Author Report for: He LNo contact information in database for He L
Chen Q, Liu J, Liu S, Zhang J, He L, Liu R, Jiang H, Han X, Zhang K Ref: Analytical Chemistry, :, 2023 : PubMed ESTHER: Chen_2023_Anal.Chem__ PubMedSearch: Chen 2023 Anal.Chem PubMedID: 36802493 Abstract Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0-90 microM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 microM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents. Title: Responses of gut microbiomes to commercial polyester polymer biodegradation in Tenebrio molitor Larvae He L, Yang SS, Ding J, He ZL, Pang JW, Xing DF, Zhao L, Zheng HS, Ren NQ, Wu WM Ref: J Hazard Mater, 457:131759, 2023 : PubMed ESTHER: He_2023_J.Hazard.Mater_457_131759 PubMedSearch: He 2023 J.Hazard.Mater 457 131759 PubMedID: 37276692 Abstract Polyethylene terephthalate (PET) is a mass-produced fossil-based plastic polymer that contributes to catastrophic levels of plastic pollution. Here we demonstrated that Tenebrio molitor (mealworms) was capable of rapidly biodegrading two commercial PET resins (microplastics) with respective weight-average molecular weight (M(w)) of 39.33 and 29.43 kDa and crystallinity of 22.8 +/- 3.06% and 18 +/- 2.25%, resulting in an average mass reduction of 71.03% and 73.28% after passage of their digestive tract, and respective decrease by 9.22% and 11.36% in M(w) of residual PET polymer in egested frass. Sequencing of 16 S rRNA gene amplicons of gut microbial communities showed that dominant bacterial genera were enriched and associated with PET degradation. Also, PICRUSt prediction exhibited that oxidases (monooxygenases and dioxygenases), hydrolases (cutinase, carboxylesterase and chitinase), and PET metabolic enzymes, and chemotaxis related functions were up-regulated in the PET-fed larvae. Additionally, metabolite analyses revealed that PET uptake caused alterations of stress response and plastic degradation related pathways, and lipid metabolism pathways in the T. molitor larvae could be reprogrammed when the larvae fed on PET. This study provides new insights into gut microbial community adaptation to PET diet under nutritional stress (especially nitrogen deficiency) and its contribution to PET degradation. Title: A potential novel biomarker: comprehensive analysis of prognostic value and immune implication of CES3 in colonic adenocarcinoma He L, Zhao C, Xu J, Li W, Lu Y, Gong Y, Gu D, Wang X, Guo F Ref: J Cancer Research Clin Oncol, :, 2023 : PubMed ESTHER: He_2023_J.Cancer.Res.Clin.Oncol__ PubMedSearch: He 2023 J.Cancer.Res.Clin.Oncol PubMedID: 37480527 Gene_locus related to this paper: human-CES3 Abstract PURPOSE: Colon cancer is the most common malignant tumor in the intestine. Abnormal Carboxylesterases 3 (CES3) expression had been reported to be correlated to multiple tumor progression. However, the association among CES3 expression and prognostic value and immune effects in colonic adenocarcinoma (COAD) were unclear. PATIENTS AND METHODS: The transcription and expression data of CES3 and corresponding clinical information was downloaded from The Cancer Genome Atlas (TCGA). The CES3 protein expression and the prognostic value were verified based on tissue microarray data. The Cancer immune group Atlas (TCIA), Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and the GSE78220 immunotherapy cohort were used to forecast immunotherapy efficacy. Finally, a prognostic immune signature was constructed and verified. RESULTS: Compared with normal colon tissues, the expression of mRNA and protein levels of CES3 were downregulated in tumor tissues. CES3 expression was associated with TIICs. Hihg-CES3 COAD patients had better efficacy of concurrent immunotherapy. CES3-related immune genes (CRIs) were identified and were then used to construct prognostic immune signature and had been successfully verified in GES39582. CONCLUSION: CES3 might be a potential immune-related gene and promising prognostic biomarker in COAD. Title: PI3K-Akt signaling pathway based on network pharmacology for the anti-Alzheimer's disease effect of licorice stem flavonoids Pei H, He L, Shi M, Guo X, Chen W, Li J, He Z, Du R Ref: Aging (Albany NY), 15:, 2023 : PubMed ESTHER: Pei_2023_Aging.(Albany.NY)_15_ PubMedSearch: Pei 2023 Aging.(Albany.NY) 15 PubMedID: 37166431 Abstract Active ingredients were screened by TCMSP and swissADME, meanwhile, PharmMapper combined with UniProt database was used to predict the active ingredient target information, GeneCard database was employed to obtain Alzheimer's disease (AD)-related genes, Cytoscapes 3.7.2 software was utilized to map the active ingredient-target effect. Besides, Cytoscapes 3.7.2 software Bisogenet and Cyto NCA plug-in combined with STRING platform were utilized to map the protein-protein interaction (PPI) network, DAVID was employed for GO annotation, while KEGG plug-in was used for KEGG pathway enrichment. Mice were tested for inflammatory damage induced by intracerebral injection of lipopolysaccharide (LPS), as well as learning memory and anxiety by water maze and open field tests. In addition, the expression of Caspase-3 and Caspase-9, together with inflammatory factors TNF-alpha, IL-6, and IL-1beta was analyzed in serum. The expression levels of proteins related to PI3K-Akt signaling pathway in the brain were detected by Western blot (WB) assay. According to the results of network pharmacology, there were 35 active ingredients of licorice stem and leaf flavonoids screened, which exerted the anti-Alzheimer's disease (AD) effects via 67 targets and activated 41 signaling pathways including the PI3K-Akt pathway. Furthermore, Behavioural results revealed that Licorice stem and leaf flavonoids improved the learning and memory abilities of model mice and significantly improved the anxiety caused by inflammatory brain damage. Moreover, as suggested by HE staining and TUNEL staining of brain sections, Glycyrrhiza glabra stem and leaf flavonoids alleviated morphological lesions and cell nuclear damage in brain tissue. Results: of brain homogenate supernatant assay demonstrated that Glycyrrhiza glabra stem and leaf flavonoids had a significant effect on the levels of oxidative indicators superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), acetylcholine (Ach), acetylcholinesterase (AchE), Caspase-3, Caspase-9 and serum inflammatory factors TNF-alpha, IL-6 and IL-1beta. Additionally, WB assay results indicated that the PI3K-Akt signaling pathway was activated. Title: Systematic assessment of cyflumetofen toxicity in soil-earthworm (Eisenia fetida) microcosms Shi L, Zhang P, Xu J, Wu X, Pan X, He L, Dong F, Zheng Y Ref: J Hazard Mater, 452:131300, 2023 : PubMed ESTHER: Shi_2023_J.Hazard.Mater_452_131300 PubMedSearch: Shi 2023 J.Hazard.Mater 452 131300 PubMedID: 37002996 Abstract Cyflumetofen was widely applied in agriculture with its excellent acaricidal effect. However, the impact of cyflumetofen on the soil non-target organism earthworm (Eisenia fetida) is unclear. This study aimed to elucidate the bioaccumulation of cyflumetofen in soil-earthworm systems and the ecotoxicity of earthworms. The highest concentration of cyflumetofen enriched by earthworms was found on the 7th day. Long-term exposure of earthworms to the cyflumetofen (10 mg/kg) could suppress protein content and increases Malondialdehyde content leading to severe peroxidation. Transcriptome sequencing analysis demonstrated that catalase and superoxide-dismutase activities were significantly activated while genes involved in related signaling pathways were significantly upregulated. In terms of detoxification metabolic pathways, high concentrations of cyflumetofen stimulated the number of Differentially-Expressed-Genes involved in the detoxification pathway of the metabolism of glutathione. Identification of three detoxification genes (LOC100376457, LOC114329378, and JGIBGZA-33J12) had synergistic detoxification. Additionally, cyflumetofen promoted disease-related signaling pathways leading to higher disease risk, affecting the transmembrane capacity and cell membrane composition, ultimately causing cytotoxicity. Superoxide-Dismutase in oxidative stress enzyme activity contributed more to detoxification. Carboxylesterase and glutathione-S-transferase activation play a major detoxification role in high-concentration treatment. Altogether, these results contribute to a better understanding of toxicity and defense mechanisms involved in long-term cyflumetofen exposure in earthworms. Title: Genome-wide identification and expression analysis of the cotton patatin-related phospholipase A genes and response to stress tolerance Wei Y, Chong Z, Lu C, Li K, Liang C, Meng Z, Wang Y, Guo S, He L, Zhang R Ref: Planta, 257:49, 2023 : PubMed ESTHER: Wei_2023_Planta_257_49 PubMedSearch: Wei 2023 Planta 257 49 PubMedID: 36752875 Abstract Patatin-related phospholipase A genes were involved in the response of Gossypium hirsutum to drought and salt tolerance. pPLA (patatin-related phospholipase A) is a key enzyme that catalyzes the initial step of lipid hydrolysis, which is involved in biological processes, such as drought, salt stress, and freezing injury. However, a comprehensive analysis of the pPLA gene family in cotton, especially the role of pPLA in the response