Author Report for: Li MNo contact information in database for Li M
Jiang N, Li X, Wang Q, Baihetiyaer B, Fan X, Li M, Sun H, Yin X, Wang J Ref: Chemosphere, :137846, 2023 : PubMed ESTHER: Jiang_2023_Chemosphere__137846 PubMedSearch: Jiang 2023 Chemosphere 137846 PubMedID: 36646180 Abstract Propofol is an intravenous anesthetic injection extensively used in clinic, which has been proved to be neurotoxic in humans. Improper use and disposal of propofol may lead to its release into the aquatic environment, but the potential ecological risk of propofol to aquatic organisms remains poorly understood. For this study, we comprehensively explored the ecotoxicological effects and potential mechanisms of propofol (0.04, 0.2 and 2 mg L(-1)) on 120 hpf zebrafish (Danio rerio) embryos from physiological, biochemical, and molecular perspectives. The results showed that propofol has moderate toxicity on zebrafish embryos (96 h LC(50) = 4.260 mg L(-1)), which could significantly reduce the hatchability and delay the development. Propofol can trigger reactive oxygen species (ROS) generation, lipid peroxidation (Malondialdehyde, MDA) and DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG). The glutathione peroxidase (GPX) activity of zebrafish embryos in 0.04 and 0.2 mg L(-1) propofol treatment group was activated in response to oxidative damage, while activities of superoxide dismutase (SOD), catalase (CAT) and GPX in zebrafish treated with 2 mg L(-1) was significant inhibited compared with the control group (p0.05). Moreover, the expression of antioxidant genes and related pathways was inhibited. Apoptosis was investigated at genes level and histochemistry. Molecular docking confirmed that propofol could change in the secondary structure of acetylcholinesterase (AChE) and competitively inhibited acetylcholine (ACh) binding to AChE, which may disturb the nervous system. These results described toxic response and molecular mechanism in zebrafish embryos, providing multiple aspects about ecological risk assessment of propofol in water environment. Title: Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population Bai X, Sun Y, Li Y, Li M, Cao Z, Huang Z, Zhang F, Yan P, Wang L and Zuo T <9 more author(s)> Bai X, Sun Y, Li Y, Li M, Cao Z, Huang Z, Zhang F, Yan P, Wang L, Luo J, Wu J, Fan D, Chen H, Zhi M, Lan P, Zeng Z, Wu X, Miao Y, Zuo T (- 9) Ref: Microbiome, 10:147, 2022 : PubMed ESTHER: Bai_2022_Microbiome_10_147 PubMedSearch: Bai 2022 Microbiome 10 147 PubMedID: 36100953 Abstract BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis. METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations. RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the alpha-diversity (intrinsic microbial diversity) and the beta-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization. CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract. Title: Neuroligin-1 plays an important role in methamphetamine-induced hippocampal synaptic plasticity Cao C, Wang L, Zhang J, Liu Z, Li M, Xie S, Chen G, Xu X Ref: Toxicol Lett, 361:1, 2022 : PubMed ESTHER: Cao_2022_Toxicol.Lett_361_1 PubMedSearch: Cao 2022 Toxicol.Lett 361 1 PubMedID: 35331841 Abstract The neurotoxic effects of methamphetamine (METH) include not only neuronal apoptosis and autophagy, but also lead to substance use disorder and have become increasingly prominent. Studies suggest that synaptic plasticity may be the structural basis of METH-induced neurological impairment. Neuroligins are postsynaptic adhesion molecules involved in the regulation of synaptic organization and function. Animal studies have shown that neuroligin (NLG)- 1 is involved in memory formation; however, its role in METH-induced neurotoxicity is not clear. In the present study, we used 1 mM METH in vitro; mice in the acute and subacute exposure groups received intraperitoneal injections of 30 mg/kg METH (1 injection) or 15 mg/kg METH (8 separate injections at 12-h intervals). We found that the expression of NLG-1, Synapsin-1, and postsynaptic density-95 were increased after METH exposure. We further observed that METH-induced inhibition of long-term potentiation and spatial memory loss could be alleviated when mice were pretreated with NLG-1 small interfering RNA. Therefore, our study provides evidence that NLG-1 is involved in METH-induced hippocampal synaptic plasticity and may be a potential target for the treatment of METH-induced neurotoxicity. Title: Evaluation on the Metabolic Activity of Two Carboxylesterase Isozymes in Mouse Liver Microsomes by a LC-MS/MS Method Lan L, Li M, Xu Y, Ren X, Zhang C Ref: Journal of Chromatography Sci, :, 2022 : PubMed ESTHER: Lan_2022_J.Chromatogr.Sci__ PubMedSearch: Lan 2022 J.Chromatogr.Sci PubMedID: 36585777 Abstract An applicable method for the precise measurement of major carboxylesterase (CESs) activity in liver still limited. Clopidogrel and irinotecan are specific substrates for CES1 and CES2, respectively. Clopidogrel is metabolized to the inactive metabolite clopidogrel carboxylate (CCAM) by CES1. Irinotecan is metabolized to the active metabolite 7-ethyl-10-hydroxycamptothecin (SN-38) by CES2. In the present study, the LC-MS/MS method for the determination of CCAM and SN-38 were separately developed to characterize the metabolic activities of CES1 and CES2 in mouse liver microsomal. CCAM was separated on a Ecosil ODS column with an isocratic mobile phase consisted of 5smmol/L ammonium formate and 0.1% formic acid in water and acetonitrile (15:85, V:V) at a flow rate of 0.4mL/min. SN-38 was separated on a Waters symmetry C18 column with an gradient mobile phase consisted of 5smmol/L ammonium formate and 0.1% formic acid in water and acetonitrile at a flow rate of 0.3smL/min. Calibration curves were linear within the concentration range of 100-20,000sng/mL for CCAM and 1-200sng/mL for SN-38. The results of method showed excellent accuracy and precision. The recovery rate, matrix effect and stability inspection results were within the acceptance criteria. The optimized incubation conditions were as follows: protein concentration of microsomes were all 0.1smg/mL, incubation time was 60smin for clopidogrel and 30smin for irinotecan, respectively. This method was sensitive and applicable for the determination of the activity of CESs in the mouse liver microsomes. Title: Synthesis of Poly(Hexamethylene Succinate-Co-Ethylene Succinate) Copolymers With Different Physical Properties and Enzymatic Hydrolyzability by Regulating the Ratio of Monomer Li M, Jing J, Su T Ref: Front Bioeng Biotechnol, 10:894046, 2022 : PubMed ESTHER: Li_2022_Front.Bioeng.Biotechnol_10_894046 PubMedSearch: Li 2022 Front.Bioeng.Biotechnol 10 894046 PubMedID: 35573230 Abstract Poly(hexylene succinate) (PHS), poly(ethylene succinate) (PES), and their random copolyesters, poly(hexylene succinate-co-ethylene succinate) ((P(HS-co-ES)), were synthesized by melting polycondensation. Simply varying the ratios of HS/ES afforded control over the copolymer crystallinity, thermal and mechanical properties, wettability, and enzymatic hydrolyzability as shown by X-ray diffraction (XRD), differential scanning calorimetry (DSC), tensile tests, and water contact angle (WCA) measurements. The enzymatic hydrolysis rates of all prepared copolyesters were higher than those of the corresponding homopolyesters. The hydrolysis rates were affected by crystallinity, melting temperature, and hydrophobicity of the copolyesters, and therefore, the degradation rates could be tuned along with the ES content. The library of copolymers prepared here with tunable degradation rates, ranging from HS-enriched to ES-enriched copolyesters, is promising for a variety of different applications. The P(HS-co-ES51) copolyester that did not fully degrade is particularly promising for use in long-term storage applications, whereas P(HS-co-ES13) and P(HS-co-ES76) that rapidly degrade are good for use in very short-term applications. Title: Identification of cell wall synthesis inhibitors active against Mycobacterium tuberculosis by competitive activity-based protein profiling Li M, Patel HV, Cognetta AB, 3rd, Smith TC, 2nd, Mallick I, Cavalier JF, Previti ML, Canaan S, Aldridge BB and Seeliger JC <1 more author(s)> Li M, Patel HV, Cognetta AB, 3rd, Smith TC, 2nd, Mallick I, Cavalier JF, Previti ML, Canaan S, Aldridge BB, Cravatt BF, Seeliger JC (- 1) Ref: Cell Chemical Biology, 29:883, 2022 : PubMed ESTHER: Li_2022_Cell.Chem.Biol_29_883 PubMedSearch: Li 2022 Cell.Chem.Biol 29 883 PubMedID: 34599873 Inhibitor(s) related to this paper: AA692, EZ120P, EZ120, CyC-17, Orlistat Abstract The identification and validation of a small molecule's targets is a major bottleneck in the discovery process for tuberculosis antibiotics. Activity-based protein profiling (ABPP) is an efficient tool for determining a small molecule's targets within complex proteomes. However, how target inhibition relates to biological activity is often left unexplored. Here, we study the effects of 1,2,3-triazole ureas on Mycobacterium tuberculosis (Mtb). After screening -200 compounds, we focus on 4 compounds that form a structure-activity series. The compound with negligible activity reveals targets, the inhibition of which is functionally less relevant for Mtb growth and viability, an aspect not addressed in other ABPP studies. Biochemistry, computational docking, and morphological analysis confirms that active compounds preferentially inhibit serine hydrolases with cell wall and lipid metabolism functions and that disruption of the cell wall underlies biological activity. Our findings show that ABPP identifies the targets most likely relevant to a compound's antibacterial activity. Title: Preparation and Characterization of Magnetic Metal-Organic Frameworks Functionalized by Ionic Liquid as Supports for Immobilization of Pancreatic Lipase Li X, Jia Y, Li J, Zhang P, Li T, Lu L, Yao H, Liu J, Zhu Z and Xu L <24 more author(s)> Li X, Jia Y, Li J, Zhang P, Li T, Lu L, Yao H, Liu J, Zhu Z, Xu J, Morita S, Yamada H, Koga K, Ota W, Furuta T, Yamatsu A, Kim M, Li C, Tang W, Chen S, He J, Zhu X, Li H, Peng Y, Li M, Dai X, Li A, Qi Q, Wang W, Cao J, Jiang Z, Liu R, Suo H, Xu L (- 24) Ref: Molecules, 27:, 2022 : PubMed ESTHER: Li_2022_Molecules_27_ PubMedSearch: Li 2022 Molecules 27 PubMedID: 35630563 35956860 36234873 36296392 Abstract Enzymes are difficult to recycle, which limits their large-scale industrial applications. In this work, an ionic liquid-modified magnetic metal-organic framework composite, IL-Fe(3)O(4)@UiO-66-NH(2), was prepared and used as a support for enzyme immobilization. The properties of the support were characterized with X-ray powder diffraction (XRD), Fourier-transform infrared (FTIR) spectra, transmission electron microscopy (TEM), scanning electronic microscopy (SEM), and so on. The catalytic performance of the immobilized enzyme was also investigated in the hydrolysis reaction of glyceryl triacetate. Compared with soluble porcine pancreatic lipase (PPL), immobilized lipase (PPL-IL-Fe(3)O(4)@UiO-66-NH(2)) had greater catalytic activity under reaction conditions. It also showed better thermal stability and anti-denaturant properties. The specific activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) was 2.3 times higher than that of soluble PPL. After 10 repeated catalytic cycles, the residual activity of PPL-IL-Fe(3)O(4)@UiO-66-NH(2) reached 74.4%, which was higher than that of PPL-Fe(3)O(4)@UiO-66-NH(2) (62.3%). In addition, kinetic parameter tests revealed that PPL-IL-Fe(3)O(4)@UiO-66-NH(2) had a stronger affinity to the substrate and, thus, exhibited higher catalytic efficiency. The results demonstrated that Fe(3)O(4)@UiO-66-NH(2) modified by ionic liquids has great potential for immobilized enzymes. Title: Targeting LIPA independent of its lipase activity is a therapeutic strategy in solid tumors via induction of endoplasmic reticulum stress Liu X, Viswanadhapalli S, Kumar S, Lee TK, Moore A, Ma S, Chen L, Hsieh M, Li M and Raj GV <19 more author(s)> Liu X, Viswanadhapalli S, Kumar S, Lee TK, Moore A, Ma S, Chen L, Hsieh M, Li M, Sareddy GR, Parra K, Blatt EB, Reese TC, Zhao Y, Chang A, Yan H, Xu Z, Pratap UP, Liu Z, Roggero CM, Tan Z, Weintraub ST, Peng Y, Tekmal RR, Arteaga CL, Lippincott-Schwartz J, Vadlamudi RK, Ahn JM, Raj GV (- 19) Ref: Nat Cancer, :, 2022 : PubMed ESTHER: Liu_2022_Nat.Cancer__ PubMedSearch: Liu 2022 Nat.Cancer PubMedID: 35654861 Gene_locus related to this paper: human-LIPA Inhibitor(s) related to this paper: ERX-41 Abstract Triple-negative breast cancer (TNBC) has a poor clinical outcome, due to a lack of actionable therapeutic targets. Herein we define lysosomal acid lipase A (LIPA) as a viable molecular target in TNBC and identify a stereospecific small molecule (ERX-41) that binds LIPA. ERX-41 induces endoplasmic reticulum (ER) stress resulting in cell death, and this effect is on target as evidenced by specific LIPA mutations providing resistance. Importantly, we demonstrate that ERX-41 activity is independent of LIPA lipase function but dependent on its ER localization. Mechanistically, ERX-41 binding of LIPA decreases expression of multiple ER-resident proteins involved in protein folding. This targeted vulnerability has a large therapeutic window, with no adverse effects either on normal mammary epithelial cells or in mice. Our study implicates a targeted strategy for solid tumors, including breast, brain, pancreatic and ovarian, whereby small, orally bioavailable molecules targeting LIPA block protein folding, induce ER stress and result in tumor cell death. Title: Dual-mode colorimetric-photothermal sensing platform of acetylcholinesterase activity based on the peroxidase-like activity of Fe-N-C nanozyme Lu L, Hu X, Zeng R, Lin Q, Huang X, Li M, Tang D Ref: Anal Chim Acta, 1229:340383, 2022 : PubMed ESTHER: Lu_2022_Anal.Chim.Acta_1229_340383 PubMedSearch: Lu 2022 Anal.Chim.Acta 1229 340383 PubMedID: 36156227 Abstract Sensors based on colorimetry, fluorescence, and electrochemistry have been widely employed to detect acetylcholinesterase and its inhibitors, however, there are only a minority of strategies for AChE detection based on photothermal method. This work reports a versatile dual-mode colorimetric and photothermal biosensing platform for acetylcholinesterase (AChE) detection and its inhibitor (paraoxon-ethyl, a model of AChE inhibitors) monitor based on Fe-N-C/H(2)O(2)/3,3',5,5'-tetramethylbenzidine (TMB) system. The Fe-N-C with abundant active Fe-Nx sites shows outstanding peroxidase-mimicking activity and can be used to promote the generation of OH by H(2)O(2) to oxidize TMB. However, the introduction of mercapto molecules tending to coordinate with metal atoms result in the block of action site in Fe-N-C, thereby decrease its peroxidase-mimetic activity. The designed biosensor principle is based on the block of active sites of Fe-N-C by thiocholine (TCh, one kind of mercapto molecules) that can be produced by acetylthiocholine (ATCh) in the presence of AChE. Under optimum conditions, the limit of detection (LOD) for AChE activity is 1.9 mU mL(-1) (colorimetric) and 2.2 mU mL(-1) (photothermal), while for paraoxon-ethyl is 0.012 microg mL(-1) (colorimetric) and 0.013 microg mL(-1) (photothermal), respectively. The assay we proposed not only can be designed to monitor AChE detection and its inhibitors, but also can be easily extended for the detection of other biomolecules relate to the generation or consumption of H(2)O(2). Title: Preparation, characterization and bioactivities of selenized polysaccharides from Lonicera caerulea L. fruits Shao C, Zhong J, Liu J, Yang Y, Li M, YangYu, Xu Y, Wang L Ref: Int J Biol Macromol, :, 2022 : PubMed ESTHER: Shao_2022_Int.J.Biol.Macromol__ PubMedSearch: Shao 2022 Int.J.Biol.Macromol PubMedID: 36403769 Abstract Native polysaccharide was obtained from Lonicera caerulea L. fruits (PLP). Two selenized polysaccharides (PSLP-1 and PSLP-2) were synthesized by the microwave-assisted HNO(3)-Na(2)SeO(3) method, where the selenium (Se) contents were 228 +/-24 and 353 +/- 36 microg/g, respectively. The molecular weights of PLP, PSLP-1, and PSLP-2 were 5.9 10(4), 5.6 10(4), and 5.1 10(4) kDa, respectively. PSLP-1 and PSLP-2 contained the same type of monosaccharides as PLP but with different molar ratios. The main chain structure of the native polysaccharide was not changed after selenization. PLP, PSLP-1, and PSLP-2 contained the same six types of glycosidic bonds. Bioactivity assays revealed that the two selenized polysaccharides possessed better antioxidant activities than PLP, but their bile acid-binding abilities and inhibitory activities on acetylcholinesterase (AChE) had weakened. In summary, PLP, PSLP-1, and PSLP-2 may be promising Se supplements in functional foods and inhibitors for the treatment of AChE. Title: N-glycosylation as an effective strategy to enhance characteristics of Rhizomucor miehei lipase for biodiesel production Tian M, Wang Z, Fu J, Lv P, Liang C, Li Z, Yang L, Liu T, Li M, Luo W Ref: Enzyme Microb Technol, 160:110072, 2022 : PubMed ESTHER: Tian_2022_Enzyme.Microb.Technol_160_110072 PubMedSearch: Tian 2022 Enzyme.Microb.Technol 160 110072 PubMedID: 35689964 Abstract The construction of methanol-resistant lipases with high catalytic activity is world-shattering for biodiesel production. A semi-rational method has been constructed to enhance the properties of Rhizomucor miehei lipase with propeptide (ProRML) by introducing N-glycosylation sites in the Loop structure. The enzyme activities of the mutants N288 (1448.89 +/- 68.64 U/mg) and N142 (1073.68 +/- 33.87 U/mg) increased to 56.09 and 41.56 times relative to that of wild type ProRML (WT, 25.83 +/- 0.73 U/mg), respectively. After incubation in 50 % methanol for 2.5 h, the residual activities of N314 and N174-1 were 95 % and 85%, which were higher than the WT (27 %). Additionally, the biodiesel yield of all mutants was increased after a one-time addition of methanol for 24 h. Among them, N288 increased the quantity of biodiesel from colza oil from 9.49 % to 88 %, and N314 increased the amount of biodiesel from waste soybean oil from 8.44% to 70%. This study provides an effective method to enhance the properties of lipase and improve its application potential in biodiesel production. Title: Cornuside ameliorates cognitive impairments in scopolamine induced AD mice: Involvement of neurotransmitter and oxidative stress Wang ZX, Lian WW, He J, He XL, Wang YM, Pan CH, Li M, Zhang WK, Liu LQ, Xu JK Ref: J Ethnopharmacol, :115252, 2022 : PubMed ESTHER: Wang_2022_J.Ethnopharmacol__115252 PubMedSearch: Wang 2022 J.Ethnopharmacol 115252 PubMedID: 35405255 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Cornus officinalis Sieb. et Zucc., traditional Chinese medicine, has been widely used in the treatment of dementia. Cornel iridoid glycosides of Cornus officinalis is therapeutic to Alzheimer's disease (AD), while its pharmacodynamic material basis is not clear. Cornuside, an iridoid glycoside extracted from of Cornus officinalis Sieb. et Zucc, might be a potential anti-AD candidate. AIM OF THE STUDY: Cornuside was evaluated for its effect on scopolamine induced AD mice, and its action mechanisms were explored. MATERIALS AND METHODS: ICR mice were administered with 1 mg/kg scopolamine intraperitoneally to induce amnesia. The therapeutic effect of cornuside of cognitive function was evaluated via series of behavioral tests, including Morris water maze test, step-through test and step-down test. In addition, specific enzyme reaction tests were used to detect the content of acetylcholine (ACh) and malondialdehyde (MDA), as well as the activities of acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), choline acetyltransferase (ChAT), superoxide dismutase (SOD), catalase (CAT), monoamine oxidase (MAO) in the brain. The levels of monoamine neurotransmitters were detected by high performance liquid chromatography-electrochemical detection (HPLC-ECD). RESULTS: Cornuside ameliorated the spatial memory impairment in Morris water maze test and cognitive disruption in step-through and step-down test. Furthermore, cornuside improved the level of ACh by reducing the activities of AChE and BuChE, and increasing the activity of ChAT in hippocampus. Cornuside also increased the levels of monoamine neurotransmitters by inhibiting MAO activity in hippocampus and cortex. In addition, cornuside attenuated MDA by enhancing the activities of SOD and CAT in hippocampus and cortex. CONCLUSION: Cornuside improved cognitive dysfunction induced by scopolamine in behavioral tests. The mechanisms of cornuside were further investigated from the aspects of neurotransmitters and oxidative stress. Cornuside could inhibit oxidative stress and neurotransmitter hydrolases, increase ACh and monoamine neurotransmitters, which finally contributed to its therapeutic effect on scopolamine induced amnesia. Title: MicroRNA-199a-3p regulates proliferation and milk fat synthesis of ovine mammary epithelial cells by targeting VLDLR Wang J, Hao Z, Hu L, Qiao L, Luo Y, Hu J, Liu X, Li S, Zhao F and Zhao Z <2 more author(s)> Wang J, Hao Z, Hu L, Qiao L, Luo Y, Hu J, Liu X, Li S, Zhao F, Shen J, Li M, Zhao Z (- 2) Ref: Front Vet Sci, 9:948873, 2022 : PubMed ESTHER: Wang_2022_Front.Vet.Sci_9_948873 PubMedSearch: Wang 2022 Front.Vet.Sci 9 948873 PubMedID: 35990270 Abstract In our previous study, microRNA (miR)-199a-3p was found to be the most upregulated miRNA in mammary gland tissue during the non-lactation period compared with the peak-lactation period. However, there have been no reports describing the function of miR-199a-3p in ovine mammary epithelial cells (OMECs) and the biological mechanisms by which the miRNA affects cell proliferation and milk fat synthesis in sheep. In this study, the effect of miR-199a-3p on viability, proliferation, and milk fat synthesis of OMECs was investigated, and the target relationship of the miRNA with very low-density lipoprotein receptor (VLDLR) was also verified. Transfection with a miR-199a-3p mimic increased the viability of OMECs and the number of Edu-labeled positive OMECs. In contrast, a miR-199-3p inhibitor had the opposite effect with the miR-199a-3p mimic. The expression levels of three marker genes were also regulated by both the miR-199a-3p mimic and miR-199-3p inhibitor in OMECs. Together, these results suggest that miR-199a-3p promotes the viability and proliferation of OMECs. A dual luciferase assay confirmed that miR-199a-3p can target VLDLR by binding to the 3'-untranslated regions (3'UTR) of the gene. Further studies found a negative correlation in the expression of miR-199a-3p with VLDLR. The miR-199a-3p mimic decreased the content of triglycerides, as well as the expression levels of six milk fat synthesis marker genes in OMECs, namely, lipoprotein lipase gene (LPL), acetyl-CoA carboxylase alpha gene (ACACA), fatty acid binding protein 3 gene (FABP3), CD36, stearoyl-CoA desaturase gene (SCD), and fatty acid synthase gene (FASN). The inhibition of miR-199a-3p increased the level of triglycerides and the expression of LPL, ACACA, FABP3, SCD, and FASN in OMECs. These findings suggest that miR-199a-3p inhibited milk fat synthesis of OMECs. This is the first study to reveal the molecular mechanisms by which miR-199a-3p regulates the proliferation and milk fat synthesis of OMECs in sheep. Title: Encapsulating gold nanoclusters into metal-organic frameworks to boost luminescence for sensitive detection of copper ions and organophosphorus pesticides Wei D, Li M, Wang Y, Zhu N, Hu X, Zhao B, Zhang Z, Yin D Ref: J Hazard Mater, 441:129890, 2022 : PubMed ESTHER: Wei_2022_J.Hazard.Mater_441_129890 PubMedSearch: Wei 2022 J.Hazard.Mater 441 129890 PubMedID: 36084467 Abstract Gold nanoclusters (Au NCs) with luminescence property are emerging as promising candidates in fluorescent methods for monitoring contaminants, but low luminescence efficiency hampers their extensive applications. Herein, GSH-Au NCs@ZIF-8 was designed by encapsulating GSH-Au NCs with AIE effect into metal-organic frameworks, achieving high luminescence efficiency and good stability through the confinement effect of ZIF-8. Accordingly, a fluorescent sensing platform was constructed for the sensitive detection of copper ions (Cu(2+)) and organophosphorus pesticides (OPs). Firstly, the as-prepared GSH-Au NCs@ZIF-8 could strongly accumulate Cu(2+) due to the adsorption property of MOFs, accompanied by a significant fluorescence quenching effect with a low detection limit of 0.016 microM for Cu(2+). Besides, thiocholine (Tch), the hydrolysis product of acetylthiocholine (ATch) by acetylcholinesterase (AchE), could coordinate with Cu(2+) by sulfhydryl groups (-SH), leading to a significant fluorescence recovery, which was further used for the quantification of OPs owing to its inhibition to AChE activity. Furthermore, a hydrogel sensor was explored to accomplish equipment-free, visual, and quantitative monitoring of Cu(2+) and OPs by a smartphone sensing platform. Overall, this work provides an effective and universal strategy for enhancing the luminescence efficiency and stability of Au NCs, which would greatly promote their applications in contaminants monitoring. Title: The sarcopenia index is an effective predictor for malnutrition in patients with liver cirrhosis Wu YK, Li M, Zhang YC, Gao RZ, Su Y, Zhou Y, Zhao KL, Chen C, Wang WX Ref: Nutr Diet, :, 2022 : PubMed ESTHER: Wu_2022_Nutr.Diet__ PubMedSearch: Wu 2022 Nutr.Diet PubMedID: 35434892 Abstract AIM: Reliable and valid predictors of malnutrition in patients with cirrhosis remain scarce, especially easily accessible blood indicators. Thus, this study aimed to investigate the validity of the sarcopenia index (serum creatinine/serum cystatin C x 100) as a tool in assessing the nutritional status of patients with cirrhosis. METHODS: This prospective cohort study included 109 patients with cirrhosis who were hospitalised in Renmin Hospital of Wuhan University from August 2020 to June 2021. Malnutrition was diagnosed by the Global Leadership Initiative on Malnutrition criteria. Multivariable logistic regression was used to examine the relationship between sarcopenia index and malnutrition. The area under the receiver operating characteristic curve was used to evaluate the diagnostic performance of sarcopenia index. By contrast, we evaluated the subjective global assessment and traditional nutrition-related indicators. RESULTS: Of the 109 included patients, 71 (65.1%) were diagnosed with malnutrition. The sarcopenia index was significantly lower in malnourished patients (56.39 +/- 15.23) compared with well-nourished patients (74.95 +/- 13.18, p < 0.001). In addition, the sarcopenia index was independently correlated with malnutrition (p < 0.001). The sarcopenia index was a good tool to predict malnutrition (area under curve = 0.833), which performed better than the subjective global assessment (area under curve = 0.782) and cholinesterase (area under curve = 0.812). A low sarcopenia index indicated longer hospital stay and higher risk of 90-day re-hospitalisation. CONCLUSION: Malnutrition is highly prevalent in this population. The sarcopenia index seems to be a good predictor in nutritional assessment of patients with cirrhosis. Title: Chlorphoxim induces neurotoxicity in zebrafish embryo through activation of oxidative stress Xiong Y, Wang C, Dong M, Li M, Hu C, Xu X Ref: Environ Toxicol, :, 2022 : PubMed ESTHER: Xiong_2022_Environ.Toxicol__ PubMedSearch: Xiong 2022 Environ.Toxicol PubMedID: 36331003 Abstract It is known that chlorphoxim is a broad-spectrum and high-effective pesticide. With the wide use in agricultural practice, chlorphoxim residue is also frequently detected in water, but its potential toxicity to aquatic life is still unclear. In this study, zebrafish is used as a model to detect the toxicity of chlorphoxim. Our results showed that exposure of high concentration of chlorphoxim at 96 h post-fertilization (hpf) resulted in a high mortality and pericardium edema rate, a low hatchability rate and heart rate. The nervous system damage, swimming behavior alteration and acetylcholinesterase (AChE) inhibition were measured in zebrafish embryos after a 6 days post-fertilization (dpf) of chlorphoxim exposure. The expression of neural-related genes is abnormal in zebrafish embryos. Chlorphoxim exposure significantly increases oxidative stress in zebrafish embryos by inhibiting antioxidant enzyme (SOD and CAT) and activating reactive oxygen species (ROS). As expected, chlorphoxim exposure induces apoptosis by enhancing the expression of apoptotic genes (Bax, Bcl2, and p53). Astaxanthin (ATX), an effective antioxidant, was found to be able to rescue the neurotoxicity of chlorphoxim through relieving oxidative stress and apoptosis. Altogether, the results showed that chlorphoxim exposure led to severe neurotoxicity to zebrafish embryos, which was contributed to a more comprehensive understanding of the safety use of the organophosphorus pesticide. Title: Engineering an Ag/Au bimetallic nanoparticle-based acetylcholinesterase SERS biosensor for in situ sensitive detection of organophosphorus pesticide residues in food Xu S, Li M, Li X, Jiang Y, Yu L, Zhao Y, Wen L, Xue Q Ref: Anal Bioanal Chem, :, 2022 : PubMed ESTHER: Xu_2022_Anal.Bioanal.Chem__ PubMedSearch: Xu 2022 Anal.Bioanal.Chem PubMedID: 36333614 Abstract Developing simple, efficient, and inexpensive method for trace amount organophosphorus pesticides' (OPs) detection with high sensitivity and specificity is of significant importance for guaranteeing food safety. Herein, an Ag/Au bimetallic nanoparticle-based acetylcholinesterase (AChE) surface-enhanced Raman scattering (SERS) biosensor was constructed for in situ simple and sensitive detection of pesticide residues in food. The principle of this biosensor exploited 4-mercaptophenylboronic acid (4-MPBA)-modified Ag/Au bimetallic nanoprobes as SERS signal probe to improve sensitivity and stability. The combination of AChE and choline oxidase (CHO) can hydrolyze acetylcholine (ATCh) to generate H(2)O(2). The product of H(2)O(2) selectively oxidizes the boronate ester of 4-MPBA, decreasing the Raman intensity of the B-O symmetric stretching. In the presence of OPs, it could inhibit the production of H(2)O(2) by destroying the AChE activity, so the reduction of the SERS signal was also alleviated. Based on the principle, an Ag/Au bimetallic nanoparticle-based AChE SERS sensor was established without any complicated pretreatments. Benefiting from the synergistic effects of Ag/Au bimetallic hybrids, a linear detection range from 5x10(-9) to 5x10(-4) M was achieved with a limit of detection down to 1.7x10(-9) M using parathion-methyl (PM) as the representative model of OPs. Moreover, the SERS biosensor uses readily available reagents and is simple to implement. Importantly, the proposed SERS biosensor was used to quantitatively analyze OP residues in apple peels. The levels of OPs detected in real samples by this method were consistent with those obtained using gas chromatography-mass spectrometry (GC-MS), suggesting the proposed assay has great potential applications for OPs in situ detection in food safety fields. Title: Acetylcholinesterase-Cu(3)(PO(4))(2) hybrid nanoflowers for electrochemical detection of dichlorvos using square-wave voltammetry Yang L, Zhang X, Li M, Qu L, Liu Z Ref: Anal Methods, :, 2022 : PubMed ESTHER: Yang_2022_Anal.Methods__ PubMedSearch: Yang 2022 Anal.Methods PubMedID: 36169013 Abstract Immobilization of enzymes is one of the key steps in the development of high-performance enzymatic electrochemical biosensors, and various nanostructured materials have been designed and developed to achieve this goal. Herein, hybrid nanoflowers (HNFs) were synthesized using acetylcholinesterase (AChE) as an organic component and copper phosphate (Cu(3)(PO(4))(2)) as an inorganic component. These AChE-Cu(3)(PO(4))(2) HNFs exhibit a three-dimensional hierarchical flower-like structure, which not only has a large specific surface area but also promotes the affinity between AChE and its substrate with better catalytic activity. Not only that, the surface modification of the glassy carbon electrode (GCE) by the joint use of gold nanoparticles (AuNPs) and graphene oxide (GO) extended the electroactive area. Using square-wave voltammetry (SWV), the as-prepared biosensor (i.e., AChE-Cu(3)(PO(4))(2) HNF/AuNP/GO/GCE) demonstrated superior sensing performance in the detection of dichlorvos. The detection limit is as low as 0.07 pM, and the linear detection range can range from 0.5 pM to 10 microM. In addition, the biosensor was feasible in real agricultural samples with satisfactory recoveries (98.65% to 103.43%). The reported biosensor provides an alternative tool for the direct measurements of AChE activity and its inhibition. Besides organophosphorus pesticides represented by dichlorvos, this biosensor has the potential to detect other AChE inhibitors, such as carbamate pesticides, drugs for