbu-k1x8c9, marbu-k1xi08, marbu-k1xzh8, marbu-k1y283, marbu-k1x918, marbu-k1wzc0, marbu-k1xu92, marbu-k1xws5 Abstract BACKGROUND: The fungus Marssonina brunnea is a causal pathogen of Marssonina leaf spot that devastates poplar plantations by defoliating susceptible trees before normal fall leaf drop. Title: Assisted inhibition effect of acetylcholinesterase with n-octylphosphonic acid and application in high sensitive detection of organophosphorous pesticides by matrix-assisted laser desorption/ionization Fourier transform mass spectrometry Cai T, Zhang L, Wang H, Zhang J, Guo Y Ref: Anal Chim Acta, 706:291, 2011 : PubMed ESTHER: Cai_2011_Anal.Chim.Acta_706_291 PubMedSearch: Cai 2011 Anal.Chim.Acta 706 291 PubMedID: 22023864 Abstract A simple and practical approach to improve the sensitivity of acetylcholinesterase (AChE)-inhibited method has been developed for monitoring organophosphorous (OP) pesticide residues. In this work, matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS) was used to detect AChE activity. Due to its good salt-tolerance and low sample consumption, MALDI-FTMS facilitates rapid and high-throughput screening of OP pesticides. Here we describe a new method to obtain low detection limits via employing external reagents. Among candidate compounds, n-octylphosphonic acid (n-Octyl-PA) displays assistant effect to enhance AChE inhibition by OP pesticides. In presence of n-Octyl-PA, the percentages of AChE inhibition still kept correlation with OP pesticide concentrations. The detection limits were improved significantly even by 10(2)-10(3) folds in comparison with conventional enzyme-inhibited methods. Different detection limits of OP pesticides with different toxicities were as low as 0.005 mug L(-1) for high toxic pesticides and 0.05 mug L(-1) for low toxic pesticides. Besides, the reliability of results from this method to analyze cowpea samples had been demonstrated by liquid-chromatography tandem mass spectrometry (LC-MS/MS). The application of this commercial available assistant agent shows great promise to detect OP compounds in complicated biological matrix and broadens the mind for high sensitivity detection of OP pesticide residues in agricultural products. Title: Oxime-assisted acetylcholinesterase catalytic scavengers of organophosphates that resist aging Cochran R, Kalisiak J, Kucukkilinc TT, Radic Z, Garcia E, Zhang L, Ho KY, Amitai G, Kovarik Z and Taylor P <2 more author(s)> Cochran R, Kalisiak J, Kucukkilinc TT, Radic Z, Garcia E, Zhang L, Ho KY, Amitai G, Kovarik Z, Fokin VV, Sharpless KB, Taylor P (- 2) Ref: Journal of Biological Chemistry, 286:29718, 2011 : PubMed ESTHER: Cochran_2011_J.Biol.Chem_286_29718 PubMedSearch: Cochran 2011 J.Biol.Chem 286 29718 PubMedID: 21730071 Abstract The cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase, are primary targets of organophosphates (OPs). Exposure to OPs can lead to serious cardiovascular complications, respiratory compromise, and death. Current therapy to combat OP poisoning involves an oxime reactivator (2-PAM, obidoxime, TMB4, or HI-6) combined with atropine and on occasion an anticonvulsant. Butyrylcholinesterase, administered in the plasma compartment as a bio-scavenger, has also shown efficacy but is limited by its strict stoichiometric scavenging, slow reactivation, and a propensity for aging. Here, we characterize 10 human (h) AChE mutants that, when coupled with an oxime, give rise to catalytic reactivation and aging resistance of the soman conjugate. With the most efficient human AChE mutant Y337A/F338A, we show enhanced reactivation rates for several OP-hAChE conjugates compared with wild-type hAChE when reactivated with HI-6 (1-(2'-hydroxyiminomethyl-1'-pyridinium)-3-(4'-carbamoyl-1-pyridinium)). In addition, we interrogated an 840-member novel oxime library for reactivation of Y337A/F338A hAChE-OP conjugates to delineate the most efficient oxime-mutant enzyme pairs for catalytic bio-scavenging. Combining the increased accessibility of the Y337A mutation to oximes within the space-impacted active center gorge with the aging resistance of the F338A mutation provides increased substrate diversity in scavenging potential for aging-prone alkyl phosphate inhibitors. Title: Molecular cloning and characterization of a new cold-active esterase from a deep-sea metagenomic library Fu C, Hu Y, Xie F, Guo H, Ashforth EJ, Polyak SW, Zhu B, Zhang L Ref: Applied Microbiology & Biotechnology, 90:961, 2011 : PubMed ESTHER: Fu_2011_Appl.Microbiol.Biotechnol_90_961 PubMedSearch: Fu 2011 Appl.Microbiol.Biotechnol 90 961 PubMedID: 21336688 Gene_locus related to this paper: 9bact-d2kla1 Abstract A clone which conferred lipolytic activity at low temperature was identified from a fosmid library constructed from a South China Sea marine sediment sample. The gene responsible, estF, consisted of 1,080 bp that encoded 359 amino acid residues, with a typical N-terminal signal peptide of 28 amino acid residues. A phylogenetic analysis of amino acid sequence with other lipolytic enzymes revealed that EstF and seven closely related putative lipolytic enzymes comprised a unique clade in the phylogenetic tree. Moreover, these hypothetic esterases showed unique conservative sites in the amino acid sequence. The recombinant EstF was overexpressed and purified, and its biochemical properties were partially characterized. The optimal substrate for EstF to hydrolyze among a panel of p-nitrophenyl esters (C2 to C16) was p-nitrophenyl butyrate (C4), with a K(m) of 0.46 mM. Activity quickly decreased with substrates containing an acyl chain length longer than 10 carbons. We found that EstF was active in the temperature range of 0-60 degrees C, showed the best activity at 50 degrees C, but was unstable at 60 degrees C. It exhibited a high level of activity in the pH range of 7.0-10.0 showing the highest activity at pH 9.0. Title: Identification and characterization of a novel non-coding RNA involved in sperm maturation Ni MJ, Hu ZH, Liu Q, Liu MF, Lu MH, Zhang JS, Zhang L, Zhang YL Ref: PLoS ONE, 6:e26053, 2011 : PubMed ESTHER: Ni_2011_PLoS.One_6_e26053 PubMedSearch: Ni 2011 PLoS.One 6 e26053 PubMedID: 22022505 Abstract A long and ever-expanding roster of small ( approximately 20-30 nucleotides) RNAs has emerged during the last decade, and most can be subsumed under the three main headings of microRNAs (miRNAs), Piwi-interacting RNAs (piRNAs), and short interfering RNAs (siRNAs). Among the three categories, miRNAs is the most quickly expanded group. The most recent number of identified miRNAs is 16,772 (Sanger miRbase, April 2011). However, there are insufficient publications on their primary forms, and no tissue-specific small RNAs precursors have been reported in the epididymis. Here, we report the identification in