to drought and salt tolerance, has not been reported so far. A total of 33 pPLA genes were identified in this study using a genome-wide search approach, and phylogenetic analysis classified these genes into three groups. These genes are unevenly distributed on the 26 chromosomes of cotton, and most of them contain a few introns. The results of the collinear analysis showed that G. hirsutum contained 1-5 copies of each pPLA gene found in G. arboreum and G. raimondii. The subcellular localization analysis of Gh_D08G061200 showed that the protein was localized in the nucleus. In addition, analysis of published upland cotton transcriptome data revealed that six GhPLA genes were expressed in various tissues and organs. Two genes (Gh_A04G142100.1 and Gh_D04G181000.1) were highly expressed in all tissues under normal conditions, showing the expression characteristics of housekeeping genes. Under different drought and salt tolerance stresses, we detected four genes with different expression levels. This study helps to clarify the role of pPLA in the response to drought and salt tolerance. Title: Esterase-Responsive Polymeric Micelles Containing Tetraphenylethene and Poly(ethylene glycol) Moieties for Efficient Doxorubicin Delivery and Tumor Therapy Xu DZ, Sun XY, Liang YX, Huang HW, Liu R, Lu ZL, He L Ref: Bioconjug Chem, :, 2023 : PubMed ESTHER: Xu_2023_Bioconjug.Chem__ PubMedSearch: Xu 2023 Bioconjug.Chem PubMedID: 36621834 Abstract Enzyme-responsive drug delivery systems have drawn much attention in the field of cancer theranostics due to their high sensitivity and substrate specificity under mild conditions. In this study, an amphiphilic polymer T1 is reported, which contains a tetraphenylethene unit and a poly(ethylene glycol) chain linked by an esterase-responsive phenolic ester bond. In aqueous solution, T1 formed stable micelles via self-assembly, which showed an aggregation-induced emission enhancement of 32-fold at 532 nm and a critical micelle concentration of 0.53 microM as well as esterase-responsive activity. The hydrophobic drug doxorubicin (DOX) was efficiently encapsulated into the micelles with a drug loading of 21%. In the presence of the esterase, the selective decomposition of drug-loaded T1 micelles was observed, and DOX was subsequently released with a half-life of 5 h. In vitro antitumor studies showed that T1@DOX micelles exhibited good therapeutic effects on HeLa cells, while normal cells remained mostly intact. In vivo anticancer experiments revealed that T1@DOX micelles indeed suppressed tumor growth and had reduced side effects compared to DOX.HCl. The present work showed the potential clinical application of esterase-responsive drug delivery in cancer therapy. Title: Synergism of Feeding and Digestion Regulated by the Neuropeptide F System in Ostrinia furnacalis Larvae Zhao J, Song Y, Jiang X, He L, Wei L, Zhao Z Ref: Cells, 12:, 2023 : PubMed ESTHER: Zhao_2023_Cells_12_ PubMedSearch: Zhao 2023 Cells 12 PubMedID: 36611986 Abstract Feeding is crucial for the growth and survival of animals, including humans, but relatively little is known about how it is regulated. Here, we show that larval feeding in Ostrinia furnacalis is regulated by neuropeptide F (NPF, the homologous peptide of mammalian NPY) via the insulin signalling pathway in the midgut. Furthermore, the genes pi3k and mtor in the insulin pathway positively regulate alpha-amylase and lipase of the midgut by recruiting the transcription factors c-Myc and PPARgamma for binding to the promotors of these two enzymes. Importantly, we find that the feeding behaviour and the digestive system of midgut in O. furnacalis larvae are closely related and interactive in that knocking down alpha-amylase or lipase induces a reduction in larval feeding, while food-deprived larvae lead to fewer expressions of alpha-amylase and lipase. Importantly, it is the gut NPF that regulates the alpha-amylase and lipase, while variations of alpha-amylase and lipase may feed back to the brain NPF. This current study reveals a molecular feedback mechanism between feeding behaviour and the digestive system that is regulated by the conserved NPF via insulin signalling systems in the midgut of O. furnacalis larvae. Title: 2, 5-dichloro-1, 4-benuinone exposure to zebrafish embryos/larvae causes neurodevelopmental toxicity Chen Y, Xiao L, Gao G, He L, Zhao K, Shang X, Liu C Ref: Ecotoxicology & Environmental Safety, 243:114007, 2022 : PubMed ESTHER: Chen_2022_Ecotoxicol.Environ.Saf_243_114007 PubMedSearch: Chen 2022 Ecotoxicol.Environ.Saf 243 114007 PubMedID: 36030688 Abstract 2, 5-dichloro-1, 4-benuinone (2, 5-DCBQ) is an emerging disinfection by-product belonging to the class of halobenzoquinones (HBQs). However, there is limited evidence regarding the neurotoxic effects of 2, 5-DCBQ. To better understand the toxicological mechanisms of aquatic organisms, zebrafish embryos were exposed to 0.2 mg/L, 0.4 mg/L, and 0.6 mg/L of 2, 5-DCBQ from 4 h post-fertilization (hpf) to 120 hpf. Developmental defects, such as reduced body length, decreased heart rate, decreased pigmentation, and abnormal motor axon structure was observed. In particular, the locomotor activity of zebrafish larvae reduced with exposure to increasing 2, 5-DCBQ concentrations, and this effect was more pronounced under dark stimulation. The results indicated that the genes associated with neuronal development (gfap, mbp, syn2a, elavl3, ache, and a1-tubulin) were significantly downregulated after treatment with 2, 5-DCBQ. Furthermore, the KEGG result showed the neuroactive ligand-receptor interaction and apoptosis pathways were visibly disrupted, and we found acetylcholinesterase activity was also affected. In summary, the disinfection by-product, 2, 5-DCBQ, exhibits neurodevelopmental toxicity in zebrafish embryos, providing novel evidence for comprehensive analyses of its toxicity. Title: The Catalytic Domain of Neuropathy Target Esterase Influences Lipid Droplet Biogenesis and Lipid Metabolism in Human Neuroblastoma Cells He L, Huang F, Wang Y, Wu Y, Xu L, Chang P Ref: Metabolites, 12:, 2022 : PubMed ESTHER: He_2022_Metabolites_12_ PubMedSearch: He 2022 Metabolites 12 PubMedID: 35888761 Abstract As an endoplasmic reticulum (ER)-anchored phospholipase, neuropathy target esterase (NTE) catalyzes the deacylation of lysophosphatidylcholine (LPC) and phosphatidylcholine (PC). The catalytic domain of NTE (NEST) exhibits comparable activity to NTE and binds to lipid droplets (LD). In the current study, the nucleotide monophosphate (cNMP)-binding domains (CBDs) were firstly demonstrated not to be essential for the ER-targeting of NTE, but to be involved in the normal ER distribution and localization to LD. NEST was associated with LD surface and influenced LD formation in human neuroblastoma cells. Overexpression of NEST enhances triacylglycerol (TG) accumulation upon oleic acid loading. Quantitative targeted lipidomic analysis shows that overexpression of NEST does not alter diacylglycerol levels but reduces free fatty acids content. NEST not only lowered levels of LPC and acyl-LPC, but not PC or alkyl-PC, but also widely altered levels of other lipid metabolites. Qualitative PCR indicates that the increase in levels of TG is due to the expression of diacylglycerol acyltransferase 1 gene by NEST overexpression. Thus, NTE may broadly regulate lipid metabolism to play roles in LD biogenesis in cells. Title: Fabrication of immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoylglycerol He L, Zeng C, Wei L, Xu L, Song F, Huang J, Zhong N Ref: Food Chem, 408:135236, 2022 : PubMed ESTHER: He_2022_Food.Chem_408_135236 PubMedSearch: He 2022 Food.Chem 408 135236 PubMedID: 36549162 Abstract This study aims to fabricate immobilized lipases for efficient preparation of 1,3-dioleoyl-2-palmitoyl-glycerol (OPO) through acidolysis of glycerol tripalmitate (PPP). Twelve (three types) supports and five lipases were studied carefully. Among them, the immobilized Thermomyces lanuginosa lipase (TLL) samples exhibited overall better performance than that of other immobilized lipases. Particularly, organic groups functionalized SBA-15 (R-SBA-15) supported TLL (TLL@R-SBA-15) samples gave PPP conversion from 97.70 to 99.00s% and OPO content from 59.52 to 64.73s%. After optimization, PPP conversion up to 99.07s%, OPO content 73.15s% and sn-2 palmitic acid content 90.09s% were obtained with TLL@C(18)H(37)-SBA-15 as catalyst. Moreover, TLL@C(18)H(37)-SBA-15 exhibited better acidolysis performance from 50s degreesC than that from 60 to 80s degreesC, which helped inhibit acyl migration. In addition, after 5 cycles of reuse, TLL@C(18)H(37)-SBA-15 retained 81.04s% (based on OPO content) and 98.88s% (based on sn-2 palmitic acid content) of its initial activity, indicating it had an attractive prospect in future applications. Title: Characterization of pectin methylesterase gene family and its possible role in juice sac granulation in navel orange (Citrus sinensis Osbeck) Li Z, Wu L, Wang C, Wang Y, He L, Wang Z, Ma X, Bai F, Feng G and Song F <2 more author(s)> Li Z, Wu L, Wang C, Wang Y, He L, Wang Z, Ma X, Bai F, Feng G, Liu J, Jiang Y, Song F (- 2) Ref: BMC Genomics, 23:185, 2022 : PubMed ESTHER: Li_2022_BMC.Genomics_23_185 PubMedSearch: Li 2022 