Alzheimer's disease, etc., thus having broader applications in food safety and drug screening. Title: Notum Leads to Potential Pro-survival of OSCC Through Crosstalk Between Shh and Wnt/beta-catenin Signaling Via p-GSK3beta Yang P, Li C, Zhou Q, Zhang X, Kou Y, Feng Q, Wang H, Su R, Hasegawa T and Li M <1 more author(s)> Yang P, Li C, Zhou Q, Zhang X, Kou Y, Feng Q, Wang H, Su R, Hasegawa T, Liu H, Li M (- 1) Ref: International Journal of Biochemistryistry & Cell Biology, :106316, 2022 : PubMed ESTHER: Yang_2022_Int.J.Biochem.Cell.Biol__106316 PubMedSearch: Yang 2022 Int.J.Biochem.Cell.Biol 106316 PubMedID: 36280040 Abstract Notum, which belongs to the alpha/beta hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms. Various approaches including bioinformatics analysis, enzyme-linked immunosorbent assay and immunohistochemical staining were used to detect the expression of Notum in OSCC cells and tissues. Cell counting kit-8 assay, clone formation assay, wound healing assay, transwell assay and in-gel zymography assay were explored to evaluate the regulation of Notum in OSCC proliferation and migration. Hoechst 33342/PI assay, cell immunofluorescence, flow cytometry and in vivo tumorigenesis experiment were applied for OSCC apoptosis. Real-time quantitative polymerase chain reaction analysis was performed for mRNA level while western blotting was conducted to detect protein expression. The results showed that Notum was highly expressed in OSCC tissues and cells, and Notum promoted the proliferation and migration of OSCC cells while it inhibited their apoptosis. Furthermore, signaling pathway analysis showed that Notum led to potential pro-survival of OSCC through crosstalk between sonic hedgehog (Shh) and Wnt/beta-catenin signaling via phosphorylation of glycogen synthase kinase-3 beta. These results will help to elucidate the mechanism and also provide new ideas for targeted treatment of OSCC. Title: Development of an esterase fluorescent probe based on naphthalimide-benzothiazole conjugation and its applications for qualitative detection of esterase in orlistat-treated biosamples Yin Y, Kong X, Li M, Wang J, Dai X, Zhang Y, Lin W Ref: Anal Chim Acta, 1190:339248, 2022 : PubMed ESTHER: Yin_2022_Anal.Chim.Acta_1190_339248 PubMedSearch: Yin 2022 Anal.Chim.Acta 1190 339248 PubMedID: 34857133 Abstract Esterase is a large hydrolysis family, and widely distributed in many kinds of cells. It is responsible for multiple physiological and pathological functions including metabolism, gene expression. While abnormality of esterase is associated with many pathological activities in obesity, Wolman's disease, and cancer. Thereby, it is essential to design an effective tool for esterase in situ detection in biological systems. Herein, a novel fluorescent probe Y-1 for monitoring esterase in living cells was rationally designed. Probe Y-1 was synthesized by the conjugation between an acetylation of 4-hydroxy naphthalimide and benzothiazole group. Benzothiazole moiety is a typical Excited-state intramolecular proton transfer (ESIPT) controller. Acetate group was selected as the responsive site and ESIPT initiator. As the acetate group could block the ESIPT effect, the probe emits no fluorescence under the excitation of 455 nm. When binding with esterase, Y-1 shows distinct fluorescence with the peak at 560 nm with short time when ESIPT is on. Y-1 displays high sensitivity (LOD is 0.216 x 10(-3) U/mL), fast response (within 5 min), high selectivity and photostability towards esterase. Furthermore, the %RSD (relative standard deviation) of within-day and day-to-day precision was no more than 13.0% and the accuracy ranged from -6.5 to -12.3%. Kinetics performance of Y-1 indicates that esterase has high affinity and hydrolysis to Y-1. For biological applications, our probe is a time-dependent visualizing esterase in living HepG2 and CoLo205 cells within 15 min. After the treatment of orlistat (1 and 5 microM) for inhibiting the activity of esterase, the bright fluorescence has also been detected using our probe. Furthermore, it has been successful in monitoring the esterase in zebrafish, the data were consistent with cellular phenomena. Therefore, all these findings indicate that the robust probe Y-1 is a useful qualitative tool for detecting esterase in biological systems. Title: Targets and mechanisms of Alpinia oxyphylla Miquel fruits in treating neurodegenerative dementia Zeng P, Liu YC, Wang XM, Ye CY, Sun YW, Su HF, Qiu SW, Li YN, Wang Y and Tian Q <3 more author(s)> Zeng P, Liu YC, Wang XM, Ye CY, Sun YW, Su HF, Qiu SW, Li YN, Wang Y, Wang YC, Ma J, Li M, Tian Q (- 3) Ref: Front Aging Neurosci, 14:1013891, 2022 : PubMed ESTHER: Zeng_2022_Front.Aging.Neurosci_14_1013891 PubMedSearch: Zeng 2022 Front.Aging.Neurosci 14 1013891 PubMedID: 36533181 Abstract The dried and ripe fruits of Alpinia oxyphylla and ripe fruits of Alpinia oxyphylla Miquel (AO) have the effects of tonifying kidney-essence and nourishing intelligence and thus have been widely used in treating dementia. Alzheimer's disease (AD) is a typical form of neurodegenerative dementia with kidney-essence deficiency in Traditional Chinese Medicine (TCM). So far, there is a lack of systematic studies on the biological basis of tonifying kidney-essence and nourishing intelligence and the corresponding phytochemicals. In this study, we investigated the targets of AO in tonifying kidney-essence and nourishing intelligence based on the key pathophysiological processes of neurodegenerative dementia. According to ultra-high-performance liquid chromatography with triple quadrupole mass spectrometry data and Lipinski's rule of five, 49 bioactive phytochemicals from AO were identified, and 26 of them were found to target 168 key molecules in the treatment of neurodegenerative dementia. Nine phytochemicals of AO were shown to target acetylcholinesterase (ACHE), and 19 phytochemicals were shown to target butyrylcholinesterase (BCHE). A database of neurodegenerative dementia with kidney-essence deficiency involving 731 genes was constructed. Furthermore, yakuchinone B, 5-hydroxy-1,7-bis (4-hydroxy-3-methoxyphenyl) heptan-3-one (5-HYD), oxyhylladiketone, oxyphyllacinol, butyl-beta-D-fructopyranoside, dibutyl phthalate, chrysin, yakuchinone A, rhamnetin, and rhamnocitrin were identified as the key phytochemicals from AO that regulate the pathogenesis of neurodegenerative dementia in a multitargeted manner. The approach of studying the pharmacological mechanism underlying the effects of medicinal plants and the biological basis of TCM syndrome may be helpful in studying the translation of TCM. 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: Plin5 Bidirectionally Regulates Lipid Metabolism in Oxidative Tissues Zhang X, Xu W, Xu R, Wang Z, Wang P, Peng K, Li M, Li J, Tan Y and Pei H <1 more author(s)> Zhang X, Xu W, Xu R, Wang Z, Wang P, Peng K, Li M, Li J, Tan Y, Wang X, Pei H (- 1) Ref: Oxid Med Cell Longev, 2022:4594956, 2022 : PubMed ESTHER: Zhang_2022_Oxid.Med.Cell.Longev_2022_4594956 PubMedSearch: Zhang 2022 Oxid.Med.Cell.Longev 2022 4594956 PubMedID: 35401929 Abstract Cytoplasmic lipid droplets (LDs) can store neutral lipids as an energy source when needed and also regulate the key metabolic processes of intracellular lipid accumulation, which is associated with several metabolic diseases. The perilipins (Plins) are a family of proteins that associate with the surface of LDs. As a member of Plins superfamily, perilipin 5 (Plin5) coats LDs in cardiomyocytes, which is significantly related to reactive oxygen species (ROS) production originated from mitochondria in the heart, consequently determining the progression of diabetic cardiomyopathy. Plin5 may play a bidirectional function in lipid metabolism which is in a state of dynamic balance. In the basic state, Plin5 inhibited the binding of comparative gene identification-58 (CGI-58) to adipose triglyceride lipase (ATGL) by binding CGI-58, thus inhibiting lipolysis. However, when the body is under stress (such as cold, fasting, exercise, and other stimuli), protein kinase A (PKA) phosphorylates and activates Plin5, which then causes Plin5 to release the binding site of CGI-58 and ATGL, prompting CGI-58 to bind to ATGL and activate ATGL activity, thus accelerating the lipolysis process, revealing the indispensable role of Plin5 in lipid turnover. Here, the purpose of this review is to summarize the present understanding of the bidirectional regulation role of Plin5 in oxidative tissues and to reveal its potential role in diabetic cardiomyopathy protection. Title: Administration of Huperzine A microspheres ameliorates myocardial ischemic injury via alpha7nAChR-dependent JAK2/STAT3 signaling pathway Zhang C, Li M, Xie W, You C, Wang T, Fu F Ref: European Journal of Pharmacology, 940:175478, 2022 : PubMed ESTHER: Zhang_2022_Eur.J.Pharmacol_940_175478 PubMedSearch: Zhang 2022 Eur.J.Pharmacol 940 175478 PubMedID: 36563953 Abstract Acetylcholinesterase (AChE) inhibitor (AChEI) is well established as rst-line agents for relieving the symptoms of Alzheimer's disease (AD). Injectable sustained-release formulation of AChEI may be suitable for treating AD patients. However, it needs to know whether continuous inhibition of AChE could deteriorate or attenuate myocardial damage if myocardial ischemia (MI) occurs. Huperzine A microspheres (HAM) are a sustained-release formulation releasing sustainably huperzine A (an AChEI) for more than 7 days after a single dose of HAM. This study aimed to investigate the myocardial damage in an isoprenaline (ISO)-induced MI mice model during HAM treatment. The heart injury was evaluated by assaying serum CK-MB, Tn-I and observing histopathological changes. The levels of proinflammatory cytokines in serum were detected. The level of p-P65 and the expression of proteins in the JAK2/STAT3 signaling pathway were assayed with Western blot. Administration with a single dose of HAM resulted in inhibiting the MI-induced increases of CK-MB and Tn-I, alleviating the damage of heart tissue, and decreasing the levels of TNF-alpha and IL-6. In addition, HAM decreased the levels of p-P65, p-JAK2, and p-STAT3 in heart tissue. The effects of HAM could be weakened or abolished by the specific alpha7nAChR antagonist. These findings suggest that continuous AChE inhibition could protect the heart from ischemic damage during administration of sustained-release formulation of AChEI, which is associated with the anti-inflammatory effect of HAM by regulating alpha7nAChR-dependent JAK2/STAT3 signaling pathway. Title: Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster Zhu K, Li M, Wu H, Zhang D, Dong L, Wu Q, Chen Y, Xie J, Lu P and Hua W <13 more author(s)> Zhu K, Li M, Wu H, Zhang D, Dong L, Wu Q, Chen Y, Xie J, Lu P, Guo G, Zhang H, Zhang P, Li B, Li W, Wang Q, Zhu J, Hu W, Guo L, Wang R, Yuan C, Li H, Liu Z, Hua W (- 13) Ref: Theor Appl Genet, :, 2022 : PubMed ESTHER: Zhu_2022_Theor.Appl.Genet__ PubMedSearch: Zhu 2022 Theor.Appl.Genet PubMedID: 35006335 Abstract Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars. Title: Functional characterization of CYP6G4 from the house fly in propoxur metabolism and resistance Zhu J, Feng J, Tian K, Li C, Li M, Qiu X Ref: Pestic Biochem Physiol, 187:105186, 2022 : PubMed ESTHER: Zhu_2022_Pestic.Biochem.Physiol_187_105186 PubMedSearch: Zhu 2022 Pestic.Biochem.Physiol 187 105186 PubMedID: 36127048 Abstract The house fly (Musca domestica L.) (Diptera: Muscidae) is a global vector that can transmit >250 human and animal diseases. The control of house flies has heavily relied on the application of various chemical insecticides. The carbamate insecticide propoxur has been widely used for the control of house flies, and resistance to propoxur has been documented in many house fly populations worldwide. Previous studies have identified several propoxur resistance-conferring mutations in the target protein acetylcholinesterase; however, the molecular basis for metabolic resistance to propoxur remains unknown. In this study, we investigated the involvement of CYP6G4, a cytochrome P450 overexpressed in many insecticide resistant populations of Musca domestica, in propoxur metabolism and resistance by using combined approaches of recombinant protein-based insecticide metabolism and the Drosophila GAL4/UAS transgenic system. The recombinant CYP6G4 and its redox partners (NADPH-dependent cytochrome P450 reductase and cytochrome b5) were functionally expressed in Escherichia coli. Metabolism experiments showed that CYP6G4 was able to transform propoxur with a turnover rate of around 0.79 min(-1). Six metabolites were putatively identified, suggesting that CYP6G4 could metabolize propoxur via hydroxylation, O-depropylation and N-demethylation. Moreover, bioassay results showed that ectopic overexpression of CYP6G4 in fruit flies significantly increased their tolerance to propoxur. Our in vivo and in vitro data convincingly demonstrate that CYP6G4 contributes to propoxur metabolism and resistance. Title: Molecular and functional characterization of three novel carboxylesterases in the detoxification of permethrin in the mosquito, Culex quinquefasciatus Gong Y, Li M, Li T, Liu N Ref: Insect Sci, :, 2021 : PubMed ESTHER: Gong_2021_Insect.Sci__ PubMedSearch: Gong 2021 Insect.Sci PubMedID: 34048147 Gene_locus related to this paper: culqu-b0xfi1, culqu-b0xfi2, culqu-b0xfi3 Abstract Carboxylesterases (CarEs) belong to a super family of multifunctional enzymes associated with the degradation of endogenous and exogenous compounds. Many insect CarEs are known to play important roles in catalyzing the hydrolysis of organophosphates (OPs), carbamates, and synthetic pyrethroids (SPs). The elevation of esterase activity through gene amplification and overexpression of estalpha2 and estbeta2 genes contributes to the development of resistance to OP insecticides in the mosquito Culex quinquefasciatus. Three additional CarE genes are upregulated in permethrin-resistant Cx. quinquefasciatus according to an RNA-seq analysis, but their function remains unknown. In this study, we, for the first time, characterized the function of these three novel genes using in vitro protein expression, an insecticide metabolism study and molecular docking analysis. All three CarE genes were significantly overexpressed in resistant mosquito larvae, but not adults, compared to susceptible strain. No gene copy differences in these three genes were found in the mosquitoes tested. In vitro high-performance liquid chromatography (HPLC) revealed that CPIJ018231, CPIJ018232, and CPIJ018233 metabolized 30.4% +/- 2.9%, 34.7% +/- 6.8%, and 23.2% +/- 2.2% of the permethrin, respectively. No mutations in resistant strains might significantly affect their CarE hydrolysis ability. A docking analysis further confirmed that these three CarEs from resistant strain all potentially metabolize permethrin. Taken together, these three carboxylesterase genes could play important roles in the development of permethrin resistance in Cx. quinquefasciatus larvae through transcriptional overexpression, metabolism, and detoxification. Title: Acetylcholinesterase target sites for developing environmentally friendly insecticides against Tetranychus urticae (Acari: Tetranychidae) Li C, Cao Y, Yang J, Li M, Li B, Bu C Ref: Exp Appl Acarol, :, 2021 : PubMed ESTHER: Li_2021_Exp.Appl.Acarol__ PubMedSearch: Li 2021 Exp.Appl.Acarol PubMedID: 33914192 Abstract The non-target toxicity and resistance problems of acetylcholinesterase (AChE) insecticides, such as organophosphates and carbamates, are of growing concern. To explore the potential targets for achieving inhibitor selectivity, the AChE structures at or near the catalytic pocket of Tetranychus urticae (TuAChE), honey bees, and humans were compared. The entrances to the AChE catalytic pocket differ significantly because of their different peripheral sites. The role of these potential mite-specific sites in AChE function was further elucidated by site-directed mutagenesis of these sites and then examining the catalytic activities of TuAChE mutants. The spider mite E(316), H(369), and V(105) active sites are important for AChE function. By further analyzing their physostigmine inhibitory properties and the detailed interaction between physostigmine and TuAChE, the peripheral site H(369) locating near the gorge entrance, and S(154) at the oxyanion hole, affects substrate and inhibitor trafficking. The discovery of conserved mite-specific residues in Tetranychus will enable the development of safer, effective pesticides that target residues present only in mite AChEs, potentially offering effective control against this important agricultural pest. Title: IL-6 downregulates hepatic carboxylesterases via NF-kappaB activation in dextran sulfate sodium-induced colitis Li M, Lan L, Zhang S, Xu Y, He W, Xiang D, Liu D, Ren X, Zhang C Ref: Int Immunopharmacol, 99:107920, 2021 : PubMed ESTHER: Li_2021_Int.Immunopharmacol_99_107920 PubMedSearch: Li 2021 Int.Immunopharmacol 99 107920 PubMedID: 34217990 Abstract Ulcerative colitis (UC) is associated with increased levels of inflammatory factors, which is attributed to the abnormal expression and activity of enzymes and transporters in the liver, affecting drug disposition in vivo. This study aimed to examine the impact of intestinal inflammation on the expression of hepatic carboxylesterases (CESs) in a mouse model of dextran sulfate sodium (DSS)-induced colitis. Two major CESs isoforms, CES1 and CES2, were down-regulated, accompanied by decreases in hepatic microsomal metabolism of clopidogrel and irinotecan. Meanwhile, IL-6 levels significantly increased compared with other inflammatory factors in the livers of UC mice. In contrast, using IL-6 antibody simultaneously reversed the down-regulation of CES1, CES2, pregnane X receptor (PXR), and constitutive androstane receptor (CAR), as well as the nuclear translocation of NF-kappaB in the liver. We further confirmed that treatment with NF-kappaB inhibitor abolished IL-6-induced down-regulation of CES1, CES2, PXR, and CAR in vitro. Thus, it was concluded that IL-6 represses hepatic CESs via the NF-kappaB pathway in DSS-induced colitis. These findings indicate that caution should be exercised concerning the proper and safe use of therapeutic drugs in patients with UC. Title: Prednisolone induces osteocytes apoptosis by promoting Notum expression and inhibiting PI3K/AKT/GSK3beta/beta-catenin pathway Li C, Yang P, Liu B, Bu J, Liu H, Guo J, Hasegawa T, Si H, Li M Ref: J Mol Histol, :, 2021 : PubMed ESTHER: Li_2021_J.Mol.Histol__ PubMedSearch: Li 2021 J.Mol.Histol PubMedID: 34297260 Abstract The apoptosis of mature osteocytes is the main factor causing damage to the microstructure of cortical bone in glucocorticoid-induced osteoporosis (GIOP). Our previous research found damaged areas and empty osteocytes lacunae in the tibial cortical bone of GIOP mice. However, the specific mechanism has not been clarified. Recently, a study showed that the quality of the cortical bone significantly increased by knocking out Notum, a gene encoding alpha/beta hydrolase. However, it is not clear whether Notum affects cortical bone remodeling by participating in glucocorticoids (GCs)-induced apoptosis of osteocytes. The present study aimed to explore the correlation between Notum, osteocytes apoptosis, and cortical bone quality in GIOP. Prednisolone acetate was intragastrically administered to mice for two weeks. Histochemical staining was applied to evaluate changes in GIOP and Notum expression. Osteocytes were stimulated with prednisolone, and cell viability was assessed via CCK8. Hoechst 33342/PI staining, flow cytometry, RT-PCR, and western blot were used to detect osteocytes apoptosis, siRNA transfection efficiency, and expressions of pathway related factors. The results showed that the number of empty osteocytes lacunae increased in GIOP mice. TUNEL-stained apoptotic osteocytes and Notum immuno-positive osteocytes were also observed. Furthermore, prednisolone was found to promote Notum expression and osteocytes apoptosis in vitro. Knocking down Notum via siRNA partially restored osteocytes apoptosis and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta (GSK3beta)/beta-catenin pathway. These findings showed GCs-induced osteocytes apoptosis by promoting Notum expression and inhibiting PI3K/AKT/GSK3beta/beta-catenin pathway. Thus, Notum might be a potential therapeutic target for the treatment of GIOP. Title: Reduced neuropathy target esterase in pre-eclampsia suppresses tube formation of HUVECs via dysregulation of phospholipid metabolism Li M, Shen X, Liu H, Yang B, Lu S, Tang M, Ling Y, Li Y, Kuang H Ref: Journal of Cellular Physiology, 236:4435, 2021 : PubMed ESTHER: Li_2021_J.Cell.Physiol_236_4435 PubMedSearch: Li 2021 J.Cell.Physiol 236 4435 PubMedID: 33184906 Abstract Recently, studies have shown that neuropathy target esterase (NTE) is essential to placental and normal blood vessel development. However, whether it is involved in abnormal placenta angiogenesis of pre-eclampsia remains unknown. Thus, our aim was to observe the expression of NTE in pre-eclamptic placentas and its effects and mechanism of NTE on the migration and the tube formation of human umbilical vein endothelial cells (HUVECs). Immunohistochemical staining showed that the NTE protein was intensely located in blood vessels of the normal pregnant placenta. However, western blot revealed that the expression level of NTE protein was significantly reduced in pre-eclamptic placenta. The results indicated that overexpression of NTE significantly promoted the migration and the tube formation of HUVECs compared with those of the control and scramble short hairpin RNA (shRNA) group. Conversely, NTE shRNA obviously inhibited the migration and the tube formation of HUVECs. Additionally, chromatography assay evidenced that NTE overexpression significantly reduced the level of phosphatidylcholine (PC) of HUVECs, but NTE shRNA obviously increased the level of PC of HUVECs. Furthermore, exogenous PC and lysophosphatidylcholine (LPC) significantly inhibited the tube formation of HUVECs in a dose-dependent manner. Collectively, our results suggest that reduced NTE in placenta may contribute to abnormal placenta angiogenesis of pre-eclampsia via the dysregulation of PC and LPC metabolism. Title: Impact of Peripheral alpha7-Nicotinic Acetylcholine Receptors on Cardioprotective Effects of Donepezil in Chronic Heart Failure Rats Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Akiyama T, Sugimachi M Ref: Cardiovasc Drugs Ther, 35:877, 2021 : PubMed ESTHER: Li_2021_Cardiovasc.Drugs.Ther_35_877 PubMedSearch: Li 2021 Cardiovasc.Drugs.Ther 35 877 PubMedID: 32860618 Abstract PURPOSE: Pharmacological modulation of parasympathetic activity with donepezil, an acetylcholinesterase inhibitor, improves the long-term survival of rats with chronic heart failure (CHF) after myocardial infarction (MI). However, its mechanism is not well understood. The alpha7-nicotinic acetylcholine receptor (alpha7-nAChR) reportedly plays an important role in the cholinergic anti-inflammatory pathway. The purpose of this study was to examine whether blockade of alpha7-nAChR, either centrally or peripherally, affects cardioprotection by donepezil during CHF. METHODS: One-week post-MI, the surviving rats were implanted with an electrocardiogram or blood pressure transmitter to monitor hemodynamics continuously. Seven days after implantation, the MI rats (n=74) were administered donepezil in drinking water or were untreated (UT). Donepezil-treated MI rats were randomly assigned to the following four groups: peripheral infusion of saline (SPDT) or an alpha7-nAChR antagonist methyllycaconitine (alpha7PDT), and brain infusion of saline (SBDT) or the alpha7-nAChR antagonist (alpha7BDT). RESULTS: After the 4-week treatment, the role of alpha7-nAChR was evaluated using hemodynamic parameters, neurohumoral states, and histological and morphological assessment. Between the peripheral infusion groups, alpha7PDT (vs. SPDT) showed significantly increased heart weight and cardiac fibrosis, deteriorated hemodynamics, increased plasma neurohumoral and cytokine levels, and significantly decreased microvessel density (as assessed by anti-von Willebrand factor-positive cells). In contrast, between the brain infusion groups, alpha7BDT (vs. SBDT) showed no changes in either cardiac remodeling or hemodynamics. CONCLUSION: Peripheral blockade of alpha7-nAChR significantly attenuated the cardioprotective effects of donepezil in CHF rats, whereas central blockade did not. This suggests that peripheral activation of alpha7-nAChR plays an important role in cholinergic pharmacotherapy for CHF. Title: An ABHD17-like hydrolase screening system to identify de-S-acylation enzymes of protein substrates in plant cells Liu X, Li M, Li Y, Chen Z, Zhuge C, Ouyang Y, Zhao Y, Lin Y, Xie Q and Lai J <1 more author(s)> Liu X, Li M, Li Y, Chen Z, Zhuge C, Ouyang Y, Zhao Y, Lin Y, Xie Q, Yang C, Lai J (- 1) Ref: Plant Cell, :, 2021 : PubMed ESTHER: Liu_2021_Plant.Cell__ PubMedSearch: Liu 2021 Plant.Cell PubMedID: 34338800 Gene_locus related to this paper: arath-AT1G66900, arath-AT2G24320, arath-AT4G31020, arath-AT5G20520, arath-AT5G38220, arath-F3C3.3, arath-AT1G13610, arath-At5g14390, arath-F22K18.40, arath-At3g01690, arath-Q9LI62 Abstract Protein S-acylation is an important post-translational modification in eukaryotes, regulating the subcellular localization, trafficking, stability, and activity of substrate proteins. The dynamic regulation of this reversible modification is mediated inversely by protein S-acyltransferases and de-S-acylation enzymes, but the de-S-acylation mechanism remains unclear in plant cells. Here we characterized a group of putative protein de-S-acylation enzymes in Arabidopsis thaliana, including 11 members of ABHD17 (Alpha/Beta Hydrolase Domain-containing Protein 17)-like Acyl Protein Thioesterases (ABAPTs). A robust system was then established for the screening of de-S-acylation enzymes of protein substrates in plant cells, based on the effects of substrate localization and confirmed via the protein S-acylation levels. Using this system, the ABAPTs, which specifically reduced the S-acylation levels and disrupted the plasma membrane localization of five immunity-related proteins, were identified respectively in Arabidopsis. Further results indicated that the de-S-acylation of RIN4 (RPM1 Interacting Protein 4), which was mediated by ABAPT8, resulted in an increase of cell death in Arabidopsis and Nicotiana benthamiana, supporting the physiological role of the ABAPTs in plants. Collectively, our current work provides a powerful and reliable system to identify the pairs of plant protein substrates and de-S-acylation enzymes for further studies on the dynamic regulation of plant protein S-acylation. Title: A survey of insecticide resistance-conferring mutations in multiple targets in Anopheles sinensis populations across Sichuan, China Qian W, Liu N, Yang Y, Liu J, He J, Chen Z, Li M, Qiu X Ref: Parasit Vectors, 14:169, 2021 : PubMed ESTHER: Qian_2021_Parasit.Vectors_14_169 PubMedSearch: Qian 2021 Parasit.Vectors 14 169 PubMedID: 33743789 Abstract BACKGROUND: Sichuan province is located in the southwest of China, and was previously a malaria-endemic region. Although no indigenous malaria case has been reported since 2011, the number of imported cases is on the rise. Insecticide-based vector control has played a central role in the prevention of malaria epidemics. However, the efficacy of this strategy is gravely challenged by the development of insecticide resistance. Regular monitoring of insecticide resistance is essential to inform evidence-based vector control. Unfortunately, almost no information is currently available on the status of insecticide resistance and associated mechanisms in Anopheles sinensis, the dominant malaria vector in Sichuan. In this study, efforts were invested in detecting the presence and frequency of insecticide resistance-associated mutations in three genes that encode target proteins of several classes of commonly used insecticides. METHODS: A total of 446 adults of An. sinensis, collected from 12 locations across Sichuan province of China, were inspected for resistance-conferring mutations in three genes that respectively encode acetylcholinesterase (AChE), voltage-gated sodium channel (VGSC), and GABA receptor (RDL) by DNA Sanger sequencing. RESULTS: The G119S mutation in AChE was detected at high frequencies (0.40-0.73). The predominant ace-1 genotype was GGC/AGC (119GS) heterozygotes. Diverse variations at codon 1014 were found in VGSC, leading to three different amino acid substitutions (L1014F/C/S). The 1014F was the predominant resistance allele and was distributed in all 12 populations at varying frequencies from 0.03 to 0.86. The A296S mutation in RDL was frequently present in Sichuan, with 296SS accounting for more than 80% of individuals in six of the 12 populations. Notably, in samples collected from Chengdu (DJY) and Deyang (DYMZ), almost 30% of individuals were found to be resistant homozygotes for all three targets. CONCLUSIONS: Resistance-related mutations in three target proteins of the four main classes of insecticides were prevalent in most populations. This survey reveals a worrisome situation of multiple resistance genotypes in Sichuan malaria vector. The data strengthen the need for regular monitoring of insecticide resistance and establishing a region-customized vector intervention strategy. Title: An amplified fluorescence polarization assay for sensitive sensing of organophosphorus pesticides via MnO(2) nanosheets Qin Y, Ye G, Liang H, Li M, Zhao J Ref: Spectrochim Acta A Mol Biomol Spectrosc, 269:120759, 2021 : PubMed ESTHER: Qin_2021_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_269_120759 PubMedSearch: Qin 2021 Spectrochim.Acta.A.Mol.Biomol.Spectrosc 269 120759 PubMedID: 34968836 Abstract It is highly desirable to develop a simple, efficient and sensitive strategy for organophosphorus pesticides (OPs) in both environment pollution and human health. Herein, a novel amplified fluorescence polarization (FP) biosensor was established for highly sensitive detection of OPs using MnO(2) nanosheets as the signal enhancer. In this system, OPs can suppress the activity of acetylcholinesterase (AChE) efficiently, blocking the hydrolysis reaction of acetylthiocholine (ATCh) to generate thiocholine (TCh) by AChE. TCh can lead the decomposition of MnO(2) nanosheets to manganese ions. So, without the influence of TCh, MnO(2) nanosheets can maintain its original shape and form a stable complex with FAM-DNA, which greatly enhanced the FP signal. This method can tremendously improve the sensitivity of FP with a detection limit of 0.01 ng/mL for diazinon. In addition, it was also applicable to determine other four OPs and investigate the level of diazinon in real water samples. Consequently, the proposed approach provides a new promising platform for detection of OPs and is expected to be used in application of environmental monitoring. Title: Multiple Genetic Mutations Related to Insecticide Resistance are Detected in Field Kazakhstani House Flies (Muscidae: Diptera) Qu R, Zhu J, Li M, Jashenko R, Qiu X Ref: Journal of Medical Entomology, :, 2021 : PubMed ESTHER: Qu_2021_J.Med.Entomol__ PubMedSearch: Qu 2021 J.Med.Entomol PubMedID: 34197608 Abstract The house fly (Musca domestica Linnaeus) is an important disease vector. Insecticide resistance is an obstacle to effective house fly control. Previous studies have demonstrated that point mutations in acetylcholinesterase (Ace), carboxylesterase (MdalphaE7) and voltage-sensitive sodium channel (Vssc), and over-expression of CYP6D1v1 confer insecticide resistance in the house fly. However, information about the status and underlying mechanisms of insecticide resistance in Kazakhstani house flies is lacking. In this study, we investigated the occurrence of genetic mutations associated with insecticide resistance in field house flies collected at six different locations in southern Kazakhstan. Four mutations (V260L, G342A/V, and F407Y) in Ace and three mutations (G137D and W251L/S) in MdalphaE7 were detected with appreciable frequencies. Notably, haplotypes carrying triple-loci mutations in Ace and double mutations in MdalphaE7 were found in Kazakhstan. The L1014H and L1014F mutations in Vssc, and CYP6D1v1 resistance allele were detected at a low frequency in some of the six investigated house fly populations. Phylogenetic analyses of haplotypes supported multiple origins of resistance mutations in Ace and MdalphaE7. These observations suggest that house flies in southern Kazakhstan may exhibit significant resistance to organophosphates and carbamates. Regular monitoring of insecticide resistance is recommended to achieve effective house fly control by chemical agents in southern Kazakhstan. Title: Enhancing bio-catalytic performance of lipase immobilized on ionic liquids