rats of an epididymis-specific, chimeric, noncoding RNA that is spliced from two different chromosomes (chromosomes 5 and 19), which we named HongrES2. HongrES2 is a 1.6 kb mRNA-like precursor that gives rise to a new microRNA-like small RNA (mil-HongrES2) in rat epididymis. The generation of mil-HongrES2 is stimulated during epididymitis. An epididymis-specific carboxylesterase named CES7 had 100% cDNA sequence homology at the 3'end with HongrES2 and its protein product could be downregulated by HongrES2 via mil-HongrES2. This was confirmed in vivo by initiating mil-HongrES2 over-expression in rats and observing an effect on sperm capacitation. Title: New structural scaffolds for centrally acting oxime reactivators of phosphylated cholinesterases Sit RK, Radic Z, Gerardi V, Zhang L, Garcia E, Katalinic M, Amitai G, Kovarik Z, Fokin VV and Taylor P <1 more author(s)> Sit RK, Radic Z, Gerardi V, Zhang L, Garcia E, Katalinic M, Amitai G, Kovarik Z, Fokin VV, Sharpless KB, Taylor P (- 1) Ref: Journal of Biological Chemistry, 286:19422, 2011 : PubMed ESTHER: Sit_2011_J.Biol.Chem_286_19422 PubMedSearch: Sit 2011 J.Biol.Chem 286 19422 PubMedID: 21464125 Abstract We describe here the synthesis and activity of a new series of oxime reactivators of cholinesterases (ChEs) that contain tertiary amine or imidazole protonatable functional groups. Equilibration between the neutral and protonated species at physiological pH enables the reactivators to cross the blood-brain barrier and distribute in the CNS aqueous space as dictated by interstitial and cellular pH values. Our structure-activity analysis of 134 novel compounds considers primarily imidazole aldoximes and N-substituted 2-hydroxyiminoacetamides. Reactivation capacities of novel oximes are rank ordered by their relative reactivation rate constants at 0.67 mm compared with 2-pyridinealdoxime methiodide for reactivation of four organophosphate (sarin, cyclosarin, VX, and paraoxon) conjugates of human acetylcholinesterase (hAChE). Rank order of the rates differs for reactivation of human butyrylcholinesterase (hBChE) conjugates. The 10 best reactivating oximes, predominantly hydroxyimino acetamide derivatives (for hAChE) and imidazole-containing aldoximes (for hBChE) also exhibited reasonable activity in the reactivation of tabun conjugates. Reactivation kinetics of the lead hydroxyimino acetamide reactivator of hAChE, when analyzed in terms of apparent affinity (1/K(ox)) and maximum reactivation rate (k(2)), is superior to the reference uncharged reactivators monoisonitrosoacetone and 2,3-butanedione monoxime and shows potential for further refinement. The disparate pH dependences for reactivation of ChE and the general base-catalyzed oximolysis of acetylthiocholine reveal that distinct reactivator ionization states are involved in the reactivation of ChE conjugates and in conferring nucleophilic reactivity of the oxime group. Title: Ultra-sensitive biosensor based on mesocellular silica foam for organophosphorous pesticide detection Wu S, Zhang L, Qi L, Tao S, Lan X, Liu Z, Meng C Ref: Biosensors & Bioelectronics, 26:2864, 2011 : PubMed ESTHER: Wu_2011_Biosens.Bioelectron_26_2864 PubMedSearch: Wu 2011 Biosens.Bioelectron 26 2864 PubMedID: 21185711 Abstract A sensitive amperometric acetylcholinesterase (AChE) biosensor was fabricated based on mesocellular silica foam (MSF), which functioned as both an enzyme immobilization matrix and a solid phase extraction (SPE) material for the preconcentration of target molecules. The hydrophilic interface, the good mechanical/chemical stability, and the suitable pore dimension of MSF provided the entrapped AChE a good environment to well maintain its bioactivity at basic condition. The AChE immobilized in MSF showed improved catalytic ability for the hydrolysis of acetylthiocholine, as evidenced by the increasing of the oxidation current of thiocholine, the enzymatic catalytic hydrolysis production of acetylthiocholine. In addition, the MSF with large surface area showed a modest adsorption capacity for monocrotophos, a model organophosphate used in this study, via the hydrogen bond or physical adsorption interaction. The combination of the SPE and the good enzyme immobilization ability in MSF significantly promoted the sensitivity of the biosensor, and the limit of detection has lowered to 0.05 ng/mL. The biosensor exhibited accuracy, good reproducibility, and acceptable stability when used for garlic samples analysis. The strategy may provide a new method to fabricate highly sensitive biosensors for the detection of ultra-trace organophosphorous pesticide infield. Title: Controlled immobilization of acetylcholinesterase on improved hydrophobic gold nanoparticle/Prussian blue modified surface for ultra-trace organophosphate pesticide detection Wu S, Lan X, Zhao W, Li Y, Zhang L, Wang H, Han M, Tao S Ref: Biosensors & Bioelectronics, 27:82, 2011 : PubMed ESTHER: Wu_2011_Biosens.Bioelectron_27_82 PubMedSearch: Wu 2011 Biosens.Bioelectron 27 82 PubMedID: 21752626 Abstract An ultrasensitive amperometric acetylcholinesterase (AChE) biosensor was fabricated by controlled immobilization of AChE on gold nanoparticles/poly(dimethyldiallylammonium chloride) protected Prussian blue (Au-PDDA-PB) nanocomposite modified electrode surface for the detection of organophorous pesticide. The Au-PDDA-PB membrane served as an excellent matrix for the immobilization of enzyme, which not only enhanced electron transfer but also possessed a relatively large surface area. In addition, the surface hydrophilicity of the Au-PDDA-PB nanocomposite was finely controlled in the static water contact angle range of 25.6-78.1 degrees by adjusting the ratio of gold nanoparticles to PDDA-PB. On an optimized hydrophobic surface, the AChE adopts an orientation with both good activity and stability, which has been proven by electrochemical methods. Benefit from the advantages of the Au-PDDA-PB nanocomposite and the good activity and stability of AChE, the biosensor shows significantly improved sensitivity to monocrotophos, a typical highly toxic organophorous pesticide, with wide linear range (1.0-1000 pg/mL and 1.0-10 ng/mL) and an ultra-low detection limit of 0.8 pg/mL. The biosensor exhibits accuracy, good reproducibility and stability. This strategy may therefore provide useful information for the controlled immobilization of protein and the design of highly sensitive biosensors. Title: Complete genome sequences of Mycobacterium tuberculosis strains CCDC5079 and CCDC5080, which belong to the Beijing family Zhang Y, Chen C, Liu J, Deng H, Pan A, Zhang L, Zhao X, Huang M, Lu B and Wan K <3 more author(s)> Zhang Y, Chen C, Liu J, Deng H, Pan A, Zhang L, Zhao X, Huang M, Lu B, Dong H, Du P, Chen W, Wan K (- 3) Ref: Journal of Bacteriology, 