BMC.Genomics 23 185 PubMedID: 35249536 Abstract BACKGROUND: Citrus is one of the most important fresh fruit crops worldwide. Juice sac granulation is a physiological disorder, which leads to a reduction in soluble solid concentration, total sugar, and titratable acidity of citrus fruits. Pectin methylesterase (PME) catalyzes the de-methylesterification of homogalacturonans and plays crucial roles in cell wall modification during plant development and fruit ripening. Although PME family has been well investigated in various model plants, little is known regarding the evolutionary property and biological function of PME family genes in citrus. RESULTS: In this study, 53 non-redundant PME genes were identified from Citrus sinensis genome, and these PME genes were divided into four clades based on the phylogenetic relationship. Subsequently, bioinformatics analyses of gene structure, conserved domain, chromosome localization, gene duplication, and collinearity were performed on CsPME genes, providing important clues for further research on the functions of CsPME genes. The expression profiles of CsPME genes in response to juice sac granulation and low-temperature stress revealed that CsPME genes were involved in the low temperature-induced juice sac granulation in navel orange fruits. Subcellular localization analysis suggested that CsPME genes were localized on the apoplast, endoplasmic reticulum, plasma membrane, and vacuole membrane. Moreover, yeast one-hybrid screening and dual luciferase activity assay revealed that the transcription factor CsRVE1 directly bound to the promoter of CsPME3 and activated its activity. CONCLUSION: In summary, this study conducts a comprehensive analysis of the PME gene family in citrus, and provides a novel insight into the biological functions and regulation patterns of CsPME genes during juice sac granulation of citrus. Title: Alternative splicing of a carboxyl/choline esterase gene enhances the fenpropathrin tolerance of Tetranychus cinnabarinus Wei P, Zeng X, Han H, Yang Y, Zhang Y, He L Ref: Insect Sci, :, 2022 : PubMed ESTHER: Wei_2022_Insect.Sci__ PubMedSearch: Wei 2022 Insect.Sci PubMedID: 36544383 Abstract Detoxification plays a crucial role in agricultural pests to withstand the pesticides, and cytochrome P450s, carboxyl/cholinesterases (CCEs), and glutathione-S-transferases are the main proteins responsible for their detoxification ability. The activity of CCEs can be up-regulated, down-regulated, or modified by mutation. However, few studies have examined the role of alternative splicing in altering the properties of CCEs. We identified two variants of TcCCE23 in Tetranychus cinnabarinus: a long version (CCE23-V1) and a short version that is 18 nucleotides shorter than CCE23-V1 (CCE23-V2). Whether splicing affects the activity of TcCCE23 remains unclear. Overexpression of CCE23-V2 in fenpropathrin resistant T. cinnabarinus revealed that splicing affected the detoxification of fenpropathrin by CCE23-V2. The mortality of mites was significantly higher when the expression of CCE23-V2 was knocked down (43.2% +/- 3.3%) via injection of CCE23-dsRNA compared with the control group injected with GFP-dsRNA under fenpropathrin exposure; however, the down-regulation of CCE23-V1 (61.3 +/- 6.3%) by CCE23-siRNA had no such effect, indicating CCE23-V2 plays a greater role in xenobiotic metabolism than CCE23-V1. The tolerance of flies overexpressing CCE23-V2 to fenpropathrin (LD(50) = 19.47 microg/g) was significantly higher than that of Gal4/UAS-CCE23-V1 transgenic flies (LD(50) = 13.11 microg/g). Molecular docking analysis showed that splicing opened a 'gate' that enlarge the substrate binding cavity of CCE23-V2, which might enhance the ability of CCE23-V2 to harbor fenpropathrin molecules. These findings suggest that splicing might enhance the detoxifying capability of TcCCE23. Generally, our data improve the understanding of the diversity and complexity of the mechanisms underlying the regulation of CCEs. This article is protected by copyright. All rights reserved. Title: Acute thiamethoxam exposure induces hepatotoxicity and neurotoxicity in juvenile Chinese mitten crab (Eriocheir sinensis) Yang Y, Yu Q, Zhang C, Wang X, He L, Huang Y, Li E, Qin J, Chen L Ref: Ecotoxicology & Environmental Safety, 249:114399, 2022 : PubMed ESTHER: Yang_2022_Ecotoxicol.Environ.Saf_249_114399 PubMedSearch: Yang 2022 Ecotoxicol.Environ.Saf 249 114399 PubMedID: 36508784 Abstract The similar nervous system structure between crustaceans and insects and the high-water solubility of thiamethoxam can lead to the more severe toxicity of thiamethoxam to crustaceans. However, the effects of thiamethoxam on crustaceans are unclear. Therefore, a 96-h acute toxicity test was performed to explore the hepatotoxicity and neurotoxicity effects of thiamethoxam on Chinese mitten crab (Eriocheir sinensis) at concentrations 0 microg/L, 150 microg/L and 300 microg/L. The antioxidant and detoxification systems (including phases I and II) were significantly activated after exposure of juvenile crabs to thiamethoxam for 24sh in 300 microg/L group, whereas the toxic activation effect in 150 microg/L group was delayed. Moreover, a similar pattern was observed for the transcription levels of immune-related genes. Further analysis of inflammatory signaling pathway-related genes showed that thiamethoxam exposure with 300 microg/L for 24sh may induce a pro-inflammatory response through the NF-kappaB pathway. In contrast, the gene expression levels in 150 microg/L group were significantly upregulated compared with 0 microg/L group after 96sh. In addition, although the acute exposure of 150 microg/L thiamethoxam did not seem to induce significant neurotoxicity, the acetylcholinesterase activity was significantly decreased in 300 microg/L group after thiamethoxam exposure for 96sh. Correspondingly, thiamethoxam exposure with 300 microg/L for 24sh resulted in significantly downregulated transcriptional levels of synaptic transmission-related genes (e.g. dopamine-, gamma-aminobutyric acid- and serotonin-related receptors). Therefore, thiamethoxam may be harmful and cause potential toxic threats such as neurotoxicity and metabolic damage to crustaceans. Title: Alpha/Beta Hydrolase Domain-Containing Protein 2 regulates the rhythm of follicular maturation and estrous stages of the female reproductive cycle Bjorkgren I, Chung DH, Mendoza S, Gabelev-Khasin L, Modzelewski A, He L, Lishko PV Ref: Front Cell Developmental Biology, 9:710864, 2021 : PubMed ESTHER: Bjorkgren_2021_Front.Cell.Dev.Biol_9_710864 PubMedSearch: Bjorkgren 2021 Front.Cell.Dev.Biol 9 710864 PubMedID: 34568325 Gene_locus related to this paper: human-ABHD2, mouse-ABHD2 Abstract Mammalian female fertility is defined by a successful and strictly periodic ovarian cycle, which is under the control of gonadotropins and steroid hormones, particularly progesterone and estrogen. The latter two are produced by the ovaries that are engaged in controlled follicular growth, maturation, and release of the eggs, i.e., ovulation. The steroid hormones regulate ovarian cycles via genomic signaling, by altering gene transcription and protein synthesis. However, despite this well-studied mechanism, steroid hormones can also signal via direct, non-genomic action, by binding to their membrane receptors. Here we show, that the recently discovered membrane progesterone receptor / hydrolase domain-containing protein 2 (ABHD2) is highly expressed in mammalian ovaries where the protein plays a novel regulatory role in follicle maturation and the sexual cycle of females. Ablation of Abhd2 caused a dysregulation of the estrous cycle rhythm with females showing shortened luteal stages while remaining in the estrus stage for a longer time. Interestingly, the ovaries of Abhd2 knockout (KO) females resemble polycystic ovary morphology (PCOM) with a high number of atretic antral follicles that could be rescued with injection of gonadotropins. Such a procedure also allowed Abhd2 KO females to ovulate a significantly increased number of mature and fertile eggs in comparison with their wild-type littermates. These results suggest a novel regulatory role of ABHD2 as an important factor in non-genomic steroid regulation of the female reproductive cycle. a preprint was published earlier Bjorkgren_2019_Biorxiv__ Title: IsPETase represents a novel biocatalyst for poly (ethylene terephthalate) (PET) hydrolysis Kan Y, He L, Luo Y, Bao R Ref: Chembiochem, :, 2021 : PubMed ESTHER: Kan_2021_Chembiochem__ PubMedSearch: Kan 2021 Chembiochem PubMedID: 33434375 Gene_locus related to this paper: idesa-mheth Abstract Poly (ethylene terephthalate) (PET) is one of the most widely used synthetic polyesters but also a main cause of plastic pollution. Since the chemical degradation of PET would be uneconomical and rather burdensome, considerable efforts have been devoted to exploring enzymatic processes for the disposal of PET waste. Many PET hydrolyzing enzymes have been consecutively reported in recent decades, some of which demonstrate excellent potential for industrial applications. This review sets out to summarize the investigation status of Is PETase, a cutinase-like enzyme from I. sakaiensis possessing ability to degrade the crystalline PET, and to gain further insight into the structure-function relationship of Is PETase. Benefiting from the continuing identification of novel cutinase-like proteins and growing availability of the engineered Is PETase, we may anticipate future developments in this type of enzyme would generate suitable biocatalyst for industrial use. Title: Assessing the Single and Combined Toxicity of Chlorantraniliprole and Bacillus thuringiensis (GO33A) against Four Selected Strains of Plutella xylostella (Lepidoptera: Plutellidae), and a Gene Expression Analysis Shabbir MZ, He L, Shu C, Yin F, Zhang J, Li ZY Ref: Toxins (Basel), 13:, 2021 : PubMed ESTHER: Shabbir_2021_Toxins.