modified magnetic polydopamine Suo H, Li M, Liu R, Xu L Ref: Colloids Surf B Biointerfaces, 206:111960, 2021 : PubMed ESTHER: Suo_2021_Colloids.Surf.B.Biointerfaces_206_111960 PubMedSearch: Suo 2021 Colloids.Surf.B.Biointerfaces 206 111960 PubMedID: 34224932 Abstract In this study, imidazolium-based ionic liquid with [tf(2)N](-) as the anion was successfully grafted to magnetic polydopamine nanoparticles (MPDA). The prepared materials were well characterized and used as supports for lipase immobilization. The immobilized lipase (PPL-ILs-MPDA) exhibited excellent activity and stability. The specific activity of PPL-ILs-MPDA was 2.15 and 1.49 folds higher than that of free PPL and PPL-MPDA. In addition, after 10 rounds of reuse, the residual activity of PPL-ILs-MPDA was 86.2 % higher than that of PPL-MPDA (75.4 %). Furthermore, the kinetic assay indicated that the affinity between PPL-ILs-MPDA and substrate had increased. Analysis of the secondary structure using circular dichroism was used to explain the mechanism underlying the improvement in the performance of PPL-ILs-MPDA. In addition, the immobilized lipase can be easily separated from the reaction system with a magnet. The observations regarding the development of new supports for lipase immobilization may provide new ideas regarding further studies in this field. Title: Improved methanol tolerance of Rhizomucor miehei lipase based on Nglycosylation within the alpha-helix region and its application in biodiesel production Tian M, Yang L, Wang Z, Lv P, Fu J, Miao C, Li M, Liu T, Luo W Ref: Biotechnol Biofuels, 14:237, 2021 : PubMed ESTHER: Tian_2021_Biotechnol.Biofuels_14_237 PubMedSearch: Tian 2021 Biotechnol.Biofuels 14 237 PubMedID: 34911574 Abstract BACKGROUND: Liquid lipases are widely used to convert oil into biodiesel. Methanol-resistant lipases with high catalytic activity are the first choice for practical production. Rhizomucor miehei lipase (RML) is a single-chain alpha/beta-type protein that is widely used in biodiesel preparation. Improving the catalytic activity and methanol tolerance of RML is necessary to realise the industrial production of biodiesel. RESULTS: In this study, a semi-rational design method was used to optimise the catalytic activity and methanol tolerance of ProRML. After N-glycosylation modification of the alpha-helix of the mature peptide in ProRML, the resulting mutants N218, N93, N115, N260, and N183 increased enzyme activity by 66.81, 13.54, 10.33, 3.69, and 2.39 times than that of WT, respectively. The residual activities of N218 and N260 were 88.78% and 86.08% after incubation in 50% methanol for 2.5 h, respectively. In addition, the biodiesel yield of all mutants was improved when methanol was added once and reacted for 24 h with colza oil as the raw material. N260 and N218 increased the biodiesel yield from 9.49% to 88.75% and 90.46%, respectively. CONCLUSIONS: These results indicate that optimising N-glycosylation modification in the alpha-helix structure is an effective strategy for improving the performance of ProRML. This study provides an effective approach to improve the design of the enzyme and the properties of lipase mutants, thereby rendering them suitable for industrial biomass conversion. Title: Responses of Asian clams (Corbicula fluminea) to low concentration cadmium stress: Whether the depuration phase restores physiological characteristics Wang Z, Kong F, Fu L, Li Y, Li M, Yu Z Ref: Environ Pollut, 284:117182, 2021 : PubMed ESTHER: Wang_2021_Environ.Pollut_284_117182 PubMedSearch: Wang 2021 Environ.Pollut 284 117182 PubMedID: 33901982 Abstract The effect of low concentration Cd stress on bivalves is unclear. In this study, Asian clams (Corbicula fluminea) were continuously exposed to 0, 0.05, 0.10, and 0.20 mg/L Cd for 14 d (exposure phase) and to artificial freshwater for 7 d (depuration phase). A total of 16 variables were measured to explore the toxic effects on C. fluminea. All physiological characteristics were significantly inhibited in the treatments (p < 0.05), and the negative effects of Cd did not return to normal levels in the short term. Tissue damage was found in the feet and gills of C. fluminea in all the treatments. On the 7th day (D7), enzyme activity in all the treatments was significantly higher (p < 0.05) than in the control group. Acetylcholinesterase, superoxide dismutase, and catalase activities were enhanced on D14 in all the treatments. However, only glutathione S-transferase activity was significantly higher in all the treatments (p < 0.05) than in the control group on D21. The instability of the enzymes indicated that the adaptability of C. fluminea became stronger throughout the experiment. In each group, the maximum bioaccumulation of Cd followed the order: 0.20 mg/L > 0.05 mg/L > 0.10 mg/L, which might be caused by the filtration capacity of C. fluminea in the 0.05-mg/L group, which was higher than that of the 0.10-mg/L group. Thus, low Cd concentrations effect the physiological characteristics, tissue health, and antioxidant system of C. fluminea and may require a long recovery time to be restored to normal levels. Title: Notum suppresses the osteogenic differentiation of periodontal ligament stem cells through the Wnt/Beta catenin signaling pathway Yang P, Li C, Kou Y, Jiang Y, Li D, Liu S, Lu Y, Hasegawa T, Li M Ref: Archives of Oral Biology, 130:105211, 2021 : PubMed ESTHER: Yang_2021_Arch.Oral.Biol_130_105211 PubMedSearch: Yang 2021 Arch.Oral.Biol 130 105211 PubMedID: 34352447 Abstract OBJECTIVES: The aims of this study were to explore: (i) the effect of Notum on periodontitis in vivo; (ii) the effect of Notum on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro; and (iii) the potential mechanism of Notum in inhibiting the osteogenic differentiation of hPDLSCs. DESIGN: C57BL/6J mice were randomly assigned into two groups: control group (n = 4) and periodontitis group (n = 4). Immunohistochemical staining was used to evaluate the expression of Notum. In in vitro experiments, Western blot, qRT- PCR and ELISA were used to examine the expression of Notum in a lipopolysaccharide-induced inflammation model. Alkaline phosphatase staining was used to evaluate alkaline phosphatase activity. Western blot and qRT - PCR were used to measure the expression of osteogenic-related markers after adding human recombinant Notum and Notum inhibitor ABC99. In addition, LiCl, an agonist of the Wnt/Beta-catenin signaling pathway, was added to explore using Western blot whether Notum was involved in regulating the osteogenic differentiation of human periodontal ligament stem cells through the Wnt/Beta-catenin signaling pathway. RESULTS: Notum was highly expressed in periodontal tissues of mice and lipopolysaccharide-induced inflammation cell model. The protein and messenger ribonucleic acid levels of hPDLSCs osteogenic markers were reduced after adding human recombinant Notum. However, the inhibitory effect of Notum on the osteogenic differentiation of hPDLSCs could be significantly reversed by adding LiCl. CONCLUSION: These results demonstrated that Notum inhibited the osteogenic differentiation of hPDLSCs probably via the Wnt/Beta-catenin the downstream signaling pathway. Title: Comparative assessment of neurotoxicity impacts induced by alkyl tri-n-butyl phosphate and aromatic tricresyl phosphate in PC12 cells Chang Y, Cui H, Jiang X, Li M Ref: Environ Toxicol, 35:1326, 2020 : PubMed ESTHER: Chang_2020_Environ.Toxicol_35_1326 PubMedSearch: Chang 2020 Environ.Toxicol 35 1326 PubMedID: 32662595 Abstract Organophosphate flame retardants (OPFRs) have become a growing concern due to their potential environmental and health risk. However, limited studies have described the toxicity, particularly neurotoxicity of alkyl and aromatic OPFRs. This study investigated the neurotoxicity of alkyl tri-n-butyl phosphate (TnBP) and aromatic tricresyl phosphate (TCP) to rat adrenal pheochromocytoma (PC12) cells for 24h. Viability detection showed dose-response toxicity effect of TCP and TnBP to PC12 cells. The half-maximal inhibitory concentration of 24h (24h-IC(50) ) of TCP and TnBP were 2415.61 and 338.09microM, respectively. Both TnBP and TCP significantly changed the acetylcholinesterase (AChE) activity, and TnBP is more likely to cause neurotoxicity to PC12 cells compared to TCP. Also, The results of LDH and caspase-3 activity detection as well as Hoechst staining suggested that cell apoptosis induced by TCP and TnBP may be the primary pathway. These findings provide a toxicity data of aromatic and alkyl-substituted OPFRs to PC12 cells, and a new insight into the toxicity of OPFRs on health risk assessment. Title: Susceptibility of Four Species of Aphids in Wheat to Seven Insecticides and Its Relationship to Detoxifying Enzymes Gong P, Chen D, Wang C, Li M, Li X, Zhang Y, Zhu X Ref: Front Physiol, 11:623612, 2020 : PubMed ESTHER: Gong_2020_Front.Physiol_11_623612 PubMedSearch: Gong 2020 Front.Physiol 11 623612 PubMedID: 33536942 Abstract Sitobion avenae (Fabricius), Rhopalosiphum padi (Linnaeus), Schizaphis graminum (Rondani), and Metopolophium dirhodum (Walker) (Hemiptera: Aphididae) are important pests of wheat and other cereals worldwide. In this study, the susceptibilities of four wheat aphid species to seven insecticides were assessed. Furthermore, the activities of carboxylesterase (CarE), glutathione S-transferase (GSTs), and cytochrome P450 monooxygenase (P450s) were determined in imidacloprid treated and untreated aphids. The results showed that the susceptibilities of four wheat aphid species to tested insecticides are different and M. dirhodum has shown higher tolerance to most insecticides. Relatively higher CarE and GST activities were observed in M. dirhodum, and P450s activities increased significantly in response to imidacloprid treatment. Moreover, susceptibility to imidacloprid were increased by the oxidase inhibitor piperonyl butoxide in M. dirhodum (20-fold). The results we have obtained imply that P450s may play an important role in imidacloprid metabolic process in M. dirhodum. We suggest that a highly species-specific approach is essential for managing M. dirhodum. Title: Identification of Highly Selective Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Inhibitors by a Covalent Fragment-Based Approach Huang F, Hu H, Wang K, Peng C, Xu W, Zhang Y, Gao J, Liu Y, Zhou H and Xu Y <3 more author(s)> Huang F, Hu H, Wang K, Peng C, Xu W, Zhang Y, Gao J, Liu Y, Zhou H, Huang R, Li M, Shen J, Xu Y (- 3) Ref: Journal of Medicinal Chemistry, 63:7052, 2020 : PubMed ESTHER: Huang_2020_J.Med.Chem_63_7052 PubMedSearch: Huang 2020 J.Med.Chem 63 7052 PubMedID: 32459096 Inhibitor(s) related to this paper: 6M08-BWL, 6M07-BWO, 6M06-BWF Abstract Covalent ligands are of great interest as therapeutic drugs or biochemical tools. Here, we reported the discovery of highly selective and irreversible inhibitors of lipoprotein-associated phospholipase A2 (Lp-PLA2) using a covalent fragment-based approach. The crystal structure of Lp-PLA2 in complex with a covalent fragment not only reveals the covalent reaction mechanism but also provides a good starting point to design compound 8, which has a more than 130,000-fold and 3900-fold increase in potency and selectivity, respectively, compared to those of the covalent fragment. Furthermore, fluorescent probes with high selectivity and sensitivity are developed to characterize Lp-PLA2 and its enzymatic activity in vitro or even in living cells in a way more convenient than immunoblotting tests or immunofluorescence imaging. Overall, we provide a paradigm for application of the covalent fragment-based strategy in covalent ligand discovery and the advantage of enol-cyclocarbamate as a new warhead in designing covalent inhibitors of serine hydrolases. Title: Admission serum cholinesterase concentration for prediction of in-hospital mortality in very elderly patients with acute ischemic stroke: a retrospective study Li M, Chen Y, Zhang Y, Liu X, Xie T, Yin J, Wang L, Gang S, Chen J and Geng T <2 more author(s)> Li M, Chen Y, Zhang Y, Liu X, Xie T, Yin J, Wang L, Gang S, Chen J, Liu L, Yang F, Geng T (- 2) Ref: Aging Clin Exp Res, :, 2020 : PubMed ESTHER: Li_2020_Aging.Clin.Exp.Res__ PubMedSearch: Li 2020 Aging.Clin.Exp.Res PubMedID: 32067216 Abstract BACKGROUND: Cholinesterase as a sensitive biomarker for prognosis in a variety of conditions but it is rare in stroke studies. The very elderly (>/= 80 years of age) represent the most susceptible group of ischemic stroke. We aimed to determine whether admission serum cholinesterase concentration had any effect on clinical outcome in very elderly patients (individuals aged >/= 80 years) with acute ischemic stroke. METHODS: A retrospective record review was conducted in two tertiary university hospitals. Elderly patients aged >/= 80 years admitted with a diagnosis of acute ischemic stroke from January 1, 2014 to November 30, 2019, who had a cholinesterase concentration drawn, were included. The patients were grouped based on the inflection points of the locally weighted regression and smoothing scatterplot (LOESS) curve between cholinesterase levels and in-hospital mortality (study outcome) with lower concentration as reference group. RESULTS: A total of 612 patients were admitted with a diagnosis of acute ischemic stroke, and 569 met the inclusion criteria. A threshold effect was identified using regression smoothing scatterplot (LOESS), with one cutoff point of 4.0 KU/L. There was a significant difference in-hospital mortality was observed (P < 0.001). After adjusted demographic and clinical features, the OR of cholinesterase for mortality was 0.43 (95% CI 0.34-0.54, P < 0.001), suggesting that lower admission cholinesterase level was an independent risk factors for all-cause mortality among patients with AIS. CONCLUSIONS: We have demonstrated a significant association between admission cholinesterase concentration and in-hospital mortality in very elderly patients with AIS. Title: Intracerebroventricular infusion of donepezil prevents cardiac remodeling and improves the prognosis of chronic heart failure rats Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M Ref: Journal de Physiologie Sci, 70:11, 2020 : PubMed ESTHER: Li_2020_J.Physiol.Sci_70_11 PubMedSearch: Li 2020 J.Physiol.Sci 70 11 PubMedID: 32066375 Abstract Oral administration of donepezil, a centrally acting acetylcholinesterase inhibitor, improves the survival of rats with chronic heart failure (CHF). The mechanisms of cardioprotective effects of donepezil, however, remain totally unknown. To elucidate potential mechanisms, we examined whether central microinfusion of donepezil would exert cardioprotection. Intracerebroventricular microinfusion pumps with cerebroventricular cannula were implanted in rats with myocardial infarction. The rats were randomly divided into central saline treatment (CST) and central donepezil treatment (CDT) groups. We evaluated cardiac remodeling and function after a 6-week treatment and examined the 160-day survival rate. Compared to the CST, the CDT markedly improved the 160-day survival rate (68% vs. 32%, P = 0.002) through the prevention of cardiac remodeling and the lowering of plasma catecholamine, brain natriuretic peptide, and angiotensin II. These results suggest that the central mechanism plays an important role in the cardioprotective effects of donepezil. Title: Inhibitory activities of flavonoids from Eupatorium adenophorum against acetylcholinesterase Li M, Gao X, Lan M, Liao X, Su F, Fan L, Zhao Y, Hao X, Wu G, Ding X Ref: Pestic Biochem Physiol, 170:104701, 2020 : PubMed ESTHER: Li_2020_Pestic.Biochem.Physiol_170_104701 PubMedSearch: Li 2020 Pestic.Biochem.Physiol 170 104701 PubMedID: 32980054 Abstract Fifteen flavonoids isolated from the Eupatorium adenophorum showed inhibitory activities against acetylcholinesterase (AChE) isolated from Caenorhabditis elegans and Spodoptera litura. Their IC(50) values ranged from 12.54 to 89.06mug/mL and 12.08 to 86.01mug/mL, respectively against the AChE isolated from the nematode and insect species. AChE was inhibited in a dose-dependent manner by all tested flavonoids, The isolated compound quercetagetin-7-O-(6-O-caffeoyl-beta-D-glucopyranoside) displayed the highest inhibitory effect against AChE from C. elegans and S. litura, with IC(50) values of 12.54 mug/mL and 12.58 mug/mL, respectively. The structure-activity relationship of flavonoids on the inhibitory activities indicated that additional phenolic hydroxyl groups in the glucose were favorable for their inhibitory effects and the degree of increase in inhibitory activity also depended on the number of phenolic hydroxyl groups. The Lineweaver-Burk and Dixon plots indicated that quercetagetin-7-O-(6-O-caffeoyl-beta-d-glucopyranoside) is a reversible inhibitor against AChE. Quercetagetin-7-O-(6-O-caffeoyl-beta-d-glucopyranoside), 5,4'-Dihydroxytlavone and quercetin-3-O-beta-d-glucopyranoside inhibited AChE in a mixed-type competitive manner and these compounds might be the dual binding site AChE inhibitors. Further, nine compounds showed poisonous effects against C. elegans and inhibitory effects on the growth and development of S. litura. Title: Walnut Oil Prevents Scopolamine-Induced Memory Dysfunction in a Mouse Model Liao J, Nai Y, Feng L, Chen Y, Li M, Xu H Ref: Molecules, 25:, 2020 : PubMed ESTHER: Liao_2020_Molecules_25_ PubMedSearch: Liao 2020 Molecules 25 PubMedID: 32252285 Abstract For thousands of years, it has been widely believed that walnut is a kind of nut that has benefits for the human body. Walnut oil, accounting for about 70% of walnut, mainly consists of polyunsaturated fatty acids. To investigate the effect of walnut oil on memory impairment in mice, scopolamine (3 mg/kg body weight/d) was used to establish the animal model during Morris Water Maze (MWM) tests. Walnut oil was administrated orally at 10 mL/kg body weight/d for 8 consecutive weeks. The results showed that walnut oil treatment ameliorated the behavior of the memory-impaired mice in the MWM test. Additionally, walnut oil obviously inhibited acetylcholinesterase activity (1.26 +/- 0.12 U/mg prot) (p = 0.013) and increased choline acetyltransferase activity (129.75 +/- 6.76 U/mg tissue wet weight) in the brains of scopolamine-treated mice (p = 0.024), suggesting that walnut oil could prevent cholinergic function damage in mice brains. Furthermore, walnut oil remarkably prevented the decrease in total superoxide dismutase activity (93.30 +/- 5.50 U/mg prot) (p = 0.006) and glutathione content (110.45 +/- 17.70 mg/g prot) (p = 0.047) and the increase of malondialdehyde content (13.79 +/- 0.96 nmol/mg prot) (p = 0.001) in the brain of scopolamine-treated mice, indicating that walnut oil could inhibit oxidative stress in the brain of mice. Furthermore, walnut oil prevented histological changes of neurons in hippocampal CA1 and CA3 regions induced by scopolamine. These findings indicate that walnut oil could prevent memory impairment in mice, which might be a potential way for the prevention of memory dysfunctions. Title: Induced fluorescent enhancement of protein-directed synthesized gold nanoclusters for selective and sensitive detection of flame retardants Liu H, Zhu N, Li M, Huang X, Wu P, Hu Z, Shuai J Ref: Sci Total Environ, 713:136488, 2020 : PubMed ESTHER: Liu_2020_Sci.Total.Environ_713_136488 PubMedSearch: Liu 2020 Sci.Total.Environ 713 136488 PubMedID: 31955081 Abstract Organophosphate flame retardants (OPFRs), typical toxic and hazardous pollutants, are called for new detection approaches to avoid laborious synthetic procedures and large and expensive instruments. Hence, a novel fluorescent probe was constructed for quantitative detection of OPFRs via heightening the fluorescence of acetylcholinesterase synthesized gold nanoclusters (AChE-AuNCs). The as-prepared AChE-AuNCs exhibited high fluorescence emission at about 398 nm with the average particle size of about 1.60 nm. When the AChE-AuNCs was applied to the proposed fluorescent detection, excellent sensitivity with wide linear range (50-1000 ng L(-1)) and low detection limit (30 ng L(-1)) for TClPP with the response time less than 1 h were achieved. The fluorescent probe could be extended to detect other three types of OPFRs (TEP, TPHP, and TBOEP) and the target pollutants could be detectable in the presence of halogenated flame retardants. The mechanism might be mainly contributed by the interaction between OPFRs and AChE-AuNCs restricting internal vibration consumption of their capping ligands. The proposed detection approach could be easily operated and was not involved with other intermediate products. Therefore, AChE-AuNCs could be a promising fluorescent probe for rapid, selective and sensitive detection of OPFRs and even in the practical application. Title: Novel small-insertion mutation in the LIPH gene in a patient with autosomal recessive woolly hair/hypotrichosis Lv H, Li M, Cheng R Ref: J Dermatol, 47:1445, 2020 : PubMed ESTHER: Lv_2020_J.Dermatol_47_1445 PubMedSearch: Lv 2020 J.Dermatol 47 1445 PubMedID: 32901930 Abstract Autosomal recessive woolly hair/hypotrichosis (ARWH/H) is a rare form of congenital alopecia, which can be caused by mutations in lipase H (LIPH), lysophosphatidic acid receptor 6 (LPAR6/P2RY5) or keratin 25 (KRT25) genes. We present a 32-year-old woman with typical clinical features of ARWH. Hair microscopy was performed to observe differences between the patient's hair and a normal sample. Next-generation sequencing was used to detect pathogenic mutations. Sanger sequencing was used to further confirm the mutations. Abnormal hair appearance was found by hair microscopy. A novel frame-shift mutation (NM_139248: c.686delinsGTAGAACCCAACCTGGCT: p.Asp229fs37X) and a reported mutation (NM_139248: exon6:c.T736A: p.C246S) in LIPH were identified in the patient. All reported mutations related to ARWH of various races were reviewed. Our study provides further evidence of the similarity of ARWH between the Chinese and Japanese population. A novel small-insertion mutation also expands the LIPH mutation spectrum. Title: Visualization of carboxylesterase 2 with a near-infrared two-photon fluorescent probe and potential evaluation of its anticancer drug effects in an orthotopic colon carcinoma mice model Wang Y, Yu F, Luo X, Li M, Zhao L Ref: Chem Commun (Camb), :, 2020 : PubMed ESTHER: Wang_2020_Chem.Commun.(Camb)__ PubMedSearch: Wang 2020 Chem.Commun.(Camb) PubMedID: 32186556 Abstract We establish a near-infrared two-photon fluorescent probe for the detection of CE2 with high selectivity and sensitivity. This probe exhibits low cytotoxicity and superior tissue penetration ability for evaluating the real-time activity of CE2 in living cells, in cancer tissues, and in a colon carcinoma mice model. 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: Anti-foodborne enteritis effect of galantamine potentially via acetylcholine anti-inflammatory pathway in fish Wu N, Xu X, Wang B, Li XM, Cheng YY, Li M, Xia XQ, Zhang YA Ref: Fish Shellfish Immunol, 97:204, 2020 : PubMed ESTHER: Wu_2020_Fish.Shellfish.Immunol_97_204 PubMedSearch: Wu 2020 Fish.Shellfish.Immunol 97 204 PubMedID: 31843701 Abstract Foodborne enteritis has become a limiting factor in aquaculture. Plant protein sources have already caused enteritic inflammation and inhibition in growth performance. Attempts have been made to find an effective solution to foodborne enteritis. Based on the previously suggested fish cholinergic anti-inflammatory pathway, galantamine, a typical cholinesterase inhibitor, was tested for the repression of pro-inflammatory cytokines for soybean meal induced enteritis by injection into grass carp. Both the phylogenetic analysis of cholinesterase, AchR and bioinformatic prediction, indicated galantamine's potential use as an enteritis drug. The result highlighted galantamine's potential effect for anti-enteritis in fish, especially in carps. Subsequently, a 4-week feeding trail using galantamine as an additive, in a zebrafish soybean meal induced enteritis model, demonstrated the prevention of enteritis. The results demonstrated that galantamine could prevent intestinal pathology, both histologically and molecularly, and also maintain growth performance. Reflected by gene expressional analysis, all mechanical, chemical and immune functions of the intestinal barrier could be protected by galantamine supplementation, which aided molecularly in the control of fish foodborne enteritis, through down-regulating Th17 type proinflammatory factors, meanwhile resuming the level of Treg type anti-inflammatory factors. Therefore, the current results shed light on fish intestinal acetylcholine anti-inflammation, by the dietary addition of galantamine, which could give rise to protection from foodborne enteritis. Title: Role of XIAP gene overexpressed bone marrow mesenchymal stem cells in the treatment of cerebral injury in rats with cerebral palsy Deng W, Fan C, Fang Y, Zhao Y, Wei Y, Li M, Teng J Ref: Cancer Cell Int, 19:273, 2019 : PubMed ESTHER: Deng_2019_Cancer.Cell.Int_19_273 PubMedSearch: Deng 2019 Cancer.Cell.Int 19 273 PubMedID: 31660045 Abstract Background: This study is performed to investigate the effects of adenovirus-mediated X-linked inhibitor of apoptosis protein (XIAP) overexpressed bone marrow mesenchymal stem cells (BMSCs) on brain injury in rats with cerebral palsy (CP). Methods: Rat's BMSCs were cultured and identified. The XIAP gene of BMSCs was modified by adenovirus expression vector Ad-XIAP-GFP. The rat model of CP with ischemia and anoxia was established by ligating the left common carotid artery and anoxia for 2 h, and BMSCs were intracerebroventricularly injected to the modeled rats. The mRNA and protein expression of XIAP in brain tissue of rats in each group was detected by RT-qPCR and western blot analysis. The neurobehavioral situation, content of acetylcholine (Ach), activity of acetylcholinesterase (AchE), brain pathological injury, apoptosis of brain nerve cells and the activation of astrocytes in CP rats were determined via a series of assays. Results: Rats with CP exhibited obvious abnormalities, increased Ach content, decreased AchE activity, obvious pathological damage, increased brain nerve cell apoptosis, as well as elevated activation of astrocyte. XIAP overexpressed BMSCs improved the neurobehavioral situation, decreased Ach content and increased AchE activity, attenuated brain pathological injury, inhibited apoptosis of brain nerve cells and the activation of astrocytes in CP rats. Conclusion: Our study demonstrates that XIAP overexpressed BMSCs can inhibit the apoptosis of brain nerve cells and the activation of astrocytes, increase AchE activity, and inhibit Ach content, so as to lower the CP caused by cerebral ischemia and hypoxia in rats. Title: Adeno-associated virus-mediated expression of human butyrylcholinesterase to treat organophosphate poisoning Gupta V, Cadieux CL, McMenamin D, Medina-Jaszek CA, Arif M, Ahonkhai O, Wielechowski E, Taheri M, Che Y and Wilson JM <5 more author(s)> Gupta V, Cadieux CL, McMenamin D, Medina-Jaszek CA, Arif M, Ahonkhai O, Wielechowski E, Taheri M, Che Y, Goode T, Limberis MP, Li M, Cerasoli DM, Tretiakova AP, Wilson JM (- 5) Ref: PLoS ONE, 14:e0225188, 2019 : PubMed ESTHER: Gupta_2019_PLoS.One_14_e0225188 PubMedSearch: Gupta 2019 PLoS.One 14 e0225188 PubMedID: 31765413 Abstract Rare diseases defined by genetic mutations are classic targets for gene therapy. More recently, researchers expanded the use of gene therapy in non-clinical studies to infectious diseases through the delivery of vectorized antibodies to well-defined antigens. Here, we further extend the utility of gene therapy beyond the "accepted" indications to include organophosphate poisoning. There are no approved preventives for the multi-organ damage resulting from acute or chronic exposure to organophosphates. We show that a single intramuscular injection of adeno-associated virus vector produces peak expression (~0.5 mg/ml) of active human butyrylcholinesterase (hBChE) in mice serum within 3-4 weeks post-treatment. This expression is sustained for up to 140 days post-injection with no silencing. Sustained expression of hBChE provided dose-dependent protection against VX in male and female mice despite detectable antibodies to hBChE in some mice, thereby demonstrating that expression of hBChE in vivo in mouse muscle is an effective prophylactic against organophosphate poisoning. Title: A sensitive fluorescence assay of organophosphorus pesticides using acetylcholinesterase and copper-catalyzed click chemistry Huang N, Qin Y, Li M, Chen T, Lu M, Zhao J Ref: Analyst, 144:3436, 2019 : PubMed ESTHER: Huang_2019_Analyst_144_3436 PubMedSearch: Huang 2019 Analyst 144 3436 PubMedID: 31020297 Abstract Organophosphorus pesticides (OPs) are widely used in agricultural fields, but exhibit high toxicity to human beings. A sensitive fluorescence assay for organophosphorus pesticides was developed using the inhibition of acetylcholinesterase (AChE) activity and the copper-catalyzed click chemical reaction. In the click reaction, two hybridized DNA probes can be ligated with copper ions, inducing a fluorescence quenching during the strand displacement reaction. AChE can hydrolyze acetylthiocholine (ATCh) to form thiocholine (TCh) which contains a thiol group. TCh will react with copper ions, blocking the click reaction and a high fluorescence signal is observed. But in the presence of OPs, the activity of AChE is inhibited, releasing a high concentration of copper ions that catalyze the click chemical reaction and resulting in decreased fluorescence signals. Taking advantage of the copper-mediated signal amplification effect, the sensitivity was improved. This assay has also been applied to detect OPs in river water samples with satisfactory results, which demonstrates that the method has great potential for practical applications in environmental protection and food safety fields. 