193:5591, 2011 : PubMed ESTHER: Zhang_2011_J.Bacteriol_193_5591 PubMedSearch: Zhang 2011 J.Bacteriol 193 5591 PubMedID: 21914894 Gene_locus related to this paper: myctu-cut3, myctu-cutas1, myctu-cutas2, myctu-Rv0160c, myctu-Rv1069c, myctu-RV1215C, myctu-Rv2045c, myctu-RV3452, myctu-RV3724, myctu-Rv3802c, myctu-y0571 Abstract Mycobacterium tuberculosis is one of most prevalent pathogens in the world. Drug-resistant strains of this pathogen caused by the excessive use of antibiotics have long posed serious threats to public health worldwide. A broader picture of drug resistance mechanisms at the genomic level can be obtained only with large-scale comparative genomic methodology. Two closely related Beijing family isolates, one resistant to four first-line drugs (CCDC5180) and one sensitive to them (CCDC5079), were completely sequenced. These sequences will serve as valuable references for further drug resistance site identification studies and could be of great importance for developing drugs targeting these sites. Title: Endocannabinoids generated by Ca2+ or by metabotropic glutamate receptors appear to arise from different pools of diacylglycerol lipase Zhang L, Wang M, Bisogno T, Di Marzo V, Alger BE Ref: PLoS ONE, 6:e16305, 2011 : PubMed ESTHER: Zhang_2011_PLoS.One_6_e16305 PubMedSearch: Zhang 2011 PLoS.One 6 e16305 PubMedID: 21305054 Abstract The identity and subcellular sources of endocannabinoids (eCBs) will shape their ability to affect synaptic transmission and, ultimately, behavior. Recent discoveries support the conclusion that 2-arachidonoyl glycerol, 2-AG, is the major signaling eCB, however, some important issues remain open. 2-AG can be synthesized by a mechanism that is strictly Ca(2+)-dependent, and another that is initiated by G-protein coupled receptors (GPCRs) and facilitated by Ca(2+). An important question is whether or not the 2-AG in these cases is synthesized by the same pool of diacylglycerol lipase alpha (DAGLalpha). Using whole-cell voltage-clamp techniques in CA1 pyramidal cells in acute in vitro rat hippocampal slices, we investigated two mechanistically distinct eCB-mediated responses to address this issue. We now report that pharmacological inhibitors of DGLalpha have quantitatively different effects on eCB-mediated responses triggered by different stimuli, suggesting that functional, and perhaps physical, distinctions among pools of DAGLalpha exist. Title: Contributions of selective knockout studies to understanding cholinesterase disposition and function Camp S, Zhang L, Krejci E, Dobbertin A, Bernard V, Girard E, Duysen EG, Lockridge O, De Jaco A, Taylor P Ref: Chemico-Biological Interactions, 187:72, 2010 : PubMed ESTHER: Camp_2010_Chem.Biol.Interact_187_72 PubMedSearch: Camp 2010 Chem.Biol.Interact 187 72 PubMedID: 20153304 Abstract The complete knockout of the acetylcholinesterase gene (AChE) in the mouse yielded a surprising phenotype that could not have been predicted from deletion of the cholinesterase genes in Drosophila, that of a living, but functionally compromised animal. The phenotype of this animal showed a sufficient compromise in motor function that precluded precise characterization of central and peripheral nervous functional deficits. Since AChE in mammals is encoded by a single gene with alternative splicing, additional understanding of gene expression might be garnered from selected deletions of the alternatively spliced exons. To this end, transgenic strains were generated that deleted exon 5, exon 6, and the combination of exons 5 and 6. Deletion of exon 6 reduces brain AChE by 93% and muscle AChE by 72%. Deletion of exon 5 eliminates AChE from red cells and the platelet surface. These strains, as well as knockout strains that selectively eliminate the AChE anchoring protein subunits PRiMA or ColQ (which bind to sequences specified by exon 6) enabled us to examine the role of the alternatively spliced exons responsible for the tissue disposition and function of the enzyme. In addition, a knockout mouse was made with a deletion in an upstream intron that had been identified in differentiating cultures of muscle cells to control AChE expression. We found that deletion of the intronic regulatory region in the mouse essentially eliminated AChE in muscle and surprisingly from the surface of platelets. The studies generated by these knockout mouse strains have yielded valuable insights into the function and localization of AChE in mammalian systems that cannot be approached in cell culture or in vitro. Title: Multi-platform next-generation sequencing of the domestic turkey (Meleagris gallopavo): genome assembly and analysis Dalloul RA, Long JA, Zimin AV, Aslam L, Beal K, Blomberg Le A, Bouffard P, Burt DW, Crasta O and Reed KM <61 more author(s)> Dalloul RA, Long JA, Zimin AV, Aslam L, Beal K, Blomberg Le A, Bouffard P, Burt DW, Crasta O, Crooijmans RP, Cooper K, Coulombe RA, De S, Delany ME, Dodgson JB, Dong JJ, Evans C, Frederickson KM, Flicek P, Florea L, Folkerts O, Groenen MA, Harkins TT, Herrero J, Hoffmann S, Megens HJ, Jiang A, de Jong P, Kaiser P, Kim H, Kim KW, Kim S, Langenberger D, Lee MK, Lee T, Mane S, Marcais G, Marz M, McElroy AP, Modise T, Nefedov M, Notredame C, Paton IR, Payne WS, Pertea G, Prickett D, Puiu D, Qioa D, Raineri E, Ruffier M, Salzberg SL, Schatz MC, Scheuring C, Schmidt CJ, Schroeder S, Searle SM, Smith EJ, Smith J, Sonstegard TS, Stadler PF, Tafer H, Tu ZJ, Van Tassell CP, Vilella AJ, Williams KP, Yorke JA, Zhang L, Zhang HB, Zhang X, Zhang Y, Reed KM (- 61) Ref: PLoS Biol, 8:, 2010 : PubMed ESTHER: Dalloul_2010_PLoS.Biol_8_E1000475 PubMedSearch: Dalloul 2010 PLoS.Biol 8 E1000475 PubMedID: 20838655 Gene_locus related to this paper: melga-g1mv74, melga-g1myh1, melga-g1n3b6, melga-g1n4i8, melga-g1n8a7, melga-g1nb53, melga-g1ndd8, melga-g1npu5, melga-g3ur65, melga-g3uur6, melga-g1njn8, melga-g1mrp7, melga-g1mzw6, melga-g1n2a7, melga-g1n608, melga-g1n2j6, melga-g1n2k0, melga-g1ncb6, melga-g1nei5, melga-g1n1j3, melga-g1nfd3, melga-g1nna9, melga-h9h0c1, melga-g1nnl1, melga-g1nhb9, melga-g1mtl7, fical-u3jnn0, melga-g1n332, melga-g1mtx9, melga-g1nns1 Abstract A synergistic combination of two next-generation sequencing platforms with a detailed comparative BAC physical contig map provided a cost-effective assembly of the genome sequence of the domestic turkey (Meleagris gallopavo). Heterozygosity of the sequenced source genome allowed discovery of more than 600,000 high quality single nucleotide variants. Despite this heterozygosity, the current genome assembly ( approximately 1.1 Gb) includes 917 Mb of sequence assigned to specific turkey chromosomes. Annotation identified nearly 16,000 genes, with 15,093 recognized as protein coding and 611 as non-coding RNA genes. Comparative analysis of the