(Basel)_13_ PubMedSearch: Shabbir 2021 Toxins.(Basel) 13 PubMedID: 33809820 Abstract Concerns about resistance development to conventional insecticides in diamondback moth (DBM) Plutella xylostella (L.), the most destructive pest of Brassica vegetables, have stimulated interest in alternative pest management strategies. The toxicity of Bacillus thuringiensis subsp. aizawai (Bt GO33A) combined with chlorantraniliprole (Chl) has not been documented. Here, we examined single and combined toxicity of chlorantraniliprole and Bt to assess the levels of resistance in four DBM strains. Additionally, enzyme activities were tested in field-original highly resistant (FOH-DBM), Bt-resistant (Bt-DBM), chlorantraniliprole-resistant (CL-DBM), and Bt + chlorantraniliprole-resistant (BtC-DBM) strains. The Bt product had the highest toxicity to all four DBM strains followed by the mixture of insecticides (Bt + Chl) and chlorantraniliprole. Synergism between Bt and chlorantraniliprole was observed; the combination of Bt + (Bt + Chl) (1:1, LC(50):LC(50)) was the most toxic, showing a synergistic effect against all four DBM strains with a poison ratio of 1.35, 1.29, 1.27, and 1.25. Glutathione S-transferase (GST) and carboxyl-esterase (CarE) activities showed positive correlations with chlorantraniliprole resistance, but no correlation was observed with resistance to Bt and Bt + Chl insecticides. Expression of genes coding for PxGST, CarE, AChE, and MFO using qRT-PCR showed that the PxGST and MFO were significantly overexpressed in Bt-DBM. However, AChE and CarE showed no difference in the four DBM strains. Mixtures of Bt with chlorantraniliprole exhibited synergistic effects and may aid the design of new combinations of pesticides to delay resistance in DBM strains substantially. Title: Gene Expression, Biochemical Characterization of a sn-1, 3 Extracellular Lipase From Aspergillus niger GZUF36 and Its Model-Structure Analysis Xing S, Zhu R, Cheng K, Cai Y, Hu Y, Li C, Zeng X, Zhu Q, He L Ref: Front Microbiol, 12:633489, 2021 : PubMed ESTHER: Xing_2021_Front.Microbiol_12_633489 PubMedSearch: Xing 2021 Front.Microbiol 12 633489 PubMedID: 33776965 Gene_locus related to this paper: aspng-EXANL1 Abstract In this study, a sn-1, 3 extracellular lipases from Aspergillus niger GZUF36 (PEXANL1) was expressed in Pichia pastoris, characterized, and the predicted structural model was analyzed. The optimized culture conditions of P. pastoris showed that the highest lipase activity of 66.5 +/- 1.4 U/mL (P < 0.05) could be attained with 1% methanol and 96 h induction time. The purified PEXANL1 exhibited the highest activity at pH 4.0 and 40 degreesC temperature, and its original activity remained unaltered in the majority of the organic solvents (20% v/v concentration). Triton X-100, Tween 20, Tween 80, and SDS at a concentration of 0.01% (w/v) enhanced, and all the metal ions tested inhibited activity of purified PEXANL. The results of ultrasound-assisted PEXANL1 catalyzed synthesis of 1,3-diaglycerides showed that the content of 1,3-diglycerides was rapidly increased to 36.90% with 25 min of ultrasound duration (P < 0.05) and later decreased to 19.93% with 35 min of ultrasound duration. The modeled structure of PEXANL1 by comparative modeling showed alpha/beta hydrolase fold. Structural superposition and molecular docking results validated that Ser162, His274, and Asp217 residues of PEXANL1 were involved in the catalysis. Small-angle X-ray scattering analysis indicated the monomer properties of PEXANL1 in solution. The ab initio model of PEXANL1 overlapped with its modeling structure. This work presents a reliable structural model of A. niger lipase based on homology modeling and small-angle X-ray scattering. Besides, the data from this study will benefit the rational design of suitable crystalline lipase variants in the future. Title: Effect of cross-linked enzyme aggregate strategy on characterization of sn-1,3 extracellular lipase from Aspergillus niger GZUF36 Zhu R, Li C, Chen C, Xing S, Cai Y, Zeng X, He L Ref: Applied Microbiology & Biotechnology, :, 2021 : PubMed ESTHER: Zhu_2021_Appl.Microbiol.Biotechnol__ PubMedSearch: Zhu 2021 Appl.Microbiol.Biotechnol PubMedID: 33559718 Abstract The sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1) has important potential applications. The cross-linked enzyme aggregate (CLEA) of purified EXANL1 (CLEA-EXANL1) achieved optimum activity recovery (148.5 +/- 0.9%), immobilization yield (100 +/- 0%), and recovered activity (99.7 +/- 0.6%) with 80% tert-butanol as the precipitant, glutaraldehyde (GA) concentration of 30 mM, GA treatment time of 1.5 h, and centrifugal speed of 6000xg. The effect of CLEA strategy on the characterization of EXANL1 was evaluated in this work. CLEA-EXANL1 exhibited a broader optimum pH range (4-6) compared with free EXANL1 (6.5). CLEA-EXANL1 presented optimum activity at 40 degreesC, which was 5 degreesC higher than that of free EXANL1. CLEA strategy decreased the maximum reaction rate and increased the Michaelis-Menten constant of EXANL1 when olive oil emulsion was used as a substrate. Moreover, after 30 days, free EXANL1 lost more than 80.0% of its activity, whereas CLEA-EXANL1 retained more than 90.0% of its activity. CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. Fourier transform infrared spectroscopy results showed that the CLEA technique increased the contents of beta-sheets and beta-turns in EXANL1 and reduced those of alpha-helixes and irregular crimps. CLEA strategy caused no change in the sn-1,3 selectivity of EXANL1. Therefore, EXANL1 in the form of CLEA is a valuable catalyst in the synthesis of 1,3-diacylglycerol. KEY POINTS: Cross-linked enzyme aggregate (CLEA) strategy broadened the optimum pH range of sn-1,3 extracellular lipase from Aspergillus niger GZUF36 (EXANL1). CLEA strategy improved the tolerance of EXANL1 in polar organic solvents. CLEA strategy caused no change in the positional selectivity of EXANL1. Title: Polymethylated acylphloroglucinols from Rhodomyrtus tomentosa exert acetylcholinesterase inhibitory effects Qin XJ, Liu H, Li PP, Ni W, He L, Khan A, Hao XJ, Liu HY Ref: Bioorg Chem, :104519, 2020 : PubMed ESTHER: Qin_2020_Bioorg.Chem__104519 PubMedSearch: Qin 2020 Bioorg.Chem 104519 PubMedID: 33293058 Abstract Chemical investigation of the twigs and leaves of Rhodomyrtus tomentosa led to the isolation and structural identification of a novel polymethylated phloroglucinol meroterpenoid (PPM) featuring a 6/6/6/6 tetracyclic system, rhotomentodione F (1), five new polymethylated polycyclic phloroglucinols (PPPs) with a rare bis-furan framework, rhotomentosones A-E (2-6), and one new adduct composed of an acylphloroglucinol and two beta-triketone units, rhotomentosone F (7), as well as five known analogues (8-12). Their structures and absolute configurations were unambiguously determined by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. All isolates were evaluated for their anti-inflammatory and acetylcholinesterase (AChE) inhibitory activities. Compound 6 displayed significant AChE inhibitory effect with an IC(50) value of 8.68 M. Further molecular docking studies of 6 revealed that the interactions with AChE residues Ser125, Glu202, and Tyr133 are crucial for AChE inhibitory activity. The current study not only enriches the chemical diversity of phloroglucinols in Myrtaceae species, but also provides potential lead compounds for the further design and development of new AChE inhibitors to treat Alzheimer's disease. Title: Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer's disease Syal C, Kosaraju J, Hamilton L, Aumont A, Chu A, Sarma SN, Thomas J, Seegobin M, Dilworth FJ and Wang J <5 more author(s)> Syal C, Kosaraju J, Hamilton L, Aumont A, Chu A, Sarma SN, Thomas J, Seegobin M, Dilworth FJ, He L, Wondisford FE, Zimmermann R, Parent M, Fernandes K, Wang J (- 5) Ref: Theranostics, 10:6337, 2020 : PubMed ESTHER: Syal_2020_Theranostics_10_6337 PubMedSearch: Syal 2020 Theranostics 10 6337 PubMedID: 32483456 Abstract Rationale: Monoacylglycerol lipase (Mgll), a hydrolase that breaks down the endocannabinoid 2-arachidonoyl glycerol (2-AG) to produce arachidonic acid (ARA), is a potential target for neurodegenerative diseases, such as Alzheimer's disease (AD). Increasing evidence shows that impairment of adult neurogenesis by perturbed lipid metabolism predisposes patients to AD. However, it remains unknown what causes aberrant expression of Mgll in AD and how Mgll-regulated lipid metabolism impacts adult neurogenesis, thus predisposing to AD during aging. Here, we identify