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: Clinical analysis of Chinese anti-low-density-lipoprotein-receptor-associated protein 4 antibodies in patients with myasthenia gravis Li M, Han J, Zhang Y, Lv J, Zhang J, Zhao X, Ren L, Fang H, Yang J and Gao F <4 more author(s)> Li M, Han J, Zhang Y, Lv J, Zhang J, Zhao X, Ren L, Fang H, Yang J, Cui X, Zhang Q, Li Q, Du Y, Gao F (- 4) Ref: Eur Journal of Neurology, 26:1296, 2019 : PubMed ESTHER: Li_2019_Eur.J.Neurol_26_1296 PubMedSearch: Li 2019 Eur.J.Neurol 26 1296 PubMedID: 31050101 Abstract BACKGROUND AND PURPOSE: Low-density-lipoprotein-receptor-associated protein 4 (LRP4) autoantibodies have recently been detected in myasthenia gravis (MG), but little is known about the clinical characteristics associated with this serological type. In this study, the clinical features of Chinese patients with anti-LRP4 antibody-positive MG were characterized. METHODS: A total of 2172 MG serum samples were collected from patients in various parts of China. An enzyme-linked immunosorbent assay was used to detect acetylcholine receptor (AChR) antibody and titin antibody, and cell-based assays were used to detect muscle-specific kinase antibody and LRP4 antibody. Clinical data for patients with MG were collected from different provinces in China. RESULTS: In total, 16 (0.8%) patients with LRP4-MG were found amongst 2172 total patients, including three patients with AChR/LRP4-MG. Additionally, 13 (2.9%) patients with LRP4-MG were found amongst 455 patients with double seronegative MG. The ratio of males to females for these 13 patients was 1:1.6, and 53.8% patients were children. A total of 91.7% of cases exhibited initial ocular involvement, and 58.3% of cases exhibited simple eye muscle involvement. Responses to acetylcholinesterase inhibitors and prednisone were observed. CONCLUSION: The expanded sample confirmed that the positive rate of LRP4 antibodies in China is lower than that in western countries. Our results highlighted the differences between LRP4-MG and other antibody groups. Children and female patients with LRP4-MG have a higher prevalence, often involving the ocular muscles and limb muscles. The clinical symptoms are mild, and satisfactory responses to treatment are often achieved. Title: A novel ABHD12 nonsense variant in Usher syndrome type 3 family with genotype-phenotype spectrum review Li T, Feng Y, Liu Y, He C, Liu J, Chen H, Deng Y, Li M, Li W and Ling J <8 more author(s)> Li T, Feng Y, Liu Y, He C, Liu J, Chen H, Deng Y, Li M, Li W, Song J, Niu Z, Sang S, Wen J, Men M, Chen X, Li J, Liu X, Ling J (- 8) Ref: Gene, 704:113, 2019 : PubMed ESTHER: Li_2019_Gene_704_113 PubMedSearch: Li 2019 Gene 704 113 PubMedID: 30974196 Gene_locus related to this paper: human-ABHD12 Abstract Usher syndrome (USH) is a clinically common autosomal recessive disorder characterized by retinitis pigmentosa (RP) and sensorineural hearing loss with or without vestibular dysfunction. In this study, we identified a Hunan family of Chinese descent with two affected members clinically diagnosed with Usher syndrome type 3 (USH3) displaying hearing, visual acuity, and olfactory decline. Whole-exome sequencing (WES) identified a nonsense variant in ABHD12 gene that was confirmed to be segregated in this family by Sanger sequencing and exhibited a recessive inheritance pattern. In this family, two patients carried homozygous variant in the ABHD12 (NM_015600: c.249C>G). Mutation of ABHD12, an enzyme that hydrolyzes an endocannabinoid lipid transmitter, caused incomplete PHARC syndrome, as demonstrated in previous reports. Therefore, we also conducted a summary based on variants in ABHD12 in PHARC patients, and in PHARC patients showing that there was no obvious correlation between the genotype and phenotype. We believe that this should be considered during the differential diagnosis of USH. Our findings predicted the potential function of this gene in the development of hearing and vision loss, particularly with regard to impaired signal transmission, and identified a novel nonsense variant to expand the variant spectrum in ABHD12. Title: Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity Lin Y, Wang Y, Lv J, Wang N, Wang J, Li M Ref: Int J Nanomedicine, 14:5817, 2019 : PubMed ESTHER: Lin_2019_Int.J.Nanomedicine_14_5817 PubMedSearch: Lin 2019 Int.J.Nanomedicine 14 5817 PubMedID: 31440049 Abstract Purpose: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. Methods: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. Results: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. Conclusion: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment. Title: Target-site mutations (AChE-G119S and kdr) in Guangxi Anopheles sinensis populations along the China-Vietnam border Yang C, Feng X, Liu N, Li M, Qiu X Ref: Parasit Vectors, 12:77, 2019 : PubMed ESTHER: Yang_2019_Parasit.Vectors_12_77 PubMedSearch: Yang 2019 Parasit.Vectors 12 77 PubMedID: 30732643 Abstract BACKGROUND: In South Asia, the epidemiology of malaria is complex, and transmission mainly occurs in remote areas near international borders. Vector control has been implemented as a key strategy in malaria prevention for decades. A rising threat to the efficacy of vector control efforts is the development of insecticide resistance, thus it is important to monitor the type and frequency of insecticide resistant alleles in the disease vectors such as An. sinensis along the China-Vietnam border. Such information is needed to synthesize effective malaria vector control strategies. METHODS: A total of 208 adults of An. sinensis, collected from seven sites in southwest Guangxi along the China-Vietnam border, were inspected for the resistance-conferring G119S mutation in acetylcholinesterase (AChE) by PCR-RFLP (polymerase chain reaction restriction fragment length polymorphism) and kdr mutations in the voltage-gated sodium channel (VGSC) by sequencing. In addition, the evolutionary origin of An. sinensis vgsc gene haplotypes was analyzed using Network 5.0. RESULTS: The frequencies of mutant 119S of AChE were between 0.61-0.85 in the seven An. sinensis populations. No susceptible homozygote (119GG) was detected in three of the seven sites (DXEC, LZSK and FCGDX). Very low frequencies of kdr (0.00-0.01) were detected in the seven populations, with most individuals being susceptible homozygote (1014LL). The 1014F mutation was detected only in the southeast part (FCGDX) at a low frequency of 0.03. The 1014S mutation was distributed in six of the seven populations with frequencies ranging from 0.04 to 0.08, but absent in JXXW. Diverse haplotypes of 1014L and 1014S were found in An. sinensis along the China-Vietnam border, while only one 1014F haplotype was detected in this study. Consistent with a previous report, resistant 1014S haplotypes did not have a single origin. CONCLUSIONS: The G119S mutation of AChE was present at high frequencies (0.61-0.85) in the An. sinensis populations along the China-Vietnam border, suggesting that the vector control authorities should be cautious when considering carbamates and organophosphates as chemicals for vector control. The low frequencies (0.00-0.11) of kdr in these populations suggest that pyrethroids remain suitable for use against An. sinensis in these regions. Title: Effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver Yang H, Wang Y, Ma C, Sun C, Liu Y, Wu K, Li M, Borjigin G, Gao F Ref: Asian-Australas J Anim Sci, 32:217, 2019 : PubMed ESTHER: Yang_2019_Asian-Australas.J.Anim.Sci_32_217 PubMedSearch: Yang 2019 Asian-Australas.J.Anim.Sci 32 217 PubMedID: 30056659 Abstract OBJECTIVE: An experiment was conducted to investigate the effects of feed intake restriction during late pregnancy on the function, anti-oxidation capability and acute phase protein synthesis of ovine liver. METHODS: Eighteen time-mated ewes with singleton fetuses were allocated to three groups: restricted group 1 (RG1, 0.18 MJ ME/kg W0.75 d, n = 6), restricted group 2 (RG2, 0.33 MJ ME/kg W0.75 d), n = 6) and a control group (CG, ad libitum, 0.67 MJ ME/kg W0.75 d, n = 6). The feed restriction period was from 90 days to 140 days of pregnancy. RESULTS: The ewe's body weight, liver weights, water, and protein content of liver in the restricted groups were reduced compared with the CG group (p<0.05), but the liver fat contents in the RG1 group were higher than those of the CG group (p<0.05). The increased hepatic collagen fibers and reticular fibers were observed in the restricted groups with the reduction of energy intake. The concentrations of nonesterified free fatty acids in the RG1 and RG2 groups were higher than those of the CG group with the reduction of energy intake (p<0.05), but there were decreased concentrations of lipoprotein lipase and hepatic lipase in both restricted groups compared with the CG group (p<0.05). In addition, the increased concentrations of beta-hydroxybutyric acid, triglycerides, malondialdehyde, total antioxidant capacity and activities of superoxide dismutase activity and catalase were found in the RG1 group, and the concentrations of cholinesterase in the RG1 group were reduced compared with the CG group (p<0.05). For the concentrations of acute phase proteins, the C-reactive protein (CRP) in the RG1 group were reduced compared with the CG group, but there were no differences in haptoglobin relative to the controls (p>0.05). CONCLUSION: The fat accumulation, increased hepatic fibrosis, antioxidant imbalance and modified synthesis of acute phase proteins were induced in ewe's liver by maternal malnutrition during late pregnancy, which were detrimental for liver function to accommodate pregnancy. Title: Neuroprotective effects of berberine in animal models of Alzheimer's disease: a systematic review of pre-clinical studies Yuan NN, Cai CZ, Wu MY, Su HX, Li M, Lu JH Ref: BMC Complement Altern Med, 19:109, 2019 : PubMed ESTHER: Yuan_2019_BMC.Complement.Altern.Med_19_109 PubMedSearch: Yuan 2019 BMC.Complement.Altern.Med 19 109 PubMedID: 31122236 Inhibitor(s) related to this paper: Berberine Abstract BACKGROUND: Berberine is an isoquinoline alkaloid extracted from various Berberis species which is widely used in East Asia for a wide range of symptoms. Recently, neuroprotective effects of berberine in Alzheimer's disease (AD) animal models are being extensively reported. So far, no clinical trial has been carried out on the neuroprotective effects of berberine. However, a review of the experimental data is needed before choosing berberine as a candidate drug for clinical experiments. We conducted a systematic review on AD rodent models to analyze the drug effects with minimal selection bias. METHODS: Five online literature databases were searched to find publications reporting studies of the effect of berberine treatment on animal models of AD. Up to March 2018, 15 papers were identified to describe the efficacy of berberine. RESULTS: The included 15 articles met our inclusion criteria with different quality ranging from 3 to 5. We analyzed data extracted from full texts with regard to pharmacological effects and potential anti-Alzheimer's properties. Our analysis revealed that in multiple memory defects animal models, berberine showed significant memory-improving activities with multiple mechanisms, such as anti-inflammation, anti-oxidative stress, cholinesterase (ChE) inhibition and anti-amyloid effects. CONCLUSION: AD is likely to be a complex disease driven by multiple factors. Yet, many therapeutic strategies based on lowering beta-amyloid have failed in clinical trials. This suggest that the threapy should not base on a single cause of Alzheimer's disease but rather a number of different pathways that lead to the disease. Overall we think that berberine can be a promising multipotent agent to combat Alzheimer's disease. Title: Shen-Yuan-Dan Capsule Attenuates Atherosclerosis and Foam Cell Formation by Enhancing Autophagy and Inhibiting the PI3K/Akt/mTORC1 Signaling Pathway Zhou M, Ren P, Zhang Y, Li S, Li M, Li P, Shang J, Liu W, Liu H Ref: Front Pharmacol, 10:603, 2019 : PubMed ESTHER: Zhou_2019_Front.Pharmacol_10_603 PubMedSearch: Zhou 2019 Front.Pharmacol 10 603 PubMedID: 31214032 Abstract Background and Aim: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a crucial role in autophagy and inflammation. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a Chinese medicine used for treating angina pectoris, has anti-atherosclerotic and anti-inflammatory effects in mice. However, its effects on autophagy and the PI3K/Akt/mTORC1 signaling pathway remain unclear. This study aimed to explore the effects of SYDC on autophagy and PI3K/Akt/mTORC1 signaling in the apolipoprotein E knockout (ApoE(-/-)) mouse model and in macrophage-derived foam cells to delineate the underlying mechanism. Methods: After 6 weeks of high-fat diet, ApoE(-/-) mice were randomly grouped into control, Lipitor, low-SYDC (SYDC-L), middle-SYDC (SYDC-M), and high-SYDC (SYDC-H) groups (n = 10). The mice were intragastrically administered the respective treatment for 6 weeks. Murine RAW264.7 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) (80 microg/ml) for 24 h and then pretreated with SYDC freeze-dried powder for another 24 h. Cells treated with SYDC were co-cultured for 24 h with LY294002, tricirbine, and rapamycin to investigate the effects on the PI3K/Akt/mTORC1 signaling pathway. Results: SYDC ameliorated blood lipid levels, reduced the atherosclerotic index and plaque areas in the aortic root in mice, and inhibited total cholesterol (TC) levels and cholinesterase (ChE)/TC ratios in ox-LDL stimulated macrophages. Moreover, SYDC up-regulated Beclin1 and LC3II/I proteins in mice and in the ox-LDL-stimulated macrophages. Moreover, SYDC inhibited AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 in mice and in ox-LDL-stimulated macrophages. Furthermore, SYDC's inhibitory of ChE/TC ratios in ox-LDL-stimulated macrophages was not changed by selective inhibition of the PI3K/Akt/mTORC1 pathway. Conclusions: Our results highlight that SYDC treatment attenuates foam cell formation by promoting autophagy via inhibiting activation of the PI3K/Akt/mTORC1 signaling pathway. This study provides new insights into the molecular mechanism underlying SYDC's therapeutic potential for treating atherosclerosis. Title: Carboxylesterase genes in pyrethroid resistant house flies, Musca domestica Feng X, Li M, Liu N Ref: Insect Biochemistry & Molecular Biology, 92:30, 2018 : PubMed ESTHER: Feng_2018_Insect.Biochem.Mol.Biol_92_30 PubMedSearch: Feng 2018 Insect.Biochem.Mol.Biol 92 30 PubMedID: 29154832 Abstract Carboxylesterases are one of the major enzyme families involved in the detoxification of pyrethroids. Up-regulation of carboxylesterase genes is thought to be a major component of insecticide resistant mechanisms in insects. Based on the house fly transcriptome and genome database, a total of 39 carboxylesterase genes of different functional clades have been identified in house flies. In this study, eleven of these genes were found to be significantly overexpressed in the resistant ALHF house fly strain compared with susceptible aabys and wild-type CS strains. Eight up-regulated carboxylesterase genes with their expression levels were further induced to a higher level in response to permethrin treatments, indicating that constitutive and inductive overexpression of carboxylesterases are co-responsible for the enhanced detoxification of insecticides. Spatial expression studies revealed these up-regulated genes to be abundantly distributed in fat bodies and genetically mapped on autosome 2 or 3 of house flies, and their expression could be regulated by factors on autosome 1, 2 and 5. Taken together, these results demonstrate that multiple carboxylesterase genes are co-upregulated in resistant house flies, providing further evidence for their involvement in the detoxification of insecticides and development of insecticide resistance. Title: Effect of Telmisartan on Preventing Learning and Memory Deficits Via Peroxisome Proliferator-Activated Receptor-gamma in Vascular Dementia Spontaneously Hypertensive Rats Gao Y, Li W, Liu Y, Wang Y, Zhang J, Li M, Bu M Ref: J Stroke Cerebrovasc Dis, 27:277, 2018 : PubMed ESTHER: Gao_2018_J.Stroke.Cerebrovasc.Dis_27_277 PubMedSearch: Gao 2018 J.Stroke.Cerebrovasc.Dis 27 277 PubMedID: 29241675 Abstract BACKGROUND: This study aimed to explore the effect of telmisartan (TEL), as a partial peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonist, in vascular dementia (VaD) rats induced by middle cerebral artery occlusion (MCAO). METHODS: Spontaneously hypertensive rats were divided into 6 groups: the sham group, model group, TEL-treated groups (1, 5, and 10 mg/kg), and TEL + GW9662 (10 mg/kg + 1 mg/kg). Using the MCAO method established the VaD rat model. Cognitive function was detected through the Morris water maze test, and matrix metalloproteinase 2 (MMP2) or matrix metalloproteinase 9 (MMP9), acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and synaptophysin (SYN) in the hippocampus of rats were measured by the immunohistochemical method. RESULTS: In the Morris water maze test, the spatial memory ability was significantly impaired in the model group and improved in the TEL groups (1, 5, and 10 mg/kg), but the improvement effect of TEL on spatial memory was inhibited by GW9662, a PPAR-gamma antagonist. Compared with the sham group, the expression levels of MMP2, MMP9, and AChE increased and the expression levels of ChAT and SYN decreased significantly in the model group. Interestingly, TEL (1, 5, and 10 mg/kg) significantly reduced the expression levels of MMP2, MMP9, and AChE and significantly improved the expression levels of ChAT and SYN in a dose-dependent manner. However, cotreatment with GW9662 inhibited the TEL-mediated improvement effects on MMPs, the cholinergic system, and SYN. CONCLUSION: This study suggested that TEL had improvement effects in VaD rats via the PPAR-gamma pathway. Title: A non-competitive surface plasmon resonance immunosensor for rapid detection of triazophos residue in environmental and agricultural samples Guo Y, Liu R, Liu Y, Xiang D, Gui W, Li M, Zhu G Ref: Sci Total Environ, 613-614:783, 2018 : PubMed ESTHER: Guo_2018_Sci.Total.Environ_613-614_783 PubMedSearch: Guo 2018 Sci.Total.Environ 613-614 783 PubMedID: 28946376 Abstract The wide application of an organophosphate pesticide triazophos raises concern on the environmental pollution and the potential risk to human health. Thus, it is crucial to regularly monitor triazophos residue in the environment and agro-products. Herein we described a non-competitive immunoassay for trace detection of triazophos using a direct surface plasmon resonance (SPR) biosensor. Two anti-triazophos monoclonal antibodies (mAbs) were immobilized on the sensor chip and characterized by SPR-based kinetic analysis. The mAb with relatively slow dissociation rate was used for direct immunosensing of triazophos. The biosensor assay showed a high specificity and a low detection limit of 0.096ngmL-1 to triazophos, with the linear detection range of 0.98-8.29ngmL-1. Under the optimal condition, the sensor chip could be regenerated for 160cycles at least. Moreover, the sensitive method was applied to determine triazophos in the spiked environmental water and agricultural products, as well as in unknown real-life samples (including Chinese cabbage, cucumber, and apple). Desirable results demonstrated that the newly-developed immunosensor could be used as a rapid, convenient, and reliable tool to regularly monitor triazophos and meet the detection requirement of its maximum residue limits. Title: The Cholinergic and Adrenergic Autocrine Signaling Pathway Mediates Immunomodulation in Oyster Crassostrea gigas Liu Z, Wang L, Lv Z, Zhou Z, Wang W, Li M, Yi Q, Qiu L, Song L Ref: Front Immunol, 9:284, 2018 : PubMed ESTHER: Liu_2018_Front.Immunol_9_284 PubMedSearch: Liu 2018 Front.Immunol 9 284 PubMedID: 29535711 Abstract It is becoming increasingly clear that neurotransmitters impose direct influence on regulation of the immune process. Recently, a simple but sophisticated neuroendocrine-immune (NEI) system was identified in oyster, which modulated neural immune response via a "nervous-hemocyte"-mediated neuroendocrine immunomodulatory axis (NIA)-like pathway. In the present study, the de novo synthesis of neurotransmitters and their immunomodulation in the hemocytes of oyster Crassostrea gigas were investigated to understand the autocrine/paracrine pathway independent of the nervous system. After hemocytes were exposed to lipopolysaccharide (LPS) stimulation, acetylcholine (ACh), and norepinephrine (NE) in the cell supernatants, both increased to a significantly higher level (2.71- and 2.40-fold, p < 0.05) comparing with that in the control group. The mRNA expression levels and protein activities of choline O-acetyltransferase and dopamine beta-hydroxylase in hemocytes which were involved in the synthesis of ACh and NE were significantly elevated at 1 h after LPS stimulation, while the activities of acetylcholinesterase and monoamine oxidase, two enzymes essential in the metabolic inactivation of ACh and NE, were inhibited. These results demonstrated the existence of the sophisticated intracellular machinery for the generation, release and inactivation of ACh and NE in oyster hemocytes. Moreover, the hemocyte-derived neurotransmitters could in turn regulate the mRNA expressions of tumor necrosis factor (TNF) genes, the activities of superoxide dismutase, catalase and lysosome, and hemocyte phagocytosis. The phagocytic activities of hemocytes, the mRNA expressions of TNF and the activities of key immune-related enzymes were significantly changed after the block of ACh and NE receptors with different kinds of antagonists, suggesting that autocrine/paracrine self-regulation was mediated by transmembrane receptors on hemocyte. The present study proved that oyster hemocyte could de novo synthesize and release cholinergic and adrenergic neurotransmitters, and the hemocyte-derived ACh/NE could then execute a negative regulation on hemocyte phagocytosis and synthesis of immune effectors with similar autocrine/paracrine signaling pathway identified in vertebrate macrophages. Findings in the present study demonstrated that the immune and neuroendocrine system evolved from a common origin and enriched our knowledge on the evolution of NEI system. Title: Neurexin-Neuroligin 1 regulates synaptic morphology and function via the WAVE regulatory complex in Drosophila neuromuscular junction Xing G, Li M, Sun Y, Rui M, Zhuang Y, Lv H, Han J, Jia Z, Xie W Ref: Elife, 7:, 2018 : PubMed ESTHER: Xing_2018_Elife_7_ PubMedSearch: Xing 2018 Elife 7 PubMedID: 29537369 Abstract Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of Neuroligin functions remain unclear. We found that Drosophila Neuroligin1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner Neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 knockout mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction. Title: Intestinal damage, neurotoxicity and biochemical responses caused by tris (2-chloroethyl) phosphate and tricresyl phosphate on earthworm Yang Y, Xiao Y, Chang Y, Cui Y, Klobucar G, Li M Ref: Ecotoxicology & Environmental Safety, 158:78, 2018 : PubMed ESTHER: Yang_2018_Ecotoxicol.Environ.Saf_158_78 PubMedSearch: Yang 2018 Ecotoxicol.Environ.Saf 158 78 PubMedID: 29660616 Abstract Organophosphate esters (OPEs) draw growing concern about characterizing the potential risk on environmental health due to its wide usage and distribution. Two typical types of organophosphate esters (OPEs): tris (2-chloroethyl) phosphate (TCEP) and tricresyl phosphate (TCP) were selected to evaluate toxicity of OPEs to the soil organism like earthworm (Eisenia fetida). Histopathological examination (H&E), oxidative stress, DNA damage and RT-qPCR was used to identify the effects and potential mechanism of their toxicity. Hameatoxylin and eosin (H&E) demonstrated that intestinal cells suffered serious damage, and the observed up-regulation of chitinase and cathepsin L in mRNA levels confirmed it. Both TCEP and TCP significantly increased the DNA damage when the concentrations exceeded 1mg/kg (p<0.01), and a dose-response relationship was observed. In addition, TCEP and TCP also changed the acetylcholinesterase (AChE) activity and expression of genes associated with neurotoxic effects in earthworms even under exposure to low OPEs concentration (0.1mg/kg). Moreover, genes associated with nicotinic acetylcholine receptors (nAChR) and carrier protein further demonstrated that highest concentration of TCEP (10mg/kg) may have an overloading impact on the cholinergic system of E. fetida. Integrated Biological Response index (IBRv2) showed that TCEP exerted stronger toxicity than TCP under the same concentrations. We deduced that the observed intestinal damage, oxidative stress and neurotoxic effect might be the primary mechanisms of TCEP and TCP toxicity. This study provides insight into the toxicological effects of OPEs on earthworm model, and may be useful for risk assessment of OPEs on soil ecosystems. Title: A Possible Mechanism: Vildagliptin Prevents Aortic Dysfunction through Paraoxonase and Angiopoietin-Like 3 Zhang Q, Xiao X, Zheng J, Li M, Yu M, Ping F, Wang T, Wang X Ref: Biomed Res Int, 2018:3109251, 2018 : PubMed ESTHER: Zhang_2018_Biomed.Res.Int_2018_3109251 PubMedSearch: Zhang 2018 Biomed.Res.Int 2018 3109251 PubMedID: 29951533 Abstract The collected data have revealed the beneficial effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on the vascular endothelium, including vildagliptin. However, the involved mechanisms are not yet clear. In this study, Sprague-Dawley rats were randomly divided into the following four groups: control, diabetic, diabetic + low-dose vildagliptin (10 mg/kg/d), and diabetic + high-dose vildagliptin (20 mg/kg/d). The diabetic model was created by feeding a high-fat diet for four weeks and injection of streptozotocin. Then, vildagliptin groups were given oral vildagliptin for twelve weeks, and the control and diabetic groups were given the same volume of saline. The metabolic parameters, endothelial function, and whole genome expression in the aorta were examined. After 12 weeks of treatment, vildagliptin groups showed significantly reduced blood glucose, blood total cholesterol, and attenuated endothelial dysfunction. Notably, vildagliptin may inhibit angiopoietin-like 3 (Angptl3) and betaine-homocysteine S-methyltransferase (Bhmt) expression and activated paraoxonase-1 (Pon1) in the aorta of diabetic rats. These findings may demonstrate the vasoprotective pathway of vildagliptin in vivo. Title: Trefoil Factor 3, Cholinesterase and Homocysteine: Potential Predictors for Parkinson's Disease Dementia and Vascular Parkinsonism Dementia in Advanced Stage Zou J, Chen Z, Liang C, Fu Y, Wei X, Lu J, Pan M, Guo Y, Liao X and Wang Q <5 more author(s)> Zou J, Chen Z, Liang C, Fu Y, Wei X, Lu J, Pan M, Guo Y, Liao X, Xie H, Wu D, Li M, Liang L, Wang P, Wang Q (- 5) Ref: Aging Dis, 9:51, 2018 : PubMed ESTHER: Zou_2018_Aging.Dis_9_51 PubMedSearch: Zou 2018 Aging.Dis 9 51 PubMedID: 29392081 Abstract Trefoil factor 3 (TFF3), cholinesterase activity (ChE activity) and homocysteine (Hcy) play critical roles in modulating recognition, learning and memory in neurodegenerative diseases, such as Parkinson's disease dementia (PDD) and vascular parkinsonism with dementia (VPD). However, whether they can be used as reliable predictors to evaluate the severity and progression of PDD and VPD remains largely unknown. METHODS: We performed a cross-sectional study that included 92 patients with PDD, 82 patients with VPD and 80 healthy controls. Serum levels of TFF3, ChE activity and Hcy were measured. Several scales were used to rate the severity of PDD and VPD. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of PDD and VPD patients compared to healthy subjects. RESULTS: Compared with healthy subjects, the serum levels of TFF3 and ChE activity were lower, while Hcy was higher in the PDD and VPD patients. These findings were especially prominent in male patients. The three biomarkers displayed differences between PDD and VPD sub-groups based on genders and UPDRS (III) scores' distribution. Interestingly, these increased serum Hcy levels were significantly and inversely correlated with decreased TFF3/ChE activity levels. There were significant correlations between TFF3/ChE activity/Hcy levels and PDD/VPD severities, including motor dysfunction, declining cognition and mood/gastrointestinal symptoms. Additionally, ROC curves for the combination of TFF3, ChE activity and Hcy showed potential diagnostic value in discriminating PDD and VPD patients from healthy controls. CONCLUSIONS: Our findings suggest that serum TFF3, ChE activity and Hcy levels may underlie the pathophysiological mechanisms of PDD and VPD. As the race to find biomarkers or predictors for these diseases intensifies, a better understanding of the roles of TFF3, ChE activity and Hcy may yield insights into the pathogenesis of PDD and VPD. Title: Functional characterization of carboxylesterase gene mutations involved in Aphis gossypii resistance to organophosphate insecticides Gong YH, Ai GM, Li M, Shi XY, Diao QY, Gao XW Ref: Insect Molecular Biology, 26:702, 2017 : PubMed ESTHER: Gong_2017_Insect.Mol.Biol_26_702 PubMedSearch: Gong 2017 Insect.Mol.Biol 26 702 PubMedID: 28799241 Gene_locus related to this paper: aphgo-cxest Abstract Carboxylesterases (CarEs) play an important role in detoxifying insecticides in insects. Over-expression and structural modification of CarEs have been implicated in the development of organophosphate (OP) insecticide resistance in insects. A previous study identified four nonsynonymous mutations (resulting in four amino acid residue substitutions) in the open reading frame of the carboxylesterase gene of resistant cotton aphids compared to the omethoate susceptible strain, which has possibly influenced the development of resistance to omethoate (a systemic OP insecticide). The current study further characterized the function of these mutations, both alone and in combination, in the hydrolysis of OP insecticides. The metabolism results suggest that the combination of four mutations, mainly existing in the laboratory-selected OP-resistant cotton aphid population, increased the OP hydrolase activity (approximately twofold) at the cost of detectable carboxylesterase activity. The functional studies of single or multiple mutations suggest the positive effect of H104R, A128V and T333P on the acquisition of OP hydrolase activity, especially the combination of H104R with A128V or T333P. K484R substitution decreased both the OP hydrolase activity and the CarE activity, indicating that this mutation primarily drives the negative effect on the acquisition of OP hydrolase activity amongst these four mutations in the resistant strain. The modelling and docking results are basically consistent with the metabolic results, which strongly suggest that the structural gene modification is the molecular basis for the OP resistance in this laboratory-selected cotton aphid strain. Title: Three New Ergot Alkaloids from the Fruiting Bodies of Xylaria nigripes (Kl.) Sacc Hu D, Li M Ref: Chem Biodivers, 14:, 2017 : PubMed ESTHER: Hu_2017_Chem.Biodivers_14_ PubMedSearch: Hu 2017 Chem.Biodivers 14 PubMedID: 27448231 Abstract Three new ergot alkaloids, xylanigripones A - C (1 - 3) together with three known compounds, agroclavine (4), 8,9-didehydro-10-hydroxy-6,8-dimethylergolin (5), and (6S)-agroclavine N-oxide (6) were isolated from the fungus Xylaria nigripes (Kl.) Sacc. Their structures were elucidated by comprehensive spectroscopic analyses and high-resolution mass spectrometry as well as by comparison with the literature. The absolute configuration was determined by Density Functional Theory (DFT) calculation methods. In addition, all of the compounds were evaluated for bioactivity via a cytotoxicity assay, an acetylcholinesterase inhibition assay and a cholesterol ester transfer protein inhibition assay. Title: Differential physiological effects of neonicotinoid insecticides on honey bees: A comparison between Apis mellifera and Apis cerana Li Z, Li M, He J, Zhao X, Chaimanee V, Huang WF, Nie H, Zhao Y, Su S Ref: Pestic Biochem Physiol, 140:1, 2017 : PubMed ESTHER: Li_2017_Pestic.Biochem.Physiol_140_1 PubMedSearch: Li 2017 Pestic.Biochem.Physiol 140 1 PubMedID: 28755688 Abstract Acute toxicities (LD50s) of imidacloprid and clothianidin to Apis mellifera and A. cerana were investigated. Changing patterns of immune-related gene expressions and the activities of four enzymes between the two bee species were compared and analyzed after exposure to sublethal doses of insecticides. Results indicated that A. cerana was more sensitive to imidacloprid and clothianidin than A. mellifera. The acute oral LD50 values of imidacloprid and clothianidin for A. mellifera were 8.6 and 2.0ng/bee, respectively, whereas the corresponding values for A. cerana were 2.7 and 0.5ng/bee. The two bee species possessed distinct abilities to mount innate immune response against neonicotinoids. After 48h of imidacloprid treatment, carboxylesterase (CCE), prophenol oxidase (PPO), and acetylcholinesterase (AChE) activities were significantly downregulated in A. mellifera but were upregulated in A. cerana. Glutathione-S-transferase (GST) activity was significantly elevated in A. mellifera at 48h after exposure to imidacloprid, but no significant change was observed in A. cerana. AChE was downregulated in both bee species at three different time points during clothianidin exposure, and GST activities were upregulated in both species exposed to clothianidin. Different patterns of immune-related gene expression and enzymatic activities implied distinct detoxification and immune responses of A. cerana and A. mellifera to imidacloprid and clothianidin. Title: Proteolytic cleavage is required for functional neuroligin 2 maturation and trafficking in Drosophila Tu R, Qian J, Rui M, Tao N, Sun M, Zhuang Y, Lv H, Han J, Li M, Xie W Ref: J Molecular & Cellular Biology, 9:231, 2017 : PubMed ESTHER: Tu_2017_J.Mol.Cell.Biol_9_231 PubMedSearch: Tu 2017 J.Mol.Cell.Biol 9 231 PubMedID: 28498949 Abstract Neuroligins (Nlgs) are transmembrane cell adhesion molecules playing essential roles in synapse development and function. Genetic mutations in neuroligin genes have been linked with some neurodevelopmental disorders such as autism. These mutated Nlgs are mostly retained in the endoplasmic reticulum (ER). However, the mechanisms underlying normal Nlg maturation and trafficking have remained largely unknown. Here, we found that Drosophila neuroligin 2 (DNlg2) undergoes proteolytic cleavage in the ER in a variety of Drosophila tissues throughout developmental stages. A region encompassing Y642-T698 is required for this process. The immature non-cleavable DNlg2 is retained in the ER and non-functional. The C-terminal fragment of DNlg2 instead of the full-length or non-cleavable DNlg2 is able to rescue neuromuscular junction defects and GluRIIB reduction induced by dnlg2 deletion. Intriguingly, the autism-associated R598C mutation in DNlg2 leads to similar marked defects in DNlg2 proteolytic process and ER export, revealing a potential role of the improper Nlg cleavage in autism pathogenesis. Collectively, our findings uncover a specific mechanism that controls DNlg2 maturation and trafficking via proteolytic cleavage in the ER, suggesting that the perturbed proteolytic cleavage of Nlgs likely contributes to autism disorder. Title: Juvenile Hormone Epoxide Hydrolase: a Promising Target for Hemipteran Pest Management Tusun A, Li M, Liang X, Yang T, Yang B, Wang G Ref: Sci Rep, 7:789, 2017 : PubMed ESTHER: Tusun_2017_Sci.Rep_7_789 PubMedSearch: Tusun 2017 Sci.Rep 7 789 PubMedID: 28400585 Abstract Juvenile hormone epoxide hydrolase (JHEH) has attracted great interest because of its critical role in the