turkey, chicken, and zebra finch genomes, and comparing avian to mammalian species, supports the characteristic stability of avian genomes and identifies genes unique to the avian lineage. Clear differences are seen in number and variety of genes of the avian immune system where expansions and novel genes are less frequent than examples of gene loss. The turkey genome sequence provides resources to further understand the evolution of vertebrate genomes and genetic variation underlying economically important quantitative traits in poultry. This integrated approach may be a model for providing both gene and chromosome level assemblies of other species with agricultural, ecological, and evolutionary interest. Title: Novel lipolytic genes from the microbial metagenomic library of the South China Sea marine sediment Hu Y, Fu C, Huang Y, Yin Y, Cheng G, Lei F, Lu N, Li J, Ashforth EJ and Zhu B <1 more author(s)> Hu Y, Fu C, Huang Y, Yin Y, Cheng G, Lei F, Lu N, Li J, Ashforth EJ, Zhang L, Zhu B (- 1) Ref: FEMS Microbiol Ecol, 72:228, 2010 : PubMed ESTHER: Hu_2010_FEMS.Microbiol.Ecol_72_228 PubMedSearch: Hu 2010 FEMS.Microbiol.Ecol 72 228 PubMedID: 20337707 Gene_locus related to this paper: 9bact-b8y567, 9bact-b8y568, 9bact-b8y561, 9bact-b8y562, 9bact-b8y566, 9bact-b8y553, 9bact-b8y558, 9bact-b8y563 Abstract Metagenomic cloning is a powerful tool for the discovery of novel genes and biocatalysts from environmental microorganisms. Based on activity screening of a marine sediment microbial metagenomic library, a total of 19 fosmid clones showing lipolytic activity were identified. After subcloning, 15 different lipolytic genes were obtained; their encoded proteins showed 32-68% amino acid identity with proteins in the database. Multiple sequence alignment and phylogenetic tree analysis demonstrated that most of these predicted proteins are new members of known families of bacterial lipolytic enzymes. However, two proteins, FLS18C and FLS18D, could not be assigned to any known family, thus probably representing a novel family of the bacterial lipolytic enzyme. The activity assay results indicated that most of these lipolytic enzymes showed optimum temperature for hydrolysis at 40-50 degrees C with p-nitrophenol butyrate as a substrate. The lipolytic gene fls18D was overexpressed, and the resulting protein FLS18D was characterized as an alkaline esterase. Furthermore, the whole sequence of fosmid pFL18 containing FLS18C and FLS18D was shotgun sequenced, and a total of 26 ORFs on it were analyzed and annotated. Title: Reduced glutathione attenuates liver injury induced by methyl parathion in rats Jiang N, Lu L, Wang T, Zhang L, Xin W, Fu F Ref: Toxicol Mech Methods, 20:69, 2010 : PubMed ESTHER: Jiang_2010_Toxicol.Mech.Methods_20_69 PubMedSearch: Jiang 2010 Toxicol.Mech.Methods 20 69 PubMedID: 20100039 Abstract The aim of this study was to investigate whether exogenous reduced glutathione (GSH) could protect liver injury induced by methyl parathion. Rats were allocated into four groups named as control, MP (methyl parathion poisoning), MP+GSH1 (methyl parathion poisoning treated with GSH 600 mg/kg), and MP+GSH2 (methyl parathion poisoning treated with GSH 1200 mg/kg). Each one of the last three groups was assigned into 6 h, 24 h, and 72 h sub-groups. The activities of acetylcholinesterase (AChE), glutamate pyruvate transaminase (GPT), and glutamic oxalacetic transaminase (GOT) in plasma, and superoxide dismutase (SOD) and glutathione peroxidase (GPx) in liver were assayed. The malondialdehyde (MDA) in liver was also determined. Histopathological changes in liver were observed. Results showed that AChE activity was significantly inhibited by methyl parathion and attenuated after GSH administered. GSH could relieve hepatocellular edema and fatty degeneration, and attenuate the increased activities of GPT and GOT. GSH treatment increased the SOD and GPx activities, but had no effect on the MDA level. These results indicated that GSH could attenuate liver injury induced by methyl parathion. Title: Effects of galantamine on beta-amyloid release and beta-site cleaving enzyme 1 expression in differentiated human neuroblastoma SH-SY5Y cells Li Q, Wu D, Zhang L, Zhang Y Ref: Experimental Gerontology, 45:842, 2010 : PubMed ESTHER: Li_2010_Exp.Gerontol_45_842 PubMedSearch: Li 2010 Exp.Gerontol 45 842 PubMedID: 20600777 Abstract Galantamine (Gal) is an acetylcholinesterase inhibitor and used to treat the symptoms of Alzheimer's disease (AD). Recent studies show that Gal may affect amyloid precursor protein (APP) metabolism and increase release of secretory APPalpha (sAPPalpha). However the effect of Gal on amyloid-beta peptide (Abeta) release and beta-site cleaving enzyme 1 (BACE1) expression is still unknown. Consequently, we investigated the effect of Gal on the level of Abeta and BACE1. In a differentiated human neuroblastoma cell line (SH-SY5Y), Gal (0.3 muM) was found to significantly decrease Abeta release and BACE1 expression following treatment for 6, 12, and 24h. Increasing Gal to 0.9 muM or 10 muM had no further effect. The effect of Gal (0.3 muM for 18h) was maximal on BACE1 expression but not on Abeta secretion. At higher concentration (0.9 muM and 10 muM), Gal had no effect on the level of full-length APP but could still stimulate further decrease in Abeta secretion and release of sAPPalpha. These observations suggested that 0.3 muM Gal exerts its effect on Abeta production by inhibiting BACE1 expression, while 0.9 muM or 10 muM Gal mainly reduces Abeta production by stimulating the non-amyloidogenic pathway to decrease the amount of APP substrate available for beta-secretase cleavage. In addition, alpha7 nicotinic acetylcholine receptor (alpha7nAChR) and multiple second messengers (including PKC, MEK, and p38MAPK) were found to be involved in the regulation of Gal-inhibited Abeta release and BACE1 expression. Title: Association of the LIPG 584C > T polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations Liu WY, Yin RX, Zhang L, Cao XL, Miao L, Wu DF, Aung LH, Hu XJ, Lin WX, Yang DZ Ref: Lipids Health Dis, 9:110, 2010 : PubMed ESTHER: Liu_2010_Lipids.Health.Dis_9_110 PubMedSearch: Liu 2010 Lipids.Health.Dis 9 110 PubMedID: 20923576 Abstract BACKGROUND: Endothelial lipase (EL) is a major determinant of high-density lipoprotein-cholesterol (HDL-C) metabolism, but the association of endothelial lipase gene (LIPG) polymorphism and serum HDL-C levels is scarce and conflicting in diverse populations. Bai Ku Yao is an isolated subgroup of the Yao minority in China. This study was designed to detect the association of LIPG 584C > T (rs2000813) polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. METHODS: A total of 645 subjects of Bai Ku Yao and 638 participants of Han Chinese were randomly selected