Mgll as an aging-induced factor that impairs adult neurogenesis and spatial memory in AD, and show that metformin, an FDA-approved anti-diabetic drug, can reduce the expression of Mgll to reverse impaired adult neurogenesis, prevent spatial memory decline and reduce beta-amyloid accumulation. Methods: Mgll expression was assessed in both human AD patient post-mortem hippocampal tissues and 3xTg-AD mouse model. In addition, we used both the 3xTg-AD animal model and the CbpS436A genetic knock-in mouse model to identify that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway, involving atypical protein kinase C (aPKC)-stimulated Ser436 phosphorylation of histone acetyltransferase CBP through biochemical methods. Furthermore, we performed in vivo adult neurogenesis assay with BrdU/EdU labelling and Morris water maze task in both animal models following pharmacological treatments to show the key role of Mgll in metformin-corrected neurogenesis and spatial memory deficits of AD through reactivating the aPKC-CBP pathway. Finally, we performed in vitro adult neurosphere assays using both animal models to study the role of the aPKC-CBP mediated Mgll repression in determining adult neural stem/progenitor cell (NPC) fate. Results: Here, we demonstrate that aging-dependent induction of Mgll is observed in the 3xTg-AD model and human AD patient post-mortem hippocampal tissues. Importantly, we discover that elevated Mgll expression is caused by the attenuation of the aPKC-CBP pathway. The accumulation of Mgll in the 3xTg-AD mice reduces the genesis of newborn neurons and perturbs spatial memory. However, we find that metformin-stimulated aPKC-CBP pathway decreases Mgll expression to recover these deficits in 3xTg-AD. In addition, we reveal that elevated Mgll levels in cultured adult NPCs from both 3xTg-AD and CbpS436A animal models are responsible for their NPC neuronal differentiation deficits. Conclusion: Our findings set the stage for development of a clinical protocol where Mgll would serve as a biomarker in early stages of AD to identify potential metformin-responsive AD patients to restore their neurogenesis and spatial memory. Title: Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, He L, Chen Y, Wu J and Li F <3 more author(s)> Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q, He L, Chen Y, Wu J, Shi Z, Zhou Y, Du L, Li F (- 3) Ref: J Virol, 94:, 2020 : PubMed ESTHER: Wan_2020_J.Virol_94_ PubMedSearch: Wan 2020 J.Virol 94 PubMedID: 31826992 Abstract Antibody-dependent enhancement (ADE) of viral entry has been a major concern for epidemiology, vaccine development, and antibody-based drug therapy. However, the molecular mechanism behind ADE is still elusive. Coronavirus spike protein mediates viral entry into cells by first binding to a receptor on the host cell surface and then fusing viral and host membranes. In this study, we investigated how a neutralizing monoclonal antibody (MAb), which targets the receptor-binding domain (RBD) of Middle East respiratory syndrome (MERS) coronavirus spike, mediates viral entry using pseudovirus entry and biochemical assays. Our results showed that MAb binds to the virus surface spike, allowing it to undergo conformational changes and become prone to proteolytic activation. Meanwhile, MAb binds to cell surface IgG Fc receptor, guiding viral entry through canonical viral-receptor-dependent pathways. Our data suggest that the antibody/Fc-receptor complex functionally mimics viral receptor in mediating viral entry. Moreover, we characterized MAb dosages in viral-receptor-dependent, Fc-receptor-dependent, and both-receptors-dependent viral entry pathways, delineating guidelines on MAb usages in treating viral infections. Our study reveals a novel molecular mechanism for antibody-enhanced viral entry and can guide future vaccination and antiviral strategies.IMPORTANCE Antibody-dependent enhancement (ADE) of viral entry has been observed for many viruses. It was shown that antibodies target one serotype of viruses but only subneutralize another, leading to ADE of the latter viruses. Here we identify a novel mechanism for ADE: a neutralizing antibody binds to the surface spike protein of coronaviruses like a viral receptor, triggers a conformational change of the spike, and mediates viral entry into IgG Fc receptor-expressing cells through canonical viral-receptor-dependent pathways. We further evaluated how antibody dosages impacted viral entry into cells expressing viral receptor, Fc receptor, or both receptors. This study reveals complex roles of antibodies in viral entry and can guide future vaccine design and antibody-based drug therapy. Title: Therapeutic efficacy and immunoregulatory effect of Qiangji Jianli Capsule for patients with myasthenia gravis: Study protocol for a series of randomized, controlled N-of-1 trials Weng S, Fan Z, Qiu G, Liu F, Huang L, Li J, Jiang X, Song Z, Gao Y and Jiang Q <5 more author(s)> Weng S, Fan Z, Qiu G, Liu F, Huang L, Li J, Jiang X, Song Z, Gao Y, Zhong Z, He L, Kang L, Wu Y, Chen B, Jiang Q (- 5) Ref: Medicine (Baltimore), 99:e23679, 2020 : PubMed ESTHER: Weng_2020_Medicine.(Baltimore)_99_e23679 PubMedSearch: Weng 2020 Medicine.(Baltimore) 99 e23679 PubMedID: 33371107 Abstract INTRODUCTION: Myasthenia gravis (MG) is an autoimmune disease in which antibodies directly target components of the neuromuscular junction, causing neuromuscular conduction damage that leads to muscle weakness. The current pharmaceutical treatment for MG is still not ideal to address the problems of disease progression, high recurrence rate, and drug side effects. Clinical observations suggest that traditional Chinese medicine (TCM) can strengthen immunity and improve symptoms of MG patients, delay the progression of the disease, reduce or even prevent the need for immunosuppressive therapy when used in combination with acetylcholinesterase inhibitors or low-dose prednisone, as well as improve the quality of life of patients. The Qiangji Jianli Capsule (QJC) is a combination of medicinal herbs which is used in traditional Chinese medicine. Since MG is a rare disorder, randomized controlled trials comparing large cohorts are difficult to conduct. Therefore, we proposed to aggregate data from a small series of N-of-1 trials to assess the effect of the Chinese medical prescription QJC, which strengthens the spleen and nourishes Qi, as an add-on treatment for MG with spleen and stomach Qi deficiency syndrome. METHODS AND ANALYSIS: Single-center, randomized, double-blind, multiple crossover N-of-1 studies will compare QJC versus placebo in 5 adult MG patients with spleen and stomach Qi deficiency syndrome. Patients will undergo 3 cycles of two 4-week intervention periods. According to the treatment schedule, patients will continue to be treated with pyridine bromide tablets, prednisone acetate, tablets and/or tacrolimus capsules throughout the entire trial. Each period consisting of 4-week oral add-on treatment with QJC will be compared with 4-week add-on treatment with a placebo. The primary endpoints are quantitative myasthenia gravis (QMG) test; measurement of the amount of Treg cells and cytokines such as interferon-gamma (IFN-gamma), interleukin-4 (IL-4), interleukin-17A (IL-17A), and transforming growth factor-beta (TGF-beta); and corticosteroid or immunosuppressive agent dosage. Secondary outcome measures: Clinical: Evaluation of the effect of TCM syndromes; MG-activities of daily living (MG-ADL) scales; adverse events. ETHICS AND DISSEMINATION: This study was approved by The First Affiliated Hospital of Guangzhou University of Chinese Medicine (GZUCM), No. ZYYECK[2019]038. The results will be published in a peer-reviewed publication. Regulatory stakeholders will comment on the suitability of the trial for market authorization and reimbursement purposes. Trial registration: Chinese Clinical Trial Register, ID: ChiCTR2000033516. Registered on 3 June 2020, http://www.chictr.org.cn/showprojen.aspx?proj=54618. Title: Gene cloning, expression, purification and characterization of a sn-1,3 extracellular lipase from Aspergillus niger GZUF36 Xing S, Zhu R, Li C, He L, Zeng X, Zhang Q Ref: J Food Sci Technol, 57:2669, 2020 : PubMed ESTHER: Xing_2020_J.Food.Sci.Technol_57_2669 PubMedSearch: Xing 2020 J.Food.Sci.Technol 57 2669 PubMedID: 32549617 Gene_locus related to this paper: aspng-EXANL1 Abstract Sn-1,3 extracellular Aspergillus niger GZUF36 lipase (EXANL1) has wide application potential in the food industry. However, the A. niger strain has defects such as easy degradation and instability in the expression of sn-1,3 lipase. To obtain a stable expression of this lipase and its subsequent enzymatic properties, the gene encoding EXANL1 was cloned and expressed in Escherichia coli BL21 (DE3) cells using pET-28a as the expression vector. The temperature-induced conditions were optimized, and we successfully achieved its active expression in E. coli. These conditions significantly influenced the active expression of EXANL1 (P < 0.05), and the highest enzyme activity of the supernatant of lysis cells expressed at 20 degreesC was at 7.02 +/- 0.05 U/mL. The expressed recombinant EXANL1 was purified using Ni-NTA, showing an estimated relative molecular mass of 35 kDa. The recombinant