regulation of juvenile hormone (JH) in insects. In this study, one JHEH gene from Apolygus lucorum (AlucJHEH) was characterized in terms of deduced amino acid sequence, phylogeny, homology modeling and docking simulation. The results reveals a conserved catalytic mechanism of AlucJHEH toward JH. Our study also demonstrates that the mRNA of AlucJHEH gene was detectable in head, thorax and abdomen from all life stages. To functionally characterize the AlucJHEH gene, three fragments of double-stranded RNAs (dsRNAs) were designed to target different regions of the sequence. Injection of 3rd nymphs with dsRNA fragments successfully knocked down the target gene expression, and a significantly decreased survival rate was observed, together with a molting block, These findings confirm the important regulatory roles of AlucJHEH in A. lucorum and indicate this gene as a promising target for future hemipterans pest control. Title: Screening of a natural compound library identifies emodin, a natural compound from Rheum palmatum Linn that inhibits DPP4 Wang Z, Yang L, Fan H, Wu P, Zhang F, Zhang C, Liu W, Li M Ref: PeerJ, 5:e3283, 2017 : PubMed ESTHER: Wang_2017_PeerJ_5_e3283 PubMedSearch: Wang 2017 PeerJ 5 e3283 PubMedID: 28507818 Abstract Historically, Chinese herbal medicines have been widely used in the treatment of hyperglycemia, but the mechanisms underlying their effectiveness remain largely unknown. Here, we screened a compound library primarily comprised of natural compounds extracted from herbs and marine organisms. The results showed that emodin, a natural compound from Rheum palmatum Linn, inhibited DPP4 activity with an in vitro IC50 of 5.76 microM without inhibiting either DPP8 or DPP9. A docking model revealed that emodin binds to DPP4 protein through Glu205 and Glu206, although with low affinity. Moreover, emodin treatment (3, 10 and 30 mg/kg, P.O.) in mice decreased plasma DPP4 activity in a dose-dependent manner. Our study suggests that emodin inhibits DPP4 activity and may represent a novel therapeutic for the treatment of type 2 diabetes. Title: Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3 Yao Y, Wang W, Jing L, Wang Y, Li M, Hou X, Wang J, Peng T, Teng J, Jia Y Ref: Neurochem Res, 42:446, 2017 : PubMed ESTHER: Yao_2017_Neurochem.Res_42_446 PubMedSearch: Yao 2017 Neurochem.Res 42 446 PubMedID: 27812761 Abstract microRNAs are a class of non-coding RNAs including approximately 22 nucleotides in length and play a pivotal role in post-transcriptional gene regulation. Currently, the role of miRNAs in the pathophysiology of ischemic stroke has been the subject of recent investigations. In particular, antagomirs to microRNA (miRNA) let-7f have been found to be neuroprotective in vivo, although the detailed function of let-7f during cerebral ischemia has not been fully illustrated. NDRG3 is an N-myc downstream-regulated gene (NDRG) family member that has been observed in the nuclei in most brain cells. Recently, a NDRG3-mediated lactate signaling, in which stabilized NDRG3 protein can promote angiogenesis and cell growth by activating the Raf-ERK pathway in hypoxia was discovered. In this study, we preliminarily explored the change in the expression of the NDRG3 protein which indicated that NDRG3 protein is an oxygen-regulated protein in neurons in rat cerebral ischemia in vivo and in vitro. We further identified let-7f as an upstream regulator of NDRG3 by the lentiviral transfection of rat cortical neurons and the dual luciferase analysis of human genes. In addition, a dual-color fluorescence in situ hybridization assay showed that when the expression of let-7f was elevated, the expression of NDRG3 mRNA was accordingly reduced in rat cerebral ischemia. Taken together, our results identify a new regulatory mechanism of let-7f on NDRG3 expression in the hypoxic response of cerebral ischemia and raise the possibility that the let-7f/NDRG3 pathway may serve as a potential target for the treatment of ischemic stroke. Title: Depletion of juvenile hormone esterase extends larval growth in Bombyx mori Zhang Z, Liu X, Shiotsuki T, Wang Z, Xu X, Huang Y, Li M, Li K, Tan A Ref: Insect Biochemistry & Molecular Biology, 81:72, 2017 : PubMed ESTHER: Zhang_2017_Insect.Biochem.Mol.Biol_81_72 PubMedSearch: Zhang 2017 Insect.Biochem.Mol.Biol 81 72 PubMedID: 28057597 Abstract Two major hormones, juvenile hormone (JH) and 20-hydroxyecdysone (20E), regulate insect growth and development according to their precisely coordinated titres, which are controlled by both biosynthesis and degradation pathways. Juvenile hormone esterase (JHE) is the primary JH-specific degradation enzyme that plays a key role in regulating JH titers, along with JH epoxide hydrolase (JHEH) and JH diol kinase (JHDK). In the current study, a loss-of-function analysis of JHE in the silkworm, Bombyx mori, was performed by targeted gene disruption using the transgenic CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/RNA-guided Cas9 nucleases) system. Depletion of B. mori JHE (BmJHE) resulted in the extension of larval stages, especially the penultimate and ultimate larval stages, without deleterious effects to silkworm physiology. The expression of JHEH and JHDK was upregulated in mutant animals, indicating the existence of complementary routes in the JH metabolism pathway in which inactivation of one enzyme will activate other enzymes. RNA-Seq analysis of mutant animals revealed that genes involved in protein processing in the endoplasmic reticulum and in amino acid metabolism were affected by BmJHE depletion. Depletion of JHE and subsequent delayed JH metabolism activated genes in the TOR pathway, which are ultimately responsible for extending larval growth. The transgenic Cas9 system used in the current study provides a promising approach for analysing the actions of JH, especially in nondrosophilid insects. Furthermore, prolonging larval stages produced larger larvae and cocoons, which is greatly beneficial to silk production. Title: Repetitive transcranial magnetic stimulation improves cognitive function of Alzheimer's disease patients Zhao J, Li Z, Cong Y, Zhang J, Tan M, Zhang H, Geng N, Li M, Yu W, Shan P Ref: Oncotarget, 8:33864, 2017 : PubMed ESTHER: Zhao_2017_Oncotarget_8_33864 PubMedSearch: Zhao 2017 Oncotarget 8 33864 PubMedID: 27823981 Abstract Repetitive transcranial magnetic stimulation (rTMS) acts as a kind of widely-applied and non-invasive method in the intervention of some neurological disorders. This prospective, randomized, double-blind, placebo-controlled trial investigates the effect of rTMS on 30 cases of Alzheimer's disease (AD) participants, who were classified into mild and moderate groups. Neuropsychological tests were carried out using the AD Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and World Health Organization University of California-Los Angeles, Auditory Verbal Learning Test (WHO-UCLA AVLT) before, immediately after, and 6 weeks after the intervention. In this work, data from 30 AD patients revealed that there was no obvious interaction effect of time-by-group. The ADAS-cog, MMSE and WHO-UCLA AVLT score in the rTMS group was significantly improved compared with baselines at 6 weeks after treatment (all p<0.05). Meanwhile, MoCA scores were also obviously ameliorated in the mild AD patients with rTMS. Besides, subgroup analysis showed that the effect of rTMS on the memory and language of mild AD patients was superior to those of moderate AD patients. In conclusion, our findings suggested that repetitive transcranial magnetic stimulation improves cognitive function, memory and language level of AD patients, especially in the mild stage of AD. Thus, rTMS can be recommended as a promising adjuvant therapy combined with cholinesterase inhibitors at the mild stage of AD patients. Title: Targeting of cancerassociated fibroblasts enhances the efficacy of cancer chemotherapy by regulating the tumor microenvironment Li M, Yin T, Shi H, Wen Y, Zhang B, Chen M, Xu G, Ren K, Wei Y Ref: Mol Med Rep, 13:2476, 2016 : PubMed ESTHER: Li_2016_Mol.Med.Rep_13_2476 PubMedSearch: Li 2016 Mol.Med.Rep 13 2476 PubMedID: 26846566 Abstract Cancerassociated fibroblasts (CAFs), key components of the tumor stroma, can regulate tumorigenesis by altering the tumor microenvironment in variety of ways to promote angiogenesis, recruit inflammatory immune cells and remodel the extracellular matrix. Using a murine xenograft model of colon carcinoma, the present study observed that oxaliplatin increased the accumulation of CAFs and stimulated the production of cytokines associated with CAFs. When oxaliplatin was combined with the smallmolecule dipeptidyl peptidase inhibitor PT100, which inhibits CAFs by targeting fibroblast activation protein (FAP), the accumulation of CAFs was markedly reduced, xenograft tumor growth was significantly suppressed and the survival of the mice increased, compared to those of mice treated with oxaliplatin or PT100 alone. Furthermore, the xenograft tumor tissues of mice treated with oxaliplatin and PT100 contained lower numbers of tumorassociated macrophages and dendritic cells, expressed lower levels of cytokines associated with CAFs and had a lower density of CD31+ endothelial cells. The present study demonstrated that pharmacological inhibition of CAFs improved the response to chemotherapy, reduced the recruitment of immune tumorpromoting cells and inhibited angiogenesis. Combining chemotherapy with agents which target CAFs may represent a novel strategy for improving the efficacy of chemotherapy and reducing chemoresistance. Title: Cloning and characterization of a novel lipase from Stenotrophomonas maltophilia GS11: The first member of a new bacterial lipase family XVI Li M, Yang LR, Xu G, Wu JP Ref: J Biotechnol, 228:30, 2016 : PubMed ESTHER: Li_2016_J.Biotechnol_228_30 PubMedSearch: Li 2016 J.Biotechnol 228 30 PubMedID: 27117245 Gene_locus related to this paper: stema-s4tny8 Abstract Bacterial lipases are an important group of enzymes that offer enormous potential in organic synthesis, and there is considerable interest in identifying and developing novel bacterial lipases. In previous studies, strains of the genus Stenotrophomonas were proved to be potential source of lipases, but there is little genetic information describing lipase from the genus Stenotrophomonas. We have cloned and characterized a novel lipase (LipSM54), the first lipase described from the genus Stenotrophomonas. Enzymatic study showed that LipSM54 was a cold-active, solvent-tolerant and alkaline lipase. Using bioinformatics tools, LipSM54 was found to be related only to several putative lipases from different bacterial origins, none of which could be assigned to any previously described bacterial lipase family. LipSM54 and these related putative lipases share four conserved motifs around the catalytic residues. These motifs clearly distinguish them from the known bacterial lipase families. Consequently, LipSM54 is the first characterized member of the novel bacterial lipase family. Title: A novel thermostable and organic solvent-tolerant lipase from Xanthomonas oryzae pv. oryzae YB103: screening, purification and characterization Mo Q, Liu A, Guo H, Zhang Y, Li M Ref: Extremophiles, 20:157, 2016 : PubMed ESTHER: Mo_2016_Extremophiles_20_157 PubMedSearch: Mo 2016 Extremophiles 20 157 PubMedID: 26791383 Abstract Thermostable lipases offer major biotechnological advantages over mesophilic lipases. In this study, an intracellular thermostable and organic solvent-tolerant lipase-producing strain YB103 was isolated from soil samples and identified taxonomically as Xanthomonas oryzae pv. oryzae. The lipase from X. oryzae pv. oryzae YB103 (LipXO) was purified 101.1-fold to homogeneity with a specific activity of 373.9 U/mg. The purified lipase showed excellent thermostability, exhibiting 51.1 % of its residual activity after incubation for 3 days at 70 degrees C. The enzyme showed optimal activity at 70 degrees C, suggesting it is a thermostable lipase. LipXO retained 75.1-154.1 % of its original activity after incubation in 20 % (v/v) hydrophobic organic solvents at 70 degrees C for 24 h. Furthermore, LipXO displayed excellent stereoselectivity (e.e.p >99 %) toward (S)-1-phenethyl alcohol in n-hexane. These unique properties of LipXO make it promising as a biocatalyst for industrial processes. Title: Complete Genome Sequence of Fish Pathogen Aeromonas hydrophila JBN2301 Yang W, Li N, Li M, Zhang D, An G Ref: Genome Announc, 4:, 2016 : PubMed ESTHER: Yang_2016_Genome.Announc_4_ PubMedSearch: Yang 2016 Genome.Announc 4 PubMedID: 26823580 Gene_locus related to this paper: aerhy-a0a0s3bhm4 Abstract Aeromonas hydrophila is one of the most important fish pathogens in China. Here, we report complete genome sequence of a virulent strain, A. hydrophila JBN2301, which was isolated from diseased crucian carp. Title: The in Vitro and in Vivo Degradation of Cross-Linked Poly(trimethylene carbonate)-Based Networks Yang L, Li J, Li M, Gu Z Ref: Polymers (Basel), 8:, 2016 : PubMed ESTHER: Yang_2016_Polymers.(Basel)_8_ PubMedSearch: Yang 2016 Polymers.(Basel) 8 PubMedID: 30979246 Abstract The degradation of the poly(trimethylene carbonate) (PTMC) and poly(trimethylene carbonate-co-sigma-caprolactone) (P(TMC-co-CL)) networks cross-linked by 0.01 and 0.02 mol % 2,2'-bis(trimethylene carbonate-5-yl)-butylether (BTB) was carried out in the conditions of hydrolysis and enzymes in vitro and subcutaneous implantation in vivo. The results showed that the cross-linked PTMC networks exhibited much faster degradation in enzymatic conditions in vitro and in vivo versus in a hydrolysis case due to the catalyst effect of enzymes; the weight loss and physical properties of the degraded networks were dependent on the BTB amount. The morphology observation in lipase and in vivo illustrated that enzymes played an important role in the surface erosion of cross-linked PTMC. The hydrolytic degradation rate of the cross-linked P(TMC-co-CL) networks increased with increasing sigma-caprolactone (CL) content in composition due to the preferential cleavage of ester bonds. Cross-linking is an effective strategy to lower the degradation rate and enhance the form-stability of PTMC-based materials. Title: Genome sequencing of the perciform fish Larimichthys crocea provides insights into molecular and genetic mechanisms of stress adaptation Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T and Chen X <19 more author(s)> Ao J, Mu Y, Xiang LX, Fan D, Feng M, Zhang S, Shi Q, Zhu LY, Li T, Ding Y, Nie L, Li Q, Dong WR, Jiang L, Sun B, Zhang X, Li M, Zhang HQ, Xie S, Zhu Y, Jiang X, Wang X, Mu P, Chen W, Yue Z, Wang Z, Wang J, Shao JZ, Chen X (- 19) Ref: PLoS Genet, 11:e1005118, 2015 : PubMed ESTHER: Ao_2015_PLoS.Genet_11_E1005118 PubMedSearch: Ao 2015 PLoS.Genet 11 E1005118 PubMedID: 25835551 Gene_locus related to this paper: larcr-a0a0f8ay25, larcr-a0a0f8cf53, larcr-a0a0f8cir1, larcr-a0a0f8d1j2, larcr-a0a0f8alq6, larcr-a0a0f8bdu4, larcr-a0a0f8abw1, larcr-a0a0f8ahh1, larcr-a0a0f8avc6, larcr-a0a0f8al93, larcr-a0a0f8aed8, larcr-a0a0f7ir14, larcr-a0a0f8aje8, larcr-k9lsm3, larcr-a0a0f8but5, larcr-a0a0f8af44 Abstract The large yellow croaker Larimichthys crocea (L. crocea) is one of the most economically important marine fish in China and East Asian countries. It also exhibits peculiar behavioral and physiological characteristics, especially sensitive to various environmental stresses, such as hypoxia and air exposure. These traits may render L. crocea a good model for investigating the response mechanisms to environmental stress. To understand the molecular and genetic mechanisms underlying the adaptation and response of L. crocea to environmental stress, we sequenced and assembled the genome of L. crocea using a bacterial artificial chromosome and whole-genome shotgun hierarchical strategy. The final genome assembly was 679 Mb, with a contig N50 of 63.11 kb and a scaffold N50 of 1.03 Mb, containing 25,401 protein-coding genes. Gene families underlying adaptive behaviours, such as vision-related crystallins, olfactory receptors, and auditory sense-related genes, were significantly expanded in the genome of L. crocea relative to those of other vertebrates. Transcriptome analyses of the hypoxia-exposed L. crocea brain revealed new aspects of neuro-endocrine-immune/metabolism regulatory networks that may help the fish to avoid cerebral inflammatory injury and maintain energy balance under hypoxia. Proteomics data demonstrate that skin mucus of the air-exposed L. crocea had a complex composition, with an unexpectedly high number of proteins (3,209), suggesting its multiple protective mechanisms involved in antioxidant functions, oxygen transport, immune defence, and osmotic and ionic regulation. Our results reveal the molecular and genetic basis of fish adaptation and response to hypoxia and air exposure. The data generated by this study will provide valuable resources for the genetic improvement of stress resistance and yield potential in L. crocea. Title: Identification and Characterization of ML352: A Novel, Noncompetitive Inhibitor of the Presynaptic Choline Transporter Ennis EA, Wright J, Retzlaff CL, McManus OB, Lin Z, Huang X, Wu M, Li M, Daniels JS and Blakely RD <2 more author(s)> Ennis EA, Wright J, Retzlaff CL, McManus OB, Lin Z, Huang X, Wu M, Li M, Daniels JS, Lindsley CW, Hopkins CR, Blakely RD (- 2) Ref: ACS Chem Neurosci, 6:417, 2015 : PubMed ESTHER: Ennis_2015_ACS.Chem.Neurosci_6_417 PubMedSearch: Ennis 2015 ACS.Chem.Neurosci 6 417 PubMedID: 25560927 Abstract The high-affinity choline transporter (CHT) is the rate-limiting determinant of acetylcholine (ACh) synthesis, yet the transporter remains a largely undeveloped target for the detection and manipulation of synaptic cholinergic signaling. To expand CHT pharmacology, we pursued a high-throughput screen for novel CHT-targeted small molecules based on the electrogenic properties of transporter-mediated choline transport. In this effort, we identified five novel, structural classes of CHT-specific inhibitors. Chemical diversification and functional analysis of one of these classes identified ML352 as a high-affinity (Ki = 92 nM) and selective CHT inhibitor. At concentrations that fully antagonized CHT in transfected cells and nerve terminal preparations, ML352 exhibited no inhibition of acetylcholinesterase (AChE) or cholineacetyltransferase (ChAT) and also lacked activity at dopamine, serotonin, and norepinephrine transporters, as well as many receptors and ion channels. ML352 exhibited noncompetitive choline uptake inhibition in intact cells and synaptosomes and reduced the apparent density of hemicholinium-3 (HC-3) binding sites in membrane assays, suggesting allosteric transporter interactions. Pharmacokinetic studies revealed limited in vitro metabolism and significant CNS penetration, with features predicting rapid clearance. ML352 represents a novel, potent, and specific tool for the manipulation of CHT, providing a possible platform for the development of cholinergic imaging and therapeutic agents. Title: Distribution and frequency of G119S mutation in ace-1 gene within Anopheles sinensis populations from Guangxi, China Feng X, Yang C, Yang Y, Li J, Lin K, Li M, Qiu X Ref: Malar J, 14:470, 2015 : PubMed ESTHER: Feng_2015_Malar.J_14_470 PubMedSearch: Feng 2015 Malar.J 14 470 PubMedID: 26608572 Gene_locus related to this paper: anoga-ACHE1 Abstract BACKGROUND: Malaria is one of the most serious vector-borne diseases in the world. Vector control is an important measure for malaria prevention and elimination. However, this strategy is under threat as disease vectors are developing resistance to insecticides. Therefore, it is important to monitor mechanisms responsible for insecticide resistance. In this study, the presence of G119S mutation in the acetyl cholinesterase-encoding gene (ace-1) was investigated in nine Anopheles sinensis populations sampled across Guangxi Zhuang Autonomous Region China. Title: Efficacy and safety of galantamine treatment for patients with Alzheimer's disease: a meta-analysis of randomized controlled trials Jiang D, Yang X, Li M, Wang Y Ref: J Neural Transm, 122:1157, 2015 : PubMed ESTHER: Jiang_2015_J.Neural.Transm_122_1157 PubMedSearch: Jiang 2015 J.Neural.Transm 122 1157 PubMedID: 25547862 Abstract Cholinesterase inhibitors treatment is considered as a common therapeutic approach for Alzheimer's disease (AD) by numerous reported studies, but the role of currently available drugs for AD is still controversial. Our study aimed to evaluate the efficacy and safety of galantamine for the treatment of AD, and provide the basis and reference for clinical rational drug use. Randomized controlled trials (RCTs) of galantamine for AD published up to April 30, 2014 were searched. A random or fixed-effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean difference (MD) with a 95 % confidence interval (CI). Heterogeneity was assessed by Q test and I (2) statistic. The outcome measurements were as follows: the changes of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Neuropsychiatric Inventory (NPI), Clinicians' Interview-Based Impression of Change with Caregiver's Input (CIBIC+), adverse effects and dropouts. Eleven articles with 4,074 participants were included. Administration of galantamine for 8-28 weeks (16-40 mg daily) led to significant improvements in ADAS-cog score [P < 0.00001, MD = -2.95, 95 % CI (-3.32, -2.57)], MMSE score [P = 0.003, MD = 2.50, 95 % CI (0.86, 4.15)], NPI score [P = 0.001, MD = -1.58, 95 % CI (-2.54, -0.62)], and CIBIC+ scale [P < 0.00001, RR = 1.26, 95 % CI (1.15, 1.39)], but not in ADL score [P = 0.43, MD = 0.71, 95 % CI (-1.07, 2.48)]. More adverse events and dropouts occurred in the galantamine group than that in the placebo group, the differences were statistically significant (all P < 0.05). Galantamine could significantly improve cognitive, behavioral, and global performances in patients with AD. In addition, we need to use it with caution in the clinical treatment. Title: The timing of acid-induced increase in saliva secretion in transplanted submandibular glands Liu XJ, Li M, Su JZ, Xie Z, Yu GY Ref: Int J Oral Maxillofac Surg, 44:1041, 2015 : PubMed ESTHER: Liu_2015_Int.J.Oral.Maxillofac.Surg_44_1041 PubMedSearch: Liu 2015 Int.J.Oral.Maxillofac.Surg 44 1041 PubMedID: 25697065 Abstract The purpose of this study was to determine the timing of acid-induced increase in saliva secretion and to investigate the possibility of parasympathetic reinnervation of transplanted submandibular glands (SMGs). Citric acid stimulation-induced changes in secretion of transplanted SMGs were evaluated in 27 patients who underwent SMG transplantation for keratoconjunctivitis sicca (KCS); (99m)Tc scintigraphy and Schirmer tests were done at 1, 3, 6, and 9 months after transplantation. Acetylcholinesterase staining was conducted to confirm the presence of parasympathetic reinnervation in three SMGs at 6 and 9 months after transplantation. Schirmer tests showed significantly increased secretion of the transplanted SMGs after acid stimulation at 6 and 9 months, but not at 1 and 3 months. On (99m)Tc scintigraphy, no decline was detected on the dynamic time-activity curve after acid stimulation at 1 and 3 months, but a decline was detected in nine glands at 6 months and in 19 glands at 9 months. No decline was observed in the remaining eight glands at 9 months after transplantation. The histology findings were consistent with scintigraphy results. In conclusion, acid-induced increase in saliva secretion occurs at >/=6 months after SMG transplantation, and parasympathetic reinnervation of the transplanted SMG might occur. Title: Identification of a novel Afipia species isolated from an Indian flying fox Pickering BS, Tyler S, Smith G, Burton L, Li M, Dallaire A, Weingartl H Ref: PLoS ONE, 10:e0121274, 2015 : PubMed ESTHER: Pickering_2015_PLoS.ONE_10_E0121274 PubMedSearch: Pickering 2015 PLoS.ONE 10 E0121274 PubMedID: 25874801 Gene_locus related to this paper: 9brad-w3rff7 Abstract An old world fruit bat Pteropus giganteus, held in captivity and suffering from necrosis of its wing digits, failed to respond to antibiotic therapy and succumbed to the infection. Samples submitted to the National Centre for Foreign Animal Disease were tested for viral infection. Vero E6 cells exhibited minor but unique cytopathic effects on second blind passage, and full CPE by passage four. Utilizing an unbiased random amplification technique from cell culture supernatant, we identified a bacterium belonging to the Bradyrhizobiaceae. Purification of cell culture supernatant on TY media revealed a slow growing bacterial isolate. In this study using electron microscopy, 16S rRNA gene analysis and whole genome sequencing, we identify a novel bacterial species associated with the site of infection belonging to the genus Afipia. This genus of bacteria is very diverse, with only a limited number of species characterized. Afipia felis, previously described as the etiological agent to cause cat scratch disease, and Afipia septicemium, most recently shown to cause disease in humans, highlight the potential for members of this genus to form a branch of opportunistic pathogens within the Bradyrhizobiaceae. Increased utilization of next generation sequencing and genomics will aid in classifying additional members of this intriguing bacterial genera. Title: Introducing a salt bridge into the lipase of Stenotrophomonas maltophilia results in a very large increase in thermal stability Wu JP, Li M, Zhou Y, Yang LR, Xu G Ref: Biotechnol Lett, 37:403, 2015 : PubMed ESTHER: Wu_2015_Biotechnol.Lett_37_403 PubMedSearch: Wu 2015 Biotechnol.Lett 37 403 PubMedID: 25257598 Abstract High thermostability of enzymes is a prerequisite for their biotechnological applications. An organic solvent-tolerant and cold-active lipase, from the Stenotrophomonas maltophilia, was unstable above 40 degrees C in previous studies. To increase the enzyme stability, possible hydrogen-bond networks were simulated by the introduction of a salt bridge in a highly flexible region of the protein. Compared with the wild-type lipase, a mutant lipase (G165D and F73R) showed a >900-fold improvement in half-life at 50 degrees C, with the optimal activity-temperature increasing from 35 to 90 degrees C. Therefore, the hydrogen-bond strategy is a powerful approach for improving enzyme stability through the introduction of a salt bridge. Title: Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits Xu H, Tao X, Wei Y, Chen J, Xing S, Cen W, Wen A, Zhu L, Tang G and Li X <3 more author(s)> Xu H, Tao X, Wei Y, Chen J, Xing S, Cen W, Wen A, Zhu L, Tang G, Li M, Jiang A, Jiang Y, Li X (- 3) Ref: Gene, 557:146, 2015 : PubMed ESTHER: Xu_2015_Gene_557_146 PubMedSearch: Xu 2015 Gene 557 146 PubMedID: 25498336 Abstract Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits. Title: High quality draft genomic sequence of Flavobacterium enshiense DK69(T) and comparison among Flavobacterium genomes Zeng Z, Chen C, Du H, Wang G, Li M Ref: Stand Genomic Sci, 10:92, 2015 : PubMed ESTHER: Zeng_2015_Stand.Genomic.Sci_10_92 PubMedSearch: Zeng 2015 Stand.Genomic.Sci 10 92 PubMedID: 26561515 Gene_locus related to this paper: 9flao-v6scv7 Abstract Flavobacterium enshiense DK69(T) is a Gram-negative, aerobic, rod-shaped, non-motile and non-flagellated bacterium that belongs to the family Flavobacteriaceae in the phylum Bacteroidetes. The high quality draft genome of strain DK69(T) was obtained and has a 3,375,260 bp genome size with a G + C content of 37.7 mol % and 2848 protein coding genes. In addition, we sequenced five more genomes of Flavobacterium type strains and performed a comparative genomic analysis among 12 Flavobacterium genomes. The results show some specific genes within the fish pathogenic Flavobacterium strains which provide information for further analysis the pathogenicity. Title: Effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver Gao F, Liu Y, Li L, Li M, Zhang C, Ao C, Hou X Ref: Anim Reprod Sci, 147:99, 2014 : PubMed ESTHER: Gao_2014_Anim.Reprod.Sci_147_99 PubMedSearch: Gao 2014 Anim.Reprod.Sci 147 99 PubMedID: 24852270 Abstract This study investigated the effects of maternal undernutrition during late pregnancy on the development and function of ovine fetal liver. Eighteen ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.175MJMEkgBW(-0.75)d(-1), n=6), Restricted Group 2 (RG2, 0.33MJMEkgBW(-0.75)d(-1), n=6) and a Control Group (CG, ad libitum, 0.67MJMEkgBW(-0.75)d(-1), n=6). Fetuses were recovered at slaughter on d 140. Fetuses in the RG1 group exhibited decreased (P<0.05) liver weight, total antioxidant capacity (T-AOC), superoxide dismutase activity (SOD), cholinesterase (CHE), total protein (TP), globulin (GLB), and alanine transaminase (ALT). In addition, intermediate changes were found in the RG2 fetuses, including decreased liver weight, T-AOC and CHE (P<0.05). In contrast, increases in fetal hepatic collagen fibers and reticular fibers, glutathione peroxidase (GSH-Px), malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOs), monoamine oxidase (MAO), albumin (ALB)/GLB, aspartate transaminase (AST), and AST/ALT were found in the RG1 fetuses (P<0.05). The RG2 fetuses had increased fetal hepatic collagen fibers, NOs and MAO (P<0.05) relative to the control fetuses. These results indicate that impaired fetal hepatic growth, fibrosis, antioxidant imbalance and dysfunction were associated with maternal undernutrition. Title: Eucommia ulmoides Oliv.: Ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine He X, Wang J, Li M, Hao D, Yang Y, Zhang C, He R, Tao R Ref: J Ethnopharmacol, 151:78, 2014 : PubMed ESTHER: He_2014_J.Ethnopharmacol_151_78 PubMedSearch: He 2014 J.Ethnopharmacol 151 78 PubMedID: 24296089 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Eucommia ulmoides Oliv. (Family Eucommiaceae), also known as Du-zhong (Chinese: ), Tuchong (in Japanese), is the sole species of the genus Eucommia. The leaf, stem, and bark as well as staminate flower of Eucommia ulmoides have been traditionally used to cure many diseases in China, Japan, Korea, among others. The aim of this review is to comprehensively outline the botanical description, ethnopharmacology, phytochemistry, biological activities, and toxicology of Eucommia ulmoides and to discuss possible trends for further study of Eucommia ulmoides. MATERIALS AND Title: Adding the acetylcholinesterase inhibitor, donepezil, to losartan treatment markedly improves long-term survival in rats with chronic heart failure Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Sugimachi M Ref: Eur J Heart Fail, 16:1056, 2014 : PubMed ESTHER: Li_2014_Eur.J.Heart.Fail_16_1056 PubMedSearch: Li 2014 Eur.J.Heart.Fail 16 1056 PubMedID: 25201490 Abstract AIMS: Modulation of vagal tone using electrical vagal nerve stimulation or pharmacological acetylcholinesterase inhibition by donepezil exerts beneficial effects in an animal model of chronic heart failure (CHF). Considering different treatment mechanisms underlying renin-angiotensin system (RAS) suppression and parasympathetic activation, we hypothesized that parasympathetic activation together with RAS inhibition could attenuate CHF progression. To test this hypothesis, we investigated the therapeutic effects of a combination of donepezil and losartan in CHF rats with extensive myocardial infarction (MI). METHODS AND Title: Temporal specification and bilaterality of human neocortical topographic gene expression Pletikos M, Sousa AM, Sedmak G, Meyer KA, Zhu Y, Cheng F, Li M, Kawasawa YI, Sestan N Ref: Neuron, 81:321, 2014 : PubMed ESTHER: Pletikos_2014_Neuron_81_321 PubMedSearch: Pletikos 2014 Neuron 81 321 PubMedID: 24373884 Abstract Transcriptional events involved in the development of human cerebral neocortex are poorly understood. Here, we analyzed the temporal dynamics and laterality of gene expression in human and macaque monkey neocortex. We found that interareal differences exhibit a temporal hourglass pattern, dividing the human neocortical development into three major phases. The first phase, corresponding to prenatal development, is characterized by the highest number of differential expressed genes among areas and gradient-like expression patterns, including those that are different between human and macaque. The second, preadolescent phase, is characterized by lesser interareal expression differences and by an increased synchronization of areal transcriptomes. During the third phase, from adolescence onward, differential expression among areas increases again driven predominantly by a subset of areas, without obvious gradient-like patterns. Analyses of left-right gene expression revealed population-level global symmetry throughout the fetal and postnatal time span. Thus, human neocortical topographic gene expression is temporally specified and globally symmetric. Title: Genome of the house fly, Musca domestica L., a global vector of diseases with adaptations to a septic environment