from our previous stratified randomized cluster samples. Genotyping of the LIPG 584C > T was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. RESULTS: The levels of serum total cholesterol (TC), HDL-C, low-density lipoprotein cholesterol (LDL-C) and apolipoprotein (Apo) AI and ApoB were lower in Bai Ku Yao than in Han (P < 0.05 - 0.001). The frequency of C and T alleles was 73.5% and 26.5% in Bai Ku Yao, and 67.9% and 32.1% in Han (P < 0.01); respectively. The frequency of CC, CT and TT genotypes was 50.4%, 46.2% and 3.4% in Bai Ku Yao, and 41.4%, 53.1% and 5.5% in Han (P < 0.01); respectively. Serum HDL-C levels in both ethnic groups were different among the three genotypes (P < 0.05 for each). Serum TC levels in both ethnic groups were also different between the CC and CT/TT genotypes (P < 0.05 for each). The T allele carriers had higher serum HDL-C and TC levels than the T allele noncarriers. Multivariate logistic regression analysis showed that the levels of HDL-C and ApoB were correlated with genotypes in Bai Ku Yao (P < 0.05 for each), whereas the levels of TC and HDL-C were associated with genotypes in Han Chinese (P < 0.05 and P < 0.01). Serum lipid parameters were also correlated with several environmental factors in the both ethnic groups. CONCLUSIONS: The frequency of LIPG 584T allele is lower in Bai Ku Yao than in Han Chinese. The LIPG 584T allele is associated with increased serum HDL-C, TC and ApoB levels. The differences in serum HDL-C, TC and ApoB levels between the two ethnic groups might partly result from different genotypic and allelic frequencies of LIPG 584C > T or different LIPG-enviromental interactions. Title: A novel series of [3.2.1] azabicyclic biaryl ethers as alpha3beta4 and alpha6/4beta4 nicotinic receptor agonists Lowe JA, 3rd, DeNinno SL, Coe JW, Zhang L, Mente S, Hurst RS, Mather RJ, Ward KM, Shrikhande A and McDowell LL <13 more author(s)> Lowe JA, 3rd, DeNinno SL, Coe JW, Zhang L, Mente S, Hurst RS, Mather RJ, Ward KM, Shrikhande A, Rollema H, Johnson DE, Horner W, Gorczyca R, Tingley FD, 3rd, Kozak R, Majchrzak MJ, Tritto T, Sadlier J, Shaffer CL, Ellerbrock B, Osgood SM, MacDougall MC, McDowell LL (- 13) Ref: Bioorganic & Medicinal Chemistry Lett, 20:4749, 2010 : PubMed ESTHER: Lowe_2010_Bioorg.Med.Chem.Lett_20_4749 PubMedSearch: Lowe 2010 Bioorg.Med.Chem.Lett 20 4749 PubMedID: 20663668 Abstract We report the synthesis of a series of [3.2.1]azabicyclic biaryl ethers as selective agonists of alpha3- and alpha6-containing nicotinic receptors. In particular, compound 17a from this series is a potent alpha3beta4 and alpha6/4beta4 receptor agonist in terms of both binding and functional activity. Compound 17a also shows potent in vivo activity in CNS-mediated animal models that are sensitive to antipsychotic drugs. Compound 17a may thus be a useful tool for studying the role of alpha3beta4 and alpha6/4beta4 nicotinic receptors in CNS pharmacology. Title: A catalog of reference genomes from the human microbiome Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E and Zhu D <73 more author(s)> Nelson KE, Weinstock GM, Highlander SK, Worley KC, Creasy HH, Wortman JR, Rusch DB, Mitreva M, Sodergren E, Chinwalla AT, Feldgarden M, Gevers D, Haas BJ, Madupu R, Ward DV, Birren BW, Gibbs RA, Methe B, Petrosino JF, Strausberg RL, Sutton GG, White OR, Wilson RK, Durkin S, Giglio MG, Gujja S, Howarth C, Kodira CD, Kyrpides N, Mehta T, Muzny DM, Pearson M, Pepin K, Pati A, Qin X, Yandava C, Zeng Q, Zhang L, Berlin AM, Chen L, Hepburn TA, Johnson J, McCorrison J, Miller J, Minx P, Nusbaum C, Russ C, Sykes SM, Tomlinson CM, Young S, Warren WC, Badger J, Crabtree J, Markowitz VM, Orvis J, Cree A, Ferriera S, Fulton LL, Fulton RS, Gillis M, Hemphill LD, Joshi V, Kovar C, Torralba M, Wetterstrand KA, Abouellleil A, Wollam AM, Buhay CJ, Ding Y, Dugan S, Fitzgerald MG, Holder M, Hostetler J, Clifton SW, Allen-Vercoe E, Earl AM, Farmer CN, Liolios K, Surette MG, Xu Q, Pohl C, Wilczek-Boney K, Zhu D (- 73) Ref: Science, 328:994, 2010 : PubMed ESTHER: Nelson_2010_Science_328_994 PubMedSearch: Nelson 2010 Science 328 994 PubMedID: 20489017 Gene_locus related to this paper: strp2-q04l35, strpn-AXE1, strpn-pepx Abstract The human microbiome refers to the community of microorganisms, including prokaryotes, viruses, and microbial eukaryotes, that populate the human body. The National Institutes of Health launched an initiative that focuses on describing the diversity of microbial species that are associated with health and disease. The first phase of this initiative includes the sequencing of hundreds of microbial reference genomes, coupled to metagenomic sequencing from multiple body sites. Here we present results from an initial reference genome sequencing of 178 microbial genomes. From 547,968 predicted polypeptides that correspond to the gene complement of these strains, previously unidentified ("novel") polypeptides that had both unmasked sequence length greater than 100 amino acids and no BLASTP match to any nonreference entry in the nonredundant subset were defined. This analysis resulted in a set of 30,867 polypeptides, of which 29,987 (approximately 97%) were unique. In addition, this set of microbial genomes allows for approximately 40% of random sequences from the microbiome of the gastrointestinal tract to be associated with organisms based on the match criteria used. Insights into pan-genome analysis suggest that we are still far from saturating microbial species genetic data sets. In addition, the associated metrics and standards used by our group for quality assurance are presented. Title: Discovery of 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (CP-810,123), a novel alpha 7 nicotinic acetylcholine receptor agonist for the treatment of cognitive disorders in schizophrenia: synthesis, SAR development, and in vivo efficacy in cognition models O'Donnell CJ, Rogers BN, Bronk BS, Bryce DK, Coe JW, Cook KK, Duplantier AJ, Evrard E, Hajos M and Zhang L <16 more author(s)> O'Donnell CJ, Rogers BN, Bronk BS, Bryce DK, Coe JW, Cook KK, Duplantier AJ, Evrard E, Hajos M, Hoffmann WE, Hurst RS, Maklad N, Mather RJ, McLean S, Nedza FM, O'Neill BT, Peng L, Qian W, Rottas MM, Sands SB, Schmidt AW, Shrikhande AV, Spracklin DK, Wong DF, Zhang A, Zhang L (- 16) Ref: Journal of Medicinal Chemistry, 53:1222, 2010 : PubMed ESTHER: O'Donnell_2010_J.Med.Chem_53_1222 PubMedSearch: O'Donnell 2010 J.Med.Chem 53 1222 PubMedID: 20043678 Abstract A novel alpha 7 nAChR agonist, 4-(5-methyloxazolo[4,5-b]pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane (24, CP-810,123), has been identified as a potential treatment for cognitive deficits associated with psychiatric or neurological conditions including schizophrenia and Alzheimer's disease. Compound 24 is a potent and