EXANL1 exhibited maximum activity at 35 degreesC and pH 4.0, with a wide acid pH range. Thin-layer chromatography analysis showed that the enzyme displayed sn-1,3 positional selectivity toward triolein. The recombinant EXANL1 could maintain its relative activities (> 80%) after 24 h of incubation at pH 3-10, suggesting its suitability for a wide range of industrial applications. After comparing these properties with those of the other A. niger lipases, we found that some key amino acids may play a decisive role in enzymology. This work laid a foundation for the stable expression of the EXANL1 gene and its potential industrial application. Title: Symbiotic Fungus Affected the Asian Citrus Psyllid (ACP) Resistance to Imidacloprid and Thiamethoxam Yi T, Lei L, He L, Yi J, Li L, Dai L, Hong Y Ref: Front Microbiol, 11:522164, 2020 : PubMed ESTHER: Yi_2020_Front.Microbiol_11_522164 PubMedSearch: Yi 2020 Front.Microbiol 11 522164 PubMedID: 33391190 Abstract The Asian citrus psyllid (ACP), Diaphorina citri (Kuwayama) (Hemiptera: Liviidae), is a notorious Rutaceae plant pest. Frequent and extensive use of pesticides has resulted in severe insecticide resistance in ACP populations. Fully understanding the mechanism of ACP resistance to pesticides is vital for us to control or delay the development of resistance. Therefore, we compared the difference in resistance to imidacloprid and thiamethoxam between Hunan (Yongzhou, Chenzhou) and Guangdong (Guangzhou) ACP populations and analyzed the correlations between the resistance level and genes and symbiotic fungi. The results showed that the resistance of the Guangdong ACP population to imidacloprid and thiamethoxam was lower than that of Hunan ACP population, and the relative expression of genes associated with P450 mono-oxygenase and acetylcholinesterase was significantly lower in the Guangdong ACP population than in Hunan ACP population. The differences of mean relative abundances of four symbiotic bacteria among three populations were marginally significant; however, the mean relative abundance of 16 fungi among three populations was significantly different, and positive linear correlations were observed between the resistance level and two fungi (Aspergillus niger and Aureobasidium pullulans) and two genes (CYP4C70 and CYP4DB1). Negative correlations were only observed between the resistance level and two fungi (Golubevia pallescens and Acremonium sclerotigenum). Moreover, four fungi were unique to the Chenzhou population which was the highest resistance to imidacloprid and thiamethoxam. These findings suggested the P450 mono-oxygenase and symbiotic fungi together affected ACP resistance to imidacloprid and thiamethoxam. In the future, we may use environmental G. pallescens and A. sclerotigenum to control or delay ACP resistance. Title: Effect of salt promote the muscle triglyceride hydrolysis during dry-salting by inducing the phosphorylation of adipose tissue triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) and lipid droplets splitting Zhao S, He L, Zhang M, Liu X, Jin G Ref: Food Chem, 327:127061, 2020 : PubMed ESTHER: Zhao_2020_Food.Chem_327_127061 PubMedSearch: Zhao 2020 Food.Chem 327 127061 PubMedID: 32454271 Abstract This study mainly investigated the effect of different salt concentrations (1, 3, or 5%) on triglycerides (TG) hydrolysis in muscle during salting by analyzing moisture distribution, TG hydrolysis, TG hydrolase activity, native and phosphorylated adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content, lipid droplets morphology, and muscle microstructure. The results showed that increasing salt concentration could significantly decrease T21 moisture proportion and relaxation time (p < 0.05), which was more beneficial to the lipase activity. The TG hydrolase activity increased first and then decreased with the salt concentration increasing during dry-salting process, and 3% salt concentration was the point of inflection. Western blot (WB) analysis detected both ATGL, HSL and their phosphorylated proteins, which were increased with the salt content increase. The microstructure analysis showed that the lipid droplets were split into small lipid droplets with the increase of salt content, which was more conducive to the triglycerides hydrolysis. Title: Optimization of the benzamide fragment targeting the S2' site leads to potent dipeptidyl peptidase-IV inhibitors Deng X, Wang N, Meng L, Zhou S, Huang J, Xing J, He L, Jiang W, Li Q Ref: Bioorg Chem, :103366, 2019 : PubMed ESTHER: Deng_2019_Bioorg.Chem__103366 PubMedSearch: Deng 2019 Bioorg.Chem 103366 PubMedID: 31640932 Abstract Our recently successful identification of benzoic acid-based DPP-4 inhibitors spurs the further quest for in-depth structure-activity relationships (SAR) study in S2' site DPP-4. Thus novel benzamide fragments were designed to target the S2' site to compromise lipophilicity and improve oral activity. Exploring SAR by introduction of a variety of amide and halogen on benzene ring led to identification of several compounds, exerting moderated to excellent DPP-4 activities, in which 4'-chlorine substituted methyl amide 17g showed most potent DPP-4 activity with the IC50 value of 1.6nM. Its activity was superior to reference alogliptin. Docking study ideally verified and interpreted the obtained SAR of designed compounds. As a continuation, DPP-8/9 assays revealed the designed compounds exhibited good selectivity over DPP-8 and DPP-9. Subsequent cell-based test indicated compound 17g displayed low toxicity toward the LO2 cell line up to 100muM. In vivo evaluation showed compound 17g robustly improved the glucose tolerance in normal mice. Importantly, 17g exhibited reasonable pharmacokinetic (PK) profiles for oral delivery. Overall, compound 17g has the potential to a safe and efficacious DPP-4 inhibitor for T2DM treatment. Title: Complement Receptor C5aR1 Inhibition Reduces Pyroptosis in hDPP4-Transgenic Mice Infected with MERS-CoV Jiang Y, Li J, Teng Y, Sun H, Tian G, He L, Li P, Chen Y, Guo Y and Sun S <2 more author(s)> Jiang Y, Li J, Teng Y, Sun H, Tian G, He L, Li P, Chen Y, Guo Y, Zhao G, Zhou Y, Sun S (- 2) Ref: Viruses, 11:, 2019 : PubMed ESTHER: Jiang_2019_Viruses_11_ PubMedSearch: Jiang 2019 Viruses 11 PubMedID: 30634407 Abstract Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic virus with a crude mortality rate of ~35%. Previously, we established a human DPP4 transgenic (hDPP4-Tg) mouse model in which we studied complement overactivation-induced immunopathogenesis. Here, to better understand the pathogenesis of MERS-CoV, we studied the role of pyroptosis in THP-1 cells and hDPP4 Tg mice with MERS-CoV infection. We found that MERS-CoV infection induced pyroptosis and over-activation of complement in human macrophages. The hDPP4-Tg mice infected with MERS-CoV overexpressed caspase-1 in the spleen and showed high IL-1beta levels in serum, suggesting that pyroptosis occurred after infection. However, when the C5a-C5aR1 axis was blocked by an anti-C5aR1 antibody (Ab), expression of caspase-1 and IL-1beta fell. These data indicate that MERS-CoV infection induces overactivation of complement, which may contribute to pyroptosis and inflammation. Pyroptosis and inflammation were suppressed by inhibiting C5aR1. These results will further our understanding of the pathogenesis of MERS-CoV infection. Title: Distribution characteristics of sweat gland nerve fibres in normal humans identified by acetylcholinesterase histochemical staining Ling L, Liu Y, Sun Y, Cai Y, Jiang Y, Chen L, He L, Xue J Ref: Clin Neurol Neurosurg, 189:105620, 2019 : PubMed ESTHER: Ling_2019_Clin.Neurol.Neurosurg_189_105620 PubMedSearch: Ling 2019 Clin.Neurol.Neurosurg 189 105620 PubMedID: 31812030 Abstract OBJECTIVE: To quantitatively analyze distribution characteristics of sweat gland nerve fibres (SGNF) in normal Chinese individuals for obtaining a reference for early diagnosis of peripheral neuropathy. PATIENTS AND METHODS: Skin biopsy samples were collected from 192 normal Chinese individuals and divided into six, four and two groups according to anatomic sites, age and gender, respectively. SGNF morphology was observed and SGNF density (SGNFD) was determined. RESULTS: There was a significant difference in SGNFD among different anatomic sites, age and gender. A degressive tendency was observed from proximal to distal anatomic sites. SGNFD was the lowest in subjects in the 21-40-year-old age group, but was the highest in subjects in the >61-year-old age group. Overall, SGNFD fluctuated with age. SGNFD in males was significantly higher than that in females. CONCLUSIONS: Distribution characteristics of SGNF in normal individuals may serve as a reference for early diagnosis of nerve fibre damage. Title: Functional analysis of four upregulated carboxylesterase genes associated with fenpropathrin resistance in Tetranychus cinnabarinus (Boisduval) Wei P, Li J, Liu X, Nan C, Shi L, Zhang Y, Li C, He L Ref: Pest Manag Sci, 75:252, 2019 : PubMed ESTHER: Wei_2019_Pest.Manag.Sci_75_252 PubMedSearch: Wei 2019 Pest.Manag.Sci 75 252 PubMedID: 29877064 Gene_locus related to this paper: tetur-t1k786 Abstract BACKGROUND: Carboxylesterases (CarEs) are important in pesticide resistance. Four overexpressed CarE genes with