Scott JG, Warren WC, Beukeboom LW, Bopp D, Clark AG, Giers SD, Hediger M, Jones AK, Kasai S and Liu N <16 more author(s)> Scott JG, Warren WC, Beukeboom LW, Bopp D, Clark AG, Giers SD, Hediger M, Jones AK, Kasai S, Leichter CA, Li M, Meisel RP, Minx P, Murphy TD, Nelson DR, Reid WR, Rinkevich FD, Robertson HM, Sackton TB, Sattelle DB, Thibaud-Nissen F, Tomlinson C, van de Zande L, Walden KK, Wilson RK, Liu N (- 16) Ref: Genome Biol, 15:466, 2014 : PubMed ESTHER: Scott_2014_Genome.Biol_15_466 PubMedSearch: Scott 2014 Genome.Biol 15 466 PubMedID: 25315136 Gene_locus related to this paper: musdo-a0a1i8n2v5, musdo-a0a1i8n5k8 Abstract BACKGROUND: Adult house flies, Musca domestica L., are mechanical vectors of more than 100 devastating diseases that have severe consequences for human and animal health. House fly larvae play a vital role as decomposers of animal wastes, and thus live in intimate association with many animal pathogens. RESULTS: We have sequenced and analyzed the genome of the house fly using DNA from female flies. The sequenced genome is 691 Mb. Compared with Drosophila melanogaster, the genome contains a rich resource of shared and novel protein coding genes, a significantly higher amount of repetitive elements, and substantial increases in copy number and diversity of both the recognition and effector components of the immune system, consistent with life in a pathogen-rich environment. There are 146 P450 genes, plus 11 pseudogenes, in M. domestica, representing a significant increase relative to D. melanogaster and suggesting the presence of enhanced detoxification in house flies. Relative to D. melanogaster, M. domestica has also evolved an expanded repertoire of chemoreceptors and odorant binding proteins, many associated with gustation. CONCLUSIONS: This represents the first genome sequence of an insect that lives in intimate association with abundant animal pathogens. The house fly genome provides a rich resource for enabling work on innovative methods of insect control, for understanding the mechanisms of insecticide resistance, genetic adaptation to high pathogen loads, and for exploring the basic biology of this important pest. The genome of this species will also serve as a close out-group to Drosophila in comparative genomic studies. Title: Leonurus japonicus Houtt.: ethnopharmacology, phytochemistry and pharmacology of an important traditional Chinese medicine Shang X, Pan H, Wang X, He H, Li M Ref: J Ethnopharmacol, 152:14, 2014 : PubMed ESTHER: Shang_2014_J.Ethnopharmacol_152_14 PubMedSearch: Shang 2014 J.Ethnopharmacol 152 14 PubMedID: 24412548 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Leonurus japonicus Houtt. (Labiatae), commonly called Chinese motherwort ([Symbol: see text]), is an herbaceous flowering plant native to Asia. For thousands of years in China, the aerial part of Leonurus japonicus has been used to treat menoxenia, dysmenorrhea, amenorrhea, lochia, edema of the body, oliguresis, sores, ulcerations and other diseases in women. Now, Leonurus japonicus is listed in the Pharmacopoeia of the People's Republic of China. The present paper reviewed the ethnopharmacology, phytochemistry, biological actions and toxicology of Leonurus japonicus. MATERIALS AND Title: Galanthamine, an acetylcholine inhibitor, prevents prepulse inhibition deficits induced by adolescent social isolation or MK-801 treatment Shao S, Li M, Du W, Shao F, Wang W Ref: Brain Research, 1589:105, 2014 : PubMed ESTHER: Shao_2014_Brain.Res_1589_105 PubMedSearch: Shao 2014 Brain.Res 1589 105 PubMedID: 25281804 Abstract Adolescence is a critical period for neurodevelopment. MK-801 treatment and social isolation are important animal models for various neurodevelopmental disorders. Dysfunctions in the central cholinergic system are involved in creating the cognitive deficits observed in neurological diseases. In the present study, we aimed to investigate whether the acetylcholinesterase inhibitor galanthamine could reverse pre-cognitive prepulse inhibition (PPI) deficits and spatial learning deficits of adult rats in the Morris water maze. We induced these effects using either adolescent MK-801 treatment or social isolation from postnatal day (PND) 38-51. Our results showed that both adolescent social isolation and MK-801 treatment impaired PPI in adult rats, but neither had an effect on spatial learning. Furthermore, galanthamine injections over 7 days significantly enhanced PPI of normal rats and improved PPI disruption induced by adolescent pharmacological and rearing interventions. The results suggest that acetylcholinesterase inhibitors, such as galanthamine, might have the potential to improve pre-cognition in neurodevelopmental diseases by improving auditory sensory gating. Title: Duplication of acetylcholinesterase gene in diamondback moth strains with different sensitivities to acephate Sonoda S, Shi X, Song D, Liang P, Gao X, Zhang Y, Li J, Liu Y, Li M and Miyata T <4 more author(s)> Sonoda S, Shi X, Song D, Liang P, Gao X, Zhang Y, Li J, Liu Y, Li M, Matsumura M, Sanada-Morimura S, Minakuchi C, Tanaka T, Miyata T (- 4) Ref: Insect Biochemistry & Molecular Biology, 48:83, 2014 : PubMed ESTHER: Sonoda_2014_Insect.Biochem.Mol.Biol_48_83 PubMedSearch: Sonoda 2014 Insect.Biochem.Mol.Biol 48 83 PubMedID: 24632376 Abstract This study examined the acetylcholinesterase 1 gene (AChE1) in Plutella xylostella strains with different sensitivities to acephate. Multiple haplotypes of the gene were found in the field-collected strains including distinct haplotypes carrying one or both previously reported mutations (A298S and G324A). Moreover, sequencing results indicated the presence of duplicated copies of the gene in the field-collected strains. No correlation was found between copy numbers of AChE1 and levels of resistance to acephate suggesting that extensive AChE1 duplication is not a major resistance factor at least in some P. xylostella strains. Proportions of the A298S and G324A mutations showed no correlation with levels of resistance to acephate. This suggests that acephate resistance of P. xylostella is complex and cannot be evaluated based on the AChE1 copy number or proportions of the resistance mutations alone. Title: A Novel Risk Haplotype of ALOX5AP Gene is Associated with Ischemic Stroke in Chinese Han Population Yang D, He Y, Li M, Shi C, Song G, Wang Q, Fan Y, Feng Q, Zheng H Ref: Journal of Molecular Neuroscience, 53:493, 2014 : PubMed ESTHER: Yang_2014_J.Mol.Neurosci_53_493 PubMedSearch: Yang 2014 J.Mol.Neurosci 53 493 PubMedID: 24198186 Abstract Previous studies have implicated that two at-risk haplotypes (HapA and HapB) of gene-encoding 5-lipoxygenase-activating protein (ALOX5AP) were significantly associated with stroke. The aim of this study was to explore the association between haplotypes of ALOX5AP gene and risk for ischemic stroke (IS) in Chinese Han population. A total of 492 patients with IS and 490 matched control subjects were recruited. Six ALOX5AP SNPs (SG13S377, SG13S114, SG13S41, SG13S89, SG13S32 and SG13S35) were genotyped by SNaPshot minisequence technique. A common genetic variant SG13S114/AA in the ALOX5AP gene was associated with IS in this Chinese cohort (OR = 2.514, 95 % CI = 1.667 ~ 3.790). HapA (TGA) and HapB (AAAG) had no significant difference in the patients (36.3 and 18.5 %, respectively) and controls (37.6 and 16.3 %, respectively) (P = 0.631 and P = 0.375, respectively). But, the frequency of Hap (GAAG) was significantly higher in the patients than that in the controls after Bonferroni's adjustment (P = 0.006). To conclude, SG13S114/AA of the ALOX5AP gene was associated with an increased risk for IS. A novel risk haplotype, Hap (GAAG) was a genetic risk factor for IS in this Chinese population. 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: 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: Whole-genome sequencing of the snub-nosed monkey provides insights into folivory and evolutionary history Zhou X, Wang B, Pan Q, Zhang J, Kumar S, Sun X, Liu Z, Pan H, Lin Y and Li R <24 more author(s)> Zhou X, Wang B, Pan Q, Zhang J, Kumar S, Sun X, Liu Z, Pan H, Lin Y, Liu G, Zhan W, Li M, Ren B, Ma X, Ruan H, Cheng C, Wang D, Shi F, Hui Y, Tao Y, Zhang C, Zhu P, Xiang Z, Jiang W, Chang J, Wang H, Cao Z, Jiang Z, Li B, Yang G, Roos C, Garber PA, Bruford MW, Li R (- 24) Ref: Nat Genet, 46:1303, 2014 : PubMed ESTHER: Zhou_2014_Nat.Genet_46_1303 PubMedSearch: Zhou 2014 Nat.Genet 46 1303 PubMedID: 25362486 Gene_locus related to this paper: rhibe-a0a2k6jtl7, rhibe-ACHE, rhibe-a0a2k6k3y7, rhibe-a0a2k6k493, rhibe-a0a2k6lev4, rhibe-a0a2k6lfa5, rhibe-a0a2k6m6k8, rhiro-a0a2k6p1u8, rhiro-a0a2k6q1t8, rhiro-a0a2k6q1w3, rhibe-a0a2k6n5t9, rhibe-a0a2k6ju46, rhibe-a0a2k6kt48, rhibe-a0a2k6llm5, rhibe-a0a2k6lnt5, rhiro-a0a2k6qzp6, rhiro-a0a2k6q4a6, rhibe-a0a2k6kn93, rhibe-a0a2k6lm22, rhibe-a0a2k6jwp8, rhiro-a0a2k6qun2, rhiro-a0a2k6nj56, rhiro-a0a2k6n885, rhiro-a0a2k6nnj4, rhiro-a0a2k6n7n5, rhibe-a0a2k6jvz4, rhiro-a0a2k6nfk9, rhiro-a0a2k6qjv0, rhibe-a0a2k6jn19, rhibe-a0a2k6k333, rhibe-a0a2k6mff5 Abstract Colobines are a unique group of Old World monkeys that principally eat leaves and seeds rather than fruits and insects. We report the sequencing at 146x coverage, de novo assembly and analyses of the genome of a male golden snub-nosed monkey (Rhinopithecus roxellana) and resequencing at 30x coverage of three related species (Rhinopithecus bieti, Rhinopithecus brelichi and Rhinopithecus strykeri). Comparative analyses showed that Asian colobines have an enhanced ability to derive energy from fatty acids and to degrade xenobiotics. We found evidence for functional evolution in the colobine RNASE1 gene, encoding a key secretory RNase that digests the high concentrations of bacterial RNA derived from symbiotic microflora. Demographic reconstructions indicated that the profile of ancient effective population sizes for R. roxellana more closely resembles that of giant panda rather than its congeners. These findings offer new insights into the dietary adaptations and evolutionary history of colobine primates. Title: Toxicological effects of multi-walled carbon nanotubes adsorbed with nonylphenol on earthworm Eisenia fetida Hu C, Cai Y, Wang W, Cui Y, Li M Ref: Environ Sci Process Impacts, 15:2125, 2013 : PubMed ESTHER: Hu_2013_Environ.Sci.Process.Impacts_15_2125 PubMedSearch: Hu 2013 Environ.Sci.Process.Impacts 15 2125 PubMedID: 24104387 Abstract The high surface area of multi-walled carbon nanotubes (MWCNTs) tends to adsorb a large variety of toxic chemicals, which may enhance the toxicity of both MWCNTs and chemicals to organisms. In order to evaluate the combined toxicity of nonylphenol (NP) and MWCNTs to the earthworm Eisenia fetida in soil, artificial soil systems containing distilled water, 0.1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs, 1 g kg(-1) MWCNTs absorbed 5 mg kg(-1) NP, and 10 mg kg(-1) NP alone were prepared and exposed to earthworms for 7 days. Antioxidative responses, and activities of cellulase, Na(+), K(+)-ATPase and acetylcholinesterase (TChE) as well as DNA damage were chosen as toxicological endpoints. The results showed that 1 g kg(-1) MWCNTs adsorbed 5 mg kg(-1) NP from the soil which caused much more adverse effects on the earthworms than each chemical alone, evident from the responses of cellulase, Na(+), K(+)-ATPase and comet assay. This study indicated that MWCNTs facilitated the bioavailability of NP to the earthworm and increased the harmful effects of NP. Title: Draft genome of the mountain pine beetle, Dendroctonus ponderosae Hopkins, a major forest pest Keeling CI, Yuen MM, Liao NY, Roderick Docking T, Chan SK, Taylor GA, Palmquist DL, Jackman SD, Nguyen A and Bohlmann J <10 more author(s)> Keeling CI, Yuen MM, Liao NY, Roderick Docking T, Chan SK, Taylor GA, Palmquist DL, Jackman SD, Nguyen A, Li M, Henderson H, Janes JK, Zhao Y, Pandoh P, Moore R, Sperling FA, DP WH, Birol I, Jones SJ, Bohlmann J (- 10) Ref: Genome Biol, 14:R27, 2013 : PubMed ESTHER: Keeling_2013_Genome.Biol_14_R27 PubMedSearch: Keeling 2013 Genome.Biol 14 R27 PubMedID: 23537049 Gene_locus related to this paper: denpd-j3jwt7, denpd-j3jt98, denpd-j3jtm4, denpd-j3jub5, denpd-j3juf0, denpd-j3jun6, denpd-j3jvv1, denpd-j3jw22, denpd-j3jwb0, denpd-j3jwv2, denpd-j3jwv4, denpd-j3jwz8, denpd-j3jx26, denpd-j3jx34, denpd-j3jxh9, denpd-j3jxv6, denpd-j3jy62, denpd-j3jy79, denpd-j3jyn7, denpd-j3jz59, denpd-j3jzj2, denpd-n6umq8, denpd-j3jyt2, denpd-u4upn0.1, denpd-n6t493, denpd-u4up38, denpd-n6uaj3, denpd-u4umd6, denpd-u4u438, denpd-n6ue67.1, denpd-n6ue67.2, denpd-u4uj02, denpd-u4ux57, denpd-n6uar4, denpd-n6uu12, denpd-n6trb6, denpd-u4u8e2, denpd-j3jv02 Abstract BACKGROUND: The mountain pine beetle, Dendroctonus ponderosae Hopkins, is the most serious insect pest of western North American pine forests. A recent outbreak destroyed more than 15 million hectares of pine forests, with major environmental effects on forest health, and economic effects on the forest industry. The outbreak has in part been driven by climate change, and will contribute to increased carbon emissions through decaying forests. Title: Donepezil markedly improves long-term survival in rats with chronic heart failure after extensive myocardial infarction Li M, Zheng C, Kawada T, Inagaki M, Uemura K, Shishido T, Sugimachi M Ref: Circ J, 77:2519, 2013 : PubMed ESTHER: Li_2013_Circ.J_77_2519 PubMedSearch: Li 2013 Circ.J 77 2519 PubMedID: 23832513 Abstract Background: Vagal activation by electrical stimulation has been shown to improve the long-term survival of rats with chronic heart failure (CHF) after extensive myocardial infarction (MI). Acetylcholinesterase inhibition increases synaptic acetylcholine, and can disproportionately increase vagal tone. To develop an alternative therapy for CHF using a clinically available drug, the present study investigated whether oral donepezil, an acetylcholinesterase inhitor, could reproduce the beneficial effects of electrical vagal stimulation in rats. Methods and Results: At 2 weeks after ligation of the proximal left coronary artery, resulting in extensive MI, surviving rats were randomly assigned to donepezil-treated and untreated groups. Donepezil treatment started 14 days after MI significantly decreased the heart rate (325+/-6 vs. 355+/-10beats/min, P<0.05) and improved 140-day survival (29% to 54%, P=0.03) by preventing pump failure (cardiac index: +29%, P<0.001; left ventricular+dp/dtmax: +18%, P<0.01; left ventricular end-diastolic pressue: -26%, P<0.01) and cardiac remodeling (biventricular weight: 2.73+/-0.04 vs. 3.06+/-0.08g/kg, P<0.001). In addition, donepezil treatment lowered the levels of plasma arginine vasopressin, brain natriuretic peptide, catecholamine, and tissue pro-inflammation markers. Conclusions: Oral donepezil markedly improved the long-term survival of CHF rats by preventing pump failure and cardiac remodeling, indicating that donepezil may be a new alternative therapy for CHF. (Circ J 2013; 77: 2519-2525). Title: Draft Genome Sequence of Pseudomonas plecoglossicida Strain NB2011, the Causative Agent of White Nodules in Large Yellow Croaker (Larimichthys crocea) Mao Z, Li M, Chen J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Mao_2013_Genome.Announc_1_e00586 PubMedSearch: Mao 2013 Genome.Announc 1 e00586 PubMedID: 23929479 Gene_locus related to this paper: 9psed-s2k464, psepu-PIP, 9psed-s2k0h8, 9psed-s2jxx1, 9psed-s2kmi2 Abstract We describe the draft genome sequence of Pseudomonas plecoglossicida strain NB2011, the causative agent of white nodules in cultured large yellow croaker (Larimichthys crocea) in China. The draft genome sequence of the bacterium consists of 5.41 million bp, with a G+C content of 62.8%. A total of 4,952 genes were identified. Title: Casuarinines A-J, Lycodine-Type Alkaloids from Lycopodiastrum casuarinoides Tang Y, Fu Y, Xiong J, Li M, Ma GL, Yang GX, Wei BG, Zhao Y, Zhang HY, Hu JF Ref: Journal of Natural Products, 76:1475, 2013 : PubMed ESTHER: Tang_2013_J.Nat.Prod_76_1475 PubMedSearch: Tang 2013 J.Nat.Prod 76 1475 PubMedID: 23941108 Abstract Ten new lycodine-type alkaloids, named casuarinines A-J (1-10), along with eight known analogues (11-18), were isolated from the whole plant of Lycopodiastrum casuarinoides . The new structures were established by spectroscopic methods and chemical transformations. Casuarinines A-D (1-4) and J (10) are common lycodine alkaloids possessing four connected six-membered rings, while tricyclic casuarinines E-H (5-8) are the piperidine ring cleavage products. In particular, casuarinine I (9) has an unprecedented five-membered tetrahydropyrrole ring instead of the piperidine ring. A plausible biosynthetic pathway to 9 is proposed. Among the compounds reported, casuarinine H (8) exhibited significant neuroprotective effect against hydrogen peroxide (H2O2)-induced neuronal cell damage in human neuroblastoma SH-SY5Y cells, while casuarinines C (3) and I (9) showed moderate inhibitory activity against acetylcholinesterase (AChE). Title: Human serum albumin-based design of a diflunisal prodrug Yang F, Ma ZY, Zhang Y, Li GQ, Li M, Qin JK, Lockridge O, Liang H Ref: Eur J Pharm Biopharm, 84:549, 2013 : PubMed ESTHER: Yang_2013_Eur.J.Pharm.Biopharm_84_549 PubMedSearch: Yang 2013 Eur.J.Pharm.Biopharm 84 549 PubMedID: 23416065 Abstract The cyclooxygenase-2 inhibitor, diflunisal, is used in the clinic for its anti-inflammatory activity. About 99% of a dose of diflunisal is unavailable for reaction with the target enzyme, because diflunisal strongly binds to human serum albumin (HSA). To reduce the binding affinity of diflunisal to albumin, we designed and synthesized the prodrug acetyldiflunisal. The crystal structure of HSA complexed with fatty acid and acetyldiflunisal revealed that acetyldiflunisal binds to the IIA subdomain and that upon binding, it acetylates lysine 199. Mass spectrometry confirmed that acetyldiflunisal acetylates Lys199. The acetylated albumin had twofold weaker binding affinity for diflunisal as demonstrated by fluorescence quenching. Reduced binding affinity means that diflunisal is more easily released from acetylated albumin into the circulation. Therefore, lower doses of acetyldiflunisal compared to diflunisal will be required. Taken together, our results not only provide a template for design of HSA-based prodrugs, but also pave the way toward more effective use of diflunisal in the clinic. Title: Role of Met93 and Thr96 in the Lid Hinge Region of Rhizopus chinensis Lipase Zhu SS, Li M, Yu X, Xu Y Ref: Appl Biochem Biotechnol, 170:436, 2013 : PubMed ESTHER: Zhu_2013_Appl.Biochem.Biotechnol_170_436 PubMedSearch: Zhu 2013 Appl.Biochem.Biotechnol 170 436 PubMedID: 23546870 Gene_locus related to this paper: rhich-a3fm73 Abstract We engineered Rhizopus chinensis lipase to study its critical amino acid role in catalytic properties. Based on the amino acid sequence and three-dimensional model of the lipase, residues located in its lid hinge region (Met93 and Thr96) were replaced with corresponding amino acid residues (Ile93 and Asn96) found in the lid hinge region of Rhizopus oryzae lipase. The substitutions in the lid hinge region affected not only substrate specificity but also the thermostability of the lipase. Both lipases preferred p-nitrophenyl laurate and glyceryl trilaurate (C12). However, the variant S4-3O showed a slight decline in activity toward long-chain fatty acid (C16-C18). When enzymes activities decreased by half, the temperature of the variant (45 degrees C) was 22 degrees C lower than the parent (67 degrees C), probably substantially destabilized the structure of the lid region. The interfacial kinetic analysis of S4-3O suggested that the lower catalytic efficiency was due to a higher K m* value. According to the lipase structure investigated, Ile93Met played a role of narrowing the size of the hydrophobic patch, which affected the substrate binding affinity, and Asn96Thr destabilized the structure of the lipase by disrupting the H-bond interaction in the lid region. Title: Genome sequence of Streptomyces auratus strain AGR0001, a phoslactomycin-producing actinomycete Han X, Li M, Ding Z, Zhao J, Ji K, Wen M, Lu T Ref: Journal of Bacteriology, 194:5472, 2012 : PubMed ESTHER: Han_2012_J.Bacteriol_194_5472 PubMedSearch: Han 2012 J.Bacteriol 194 5472 PubMedID: 22965094 Gene_locus related to this paper: 9acto-j2ju40, 9acto-j1zwn4, 9acto-j2a066, 9acto-j2jvz9, 9actn-j1zqi7 Abstract Streptomyces auratus strain AGR0001 produces neophoslactomycin A, a novel analog of phoslactomycin that possesses potent activity against some phytopathogenic fungi. Here, the draft genome sequence of S. auratus strain AGR0001 is presented, which would provide insight into the biosynthetic mechanism of neophoslactomycin A. Title: Complete genome sequence of the metabolically versatile halophilic archaeon Haloferax mediterranei, a poly(3-hydroxybutyrate-co-3-hydroxyvalerate) producer Han J, Zhang F, Hou J, Liu X, Li M, Liu H, Cai L, Zhang B, Chen Y and Xiang H <2 more author(s)> Han J, Zhang F, Hou J, Liu X, Li M, Liu H, Cai L, Zhang B, Chen Y, Zhou J, Hu S, Xiang H (- 2) Ref: Journal of Bacteriology, 194:4463, 2012 : PubMed ESTHER: Han_2012_J.Bacteriol_194_4463 PubMedSearch: Han 2012 J.Bacteriol 194 4463 PubMedID: 22843593 Abstract Haloferax mediterranei, an extremely halophilic archaeon, has shown promise for production of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) from unrelated cheap carbon sources. Here we report the complete genome (3,904,707 bp) of H. mediterranei CGMCC 1.2087, consisting of one chromosome and three megaplasmids. Title: Transcriptome and full-length cDNA resources for the mountain pine beetle, Dendroctonus ponderosae Hopkins, a major insect pest of pine forests Keeling CI, Henderson H, Li M, Yuen M, Clark EL, Fraser JD, Huber DP, Liao NY, Docking TR and Bohlmann J <5 more author(s)> Keeling CI, Henderson H, Li M, Yuen M, Clark EL, Fraser JD, Huber DP, Liao NY, Docking TR, Birol I, Chan SK, Taylor GA, Palmquist D, Jones SJ, Bohlmann J (- 5) Ref: Insect Biochemistry & Molecular Biology, 42:525, 2012 : PubMed ESTHER: Keeling_2012_Insect.Biochem.Mol.Biol_42_525 PubMedSearch: Keeling 2012 Insect.Biochem.Mol.Biol 42 525 PubMedID: 22516182 Gene_locus related to this paper: denpd-j3jwt7, denpd-j3jt98, denpd-j3jtm4, denpd-j3jtp6, denpd-j3jub5, denpd-j3juf0, denpd-j3jun6, denpd-j3jv22, denpd-j3jvv1, denpd-j3jw22, denpd-j3jwb0, denpd-j3jwv2, denpd-j3jwv4, denpd-j3jwz8, denpd-j3jx26, denpd-j3jx34, denpd-j3jxh9, denpd-j3jxv6, denpd-j3jy62, denpd-j3jy79, denpd-j3jyn7, denpd-j3jz59, denpd-j3jzj2, denpd-j3jyt2, denpd-j3jv02 Abstract Bark beetles (Coleoptera: Curculionidae: Scolytinae) are major insect pests of many woody plants around the world. The mountain pine beetle (MPB), Dendroctonus ponderosae Hopkins, is a significant historical pest of western North American pine forests. It is currently devastating pine forests in western North America--particularly in British Columbia, Canada--and is beginning to expand its host range eastward into the Canadian boreal forest, which extends to the Atlantic coast of North America. Limited genomic resources are available for this and other bark beetle pests, restricting the use of genomics-based information to help monitor, predict, and manage the spread of these insects. To overcome these limitations, we generated comprehensive transcriptome resources from fourteen full-length enriched cDNA libraries through paired-end Sanger sequencing of 100,000 cDNA clones, and single-end Roche 454 pyrosequencing of three of these cDNA libraries. Hybrid de novo assembly of the 3.4 million sequences resulted in 20,571 isotigs in 14,410 isogroups and 246,848 singletons. In addition, over 2300 non-redundant full-length cDNA clones putatively containing complete open reading frames, including 47 cytochrome P450s, were sequenced fully to high quality. This first large-scale genomics resource for bark beetles provides the relevant sequence information for gene discovery; functional and population genomics; comparative analyses; and for future efforts to annotate the MPB genome. These resources permit the study of this beetle at the molecular level and will inform research in other Dendroctonus spp. and more generally in the Curculionidae and other Coleoptera. Title: t-AUCB, an improved sEH inhibitor, suppresses human glioblastoma cell growth by activating NF-kappaB-p65 Li J, Liu H, Xing B, Yu Y, Wang H, Chen G, Gu B, Zhang G, Wei D and Hu W <2 more author(s)> Li J, Liu H, Xing B, Yu Y, Wang H, Chen G, Gu B, Zhang G, Wei D, Gu P, Li M, Hu W (- 2) Ref: J Neurooncol, 108:385, 2012 : PubMed ESTHER: Li_2012_J.Neurooncol_108_385 PubMedSearch: Li 2012 J.Neurooncol 108 385 PubMedID: 22382785 Inhibitor(s) related to this paper: t-AUCB Abstract Although sEH inhibitors are well studied in inflammatory and cardiovascular diseases, their effects on gliomas are unclear. In this study, we investigated the effects of t-AUCB, a more potent and selective sEH inhibitor, on U251 and U87 human glioblastoma cell lines and the HepG2 human hepatocellular carcinoma cell line. Our results showed that t-AUCB efficiently inhibited sEH activities in all three cell lines (the inhibition rate was more than 80% in each) and suppressed U251 and U87 cell growth in a dose-dependent manner, but exhibited no cell growth inhibition on HepG2. We detected high levels of phosphorylated NF-kappaB-p65 (Ser536) in t-AUCB-treated U251 and U87 cells, and then found that the NF-kappaB inhibitor PDTC can completely abolish t-AUCB-induced growth inhibition. This indicated that t-AUCB suppresses U251 and U87 cell growth by activating NF-kappaB-p65. Moreover, we found that t-AUCB induces cell-cycle G0/G1 phase arrest by regulating Cyclin D1 mRNA and protein levels and CDC2 (Thr161) phosphorylation level. We propose to further test this promising reagent for its anti-glioma activity in clinical relevant orthotopic brain glioma models. Title: Systematic review on the efficacy and safety of herbal medicines for vascular dementia Man SC, Chan KW, Lu JH, Durairajan SS, Liu LF, Li M Ref: Evid Based Complement Alternat Med, 2012:426215, 2012 : PubMed ESTHER: Man_2012_Evid.Based.Complement.Alternat.Med_2012_426215 PubMedSearch: Man 2012 Evid.Based.Complement.Alternat.Med 2012 426215 PubMedID: 22235231 Abstract We present a systematic review of existing research that aims to assess the efficacy and safety of herbal medications (HM), as either monotherapy or adjunct to orthodox medications (OM), mainly comprised of cholinesterase inhibitors, for vascular dementia (VaD). We included 47 studies conducted in mainland China, each testing different HM. Of 43 HM monotherapy studies, 37 reported HM to be significantly better than OM or placebo; six reported similar efficacy between HM and OM. All four HM adjuvant studies reported significant efficacy. No major adverse events for HM were reported. Heterogeneity in diagnostic criteria, interventions and outcome measures hindered comprehensive data analysis. Studies suggested that HM can be a safe and effective treatment for VaD, either alone or in conjunction with OM. However, methodological flaws in the design of the studies limited the extent to which the results could be interpreted. Thirty most commonly used herbal constituents, including Rhizoma Chuanxiong (Chuanxiong in Chinese), Radix Polygoni Multiflori (Heshouwu in Chinese) and Radix Astragali (Huangqi in Chinese). were ranked. Further multi-center trials with large sample sizes, high methodological quality and standardized HM ingredients are necessary for clinical recommendations to be made. Title: PCR-RFLP methods for detection of insecticide resistance-associated mutations in the house fly (Musca domestica) Qiu X, Pan J, Li M, Li Y Ref: Pesticide Biochemistry and Physiology, 104:201, 2012 : PubMed ESTHER: Qiu_2012_Pestic.Biochem.Physiol_104_201 PubMedSearch: Qiu 2012 Pestic.Biochem.Physiol 104 201 Abstract Several resistance-associated mutations have been previously documented in the house fly Musca domestica, an important sanitary pest of humans and animals world-wide. Sensitive detection of resistance is crucial for effective insecticide applications. We have developed simple PCR-RFLP assays for reliably detecting the G342A/V mutations in the acetylcholinesterase (Ace), the L1014F/H in voltage sensitive sodium channel (Vssc) and the W251L/S in the carboxylesterase (mdaE7). These accurate diagnostics are useful to monitor the frequency of the resistance mutations, thus, help to avoid ineffective insecticide application in fly control practice 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: Dense genotyping of candidate gene loci identifies variants associated with high-density lipoprotein cholesterol Edmondson AC, Braund PS, Stylianou IM, Khera AV, Nelson CP, Wolfe ML, Derohannessian SL, Keating BJ, Qu L and Rader DJ <11 more author(s)> Edmondson AC, Braund PS, Stylianou IM, Khera AV, Nelson CP, Wolfe ML, Derohannessian SL, Keating BJ, Qu L, He J, Tobin MD, Tomaszewski M, Baumert J, Klopp N, Doring A, Thorand B, Li M, Reilly MP, Koenig W, Samani NJ, Rader DJ (- 11) Ref: Circ Cardiovasc Genet, 4:145, 2011 : PubMed ESTHER: Edmondson_2011_Circ.Cardiovasc.Genet_4_145 PubMedSearch: Edmondson 2011 Circ.Cardiovasc.Genet 4 145 PubMedID: 21303902 Gene_locus related to this paper: human-LIPG Abstract BACKGROUND: Plasma levels of high-density lipoprotein cholesterol (HDL-C) are known to be heritable, but only a fraction of the heritability is explained. We used a high-density genotyping array containing single-nucleotide polymorphisms (SNPs) from HDL-C candidate genes selected on known biology of HDL-C metabolism, mouse genetic studies, and human genetic association studies. SNP selection was based on tagging SNPs and included low-frequency nonsynonymous SNPs. METHODS AND Title: Transcription and induction profiles of two esterase genes in susceptible and acaricide-resistant Tetranychus cinnabarinus Feng Y-n, Yan J, Sun W, Zhao S, Lu W-C, Li M, He L Ref: Pesticide Biochemistry and Physiology, 100:70, 2011 : PubMed ESTHER: Feng_2011_Pestic.Biochem.Physiol_100_70 PubMedSearch: Feng 2011 Pestic.Biochem.Physiol 100 70 Abstract The carmine spider mite Tetranychus cinnabarinus is the most serious of crop mite pests in China. Their ability to rapidly develop resistance to acaricides has caused difficulty in controlling this mite. In this study, the molecular mechanism of acaricide resistance associated with esterase genes TCE1 and TCE2 was investigated in susceptible and acaricide-resistant strains of T. cinnabarinus. The quantitative real-time PCR (qrtPCR) method was adopted to compare the expression level of two esterase genes TCE1 and TCE2 among four different strains (abamectin-resistant, AbR; fenpropathrin-resistant, FeR; omethoate-resistant, OmR and susceptible strains, S) of T. cinnabarinus. The relative expression level of TCE2 was 1.39-2.47 fold in the three resistant strains compared with the S strain. And after inducing with abamectin, fenpropathrin, and omethoate the highest expression level of TCE2 in the S was 1.64-, 2.92- and 2.24-fold compared with the control, respectively, and this difference was found to be significant. However, there was no obvious difference of the mRNA relative expression levels of TCE1 genes among the four strains, and those of TCE1 were not higher than the control throughout the study. Furthermore, the expression modes of TCE1 and TCE2 in AbR and FeR were similar with that in the S after being treated with abamectin and fenpropathrin, respectively. These results indicated that the enhanced expression of esterase gene TCE2 was associated with acaricide-resistance in T. cinnabarinus. Title: Complete genome sequence of Bacillus thuringiensis subsp. chinensis strain CT-43 He J, Wang J, Yin W, Shao X, Zheng H, Li M, Zhao Y, Sun M, Wang S, Yu Z Ref: Journal of Bacteriology, 193:3407, 2011 : PubMed ESTHER: He_2011_J.Bacteriol_193_3407 PubMedSearch: He 2011 J.Bacteriol 193 3407 PubMedID: 21551307 Gene_locus related to this paper: bacan-BA3703, bacan-BA5009, bacan-DHBF, bacce-BC0192, bacce-BC0968, bacce-BC1788, bacce-BC2141, bacce-BC4854, bacce-BC4862, bacce-PHAC, baccr-pepx Abstract Bacillus thuringiensis has been widely used as an agricultural biopesticide for a long time. As a producing strain, B. thuringiensis subsp. chinensis strain CT-43 is highly toxic to lepidopterous and dipterous insects. It can form various parasporal crystals consisting of Cry1Aa3, Cry1Ba1, Cry1Ia14, Cry2Aa9, and Cry2Ab1. During fermentation, it simultaneously generates vegetative insecticidal protein Vip3Aa10 and the insecticidal nucleotide analogue thuringiensin. Here, we report the finished, annotated genome sequence of B. thuringiensis strain CT-43. Title: Mining the LIPG allelic spectrum reveals the contribution of rare and common regulatory variants to HDL cholesterol Khetarpal SA, Edmondson AC, Raghavan A, Neeli H, Jin W, Badellino KO, Demissie S, Manning AK, Derohannessian SL and Rader DJ <4 more author(s)> Khetarpal