selective compound with excellent pharmaceutical properties. In rodent, the compound displays high oral bioavailability and excellent brain penetration affording high levels of receptor occupancy and in vivo efficacy in auditory sensory gating and novel object recognition. The structural diversity of this compound and its preclinical in vitro and in vivo package support the hypothesis that alpha 7 nAChR agonists may have potential as a pharmacotherapy for the treatment of cognitive deficits in schizophrenia. Title: Reverse genetic identification of CRN1 and its distinctive role in chlorophyll degradation in Arabidopsis Ren G, Zhou Q, Wu S, Zhang Y, Zhang L, Huang J, Sun Z, Kuai B Ref: J Integr Plant Biol, 52:496, 2010 : PubMed ESTHER: Ren_2010_J.Integr.Plant.Biol_52_496 PubMedSearch: Ren 2010 J.Integr.Plant.Biol 52 496 PubMedID: 20537045 Gene_locus related to this paper: arath-Q9FFZ1 Abstract Recent identification of NYE1/SGR1 brought up a new era for the exploration of the regulatory mechanism of Chlorophyll (Chl) degradation. Cluster analysis of senescence associated genes with putative chloroplast targeting sequences revealed several genes sharing a similar expression pattern with NYE1. Further characterization of available T-DNA insertion lines led to the discovery of a novel stay-green gene CRN1 (Co-regulated with NYE1). Chl breakdown was significantly restrained in crn1-1 under diversified senescence scenarios, which is comparable with that in acd1-20, but much more severe than that in nye1-1. Notably, various Chl binding proteins, especially trimeric LHCP II, were markedly retained in crn1-1 four days after dark-treatment, possibly due to a lesion in disassociation of protein-pigment complex. Nevertheless, the photochemical efficiency of PSII in crn1-1 declined, even more rapidly, two days after dark-treatment, compared to those in Col-0 and nye1-1. Our results suggest that CRN1 plays a crucial role in Chl degradation, and that loss of its function produces various side-effects, including those on the breakdown of Ch-protein complex and the maintenance of the residual photosynthetic capability during leaf senescence. Title: Functional and evolutionary insights from the genomes of three parasitoid Nasonia species Werren JH, Richards S, Desjardins CA, Niehuis O, Gadau J, Colbourne JK, Beukeboom LW, Desplan C, Elsik CG and Williamson M <147 more author(s)> Werren JH, Richards S, Desjardins CA, Niehuis O, Gadau J, Colbourne JK, Beukeboom LW, Desplan C, Elsik CG, Grimmelikhuijzen CJ, Kitts P, Lynch JA, Murphy T, Oliveira DC, Smith CD, van de Zande L, Worley KC, Zdobnov EM, Aerts M, Albert S, Anaya VH, Anzola JM, Barchuk AR, Behura SK, Bera AN, Berenbaum MR, Bertossa RC, Bitondi MM, Bordenstein SR, Bork P, Bornberg-Bauer E, Brunain M, Cazzamali G, Chaboub L, Chacko J, Chavez D, Childers CP, Choi JH, Clark ME, Claudianos C, Clinton RA, Cree AG, Cristino AS, Dang PM, Darby AC, de Graaf DC, Devreese B, Dinh HH, Edwards R, Elango N, Elhaik E, Ermolaeva O, Evans JD, Foret S, Fowler GR, Gerlach D, Gibson JD, Gilbert DG, Graur D, Grunder S, Hagen DE, Han Y, Hauser F, Hultmark D, Hunter HCt, Hurst GD, Jhangian SN, Jiang H, Johnson RM, Jones AK, Junier T, Kadowaki T, Kamping A, Kapustin Y, Kechavarzi B, Kim J, Kiryutin B, Koevoets T, Kovar CL, Kriventseva EV, Kucharski R, Lee H, Lee SL, Lees K, Lewis LR, Loehlin DW, Logsdon JM, Jr., Lopez JA, Lozado RJ, Maglott D, Maleszka R, Mayampurath A, Mazur DJ, McClure MA, Moore AD, Morgan MB, Muller J, Munoz-Torres MC, Muzny DM, Nazareth LV, Neupert S, Nguyen NB, Nunes FM, Oakeshott JG, Okwuonu GO, Pannebakker BA, Pejaver VR, Peng Z, Pratt SC, Predel R, Pu LL, Ranson H, Raychoudhury R, Rechtsteiner A, Reese JT, Reid JG, Riddle M, Robertson HM, Romero-Severson J, Rosenberg M, Sackton TB, Sattelle DB, Schluns H, Schmitt T, Schneider M, Schuler A, Schurko AM, Shuker DM, Simoes ZL, Sinha S, Smith Z, Solovyev V, Souvorov A, Springauf A, Stafflinger E, Stage DE, Stanke M, Tanaka Y, Telschow A, Trent C, Vattathil S, Verhulst EC, Viljakainen L, Wanner KW, Waterhouse RM, Whitfield JB, Wilkes TE, Williamson MS, Willis JH, Wolschin F, Wyder S, Yamada T, Yi SV, Zecher CN, Zhang L, Gibbs RA, Williamson M (- 147) Ref: Science, 327:343, 2010 : PubMed ESTHER: Werren_2010_Science_327_343 PubMedSearch: Werren 2010 Science 327 343 PubMedID: 20075255 Gene_locus related to this paper: nasvi-ACHE1, nasvi-ACHE2, nasvi-k7in31, nasvi-k7iwl9, nasvi-k7iyk8, nasvi-k7jlv1, nasvi-k7in32, nasvi-k7ind2, nasvi-k7inh0, nasvi-k7inh1, nasvi-k7inh2, nasvi-k7inp9, nasvi-k7iun7, nasvi-k7iv21, nasvi-k7ivn5, nasvi-k7ivn6, nasvi-k7iw29, nasvi-k7iwk5, nasvi-k7iwl8, nasvi-k7iz24, nasvi-k7izb4, nasvi-k7j5u6, nasvi-k7j6y1, nasvi-k7j6y2, nasvi-k7j6y4, nasvi-k7j718, nasvi-k7j755, nasvi-k7j756, nasvi-k7j757, nasvi-k7j7k5, nasvi-k7j7n7, nasvi-k7j7r8, nasvi-k7j7s8, nasvi-k7j7s9, nasvi-k7j811, nasvi-k7iny8, nasvi-k7izf2, nasvi-k7iwe2, nasvi-k7j6w4, nasvi-k7izl9, nasvi-k7jf39, nasvi-k7izl8, nasvi-k7irf1, nasvi-k7j7l1 Abstract We report here genome sequences and comparative analyses of three closely related parasitoid wasps: Nasonia vitripennis, N. giraulti, and N. longicornis. Parasitoids are important regulators of arthropod populations, including major agricultural pests and disease vectors, and Nasonia is an emerging genetic model, particularly for evolutionary and developmental genetics. Key findings include the identification of a functional DNA methylation tool kit; hymenopteran-specific genes including diverse venoms; lateral gene transfers among Pox viruses, Wolbachia, and Nasonia; and the rapid evolution of genes involved in nuclear-mitochondrial interactions that are implicated in speciation. Newly developed genome resources advance Nasonia for genetic research, accelerate mapping and cloning of quantitative trait loci, and will ultimately provide tools and knowledge for further increasing the utility of parasitoids as pest insect-control agents. Title: Template-based modeling of a psychrophilic lipase: conformational changes, novel structural features and its application in predicting the enantioselectivity of lipase catalyzed transesterification of secondary alcohols Xu T, Gao B, Zhang L, Lin J, Wang X, Wei D Ref: Biochimica & Biophysica Acta, 1804:2183, 2010 : PubMed ESTHER: Xu_2010_Biochim.Biophys.Acta_1804_2183 PubMedSearch: Xu 2010 Biochim.Biophys.Acta 1804 2183 PubMedID: 20828637 Gene_locus related to this paper: promi-c2lfd0 Abstract In order to fully explore the structure-function relationship of a Proteus lipase (LipK107) that was screened from the soil in our previous study, we have modeled the three-dimensional (3-D) structures of the enzyme in its active and inactive conformations on the basis of crystal structures of Burkholderia glumae and Pseudomonas aeruginosa lipases in the