inducible character were screened out in fenpropathrin-resistant Tetranychus cinnabarinus, but their functional roles remained to be further analyzed by RNAi and protein expression. RESULTS: Feeding a single double-stranded (ds)RNA of each of four genes led to gene-specific downregulation of mRNA, decreased esterase activity and diminished resistance in T. cinnabarinus. More interestingly, feeding four dsRNAs simultaneously led to a more significant decrease in enzymatic activity and fold resistance than feeding a single dsRNA individually, suggesting that these CarE genes were involved in fenpropathrin-resistance and had cooperative roles. The gene CarE6 was regarded as the primary and representative candidate to be functionally expressed, because silencing of CarE6 led to the most significant decrease in resistance level. The activity of CarE6 protein was competitively inhibited by fenpropathrin. It could effectively decompose 41.7 +/- 0.09% of fenpropathrin within 3 h, proving that CarE6 protein was capable of metabolizing fenpropathrin effectively in T. cinnabarinus. CONCLUSION: The results confirm that four CarE genes are cooperatively involved in fenpropathrin resistance and the metabolic enzymes encoded by these overexpressed genes do indeed metabolize acaricide in resistant T. cinnabarinus in the evolution of acaricide resistance. (c) 2018 Society of Chemical Industry. Title: Downregulation of carboxylesterase contributes to cyflumetofen resistance in Tetranychus cinnabarinus (Boisduval) Wei P, Chen M, Nan C, Feng K, Shen G, Cheng J, He L Ref: Pest Manag Sci, 75:2166, 2019 : PubMed ESTHER: Wei_2019_Pest.Manag.Sci_75_2166 PubMedSearch: Wei 2019 Pest.Manag.Sci 75 2166 PubMedID: 30653811 Gene_locus related to this paper: tetur-t1kth5, tetur-t1kx09, tetur-t1ju32, tetur-t1jth6 Inhibitor(s) related to this paper: Tribufos Abstract BACKGROUND: Increased expression or point mutations of carboxyl/cholinesterases (CCEs) have been involved in many cases of insecticide and acaricide resistance. However, it has been only rarely documented that downregulation of CCE genes is associated with resistance, although many insecticides and acaricides need hydrolytic activation in vivo. Previously, expression analysis of a laboratory-selected cyflumetofen-resistant strain of Tetranychus cinnabarinus indicated that resistance was associated with increased expression of a CCE gene of TcCCE04, but also the downregulation of two CCE genes, TcCCE12 and TcCCE23. RESULTS: Synergism experiments revealed the importance of ester hydrolysis in cyflumetofen toxicity, because treatment with S,S,S-tributylphosphorotrithioate (DEF) caused strong inhibition of cyflumetofen hydrolysis, in both the susceptible and resistant strains. Moreover, silencing expression of TcCCE12 and TcCCE23 via RNAi further decreased the susceptibility of mites to cyflumetofen significantly, suggesting that downregulated CCE genes could be involved in cyflumetofen resistance. In addition, it was shown that recombinant TcCCE12 protein could hydrolyze cyflumetofen effectively. CONCLUSION: Decreased esterase activity via downregulation of specific CCE genes most likely contributes to cyflumetofen resistance by decreased activation of cyflumetofen to its active metabolite. Mixtures of cyflumetofen and esterase-inhibition acaricides (e.g. organophosphates or carbamates) should be avoided in field applications. Title: Synthesis and biological evaluation of novel tanshinone IIA derivatives for treating pain Li QN, Huang ZP, Gu QL, Zhi ZE, Yang YH, He L, Chen KL, Wang JX Ref: Chin J Nat Med, 16:113, 2018 : PubMed ESTHER: Li_2018_Chin.J.Nat.Med_16_113 PubMedSearch: Li 2018 Chin.J.Nat.Med 16 113 PubMedID: 29455726 Inhibitor(s) related to this paper: 1-(2-Morpholine-acetamido)-tanshinone-IIA, Tanshinone-IIA Abstract Due to ineffectiveness and side effects of existing analgesics, chronic pain has become one of the most complex and difficult problems in the clinic. Monoacylglycerol lipase (MAGL) is an essential hydrolase in the endocannabinoid system and has been identified as a potential target for the treatment of pain. In the present study, we designed and synthesized twelve tanshinone IIA analogs and screened their activity against MAGL. Selected compounds were tested for analgesic activity in vivo, with the acetic acid writhing test model. Among the test compounds, compound III-3 (IC50 120 nmol.L(-1)) showed significant activity against MAGL and ameliorated the clinical progression in the mouse pain model. Additionally, compound III-3, substitution with N-methyl-2-morpholinoacetamide, demonstrated improved solubility relative to tanshinone IIA. Title: Protein Crystallography and Site-Direct Mutagenesis Analysis of the Poly(ethylene terephthalate) Hydrolase PETase from Ideonella sakaiensis Liu B, He L, Wang L, Li T, Li C, Liu H, Luo Y, Bao R Ref: Chembiochem, 19:1471, 2018 : PubMed ESTHER: Liu_2018_Chembiochem_19_1471 PubMedSearch: Liu 2018 Chembiochem 19 1471 PubMedID: 29603535 Gene_locus related to this paper: idesa-peth Abstract Unlike traditional recycling strategies, biodegradation is a sustainable solution for disposing of poly(ethylene terephthalate) (PET) waste. PETase, a newly identified enzyme from Ideonella sakaiensis, has high efficiency and specificity towards PET and is, thus, a prominent candidate for PET degradation. On the basis of biochemical analysis, we propose that a wide substrate-binding pocket is critical for its excellent ability to hydrolyze crystallized PET. Structure-guided site-directed mutagenesis revealed an improvement in PETase catalytic efficiency, providing valuable insight into how the molecular engineering of PETase can optimize its application in biocatalysis. Title: Intranasal delivery of a novel acetylcholinesterase inhibitor HLS-3 for treatment of Alzheimer's disease Qian S, He L, Wang Q, Wong YC, Mak M, Ho CY, Han Y, Zuo Z Ref: Life Sciences, 207:428, 2018 : PubMed ESTHER: Qian_2018_Life.Sci_207_428 PubMedSearch: Qian 2018 Life.Sci 207 428 PubMedID: 29966606 Abstract AIM: The present study aims to investigate the pharmacokinetics and pharmacodynamics of HLS-3, a tacrine dimer with high anti-acetylcholinesterase activity for the treatment of Alzheimer's disease. MAIN METHODS: In vitro Calu-3 and Caco-2 cell monolayer transport and liver microsomal incubation studies of HLS-3 were carried out to evaluate its nasal epithelium and intestinal membrane permeability, transporters involved in absorption and hepatic metabolism. In vivo pharmacokinetics of HLS-3 followed by central and peripheral cholinergic mediated responses and ex vivo AChE activities in rats via oral and intranasal administrations were further investigated and compared. KEY FINDINGS: Our in vitro studies suggested that HLS-3 is the substrate of both P-gp and MRPs with no significant hepatic oxidation and glucuronidation metabolism. Oral administration only delivered trace amount of HLS-3 in systemic circulation with a high faecal recovery of 70.7%, whereas intranasal administration demonstrated an absolute bioavailability of 28.9% with urinary and faecal recoveries of 1.5% and 34.0%, respectively. In comparison to oral administration of HLS-3, intranasally delivered HLS-3 exhibited significant higher central cholinergic mediated responses without obvious peripheral side effect. SIGNIFICANCE: Intranasal delivery of HLS-3 with better pharmacokinetics and pharmacodynamics performances provides a promising approach for treatment of Alzheimer's disease. Title: Eucalyptusdimers A-C, Dimeric Phloroglucinol-Phellandrene Meroterpenoids from Eucalyptus robusta Qin XJ, Feng MY, Liu H, Ni W, Rauwolf T, Porco JA, Jr., Yan H, He L, Liu HY Ref: Org Lett, 20:5066, 2018 : PubMed ESTHER: Qin_2018_Org.Lett_20_5066 PubMedSearch: Qin 2018 Org.Lett 20 5066 PubMedID: 30088934 Abstract Eucalyptusdimers A-C, three dimeric phellandrene-derived meroterpenoids featuring an unprecedented, fused skeleton between two phellandrene and two acylphloroglucinol subunits, along with one biogenetically related intermediate, (+/-)-eucalyprobusone A, were isolated from the fruits of Eucalyptus robusta. Their structures and absolute configurations were elucidated using spectroscopic data, X-ray crystallography, and electronic circular dichroism analysis. The isolated meroterpenoids were evaluated for their anti-inflammatory, acetylcholinesterase inhibitory, and protein tyrosine phosphatase 1B inhibitory effects. Title: Chronic brain toxicity response of juvenile Chinese rare minnows (Gobiocypris rarus) to the neonicotinoid insecticides imidacloprid and nitenpyram Tian X, Yang W, Wang D, Zhao Y, Yao R, Ma L, Ge C, Li X, Huang Z and Lin A <2 more author(s)> Tian X, Yang W, Wang D, Zhao Y, Yao R, Ma L, Ge C, Li X, Huang Z, He L, Jiao W, Lin A (- 2) Ref: Chemosphere, 210:1006, 2018 : PubMed ESTHER: Tian_2018_Chemosphere_210_1006 PubMedSearch: Tian 2018 Chemosphere 210 1006 PubMedID: 30208524 Abstract Imidacloprid and nitenpyram are widely used neonicotinoid pesticides worldwide and were observed to adversely affect non-target aquatic organisms. In this study, the toxic effect of imidacloprid and nitenpyram on the brain of juvenile Chinese rare minnows (Gobiocypris rarus) was investigated by determining the oxidative stress, 8-hydroxy-2-deoxyguanosine (8-OHdG) content and acetylcholinesterase (AChE) activity. The superoxide dismutase (SOD) activities did not significantly change after long-term exposure to imidacloprid and nitenpyram. A noticeable increase of catalase (CAT) activities was observed on the brain tissues under 0.1mg/L imidacloprid and under all nitenpyram treatments (p<0.05). The malondialdehyde (MDA) content increased markedly under 2.0mg/L imidacloprid and 0.1mg/L nitenpyram treatments (p<0.05). The glutathione (GSH) content in the brain significantly increased under 0.5 and 2.0mg/L imidacloprid (p<0.05). A significant decrease was observed in the mRNA levels of Cu/Zn-sod under 2.0mg/L imidacloprid and those of cat under 0.1 and 0.5mg/L nitenpyram (p<0.05). The mRNA levels of gpx1 clearly decreased under 2.0mg/L imidacloprid and under 0.1mg/L nitenpyram (p<0.05). The treatments of 0.1 and 0.5mg/L nitenpyram decreased cat expression levels markedly (p<0.05). 