SA, Edmondson AC, Raghavan A, Neeli H, Jin W, Badellino KO, Demissie S, Manning AK, Derohannessian SL, Wolfe ML, Cupples LA, Li M, Kathiresan S, Rader DJ (- 4) Ref: PLoS Genet, 7:e1002393, 2011 : PubMed ESTHER: Khetarpal_2011_PLoS.Genet_7_e1002393 PubMedSearch: Khetarpal 2011 PLoS.Genet 7 e1002393 PubMedID: 22174694 Abstract Genome-wide association studies (GWAS) have successfully identified loci associated with quantitative traits, such as blood lipids. Deep resequencing studies are being utilized to catalogue the allelic spectrum at GWAS loci. The goal of these studies is to identify causative variants and missing heritability, including heritability due to low frequency and rare alleles with large phenotypic impact. Whereas rare variant efforts have primarily focused on nonsynonymous coding variants, we hypothesized that noncoding variants in these loci are also functionally important. Using the HDL-C gene LIPG as an example, we explored the effect of regulatory variants identified through resequencing of subjects at HDL-C extremes on gene expression, protein levels, and phenotype. Resequencing a portion of the LIPG promoter and 5' UTR in human subjects with extreme HDL-C, we identified several rare variants in individuals from both extremes. Luciferase reporter assays were used to measure the effect of these rare variants on LIPG expression. Variants conferring opposing effects on gene expression were enriched in opposite extremes of the phenotypic distribution. Minor alleles of a common regulatory haplotype and noncoding GWAS SNPs were associated with reduced plasma levels of the LIPG gene product endothelial lipase (EL), consistent with its role in HDL-C catabolism. Additionally, we found that a common nonfunctional coding variant associated with HDL-C (rs2000813) is in linkage disequilibrium with a 5' UTR variant (rs34474737) that decreases LIPG promoter activity. We attribute the gene regulatory role of rs34474737 to the observed association of the coding variant with plasma EL levels and HDL-C. Taken together, the findings show that both rare and common noncoding regulatory variants are important contributors to the allelic spectrum in complex trait loci. Title: Complete genome sequence of Haloarcula hispanica, a Model Haloarchaeon for studying genetics, metabolism, and virus-host interaction Liu H, Wu Z, Li M, Zhang F, Zheng H, Han J, Liu J, Zhou J, Wang S, Xiang H Ref: Journal of Bacteriology, 193:6086, 2011 : PubMed ESTHER: Liu_2011_J.Bacteriol_193_6086 PubMedSearch: Liu 2011 J.Bacteriol 193 6086 PubMedID: 21994921 Gene_locus related to this paper: halma-q5uym0 Abstract Haloarcula hispanica is an extremely halophilic archaeon that has an unusually low restriction barrier and is therefore significant for studying archaeal genetics, metabolism, and virus-host interactions. Here we report the complete genome sequence (3,890,005 bp) of H. hispanica strain CGMCC 1.2049, consisting of two chromosomes and one megaplasmid. Title: A genome-wide association study identifies LIPA as a susceptibility gene for coronary artery disease Wild PS, Zeller T, Schillert A, Szymczak S, Sinning CR, Deiseroth A, Schnabel RB, Lubos E, Keller T and Blankenberg S <79 more author(s)> Wild PS, Zeller T, Schillert A, Szymczak S, Sinning CR, Deiseroth A, Schnabel RB, Lubos E, Keller T, Eleftheriadis MS, Bickel C, Rupprecht HJ, Wilde S, Rossmann H, Diemert P, Cupples LA, Perret C, Erdmann J, Stark K, Kleber ME, Epstein SE, Voight BF, Kuulasmaa K, Li M, Schafer AS, Klopp N, Braund PS, Sager HB, Demissie S, Proust C, Konig IR, Wichmann HE, Reinhard W, Hoffmann MM, Virtamo J, Burnett MS, Siscovick D, Wiklund PG, Qu L, El Mokthari NE, Thompson JR, Peters A, Smith AV, Yon E, Baumert J, Hengstenberg C, Marz W, Amouyel P, Devaney J, Schwartz SM, Saarela O, Mehta NN, Rubin D, Silander K, Hall AS, Ferrieres J, Harris TB, Melander O, Kee F, Hakonarson H, Schrezenmeir J, Gudnason V, Elosua R, Arveiler D, Evans A, Rader DJ, Illig T, Schreiber S, Bis JC, Altshuler D, Kavousi M, Witteman JC, Uitterlinden AG, Hofman A, Folsom AR, Barbalic M, Boerwinkle E, Kathiresan S, Reilly MP, O'Donnell CJ, Samani NJ, Schunkert H, Cambien F, Lackner KJ, Tiret L, Salomaa V, Munzel T, Ziegler A, Blankenberg S (- 79) Ref: Circ Cardiovasc Genet, 4:403, 2011 : PubMed ESTHER: Wild_2011_Circ.Cardiovasc.Genet_4_403 PubMedSearch: Wild 2011 Circ.Cardiovasc.Genet 4 403 PubMedID: 21606135 Gene_locus related to this paper: human-LIPA Abstract BACKGROUND: eQTL analyses are important to improve the understanding of genetic association results. We performed a genome-wide association and global gene expression study to identify functionally relevant variants affecting the risk of coronary artery disease (CAD). METHODS AND RESULTS: In a genome-wide association analysis of 2078 CAD cases and 2953 control subjects, we identified 950 single-nucleotide polymorphisms (SNPs) that were associated with CAD at P<10(-3). Subsequent in silico and wet-laboratory replication stages and a final meta-analysis of 21 428 CAD cases and 38 361 control subjects revealed a novel association signal at chromosome 10q23.31 within the LIPA (lysosomal acid lipase A) gene (P=3.7x10(-8); odds ratio, 1.1; 95% confidence interval, 1.07 to 1.14). The association of this locus with global gene expression was assessed by genome-wide expression analyses in the monocyte transcriptome of 1494 individuals. The results showed a strong association of this locus with expression of the LIPA transcript (P=1.3x10(-96)). An assessment of LIPA SNPs and transcript with cardiovascular phenotypes revealed an association of LIPA transcript levels with impaired endothelial function (P=4.4x10(-3)). CONCLUSIONS: The use of data on genetic variants and the addition of data on global monocytic gene expression led to the identification of the novel functional CAD susceptibility locus LIPA, located on chromosome 10q23.31. The respective eSNPs associated with CAD strongly affect LIPA gene expression level, which was related to endothelial dysfunction, a precursor of CAD. Title: Comparison of four phaC genes from Haloferax mediterranei and their function in different PHBV copolymer biosyntheses in Haloarcula hispanica Han J, Li M, Hou J, Wu L, Zhou J, Xiang H Ref: Saline Systems, 6:9, 2010 : PubMed ESTHER: Han_2010_Saline.Systems_6_9 PubMedSearch: Han 2010 Saline.Systems 6 9 PubMedID: 20727166 Abstract BACKGROUND: The halophilic archaeon Haloferax mediterranei is able to accumulate large amounts of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with high molar fraction of 3-hydroxyvalerate (3HV) from unrelated carbon sources. A Polyhydroxyalkanoate (PHA) synthase composed of two subunits, PhaCHme and PhaEHme, has been identified in this strain, and shown to account for the PHBV biosynthesis. Title: Complete genome sequence of Bacillus thuringiensis mutant strain BMB171 He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M and Yu Z <1 more author(s)> He J, Shao X, Zheng H, Li M, Wang J, Zhang Q, Li L, Liu Z, Sun M, Wang S, Yu Z (- 1) Ref: Journal of Bacteriology, 192:4074, 2010 : PubMed ESTHER: He_2010_J.Bacteriol_192_4074 PubMedSearch: He 2010 J.Bacteriol 192 4074 PubMedID: 20525827 Gene_locus related to this paper: bacan-BA3703, bacan-DHBF, bacce-BC0192, bacce-BC0968, bacce-BC1677, bacce-BC1788, bacce-BC2141, bacce-BC2171, bacce-BC2456, bacce-BC2458, bacce-BC3133, bacce-BC4102, bacce-BC4854, bacce-BC4862, bacce-BC5130, bacce-PHAC, baccr-pepx Abstract Bacillus thuringiensis has been widely used as a biopesticide for a long time. Here we report the finished and annotated genome sequence of B. thuringiensis mutant strain BMB171, an acrystalliferous mutant strain with a high transformation frequency obtained and stocked in our laboratory. Title: Induced-fit mechanism for prolyl endopeptidase Li M, Chen C, Davies DR, Chiu TK Ref: Journal of Biological Chemistry, 285:21487, 2010 : PubMed ESTHER: Li_2010_J.Biol.Chem_285_21487 PubMedSearch: Li 2010 J.Biol.Chem 285 21487 PubMedID: 20444688 Gene_locus related to this paper: aerpu-PEP Inhibitor(s) related to this paper: Z-Pro-Prolinal Abstract Prolyl peptidases cleave proteins at proline residues and are of importance for cancer, neurological function, and type II diabetes. Prolyl endopeptidase (PEP) cleaves neuropeptides and is a drug target for neuropsychiatric diseases such as post-traumatic stress disorder, depression, and schizophrenia. Previous structural analyses showing little differences between native and substrate-bound structures have suggested a lock-and-key catalytic mechanism. We now directly demonstrate from seven structures of Aeromonus punctata PEP that the mechanism is instead induced fit: the native enzyme exists in a conformationally flexible opened state with a large interdomain opening between the beta-propeller and alpha/beta-hydrolase domains; addition of substrate to preformed native crystals induces a large scale conformational change into a closed state with induced-fit adjustments of the active site, and inhibition of this conformational change prevents substrate binding. Absolute sequence conservation among 28 orthologs of residues at the active site and critical residues at the interdomain interface indicates that this mechanism is conserved in all PEPs. This finding has immediate implications for the use of conformationally targeted drug design to improve specificity of inhibition against this family of proline-specific serine proteases. Title: Crystal structure of a secreted lipase from Gibberella zeae reveals a novel double-lock mechanism Lou Z, Li M, Sun Y, Liu Y, Liu Z, Wu W, Rao Z Ref: Protein Cell, 1:760, 2010 : PubMed ESTHER: Lou_2010_Protein.Cell_1_760 PubMedSearch: Lou 2010 Protein.Cell 1 760 PubMedID: 21203917 Gene_locus related to this paper: gibze-q6wer3 Inhibitor(s) related to this paper: Ebelactone-B Abstract Fusarium graminearum (sexual stage: Gibberella zeae) is the causative agent of Fusarium Head Blight (FHB), which is one of the most destructive plant disease of cereals, accounting for high grain yield losses, especially for wheat and maize. Like other fungal pathogens, several extracellular enzymes secreted by G. zeae are known to be involved in host infection. Among these secreted lipases, G. zeae lipase (GZEL), which is encoded by the FGL1 gene, was demonstrated to be crucial to G. zeae pathogenicity. However, the precise mechanism of GZEL remains unclear due to a lack of detailed structural information. In this study, we report the crystal structure of GZEL at the atomic level. The structure of GZEL displays distinct structural differences compared to reported homologues and indicates a unique "double lock" enzymatic mechanism. To gain insight into substrate/inhibitor recognition, we proposed a model of GZEL in complex with substrate and the lipase inhibitor ebelactone B (based on the reported structures of GZEL homologues), which defines possible substrate binding sites within the catalytic cleft and suggests an "anti sn-l" binding mode. These results pave the way to elucidating the mechanism of GZEL and thus provide clues for the design of anti-FHB inhibitors. Title: Effect of the cholinesterase inhibitor donepezil on cardiac remodeling and autonomic balance in rats with heart failure Okazaki Y, Zheng C, Li M, Sugimachi M Ref: Journal de Physiologie Sci, 60:67, 2010 : PubMed ESTHER: Okazaki_2010_J.Physiol.Sci_60_67 PubMedSearch: Okazaki 2010 J.Physiol.Sci 60 67 PubMedID: 19949913 Abstract In an earlier study we demonstrated the beneficial effect of direct vagal electrical stimulation on cardiac remodeling and survival. In the study reported here, we attempted to reproduce the effect of vagal enhancement through the administration of an acetylcholinesterase inhibitor, donepezil. A rat model of heart failure following extensive healed myocardial infarction was used. Compared to their nontreated counterparts, rats given donepezil (5 mg/kg/day) in their drinking water had a smaller biventricular weight (3.40 +/- 0.13 vs. 3.02 +/- 0.21 g/kg body weight, P < 0.05), and maximal rate of rise (3256 +/- 955 vs. 3822 +/- 389 mmHg/s, P < 0.05) and the end-diastolic value (30.1 +/- 5.6 vs. 23.2 +/- 5.7 mmHg, P < 0.05) of left ventricular pressure were improved. Neurohumoral factors were suppressed in donepezil-treated rats (norepinephrine 1885 +/- 1423 vs. 316 +/- 248 pg/ml, P < 0.01; brain natriuretic peptide 457 +/- 68 vs. 362 +/- 80 ng/ml, P < 0.05), and the high-frequency component of heart rate variability showed a nocturnal increase. These findings indicated that donepezil reproduced the anti-remodeling effect of electrical vagal stimulation. Further studies are warranted to evaluate the clinical usefulness of donepezil in heart failure. Title: Genetic study of capsular switching between Neisseria meningitidis sequence type 7 serogroup A and C strains Wang Q, Shao Z, Wang X, Gao Y, Li M, Xu L, Xu J, Wang L Ref: Infect Immun, 78:3883, 2010 : PubMed ESTHER: Wang_2010_Infect.Immun_78_3883 PubMedSearch: Wang 2010 Infect.Immun 78 3883 PubMedID: 20624905 Gene_locus related to this paper: neime-r0tza2 Abstract Neisseria meningitidis is a leading cause of septicemia and meningitis worldwide. N. meningitidis capsular polysaccharides have been classified into 13 distinct serogroups which are defined by antibody reactivity and structural analysis, and the capsule plays an important role in virulence. Serogroups A, B, C, W135, and Y have been reported to be clinically important. Several newly identified serogroup C isolates belonging to the unique sequence type 7 (ST-7) were identified in China. Since most ST-7 isolates from China belonged to serogroup A, the newly identified ST-7 serogroup C strains were proposed to have arisen from those belonging to ST-7 serogroup A. In this study, six ST-7 serogroup C and three ST-7 serogroup A isolates were analyzed by pulsed-field gel electrophoresis to confirm their sequence type. In order to clarify the genetic basis of capsular switching between ST-7 serogroup A and C strains, the whole capsular gene clusters and surrounding genes of the two representative ST-7 strains belonging to serogroups A and C, respectively, were sequenced and compared. Potential recombination sites were analyzed using the RDP3 beta software, and recombination-related regions in two other ST-7 serogroup A and five ST-7 serogroup C strains were also sequenced and compared to the representative ST-7 serogroup A and C strain sequences. Title: Cloning and characterization of acetylcholinesterase 1 genes from insecticide-resistant field populations of Liposcelis paeta Pearman (Psocoptera: Liposcelididae) Wu S, Li M, Tang PA, Felton GW, Wang JJ Ref: Insect Biochemistry & Molecular Biology, 40:415, 2010 : PubMed ESTHER: Wu_2010_Insect.Biochem.Mol.Biol_40_415 PubMedSearch: Wu 2010 Insect.Biochem.Mol.Biol 40 415 PubMedID: 20385234 Gene_locus related to this paper: 9neop-D2KI31 Abstract The psocid, Liposcelis paeta Pearman, is an increasingly important polyphagous pest of stored products worldwide. Intensive use of organophosphorous insecticides for pest control has facilitated resistance development in psocids in China. Three insecticide-resistant field populations of L. paeta were collected from Nanyang city of Henan Province (NY), and Wuzhou (WZ) and Hezhou (HZ) cities of Guangxi Province, China. Previous studies have shown that psocids have different susceptibilities to insecticides. In addition, their AChE susceptibilities to paraoxon-ethyl and demeton-S-methyl also differed from each other. Acetylcholinesterase 1, which is one of the major targets for organophosphate insecticides, has been fully cloned and sequenced from these populations of L. paeta. Comparison of both nucleotide and deduced amino acid sequences revealed nucleotide polymorphisms among L. paeta ace 1 genes from different populations, but none of these polymorphisms correspond to the active sites in AChE 1 from other insects. The results of comparative quantitative real-time PCR indicated that the relative expression level of HZ ace 1 gene was the highest among three populations, which was 1.20 and 1.02-fold higher than those of NY and WZ populations, respectively. This may due to an epigenetic inheritance phenomenon, which allows organisms to respond to a particular environment through changes in gene expression. Title: Hemolytic phospholipase Rv0183 of Mycobacterium tuberculosis induces inflammatory response and apoptosis in alveolar macrophage RAW264.7 cells Xu G, Jia H, Li Y, Liu X, Li M, Wang Y Ref: Can J Microbiol, 56:916, 2010 : PubMed ESTHER: Xu_2010_Can.J.Microbiol_56_916 PubMedSearch: Xu 2010 Can.J.Microbiol 56 916 PubMedID: 21076482 Gene_locus related to this paper: myctu-rv0183 Abstract The metabolic pathway of phospholipids is one of the most important physiologic pathways in Mycobacterium tuberculosis, a typical intracellular bacterium. The hemolytic phospholipase lip gene (Rv0183) is one of 24 phospholipase genes that have been demonstrated to play critical roles in the metabolism of phospholipids in M. tuberculosis. Quantitative RT-PCR and flow cytometry were used to elucidate the immunological and pathogenic implications of the Rv0183 gene on the inflammatory response following persistent expression of Rv0183 in mouse alveolar macrophage RAW264.7 cells. Our results demonstrate that a time-course-dependent ectopic expression of Rv0183 significantly elevated the expression of IL-6, NF-kappaB, TLR-2, TLR-6, TNFalpha, and MyD88 in these alveolar macrophage cells. Furthermore, the persistent expression of Rv0183 induced RAW264.7 cell apoptosis in vitro. These findings demonstrate that the expression of Rv0183 induces an inflammatory response and cell apoptosis in the host cells, suggesting that Rv0183 may play an important role in the virulence and pathogenesis of M. tuberculosis infection. Title: Synthesis of benzofuran derivatives via rearrangement and their inhibitory activity on acetylcholinesterase Zhou X, Li M, Wang XB, Wang T, Kong LY Ref: Molecules, 15:8593, 2010 : PubMed ESTHER: Zhou_2010_Molecules_15_8593 PubMedSearch: Zhou 2010 Molecules 15 8593 PubMedID: 21116228 Abstract During a synthesis of coumarins to obtain new candidates for treating Alzheimer's Disease (AD), an unusual rearrangement of a benzopyran group to a benzofuran group occurred, offering a novel synthesis pathway of these benzofuran derivatives. The possible mechanism of the novel rearrangement was also discussed. All of the benzofuran derivatives have weak anti-AChE activities compared with the reference compound, donepezil. Title: A naturally occurring variant of endothelial lipase associated with elevated HDL exhibits impaired synthesis Brown RJ, Edmondson AC, Griffon N, Hill TB, Fuki IV, Badellino KO, Li M, Wolfe ML, Reilly MP, Rader DJ Ref: J Lipid Res, 50:1910, 2009 : PubMed ESTHER: Brown_2009_J.Lipid.Res_50_1910 PubMedSearch: Brown 2009 J.Lipid.Res 50 1910 PubMedID: 19411705 Gene_locus related to this paper: human-LIPG Abstract Human endothelial lipase (EL) is a member of a family of lipases and phospholipases that are involved in the metabolism of plasma lipoproteins. EL displays a preference to hydrolyze lipids in HDL. We report here that a naturally occurring low frequency coding variant in the EL gene (LIPG), glycine-26 to serine (G26S), is significantly more common in African-American individuals with elevated HDL cholesterol (HDL-C) levels. To test the hypothesis that this variant results in reduced EL function, we extensively characterized and compared the catalytic and noncatalytic functions of the G26S variant and wild-type (WT) EL. While the catalytic-specific activity of G26S EL is similar to WT EL, its secretion is markedly reduced. Consistent with this observation, we found that carriers of the G26S variant had significantly reduced plasma levels of EL protein. Thus, this N-terminal variant results in reduced secretion of EL protein, plausibly leading to increased HDL-C levels. Title: Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demissie S, Manning AK, Jensen MK, Rimm EB, Wang J and Rader DJ <10 more author(s)> Edmondson AC, Brown RJ, Kathiresan S, Cupples LA, Demissie S, Manning AK, Jensen MK, Rimm EB, Wang J, Rodrigues A, Bamba V, Khetarpal SA, Wolfe ML, Derohannessian S, Li M, Reilly MP, Aberle J, Evans D, Hegele RA, Rader DJ (- 10) Ref: J Clinical Investigation, 119:1042, 2009 : PubMed ESTHER: Edmondson_2009_J.Clin.Invest_119_1042 PubMedSearch: Edmondson 2009 J.Clin.Invest 119 1042 PubMedID: 19287092 Abstract Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated that these variants significantly decreased endothelial lipase activity. In addition, a meta-analysis across 5 cohorts demonstrated that the low-frequency Asn396Ser variant is significantly associated with increased HDL-C, while the common Thr111Ile variant is not. Functional analysis confirmed that the Asn396Ser variant has significantly decreased lipase activity both in vitro and in vivo, while the Thr111Ile variant has normal lipase activity. Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C. Title: The genome of the cucumber, Cucumis sativus L Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B and Du Y <77 more author(s)> Huang S, Li R, Zhang Z, Li L, Gu X, Fan W, Lucas WJ, Wang X, Xie B, Ni P, Ren Y, Zhu H, Li J, Lin K, Jin W, Fei Z, Li G, Staub J, Kilian A, van der Vossen EA, Wu Y, Guo J, He J, Jia Z, Tian G, Lu Y, Ruan J, Qian W, Wang M, Huang Q, Li B, Xuan Z, Cao J, Asan, Wu Z, Zhang J, Cai Q, Bai Y, Zhao B, Han Y, Li Y, Li X, Wang S, Shi Q, Liu S, Cho WK, Kim JY, Xu Y, Heller-Uszynska K, Miao H, Cheng Z, Zhang S, Wu J, Yang Y, Kang H, Li M, Liang H, Ren X, Shi Z, Wen M, Jian M, Yang H, Zhang G, Yang Z, Chen R, Ma L, Liu H, Zhou Y, Zhao J, Fang X, Fang L, Liu D, Zheng H, Zhang Y, Qin N, Li Z, Yang G, Yang S, Bolund L, Kristiansen K, Li S, Zhang X, Wang J, Sun R, Zhang B, Jiang S, Du Y (- 77) Ref: Nat Genet, 41:1275, 2009 : PubMed ESTHER: Huang_2009_Nat.Genet_41_1275 PubMedSearch: Huang 2009 Nat.Genet 41 1275 PubMedID: 19881527 Gene_locus related to this paper: cucsa-a0a0a0ktw5, cucsa-a0a0a0lnt6, cucsa-a0a0a0kpn7, cucsa-a0a0a0lvt9, cucsa-a0a0a0kdx8, cucsa-a0a0a0m228, cucsa-a0a0a0kz31, cucsa-a0a0a0k5t5, cucsa-a0a0a0kfs7, cucsa-a0a0a0kjj7, cucsa-a0a0a0kzs7, cucsa-a0a0a0l0a6, cucsa-a0a0a0l4w4, cucsa-a0a0a0lpz0, cucsa-a0a0a0ls66 Abstract Cucumber is an economically important crop as well as a model system for sex determination studies and plant vascular biology. Here we report the draft genome sequence of Cucumis sativus var. sativus L., assembled using a novel combination of traditional Sanger and next-generation Illumina GA sequencing technologies to obtain 72.2-fold genome coverage. The absence of recent whole-genome duplication, along with the presence of few tandem duplications, explains the small number of genes in the cucumber. Our study establishes that five of the cucumber's seven chromosomes arose from fusions of ten ancestral chromosomes after divergence from Cucumis melo. The sequenced cucumber genome affords insight into traits such as its sex expression, disease resistance, biosynthesis of cucurbitacin and 'fresh green' odor. We also identify 686 gene clusters related to phloem function. The cucumber genome provides a valuable resource for developing elite cultivars and for studying the evolution and function of the plant vascular system. Title: Effects of 3-benzidino-6-phenylpyridazine, as an acetylcholinesterase inhibitor, on outward potassium current in acutely isolated rat hippocampal pyramidal neurons Du H, Li M, Yang P Ref: Toxicol Lett, 181:104, 2008 : PubMed ESTHER: Du_2008_Toxicol.Lett_181_104 PubMedSearch: Du 2008 Toxicol.Lett 181 104 PubMedID: 18675331 Abstract As an acetylcholinesterase (AChE) inhibitor, the effects of 3-benzidino-6-phenylpyridazine (BPP) on outward potassium current including delayed rectifier potassium current (I(K(DR))) and transient outward potassium current (I(K(A))) in acutely isolated rat hippocampal pyramidal neurons were studied, using the whole cell patch-clamp technique. BPP reversibly inhibited electric eel AChE as an inhibitor, with IC(50) of 1.43 microM. BPP (0.10-100 microM) decreased I(K(DR)) and I(K(A)) in a concentration-dependent, voltage-independent and partial reversible manner, with IC(50) of 0.47 and 0.31 microM, respectively. 10 microM BPP did not affect steady-state activation of I(K(DR)) and I(K(A)). In addition, 10 microM BPP shifted the voltage dependence of steady-state inactivation of I(K(A)) towards negative potential. In conclusion, BPP potently inhibits I(K(DR)) and I(K(A)) in rat hippocampal pyramidal neurons, which may contribute to BPP's restoring the damaged central nervous system. Title: Systematic review on the efficacy and safety of herbal medicines for Alzheimer's disease Man SC, Durairajan SS, Kum WF, Lu JH, Huang JD, Cheng CF, Chung V, Xu M, Li M Ref: J Alzheimers Dis, 14:209, 2008 : PubMed ESTHER: Man_2008_J.Alzheimers.Dis_14_209 PubMedSearch: Man 2008 J.Alzheimers.Dis 14 209 PubMedID: 18560132 Abstract A systematic review was conducted to assess the efficacy and safety of herbal medications (HM), as either monotherapy or adjunct to orthodox medications (cholinesterase inhibitors and nootropic agents, OM) for Alzheimer's disease (AD). Sixteen studies testing different HM were included. Out of the 15 HM monotherapy studies, 13 reported HM to be significantly better than OM or placebo; one reported similar efficacy between HM and OM. Only the HM adjuvant study reported significant efficacy. No major adverse events for HM were reported and HMs were found to reduce the adverse effects arising from OM. Imbalance in ethnicity among participants was observed; gender distribution was unclear. Heterogeneity in diagnostic criteria, interventions and outcome measures hindered comprehensive data analysis. Studies comparing HM with OM suggest that HM can be a safe, effective treatment for AD, either alone or in conjunction with OM. Methodological flaws in the design of the studies, however, limited the extent to which the results could be interpreted. Among various HMs, the safety and tolerability of EGb761 was best established. Further multi-center trials with large sample size, high methodological qualities and standardized HM ingredients are necessary for clinical recommendations on the use of HM in treating AD. Title: Crystallization and preliminary crystallographic analysis of Gibberella zeae extracellular lipase Sun Y, Li M, Zhang Y, Liu L, Liu Y, Liu Z, Li X, Lou Z Ref: Acta Crystallographica Sect F Struct Biol Cryst Commun, 64:813, 2008 : PubMed ESTHER: Sun_2008_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_64_813 PubMedSearch: Sun 2008 Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun 64 813 PubMedID: 18765911 Gene_locus related to this paper: gibze-q6wer3 Abstract Fusarium head blight, one of the most destructive crop diseases, is mainly caused by Fusarium graminearum (known in its sexual stage as Gibberella zeae). F. graminearum secretes various extracellular enzymes that have been hypothesized to be involved in host infection. One of the extracellular enzymes secreted by this organism is the G. zeae extracellular lipase (GZEL), which is encoded by the FGL1 gene. In order to solve the crystal structure of GZEL and to gain a better understanding of the biological functions of the protein and of possible inhibitory mechanisms of lipase inhibitors, recombinant GZEL was crystallized at 291 K using PEG 3350 as a precipitant. A data set was collected to 2.8 A resolution from a single flash-cooled crystal (100 K). The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 78.4, b = 91.0, c = 195.8 A, alpha = beta = gamma = 90 degrees . The presence of four molecules was assumed per asymmetric unit, which gave a Matthews coefficient of 2.6 A(3) Da(-1). Title: Alterations in autonomic function in the guinea pig eye following exposure to dichlorvos vapor Taylor JT, Davis E, Dabisch P, Horsmon M, Li M, Mioduszewski R Ref: J Ocul Pharmacol Ther, 24:473, 2008 : PubMed ESTHER: Taylor_2008_J.Ocul.Pharmacol.Ther_24_473 PubMedSearch: Taylor 2008 J.Ocul.Pharmacol.Ther 24 473 PubMedID: 18788997 Abstract The present study investigated the effect of the organophosphate, dichlorvos (DDVP), on ocular function and cholinesterase activity in guinea pigs, using a single-animal-head-only vapor exposure system. All animals exhibited signs of mild organophosphate poisoning (e.g., salivation, chewing, lacrimation, urination, defecation, and rhinorrhea) after the 20-min exposure, regardless of the DDVP exposure concentration (e.g., 35 mg/m(3), 55 mg/m(3), and 75 mg/m(3)). Pupil constriction or miosis was the most pronounced effect seen after vapor exposure. The postexposure pupil size for the 35 mg/m(3) group was 45.8 +/- 3.68% of the preexposure baseline measurement. Postexposure pupil size in the 55- (38 +/- 1.36%) and 75 mg/m(3) (38.1 +/- 1.72%) groups was significantly less than both the preexposure baseline level and the 35 mg/m(3) group. All groups exhibited enhanced an pupillary response to light after DDVP exposure. The enhanced light response remained even after recovery from miosis (approximately 1 h after exposure). Measurement of cholinesterase activity revealed that even though pupil size had recovered, acetyl- and butyrylcholinesterase remained significantly inhibited in the blood. Title: A glimpse of streptococcal toxic shock syndrome from comparative genomics of S. suis 2 Chinese isolates Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, Zheng F, Pan X, Liu D and Yu J <16 more author(s)> Chen C, Tang J, Dong W, Wang C, Feng Y, Wang J, Zheng F, Pan X, Liu D, Li M, Song Y, Zhu X, Sun H, Feng T, Guo Z, Ju A, Ge J, Dong Y, Sun W, Jiang Y, Yan J, Yang H, Wang X, Gao GF, Yang R, Yu J (- 16) Ref: PLoS ONE, 2:e315, 2007 : PubMed ESTHER: Chen_2007_PLoS.ONE_2_E315 PubMedSearch: Chen 2007 PLoS.ONE 2 E315 PubMedID: 17375201 Gene_locus related to this paper: strsu-a4vws4, strsu-q302y4, strsy-a4vus4, strsy-a4vwf6 Abstract BACKGROUND: Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen, causing more than 200 cases of severe human infection worldwide, with the hallmarks of meningitis, septicemia, arthritis, etc. Very recently, SS2 has been recognized as an etiological agent for streptococcal toxic shock syndrome (STSS), which was originally associated with Streptococcus pyogenes (GAS) in Streptococci. However, the molecular mechanisms underlying STSS are poorly understood. METHODS AND FINDINGS: To elucidate the genetic determinants of STSS caused by SS2, whole genome sequencing of 3 different Chinese SS2 strains was undertaken. Comparative genomics accompanied by several lines of experiments, including experimental animal infection, PCR assay, and expression analysis, were utilized to further dissect a candidate pathogenicity island (PAI). Here we show, for the first time, a novel molecular insight into Chinese isolates of highly invasive SS2, which caused two large-scale human STSS outbreaks in China. A candidate PAI of approximately 89 kb in length, which is designated 89K and specific for Chinese SS2 virulent isolates, was investigated at the genomic level. It shares the universal properties of PAIs such as distinct GC content, consistent with its pivotal role in STSS and high virulence. CONCLUSIONS: To our knowledge, this is the first PAI candidate from S. suis worldwide. Our finding thus sheds light on STSS triggered by SS2 at the genomic level, facilitates further understanding of its pathogenesis and points to directions of development on some effective strategies to combat highly pathogenic SS2 infections. Title: Estradiol replacement increases the low-density lipoprotein receptor related protein (LRP) in the mouse brain Cheng X, McAsey ME, Li M, Randall S, Cady C, Nathan BP, Struble RG Ref: Neuroscience Letters, 417:50, 2007 : PubMed ESTHER: Cheng_2007_Neurosci.Lett_417_50 PubMedSearch: Cheng 2007 Neurosci.Lett 417 50 PubMedID: 17346883 Abstract Numerous epidemiology studies have shown protective effects of hormone therapy (HT) on chronic neurological diseases. We have proposed that some of the neuroprotective effects of estrogen are mediated by apolipoprotein E (apoE). Polymorphisms of receptors for apoE modify the risk for dementia. To our knowledge, no reports exist showing CNS effects of estrogen replacement on members of the low-density lipoprotein receptor family. The current study focused on the effect of estradiol-17beta (E2) replacement on protein expression of two members of the receptor family, the low-density lipoprotein receptor (LDL-r) and low-density lipoprotein receptor related protein (LRP) in ovariectomized mice. Five days of E2 replacement significantly increased LRP expression in the hippocampus, olfactory bulb and neocortex but not in cerebellum. In contrast, E2 treatment decreased LDL-r protein expression in olfactory bulb. HT modification of both apoE and LRP could have wide-spread effects on cellular function given LRP's manifold signaling functions. Title: Mitochondrial proteomic analysis and characterization