present study. Both homology models suggested that LipK107 possessed a catalytic triad (Ser79-Asp232-H254), an oxyanion hole (Leu13 and Gln80) which was used to stabilize the reaction tetrahedral intermediates, and a lid substructure that controlled the access of the substrate to the active site. The existence of the lid was further verified by carrying out the interfacial activation experiment. The conformational change of LipK107 which was caused by lid opening action was predicted by superimposing the two theoretical models for the first time. Finally, both 3-D structures were used to predict the enantioselectivity of LipK107 when the enzyme was used to catalyze the resolution of racemic 1-phenylethanol. Lid-open model of LipK107 identified the R-enantiomer as the preferred enantiomer, while lid-closed mode showed that the S-enantiomer was more favored. However, only the lid-open conformational model could led to predictions that agreed with the following the experimental result of real biocatalysis reaction of 1-phenylethanol. Title: Quantitative and qualitative changes of the carboxylesterase associated with beta-cypermethrin resistance in the housefly, Musca domestica (Diptera: Muscidae) Zhang L, Shi J, Shi X, Liang P, Gao J, Gao X Ref: Comparative Biochemistry & Physiology B Biochem Mol Biol, 156:6, 2010 : PubMed ESTHER: Zhang_2010_Comp.Biochem.Physiol.B.Biochem.Mol.Biol_156_6 PubMedSearch: Zhang 2010 Comp.Biochem.Physiol.B.Biochem.Mol.Biol 156 6 PubMedID: 20117228 Gene_locus related to this paper: musdo-EST23aes07 Abstract Mechanisms of esterase-mediated pyrethroid resistance were analyzed based on our previous works in a strain of the housefly, Musca domestica. The carboxylesterase gene, MdalphaE7, was cloned and sequenced from susceptible (CSS) and resistant (CRR) strains, and a total of nine amino acid substitutions were found. The mutation, Trp(251)-Ser appeared to play a role in beta-cypermethrin resistance and cross-resistance between organophosphates (OPs) and pyrethroids in the CRR strain. Quantitative real-time PCR showed that MdalphaE7 was over-expressed in the CRR strain, the reciprocal cross progeny F(1) and back-cross progeny BC(2) compared with the CSS strain, respectively. Two alpha-cynaoester substrates as surrogates for beta-cypermethrin and deltamethrin, were synthesized to determine the pyrethroid hydrolase activity. Results showed that carboxylesterases from the CRR strain hydrolyzed cypermethrin/deltamethrin-like substrate 9.05- and 13.53-fold more efficiently than those from the CSS strain, respectively. Our studies suggested that quantitative and qualitative changes in the carboxylesterase might contribute together to pyrethroid resistance in the CRR strain. Title: Escin attenuates cognitive deficits and hippocampal injury after transient global cerebral ischemia in mice via regulating certain inflammatory genes Zhang L, Fu F, Zhang X, Zhu M, Wang T, Fan H Ref: Neurochem Int, 57:119, 2010 : PubMed ESTHER: Zhang_2010_Neurochem.Int_57_119 PubMedSearch: Zhang 2010 Neurochem.Int 57 119 PubMedID: 20466027 Abstract Considerable evidence has been accumulated demonstrating an important role for inflammation in ischemic brain injury and its contribution to greater cerebral damage after ischemia. Blocking the inflammatory reaction promotes neuroprotection and shows therapeutic potential for clinical treatment of ischemic brain injury. Escin, a natural mixture of triterpenoid saponin isolated from the seed of the horse chestnut, demonstrates antiedematous and anti-inflammatory effects. Here we assessed neuroprotective effects of escin with a transient global cerebral ischemia model. Global cerebral ischemia was induced by occluding both common carotid arteries and withdrawing 0.3ml of blood from the tail vein in mice. Treatment with escin was initiated 0.5h after ischemia induction and given once a day for three consecutive days. Then animals were assessed using the Morris water-maze test and step-down passive avoidance test. Acetylcholinesterase (AChE) activity, histological pathology, and expression of inflammatory genes in the hippocampus were determined. The results showed escin significantly improved learning and memory recovery and reduced hippocampal damage in the cerebral ischemic mice. However, donepezil merely improved learning and memory recovery but did not ameliorate hippocampal damage in the cerebral ischemic mice. Furthermore, we found escin significantly downregulated certain inflammatory gene expression and upregulated expression of granulocyte-macrophage colony-stimulating factor (GM-CSF), which was recently reported as a neuroprotective protein in the brain. Our results indicate that inhibition of inflammation and protection of hippocampal neurons by escin may be a potentially useful therapy for ischemic brain injury. Title: Isolation and functional expression of a novel lipase gene isolated directly from oil-contaminated soil Zuo K, Zhang L, Yao H, Wang J Ref: Acta Biochim Pol, 57:305, 2010 : PubMed ESTHER: Zuo_2010_Acta.Biochim.Pol_57_305 PubMedSearch: Zuo 2010 Acta.Biochim.Pol 57 305 PubMedID: 20931089 Abstract A lipase gene SR1 encoding an extracellular lipase was isolated from oil-contaminated soil and expressed in Escherichia coli. The gene contained a 1845-bp reading frame and encoded a 615-amino-acid lipase protein. The mature part of the lipase was expressed with an N-terminal histidine tag in E. coli BL21, purified and characterized biochemically. The results showed that the purified lipase combines the properties of Pseudomonas chlororaphis and other Serratia lipases characterized so far. Its optimum pH and temperature for hydrolysis activity was pH 5.5-8.0 and 37 degrees C respectively. The enzyme showed high preference for short chain substrates (556.3+/-2.8 U/microg for C10 fatty acid oil) and surprisingly it also displayed high activity for long-chain fatty acid. The deduced lipase SR1 protein is probably from Serratia, and is organized as a prepro-protein and belongs to the GXSXG lipase family. Title: Electrochemical biosensing of methyl parathion pesticide based on acetylcholinesterase immobilized onto Au-polypyrrole interlaced network-like nanocomposite Gong J, Wang L, Zhang L Ref: Biosensors & Bioelectronics, 24:2285, 2009 : PubMed ESTHER: Gong_2009_Biosens.Bioelectron_24_2285 PubMedSearch: Gong 2009 Biosens.Bioelectron 24 2285 PubMedID: 19111456 Abstract We developed a simple strategy for designing a highly sensitive electrochemical biosensor for organophosphate pesticides (OPs) based on acetylcholinesterase (AChE) immobilized onto Au nanoparticles-polypyrrole nanowires composite film modifid glassy carbon electrode (labeled as AChE-Au-PPy/GCE). Where, the generated Au nanoparticles (AuNPs) were homogenously distributed