of the intracellular mechanisms of bis(7)-tacrine in protecting against glutamate-induced excitotoxicity in primary cultured neurons Fu H, Li W, Liu Y, Lao Y, Liu W, Chen C, Yu H, Lee NT, Chang DC and Han Y <4 more author(s)> Fu H, Li W, Liu Y, Lao Y, Liu W, Chen C, Yu H, Lee NT, Chang DC, Li P, Pang Y, Tsim KWK, Li M, Han Y (- 4) Ref: J Proteome Res, 6:2435, 2007 : PubMed ESTHER: Fu_2007_J.Proteome.Res_6_2435 PubMedSearch: Fu 2007 J.Proteome.Res 6 2435 PubMedID: 17530875 Inhibitor(s) related to this paper: Bis7-tacrine Abstract Increasing evidence supports that the mitochondrial dysfunction, mainly caused by abnormal changes in mitochondrial proteins, plays a pivotal role in glutamate-induced excitotoxicity, which is closely associated with the pathogenesis of acute and chronic neurodegenerative disorders, such as stroke and Alzheimer's disease. In this study, post-treatment of cerebellar granule neurons with bis(7)-tacrine significantly reversed declines in mitochondrial membrane potential, ATP production, and neuronal cell death induced by glutamate. Moreover, this reversal was independent of NMDA antagonism, acetylcholinesterase inhibition, and cholinergic pathways. Using two-dimensional differential in-gel electrophoresis, we conducted a comparative analysis of mitochondrial protein patterns. In all, 29 proteins exhibiting significant differences in their abundances were identified in the glutamate-treated group when compared with the control. The expression patterns in 22 out of these proteins could be reversed by post-treatment with bis(7)-tacrine. Most of the differentially expressed proteins are involved in energy metabolism, oxidative stress, and apoptosis. In particular, the altered patterns of four of these proteins were further validated by Western blot analysis. Our findings suggest that multiple signaling pathways initiated by the altered mitochondrial proteins may mediate glutamate-induced excitotoxicity and also offer potentially useful intracellular targets for the neuroprotection provided by bis(7)-tacrine. Title: Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating L-type calcium channels Fu H, Li W, Lao Y, Luo J, Lee NT, Kan KK, Tsang HW, Tsim KWK, Pang Y and Han Y <3 more author(s)> Fu H, Li W, Lao Y, Luo J, Lee NT, Kan KK, Tsang HW, Tsim KWK, Pang Y, Li Z, Chang DC, Li M, Han Y (- 3) Ref: Journal of Neurochemistry, 98:1400, 2006 : PubMed ESTHER: Fu_2006_J.Neurochem_98_1400 PubMedSearch: Fu 2006 J.Neurochem 98 1400 PubMedID: 16771827 Inhibitor(s) related to this paper: Bis7-tacrine Abstract Beta amyloid protein (Abeta) and acetylcholinesterase (AChE) have been shown to be closely implicated in the pathogenesis of Alzheimer's disease. In the current study, we investigated the effects of bis(7)-tacrine, a novel dimeric AChE inhibitor, on Abeta-induced neurotoxicity in primary cortical neurons. Bis(7)-tacrine, but not other AChE inhibitors, elicited a marked reduction of both fibrillar and soluble oligomeric forms of Abeta-induced apoptosis as evidenced by chromatin condensation and DNA specific fragmentation. Both nicotinic and muscarinic receptor antagonists failed to block the effects of bis(7)-tacrine. Instead, nimodipine, a blocker of L-type voltage-dependent Ca2+ channels (VDCCs), attenuated Abeta neurotoxicity, whereas N-, P/Q- or R-type VDCCs blockers and ionotropic glutamate receptor antagonists did not. Fluorescence Ca2+ imaging assay revealed that, similar to nimodipine, bis(7)-tacrine reversed Abeta-triggered intracellular Ca2+ increase, which was mainly contributed by the extracellular Ca2+ instead of endoplasmic reticulum and mitochondria Ca2+. Concurrently, using whole cell patch-clamping technique, it was found that bis(7)-tacrine significantly reduced the augmentation of high voltage-activated inward calcium currents induced by Abeta. These results suggest that bis(7)-tacrine attenuates Abeta-induced neuronal apoptosis by regulating L-type VDCCs, offers a novel modality as to how the agent exerts neuroprotective effects. Title: Neuroprotection via inhibition of nitric oxide synthase by bis(7)-tacrine Li W, Lee NT, Fu H, Kan KK, Pang Y, Li M, Tsim KWK, Li X, Han Y Ref: Neuroreport, 17:471, 2006 : PubMed ESTHER: Li_2006_Neuroreport_17_471 PubMedSearch: Li 2006 Neuroreport 17 471 PubMedID: 16543809 Inhibitor(s) related to this paper: Bis7-tacrine Abstract Here we report that bis(7)-tacrine, a novel acetylcholinesterase inhibitor, exerts neuroprotective effects by inhibition of nitric oxide synthase. In cortical neurons at 12 days in vitro, bis(7)-tacrine concentration-dependently reduced cell death induced by glutamate, beta-amyloid and L-arginine, but not by nitric sodium nitroprusside. N-monomethyl-L-arginine, a nitric oxide synthase inhibitor, also prevented the former three types but not the last type of the cytotoxicity; however, nitric oxide scavengers blocked all of these insults, indicating that nitric oxide mediated these neuronal injuries. Furthermore, with nitric oxide synthase activity assays, it was found that bis(7)-tacrine not only suppressed the activation of nitric oxide synthase caused by glutamate in cortical neurons, but also directly inhibited the activity of nitric oxide synthase in vitro. Title: Biodegradation of gallotannins and ellagitannins Li M, Kai Y, Qiang H, Dongying J Ref: J Basic Microbiol, 46:68, 2006 : PubMed ESTHER: Li_2006_J.Basic.Microbiol_46_68 PubMedSearch: Li 2006 J.Basic.Microbiol 46 68 PubMedID: 16463321 Abstract Nowadays, many researches have been made on gallotannin biodegradation and have gained great success in further utilization. Some of industrial applications of these findings are in the production of tannase, the biotransformation of tannic acid to gallic acid or pyrogallol and detannification of food and fodder. Although ellagitannins have the typical C-C bound which is more difficult to be degraded than gallotannins, concerted efforts are still in progress to improve ellagitannin degradation and utilization. Currently, more attention is mainly focused on intestinal microflora biodegradation of tannins especially ellagitannins which can contribute to the definition of their bioavailability for both human beings and ruminants. Also there have been endeavours to utilize the tannin-degrading activity of different fungi for ellagitannin-rich biomass, which will facilitate application of tannin-degrading enzymes in strategies for improving industrial and livestock production. Due to the complicated structures of complex tannins and condensed tannins, the biodegradation of them is much more difficult and there are fewer researches on them. Therefore, the researches on the mechanisms of gallotannin and ellagitannin biodegradation can result in the overall understanding to the biodegradation of complex tannins and condensed tannins. Biodegradation of tannins is in an incipient stage and further studies have to be carried out to exploit the potential of various tannins for largescale applications in food, fodder, medicine and tannery effluent treatment. Title: Time course of response to estradiol replacement in ovariectomized mice: brain apolipoprotein E and synaptophysin transiently increase and glial fibrillary acidic protein is suppressed McAsey ME, Cady C, Jackson LM, Li M, Randall S, Nathan BP, Struble RG Ref: Experimental Neurology, 197:197, 2006 : PubMed ESTHER: McAsey_2006_Exp.Neurol_197_197 PubMedSearch: McAsey 2006 Exp.Neurol 197 197 PubMedID: 16226751 Abstract The current study examined the effect of long-term estradiol replacement in ovariectomized mice. Estradiol-17beta (E2) pellets or vehicle pellets were implanted at the time of ovariectomy (OVX) in young adult female mice. Five mice from each group were sacrificed at 5, 14, 28 and 49 days after OVX and pellet replacement. Western blotting of homogenates from somatosensory cortex, hippocampus, olfactory bulb and cerebellum was performed to obtain concentrations of glial fibrillary acidic protein (GFAP), apolipoprotein E (apoE) and synaptophysin (SYN). At 5 days after OVX, GFAP levels were not affected by E2 replacement. In contrast to GFAP, synaptophysin and apoE concentrations were significantly elevated by 15% and 25%, respectively, in the E2-replaced group compared to the vehicle-replaced group at 5 days but by 14 days concentrations were equivalent. Late in the time course of this study, at 49 days, GFAP concentrations were higher in the E2-deprived mice but did not increase in the E2-replaced group. Immunocytochemistry for GFAP confirmed this observation. Of note was that these effects occurred in all four brain regions measured. These observations suggest that estradiol is able to suppress reactive gliosis. In addition, E2 replacement in OVX mice is associated with transiently higher levels of apoE and synaptophysin. Title: Neocortical and hippocampal glial fibrillary acidic protein immunoreactivity shows region-specific variation during the mouse estrous cycle Struble RG, Afridi S, Beckman-Randall S, Li M, Cady C, Nathan B, McAsey ME Ref: Neuroendocrinology, 83:325, 2006 : PubMed ESTHER: Struble_2006_Neuroendocrinology_83_325 PubMedSearch: Struble 2006 Neuroendocrinology 83 325 PubMedID: 16926532 Abstract Ovarian hormones modulate both neuronal and glial activation during the estrous cycle. These effects are particularly well characterized in the hypothalamus. Ovarian hormones also affect brain regions not directly related to reproductive function. In this study we used glial fibrillary acidic protein (GFAP) immunocytochemistry to quantify astroglial cells and process density in both the neocortex and hippocampus during the estrous cycle. Our data show that the density of GFAP immunoreactive processes in the hippocampus peaks on proestrus although cell density does not change. In contrast, both GFAP immunoreactive cell and process densities are elevated on diestrus and proestrus in the supragranular layer of the somatosensory cortex and reach a nadir on estrus and metestrus. This activation pattern is not apparent in the motor or cingulate cortex. Neocortical GFAP immunoreactivity appears to follow the distribution of estrogen receptor-alpha-like immunoreactivity. Our data show that ovarian hormones have regionally specific effects on glial activation within the neocortex. Characterizing glial activation by ovarian hormones is important since astroglia are the source of numerous trophic factors and play an important, although often unrecognized, role in neuronal metabolism and function. Title: Effects of carvedilol on M2 receptors and cholinesterase-positive nerves in adriamycin-induced rat failing heart Xu XL, Zang WJ, Lu J, Kang XQ, Li M, Yu XJ Ref: Auton Neurosci, 130:6, 2006 : PubMed ESTHER: Xu_2006_Auton.Neurosci_130_6 PubMedSearch: Xu 2006 Auton.Neurosci 130 6 PubMedID: 16798104 Abstract Heart failure is correlated with attenuation of parasympathetic nervous function and enhanced sympathetic activity. Carvedilol, a third-generation beta-blocker, may improve the prognosis of heart failure better than selective beta(1)-blockers. Not all of its effects, however, can be explained by direct actions on the sympathetic nervous system. This study was therefore performed to investigate the possible alterations of muscarinic cholinergic (M)(2) receptors and cholinesterase-positive nerves in different regions of the adriamycin-induced failing rat heart, and the potential effects of carvedilol on these M(2) receptors and cholinesterase-positive nerves. Karnovsky-Roots histochemical staining combined with point counting methods, and immunochemical streptavidin-biotin complex staining and image analysis were used to test the distribution of cholinesterase-positive nerves and the expression of M(2) receptors, respectively. Our results show that the cholinesterase-positive nerve system was downregulated in the adriamycin-induced failing heart group, while the density of M(2) receptors was increased in the carvedilol 3- and 10-mg/kg body weight groups, especially in the endocardial tissues of the left-ventricular free wall. It is concluded that upregulation of M(2) receptors may be one of the potential mechanisms by which carvedilol exert its action on heart failure. Title: Novel dimeric acetylcholinesterase inhibitor bis7-tacrine, but not donepezil, prevents glutamate-induced neuronal apoptosis by blocking N-methyl-D-aspartate receptors Li W, Pi R, Chan HH, Fu H, Lee NT, Tsang HW, Pu Y, Chang DC, Li C and Han Y <8 more author(s)> Li W, Pi R, Chan HH, Fu H, Lee NT, Tsang HW, Pu Y, Chang DC, Li C, Luo J, Xiong K, Li Z, Xue H, Carlier PR, Pang Y, Tsim KWK, Li M, Han Y (- 8) Ref: Journal of Biological Chemistry, 280:18179, 2005 : PubMed ESTHER: Li_2005_J.Biol.Chem_280_18179 PubMedSearch: Li 2005 J.Biol.Chem 280 18179 PubMedID: 15710623 Abstract The neuroprotective properties of bis(7)-tacrine, a novel dimeric acetylcholinesterase (AChE) inhibitor, on glutamate-induced excitotoxicity were investigated in primary cultured cerebellar granule neurons (CGNs). Exposure of CGNs to 75 mum glutamate resulted in neuronal apoptosis as demonstrated by Hoechst staining, TUNEL, and DNA fragmentation assays. The bis(7)-tacrine treatment (0.01-1 mum) on CGNs markedly reduced glutamate-induced apoptosis in dose- and time-dependent manners. However, donepezil and other AChE inhibitors, even at concentrations of inhibiting AChE to the similar extents as 1 mum bis(7)-tacrine, failed to prevent glutamate-induced excitotoxicity in CGNs; moreover, both atropine and dihydro-beta-erythroidine, the cholinoreceptor antagonists, did not affect the anti-apoptotic properties of bis(7)-tacrine, suggesting that the neuroprotection of bis(7)-tacrine appears to be independent of inhibiting AChE and cholinergic transmission. In addition, ERK1/2 and p38 pathways, downstream signals of N-methyl-d-aspartate (NMDA) receptors, were rapidly activated after the exposure of glutamate to CGNs. Bis(7)-tacrine inhibited the apoptosis and the activation of these two signals with the same efficacy as the coapplication of PD98059 and SB203580. Furthermore, using fluorescence Ca(2+) imaging, patch clamp, and receptor-ligand binding techniques, bis(7)-tacrine was found effectively to buffer the intracellular Ca(2+) increase triggered by glutamate, to reduce NMDA-activated currents and to compete with [(3)H]MK-801 with an IC(50) value of 0.763 mum in rat cerebellar cortex membranes. These findings strongly suggest that bis(7)-tacrine prevents glutamate-induced neuronal apoptosis through directly blocking NMDA receptors at the MK-801-binding site, which offers a new and clinically significant modality as to how the agent exerts neuroprotective effects. Title: Gene expression profiling in spleens of deoxynivalenol-exposed mice: immediate early genes as primary targets Kinser S, Jia Q, Li M, Laughter A, Cornwell P, Corton JC, Pestka J Ref: J Toxicol Environ Health A, 67:1423, 2004 : PubMed ESTHER: Kinser_2004_J.Toxicol.Environ.Health.A_67_1423 PubMedSearch: Kinser 2004 J.Toxicol.Environ.Health.A 67 1423 PubMedID: 15371230 Abstract Exposure to the trichothecene mycotoxin deoxynivalenol (DON) alters immune functions in vitro and in vivo. To gain further insight into DON's immunotoxic effects, microarrays were used to determine how acute exposure to this mycotoxin modulates gene expression profiles in murine spleen. B6C3F1 mice were treated orally with 25mg/kg body weight DON, and 2h later spleens were collected for macroarray analysis. Following normalization using a local linear regression model, expression of 116 out of 1176 genes was significantly altered compared to average expression levels in all treatment groups. When genes were arranged into an ontology tree to facilitate comparison of expression profiles between treatment groups, DON was found primarily to modulate genes associated with immunity, inflammation, and chemotaxis. Real-time polymerase chain reaction was used to confirm modulation for selected genes. DON was found to induce the cytokines interleukin (IL)-1alpha, IL-1beta, IL-6 and IL-11. In analogous fashion, DON upregulated expression of the chemokines macrophage inhibitory protein-2 (MIP-2), cytokine-induced chemoattractant protein-1 (CINC-1), monocyte chemoattractant protein (MCP)-1, MCP-3, and cytokine-responsive gene-2 (CRG-2). c-Fos, Fra-, c-Jun, and JunB, components of the activator protein-1 (AP-1) transcription factor complex, were induced by DON as well as another transcription factor, NR4A1. Four hydrolases were found to be upregulated by DON, including mitogen-activated protein kinase phosphatase 1 (MKP1), catalytic subunit beta isoform (CnAbeta), protein tyrosine phosphatase receptor type J (Ptprj), and protein tyrosine phosphatase nonreceptor type 8 (Ptpn8), whereas three other hydrolases, microsomal epoxide hydrolase (Eph) 1, histidine triad nucleotide binding protein (Hint), and proteosome subunit beta type 8 (Psmb8) were significantly decreased by the toxin. Finally, cysteine-rich protein 61 (CRP61) and heat-shock protein 40 (Hsp40), genes associated with signaling, were increased, while Jun kinase 2 (JNK2) was decreased. Taken together, data suggest that DON upregulated the expression of multiple immediate early genes, many of which are likely to contribute to the complex immunological effects reported for this and other trichothecenes. Title: Complete genome sequence of Yersinia pestis strain 91001, an isolate avirulent to humans Song Y, Tong Z, Wang J, Wang L, Guo Z, Han Y, Zhang J, Pei D, Zhou D and Yang R <16 more author(s)> Song Y, Tong Z, Wang J, Wang L, Guo Z, Han Y, Zhang J, Pei D, Zhou D, Qin H, Pang X, Zhai J, Li M, Cui B, Qi Z, Jin L, Dai R, Chen F, Li S, Ye C, Du Z, Lin W, Yu J, Yang H, Huang P, Yang R (- 16) Ref: DNA Research, 11:179, 2004 : PubMed ESTHER: Song_2004_DNA.Res_11_179 PubMedSearch: Song 2004 DNA.Res 11 179 PubMedID: 15368893 Gene_locus related to this paper: yerpe-BIOH, yerpe-IRP1, yerpe-PIP, yerpe-PLDB, yerpe-PTRB, yerpe-q8zey9, yerpe-Y0644, yerpe-y1616, yerpe-y3224, yerpe-YPLA, yerpe-YPO0180, yerpe-YPO0667, yerpe-YPO0773, yerpe-YPO0776, yerpe-YPO0986, yerpe-YPO1501, yerpe-YPO1997, yerpe-YPO2002, yerpe-YPO2336, yerpe-YPO2526, yerpe-YPO2638, yerpe-YPO2814 Abstract Genomics provides an unprecedented opportunity to probe in minute detail into the genomes of the world's most deadly pathogenic bacteria- Yersinia pestis. Here we report the complete genome sequence of Y. pestis strain 91001, a human-avirulent strain isolated from the rodent Brandt's vole-Microtus brandti. The genome of strain 91001 consists of one chromosome and four plasmids (pPCP1, pCD1, pMT1 and pCRY). The 9609-bp pPCP1 plasmid of strain 91001 is almost identical to the counterparts from reference strains (CO92 and KIM). There are 98 genes in the 70,159-bp range of plasmid pCD1. The 106,642-bp plasmid pMT1 has slightly different architecture compared with the reference ones. pCRY is a novel plasmid discovered in this work. It is 21,742 bp long and harbors a cryptic type IV secretory system. The chromosome of 91001 is 4,595,065 bp in length. Among the 4037 predicted genes, 141 are possible pseudo-genes. Due to the rearrangements mediated by insertion elements, the structure of the 91001 chromosome shows dramatic differences compared with CO92 and KIM. Based on the analysis of plasmids and chromosome architectures, pseudogene distribution, nitrate reduction negative mechanism and gene comparison, we conclude that strain 91001 and other strains isolated from M. brandti might have evolved from ancestral Y. pestis in a different lineage. The large genome fragment deletions in the 91001 chromosome and some pseudogenes may contribute to its unique nonpathogenicity to humans and host-specificity. Title: Genetics of metabolic variations between Yersinia pestis biovars and the proposal of a new biovar, microtus Zhou D, Tong Z, Song Y, Han Y, Pei D, Pang X, Zhai J, Li M, Cui B and Yang R <7 more author(s)> Zhou D, Tong Z, Song Y, Han Y, Pei D, Pang X, Zhai J, Li M, Cui B, Qi Z, Jin L, Dai R, Du Z, Wang J, Guo Z, Huang P, Yang R (- 7) Ref: Journal of Bacteriology, 186:5147, 2004 : PubMed ESTHER: Zhou_2004_J.Bacteriol_186_5147 PubMedSearch: Zhou 2004 J.Bacteriol 186 5147 PubMedID: 15262951 Gene_locus related to this paper: yerpe-YPLA Abstract Yersinia pestis has been historically divided into three biovars: antiqua, mediaevalis, and orientalis. On the basis of this study, strains from Microtus-related plague foci are proposed to constitute a new biovar, microtus. Based on the ability to ferment glycerol and arabinose and to reduce nitrate, Y. pestis strains can be assigned to one of four biovars: antiqua (glycerol positive, arabinose positive, and nitrate positive), mediaevalis (glycerol positive, arabinose positive, and nitrate negative), orientalis (glycerol negative, arabinose positive, and nitrate positive), and microtus (glycerol positive, arabinose negative, and nitrate negative). A 93-bp in-frame deletion in glpD gene results in the glycerol-negative characteristic of biovar orientalis strains. Two kinds of point mutations in the napA gene may cause the nitrate reduction-negative characteristic in biovars mediaevalis and microtus, respectively. A 122-bp frameshift deletion in the araC gene may lead to the arabinose-negative phenotype of biovar microtus strains. Biovar microtus strains have a unique genomic profile of gene loss and pseudogene distribution, which most likely accounts for the human attenuation of this new biovar. Focused, hypothesis-based investigations on these specific genes will help delineate the determinants that enable this deadly pathogen to be virulent to humans and give insight into the evolution of Y. pestis and plague pathogenesis. Moreover, there may be the implications for development of biovar microtus strains as a potential vaccine. Title: Five ADNFLE mutations reduce the Ca2+ dependence of the mammalian alpha4beta2 acetylcholine response Rodrigues-Pinguet N, Jia L, Li M, Figl A, Klaassen A, Truong A, Lester HA, Cohen BN Ref: The Journal of Physiology, 550:11, 2003 : PubMed ESTHER: Rodrigues-Pinguet_2003_J.Physiol_550_11 PubMedSearch: Rodrigues-Pinguet 2003 J.Physiol 550 11 PubMedID: 12754307 Abstract Five nicotinic acetylcholine receptor (nAChR) mutations are currently linked to autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE). The similarity of their clinical symptoms suggests that a common functional anomaly of the mutations underlies ADNFLE seizures. To identify this anomaly, we constructed rat orthologues (S252F, +L264, S256L, V262L, V262M) of the human ADNFLE mutations, expressed them in Xenopus oocytes with the appropriate wild-type (WT) subunit (alpha4 or beta2), and studied the Ca2+ dependence of their ACh responses. All the mutations significantly reduced 2 mM Ca2+-induced increases in the 30 microM ACh response (P < 0.05). Consistent with a dominant mode of inheritance, this reduction persisted in oocytes injected with a 1:1 mixture of mutant and WT cRNA. BAPTA injections showed that the reduction was not due to a decrease in the secondary activation of Ca2+-activated Cl- currents. The S256L mutation also abolished 2 mM Ba2+ potentiation of the ACh response. The S256L, V262L and V262M mutations had complex effects on the ACh concentration-response relationship but all three mutations shifted the concentration-response relationship to the left at [ACh] >= 30 microM. Co-expression of the V262M mutation with a mutation (E180Q) that abolished Ca2+ potentiation resulted in 2 mM Ca2+ block, rather than potentiation, of the 30 microM ACh response, suggesting that the ADNFLE mutations reduce Ca2+ potentiation by enhancing Ca2+ block of the alpha4beta2 nAChR. Ca2+ modulation may prevent presynaptic alpha4beta2 nAChRs from overstimulating glutamate release at central excitatory synapses during bouts of synchronous, repetitive activity. Reducing the Ca2+ dependence of the ACh response could trigger seizures by increasing alpha4beta2-mediated glutamate release during such bouts. Title: O-ethyl and o-methyl n-(2,3,4,6-tetra-o-acetyl-beta-d-glucopyranosyl)thiocarbamate Zhang S, Wang Z, Li M, Jiao K, Razak IA, Shanmuga Sundara Raj S, Fun HK Ref: Acta Crystallographica C, 57:566, 2001 : PubMed ESTHER: Zhang_2001_Acta.Crystallogr.C_57_566 PubMedSearch: Zhang 2001 Acta.Crystallogr.C 57 566 PubMedID: 11353253 Abstract In both the title structures, O-ethyl N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)thiocarbamate, C(17)H(25)NO(10)S, and O-methyl N-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl)thiocarbamate, C(16)H(23)NO(10)S, the hexopyranosyl ring adopts the (4)C(1) conformation. All the ring substituents are in equatorial positions. The acetoxymethyl group is in a gauche-gauche conformation. The S atom is in a synperiplanar conformation, while the C-N-C-O linkage is antiperiplanar. N-H.O intermolecular hydrogen bonds link the molecules into infinite chains and these are connected by C-H.O interactions. Title: High-efficiency Expression of Prolyl Endopeptidase from Aeromonas punctata subsp. Punctata in Escherichia coli Li M, Xu H, Chen CQ Ref: Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 32:183, 2000 : PubMed ESTHER: Li_2000_Sheng.Wu.Hua.Xue.Yu.Sheng.Wu.Wu.Li.Xue.Bao.(Shanghai)_32_183 PubMedSearch: Li 2000 Sheng.Wu.Hua.Xue.Yu.Sheng.Wu.Wu.Li.Xue.Bao.(Shanghai) 32 183 PubMedID: 12098799 Abstract The open reading frame (ORF) of prolyl endopeptidase gene from Aeromonas punctata subsp. punctata (apPEP) was amplified by PCR in three parts. The amplified DNA segments were ligated to form the complete apPEP gene, and then cloned into expression vectors pBL (temperature inducible) and pKKH (IPTG inducible), respectively. After induction, the expression amounts of recombinant apPEP in BL21/pKKH-PEP and BL21/pBL-PEP were about 30% of the total bacterial proteins, and the enzyme activities were 100 fold higher than wild strain. Expressed apPEP was mainly soluble intracellular protein. Non-reduced SDS-PAGE analysis showed that it was a monomer with molecular weight about 76 kD, which corresponded to the prediction from gene sequence. Recombinant apPEP was purified by HPLC, the purity reached 90% and specific activity was 67 u/mg. The N-terminal analysis of apPEP demonstrated that the protein sequence was identical as predicted from gene sequence. Title: [Cochleogram for assessing hair cells and efferent fibers in carboplatin-treated ear] Ding D, Li M, Zheng X Ref: Lin Chuang Er Bi Yan Hou Ke Za Zhi, 13:510, 1999 : PubMed ESTHER: Ding_1999_Lin.Chuang.Er.Bi.Yan.Hou.Ke.Za.Zhi_13_510 PubMedSearch: Ding 1999 Lin.Chuang.Er.Bi.Yan.Hou.Ke.Za.Zhi 13 510 PubMedID: 12541378 Abstract OBJECTIVE: This paper describes a convenient histochemical technique that allows one to simultaneously assess the cochlear efferent neurons and inner (IHCs) and outer hair cells (OHCs). METHOD: Selective labeling of the sensory cells and efferent fibers was carried out by first labeling the hair cells for dehydrogenase activity and then staining the efferent fibers for acetylcholinesterase activity. Double-labeled specimens were prepared as a surface preparation and counts were made of the number of hair cells and the number of discreate fiber bundles crossing the tunnel of Corti along the entire length of the cochlea. RESULT: The utility of this technique for assessing ototoxic damage was demonstrated by constructing cochleograms showing the percentage of missing hair cells and tunnel-crossing efferent fibers in chinchillas treated with carboplatin. In the region of the cochlea associated with most IHC loss and a part of OHC missing showed by succinate dehydrogenase in the region of hair cells; however, the loss of tunnel-crossing efferent fibers showed by acetylcholinesterase staining was closely correlated with the percentage of OHC loss. But, if only damage the IHC, the efferent fibers showed normal. CONCLUSION: These results suggest that carboplatin damaged efferent systems may be due to the damage of OHC. Title: Properties of Recombinant Aeromonas punctata Prolyl Endopeptidase Li M, Shen GX, Chen CQ, Wang DB Ref: Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai), 31:685, 1999 : PubMed ESTHER: Li_1999_Sheng.Wu.Hua.Xue.Yu.Sheng.Wu.Wu.Li.Xue.Bao.(Shanghai)_31_685 PubMedSearch: Li 1999 Sheng.Wu.Hua.Xue.Yu.Sheng.Wu.Wu.Li.Xue.Bao.(Shanghai) 31 685 PubMedID: 12110936 Abstract The properties of recombinant Aeromonas punctata prolyl endopeptidase(apPEP) were studied using specific substrate and peptides. Results show that the optimum catalytic temperature and pH was 34 degrees and 8.4, the stability of the apPEP was in the range of 4-32 degrees and pH 6.0-10.0, and its K(m) was 0.03 mmol/L based on the Z-Gly-Pro-betaNA. The apPEP was not sensitive to PMSF, TLCK, TPCK, Trypsion inhibitor, EDTA, tetrathionate and some metal ions, but was sensitive to SDS and Zn(2 ), and was completely inhibited by DFP. Oxytocin and calcitonin could be specifically hydrolyzed by apPEP at the carboxyl site of proline residue, but the hydrolysis efficiency of calcitonin by the enzyme was less than for oxytocin and for Z-Gly-Pro-betaNA. Title: Pharmacological activity and safety profile of P10358, a novel, orally active acetylcholinesterase inhibitor for Alzheimer's disease Smith CP, Bores GM, Petko W, Li M, Selk DE, Rush DK, Camacho F, Winslow JT, Fishkin R and Vargas HM <5 more author(s)> Smith CP, Bores GM, Petko W, Li M, Selk DE, Rush DK, Camacho F, Winslow JT, Fishkin R, Cunningham DM, Brooks KM, Roehr J, Hartman HB, Davis L, Vargas HM (- 5) Ref: Journal of Pharmacology & Experimental Therapeutics, 280:710, 1997 : PubMed ESTHER: Smith_1997_J.Pharmacol.Exp.Ther_280_710 PubMedSearch: Smith 1997 J.Pharmacol.Exp.Ther 280 710 PubMedID: 9023283 Inhibitor(s) related to this paper: P-10358 Abstract 1-[(3-Fluoro-4-pyridinyl)amino]-3-methyl-1(H)-indol-5-yl methyl carbamate (P10358) is a potent, reversible acetylcholinesterase inhibitor that produces central cholinergic stimulation after oral and parental administration in rats and mice. P10358 is a 2.5 times more potent acetylcholinesterase inhibitor than THA in vitro (IC50 = 0.10 +/- 0.02 microM vs. IC50 = 0.25 +/- 0.03 microM). It also inhibits butyrylcholinesterase activity as potently as THA (IC50 = 0.08 +/- 0.05 microM vs. IC50 = 0.07 +/- 0.01 microM). Ex vivo, P10358 (0.2 - 20 mg/kg, p.o.) produced dose-dependent inhibition of brain acetylcholinesterase activity. At 10 and 20 mg/ kg, it produced profound and long-lasting hypothermia in mice. P10358 enhanced performance in rats in a step-down passive avoidance task (0.62 and 1.25 mg/kg) and in a social recognition paradigm (0.32, 0.64 and 1.25 mg/kg) in mice. It reversed scopolamine-induced deficits in the Morris Water maze in rats (1.25 and 2.5 mg/kg) and a higher dose elevated striatal homovanillic acid levels. These behavioral and biochemical effects are consistent with central cholinergic stimulation. Hemodynamic studies in the rat demonstrated a 16-fold separation between behaviorally active doses (1.25 mg/kg) and those that elevated arterial pressure (20 mg/kg). Lethality in rats occurred at an oral dose of 80 mg/kg, but not at lower doses. Chemically, P10358 is an N-aminoindole and may not have the hepatotoxic liability associated with aminoacridine structure of tacrine. P10358 had weak affinity (>10 microM) at a variety of aminergic and peptidergic receptors and uptake carriers. These properties suggest that P10358 may be a safe and promising symptomatic treatment for Alzheimer's disease. Title: Images of purified Shaker potassium channels Li M, Unwin N, Stauffer KA, Jan YN, Jan LY Ref: Current Biology, 4:110, 1994 : PubMed ESTHER: Li_1994_Curr.Biol_4_110 PubMedSearch: Li 1994 Curr.Biol 4 110 PubMedID: 7953509 Abstract BACKGROUND: Voltage-gated K+ channels play an important role in the control of neuronal excitability and synaptic plasticity. Their low abundance and extraordinary heterogeneity have rendered their purification from natural sources difficult. We have previously cloned a voltage-gated K(+)-channel gene, Shaker, from Drosophila. The Shaker K(+)-channel polypeptide resembles one of the four internal repeats of a Na(+)- or Ca(2+)-channel alpha subunit, suggesting that this example of a K+ channel contains four identical or homologous subunits. Similar K(+)-channel polypeptides have been characterized from mammals, other vertebrate and invertebrate species, and from plants. Electrophysiological studies of K+ channels expressed in Xenopus oocytes suggest that they are indeed tetramers, and heteromultimeric K+ channels have been found in the mammalian brain. Until now, however, no K+ channel, nor any other member of the superfamily of voltage-gated ion channels, has been characterized by electron microscopy or other structural analysis. Title: Poster: Development and utilization of a panel of antisera selective for each of the subtypes of muscarinic cholinergic receptor Wolfe BB, Yasuda RP, Wall SJ, Li M, Ciesla W Ref: Life Sciences, 52(5-6):584, 1993 : PubMed | |||||||
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