onto the interlaced PPy nanowires (PPy NWs) matrix, constructing a three-dimensional porous network. This network-like nanocomposite not only provided a biocompatible microenvironment to keep the bioactivity of AChE, but also exhibited a strong synergetic effect on improving the sensing properties of OPs. The combination of AuNPs and PPyNWs greatly catalyzed the oxidation of the enzymatically generated thiocholine product, thus increasing the detection sensitivity. On the basis of the inhibition of OPs on the enzymatic activity of AChE, the conditions for OPs detection were optimized by using methyl parathion as a model OP compound. The inhibition of methyl parathion was proportional to its concentration ranging from 0.005 to 0.12 and 0.5 to 4.5 microgmL(-1). The detection limit was 2 ngmL(-1). The developed biosensor exhibited good reproducibility and acceptable stability. This study provides a new promise tool for analysis of organophosphate pesticides. Title: Facile synthesis of three bidesmosidic oleanolic acid saponins with strong inhibitory activity on pancreatic lipase Guo T, Liu Q, Wang P, Zhang L, Zhang W, Li Y Ref: Carbohydr Res, 344:1167, 2009 : PubMed ESTHER: Guo_2009_Carbohydr.Res_344_1167 PubMedSearch: Guo 2009 Carbohydr.Res 344 1167 PubMedID: 19463989 Inhibitor(s) related to this paper: Oleanolic-acid Abstract The first synthesis of scabiosaponins E (1), F (2), and G (3), three new oleanolic acid saponins with strong inhibitory activity on pancreatic lipase isolated from the Chinese traditional medicinal herb Scabiosa tschiliensis, was efficiently achieved in an one-pot strategy under the combined use of glycosyl trichloroacetimidates and p-toluene 1-thioglycosides (STol) as donors. Title: A new screening method based on yeast-expressed human dipeptidyl peptidase IV and discovery of novel inhibitors Hu CX, Huang H, Zhang L, Huang Y, Shen ZF, Cheng KD, Du GH, Zhu P Ref: Biotechnol Lett, 31:979, 2009 : PubMed ESTHER: Hu_2009_Biotechnol.Lett_31_979 PubMedSearch: Hu 2009 Biotechnol.Lett 31 979 PubMedID: 19267232 Abstract Dipeptidyl peptidase (DPP) IV inhibitors provide a new strategy for the treatment of type 2 diabetes. Human DPP-IV gene was cloned from differentiated Caco-2 cells and expressed in Pichia pastoris. The recombinant enzyme was used in a new system for screening of DPP-IV inhibitors. By high throughput screening, a novel compound (W5188) was identified from 75,000 compounds with an IC(50) of 6.5 microM. This method is highly reproducible and reliable for discovery of DPP-IV inhibitors as shown by Z' value of 0.73 and S/N ratio of 6.89. Title: The Sorghum bicolor genome and the diversification of grasses Paterson AH, Bowers JE, Bruggmann R, Dubchak I, Grimwood J, Gundlach H, Haberer G, Hellsten U, Mitros T and Rokhsar DS <35 more author(s)> Paterson AH, Bowers JE, Bruggmann R, Dubchak I, Grimwood J, Gundlach H, Haberer G, Hellsten U, Mitros T, Poliakov A, Schmutz J, Spannagl M, Tang H, Wang X, Wicker T, Bharti AK, Chapman J, Feltus FA, Gowik U, Grigoriev IV, Lyons E, Maher CA, Martis M, Narechania A, Otillar RP, Penning BW, Salamov AA, Wang Y, Zhang L, Carpita NC, Freeling M, Gingle AR, Hash CT, Keller B, Klein P, Kresovich S, McCann MC, Ming R, Peterson DG, Mehboob ur R, Ware D, Westhoff P, Mayer KF, Messing J, Rokhsar DS (- 35) Ref: Nature, 457:551, 2009 : PubMed ESTHER: Paterson_2009_Nature_457_551 PubMedSearch: Paterson 2009 Nature 457 551 PubMedID: 19189423 Gene_locus related to this paper: sorbi-b3vtb2, sorbi-c5wp75, sorbi-c5wts6, sorbi-c5wu07, sorbi-c5wvl7, sorbi-c5ww85, sorbi-c5ww86, sorbi-c5wxa4, sorbi-c5x1f6, sorbi-c5x2x9, sorbi-c5x5z9, sorbi-c5x6q0, sorbi-c5x230, sorbi-c5x290, sorbi-c5x345, sorbi-c5x399, sorbi-c5x610, sorbi-c5xbm4, sorbi-c5xct0, sorbi-c5xdv0, sorbi-c5xe87, sorbi-c5xf40, sorbi-c5xfu9, sorbi-c5xh40, sorbi-c5xh41, sorbi-c5xh42, sorbi-c5xh43, sorbi-c5xh44, sorbi-c5xh46, sorbi-c5xhr2, sorbi-c5xiw7, sorbi-c5xjf0, sorbi-c5xky2, sorbi-c5xm54, sorbi-c5xmb9, sorbi-c5xmz5, sorbi-c5xp10, sorbi-c5xpm6, sorbi-c5xr91, sorbi-c5xr92, sorbi-c5xs33, sorbi-c5xtz0, sorbi-c5xwd3, sorbi-c5y0d2, sorbi-c5y0h4, sorbi-c5y3i5, sorbi-c5y7x0, sorbi-c5y517, sorbi-c5y545, sorbi-c5ydr3, sorbi-c5yec0, sorbi-c5yf71, sorbi-c5yi32, sorbi-c5yih2, sorbi-c5ylw6, sorbi-c5yn66, sorbi-c5ynp8, sorbi-c5yt11, sorbi-c5yur5, sorbi-c5ywz3, sorbi-c5ywz4, sorbi-c5yx73, sorbi-c5yyn0, sorbi-c5z2m6, sorbi-c5z6a9, sorbi-c5z6j1, sorbi-c5z6s5, sorbi-c5z177, sorbi-Q9XE80, sorbi-c5xyg4, sorbi-c5z4q0, sorbi-c5xly4, sorbi-c5z4u8, sorbi-c5xxg5, sorbi-c5z9b9, sorbi-a0a1z5r970, sorbi-c5xhf9, sorbi-c5yxt7, sorbi-c5yxt6, sorbi-c5y1m2, sorbi-c5xdy6, sorbi-a0a194ysf6, sorbi-a0a1b6pnr2, sorbi-a0a1b6qcb9 Abstract Sorghum, an African grass related to sugar cane and maize, is grown for food, feed, fibre and fuel. We present an initial analysis of the approximately 730-megabase Sorghum bicolor (L.) Moench genome, placing approximately 98% of genes in their chromosomal context using whole-genome shotgun sequence validated by genetic, physical and syntenic information. Genetic recombination is largely confined to about one-third of the sorghum genome with gene order and density similar to those of rice. Retrotransposon accumulation in recombinationally recalcitrant heterochromatin explains the approximately 75% larger genome size of sorghum compared with rice. Although gene and repetitive DNA distributions have been preserved since palaeopolyploidization approximately 70 million years ago, most duplicated gene sets lost one member before the sorghum-rice divergence. Concerted evolution makes one duplicated chromosomal segment appear to be only a few million years old. About 24% of genes are grass-specific and 7% are sorghum-specific. Recent gene and microRNA duplications may contribute to sorghum's drought tolerance. Title: The B73 maize genome: complexity, diversity, and dynamics Schnable PS, Ware D, Fulton RS, Stein JC, Wei F, Pasternak S, Liang C, Zhang J, Fulton L and Wilson RK <147 more author(s)> Schnable PS, Ware D, Fulton RS, Stein JC, Wei F, Pasternak S, Liang C, Zhang J, Fulton L, Graves TA, Minx P, Reily AD, Courtney L, Kruchowski SS, Tomlinson C, Strong C, Delehaunty K, Fronick C, Courtney B, Rock SM, Belter E, Du F, Kim K, Abbott RM, Cotton M, Levy A, Marchetto P, Ochoa K, Jackson SM, Gillam B, Chen W, Yan L, Higginbotham J, Cardenas M, Waligorski J, Applebaum E, Phelps L, Falcone J, Kanchi K, Thane T, Scimone A, Thane N, Henke J, Wang T, Ruppert J, Shah N, Rotter K, Hodges J, Ingenthron E, Cordes M, Kohlberg S, Sgro J, Delgado B, Mead K, Chinwalla A, Leonard S, Crouse K, Collura K, Kudrna D, Currie J, He R, Angelova A, Rajasekar S, Mueller T, Lomeli R, Scara G, Ko A, Delaney K, Wissotski M, Lopez G, Campos D, Braidotti M, Ashley E, Golser W, Kim H, Lee S, Lin J, Dujmic Z, Kim W, Talag J |