2.0mg/L imidacloprid raised the 8-OHdG content. The AChE activities increased markedly under 0.5 and 2.0mg/L imidacloprid while clearly decreasing under 2.0mg/L nitenpyram (p<0.05). Therefore, our results indicate that imidacloprid and nitenpyram might cause adverse effects on juvenile Chinese rare minnows brain. Notably, imidacloprid had greater impacts on juvenile rare minnows compared to nitenpyram. Title: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A and Loos RJF <390 more author(s)> Turcot V, Lu Y, Highland HM, Schurmann C, Justice AE, Fine RS, Bradfield JP, Esko T, Giri A, Graff M, Guo X, Hendricks AE, Karaderi T, Lempradl A, Locke AE, Mahajan A, Marouli E, Sivapalaratnam S, Young KL, Alfred T, Feitosa MF, Masca NGD, Manning AK, Medina-Gomez C, Mudgal P, Ng MCY, Reiner AP, Vedantam S, Willems SM, Winkler TW, Abecasis G, Aben KK, Alam DS, Alharthi SE, Allison M, Amouyel P, Asselbergs FW, Auer PL, Balkau B, Bang LE, Barroso I, Bastarache L, Benn M, Bergmann S, Bielak LF, Bluher M, Boehnke M, Boeing H, Boerwinkle E, Boger CA, Bork-Jensen J, Bots ML, Bottinger EP, Bowden DW, Brandslund I, Breen G, Brilliant MH, Broer L, Brumat M, Burt AA, Butterworth AS, Campbell PT, Cappellani S, Carey DJ, Catamo E, Caulfield MJ, Chambers JC, Chasman DI, Chen YI, Chowdhury R, Christensen C, Chu AY, Cocca M, Collins FS, Cook JP, Corley J, Corominas Galbany J, Cox AJ, Crosslin DS, Cuellar-Partida G, D'Eustacchio A, Danesh J, Davies G, Bakker PIW, Groot MCH, Mutsert R, Deary IJ, Dedoussis G, Demerath EW, Heijer M, Hollander AI, Ruijter HM, Dennis JG, Denny JC, Angelantonio E, Drenos F, Du M, Dube MP, Dunning AM, Easton DF, Edwards TL, Ellinghaus D, Ellinor PT, Elliott P, Evangelou E, Farmaki AE, Farooqi IS, Faul JD, Fauser S, Feng S, Ferrannini E, Ferrieres J, Florez JC, Ford I, Fornage M, Franco OH, Franke A, Franks PW, Friedrich N, Frikke-Schmidt R, Galesloot TE, Gan W, Gandin I, Gasparini P, Gibson J, Giedraitis V, Gjesing AP, Gordon-Larsen P, Gorski M, Grabe HJ, Grant SFA, Grarup N, Griffiths HL, Grove ML, Gudnason V, Gustafsson S, Haessler J, Hakonarson H, Hammerschlag AR, Hansen T, Harris KM, Harris TB, Hattersley AT, Have CT, Hayward C, He L, Heard-Costa NL, Heath AC, Heid IM, Helgeland O, Hernesniemi J, Hewitt AW, Holmen OL, Hovingh GK, Howson JMM, Hu Y, Huang PL, Huffman JE, Ikram MA, Ingelsson E, Jackson AU, Jansson JH, Jarvik GP, Jensen GB, Jia Y, Johansson S, Jorgensen ME, Jorgensen T, Jukema JW, Kahali B, Kahn RS, Kahonen M, Kamstrup PR, Kanoni S, Kaprio J, Karaleftheri M, Kardia SLR, Karpe F, Kathiresan S, Kee F, Kiemeney LA, Kim E, Kitajima H, Komulainen P, Kooner JS, Kooperberg C, Korhonen T, Kovacs P, Kuivaniemi H, Kutalik Z, Kuulasmaa K, Kuusisto J, Laakso M, Lakka TA, Lamparter D, Lange EM, Lange LA, Langenberg C, Larson EB, Lee NR, Lehtimaki T, Lewis CE, Li H, Li J, Li-Gao R, Lin H, Lin KH, Lin LA, Lin X, Lind L, Lindstrom J, Linneberg A, Liu CT, Liu DJ, Liu Y, Lo KS, Lophatananon A, Lotery AJ, Loukola A, Luan J, Lubitz SA, Lyytikainen LP, Mannisto S, Marenne G, Mazul AL, McCarthy MI, McKean-Cowdin R, Medland SE, Meidtner K, Milani L, Mistry V, Mitchell P, Mohlke KL, Moilanen L, Moitry M, Montgomery GW, Mook-Kanamori DO, Moore C, Mori TA, Morris AD, Morris AP, Muller-Nurasyid M, Munroe PB, Nalls MA, Narisu N, Nelson CP, Neville M, Nielsen SF, Nikus K, Njolstad PR, Nordestgaard BG, Nyholt DR, O'Connel JR, O'Donoghue ML, Olde Loohuis LM, Ophoff RA, Owen KR, Packard CJ, Padmanabhan S, Palmer CNA, Palmer ND, Pasterkamp G, Patel AP, Pattie A, Pedersen O, Peissig PL, Peloso GM, Pennell CE, Perola M, Perry JA, Perry JRB, Pers TH, Person TN, Peters A, Petersen ERB, Peyser PA, Pirie A, Polasek O, Polderman TJ, Puolijoki H, Raitakari OT, Rasheed A, Rauramaa R, Reilly DF, Renstrom F, Rheinberger M, Ridker PM, Rioux JD, Rivas MA, Roberts DJ, Robertson NR, Robino A, Rolandsson O, Rudan I, Ruth KS, Saleheen D, Salomaa V, Samani NJ, Sapkota Y, Sattar N, Schoen RE, Schreiner PJ, Schulze MB, Scott RA, Segura-Lepe MP, Shah SH, Sheu WH, Sim X, Slater AJ, Small KS, Smith AV, Southam L, Spector TD, Speliotes EK, Starr JM, Stefansson K, Steinthorsdottir V, Stirrups KE, Strauch K, Stringham HM, Stumvoll M, Sun L, Surendran P, Swift AJ, Tada H, Tansey KE, Tardif JC, Taylor KD, Teumer A, Thompson DJ, Thorleifsson G, Thorsteinsdottir U, Thuesen BH, Tonjes A, Tromp G, Trompet S, Tsafantakis E, Tuomilehto J, Tybjaerg-Hansen A, Tyrer JP, Uher R, Uitterlinden AG, Uusitupa M, Laan SW, Duijn CM, Leeuwen N, van Setten J, Vanhala M, Varbo A, Varga TV, Varma R, Velez Edwards DR, Vermeulen SH, Veronesi G, Vestergaard H, Vitart V, Vogt TF, Volker U, Vuckovic D, Wagenknecht LE, Walker M, Wallentin L, Wang F, Wang CA, Wang S, Wang Y, Ware EB, Wareham NJ, Warren HR, Waterworth DM, Wessel J, White HD, Willer CJ, Wilson JG, Witte DR, Wood AR, Wu Y, Yaghootkar H, Yao J, Yao P, Yerges-Armstrong LM, Young R, Zeggini E, Zhan X, Zhang W, Zhao JH, Zhao W, Zhou W, Zondervan KT, Rotter JI, Pospisilik JA, Rivadeneira F, Borecki IB, Deloukas P, Frayling TM, Lettre G, North KE, Lindgren CM, Hirschhorn JN, Loos RJF (- 390) Ref: Nat Genet, 50:26, 2018 : PubMed ESTHER: Turcot_2018_Nat.Genet_50_26 PubMedSearch: Turcot 2018 Nat.Genet 50 26 PubMedID: 29273807 Abstract Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity. Title: Occurrence, distribution and ecological risks of organophosphate esters and synthetic musks in sediments from the Hun River Zeng X, Hu Q, He L, Liu Z, Gao S, Yu Z Ref: Ecotoxicology & Environmental Safety, 160:178, 2018 : PubMed ESTHER: Zeng_2018_Ecotoxicol.Environ.Saf_160_178 PubMedSearch: Zeng 2018 Ecotoxicol.Environ.Saf 160 178 PubMedID: 29804014 Abstract The Hun River is an important main tributary of the Liao River system. It is located in northeast China, and provides water resources for agriculture and industry. A man made reservoir (Dahuofang Reservoir, DHF) has been constructed mid-stream in the Hun River, supplying drinking water to surrounding cities. Pollution from organic contaminants is of great concern. In the present study, 40 sediment samples were collected and analyzed for the occurrence and distribution of two groups of emerging organic pollutants; namely, organophosphate esters (OPs) and synthetic musks (SMs). In all samples taken from upstream of the Hun River (UHR), downstream of the Hun River (DHR), and from DHF, the following concentrations were recorded: 0.141-4.39, 1.21-245, and 0.117-0.726microg/kg galaxolide (HHCB), and 0.098-3.82, 2.79-213, 0.430-0.956microg/kg tonalide (AHTN), respectively. For OPs, seven target analytes were detected in most of the sediment samples, with chlorinated OPs Tris-(2-chloroethyl) phosphate and Tris(2-chloro-isopropyl) phosphate being the dominant components, at levels varied in the range of LOD-0.810, ND-49.6, and 0.532-3.18microg/kg, and LOD-0.786, ND-60.1, and 0.352-1.32microg/kg from UHR, DHR and DHF, respectively. The elevated levels of these target compounds were detected in DHR, including its two main tributaries, Xi River and Pu River, which drain through cities with industrial development and dense populations. Our results indicate that domestic and industrial wastewater contributed to OPs and SMs sediment pollution, posing low to medium ecological risks to sediment dwelling organisms. Title: Design, synthesis, and evaluation of multitarget-directed ligands against Alzheimer's disease based on the fusion of donepezil and curcumin Yan J, Hu J, Liu A, He L, Li X, Wei H Ref: Bioorganic & Medicinal Chemistry, 25:2946, 2017 : PubMed ESTHER: Yan_2017_Bioorg.Med.Chem_25_2946 PubMedSearch: Yan 2017 Bioorg.Med.Chem 25 2946 PubMedID: 28454848 Abstract By fusing donepezil and curcumin, a novel series of compounds were obtained as multitarget-directed ligands against Alzheimer's disease. Among them, compound 11b displayed potent acetylcholinesterase (AChE) inhibition (IC50=187nM) and the highest BuChE/AChE selectivity (66.3). Compound 11b also inhibited 45.3% Abeta1-42 self-aggregation at 20muM and displayed remarkable antioxidant effects. The metal-chelating property of compound 11b was elucidated by determining the 1:1 stoichiometry for the 11b-Cu(II) complex. The excellent blood-brain barrier permeability of 11b also indicated the potential for the compound to penetrate the central nervous system. Title: Functional Analysis of Esterase TCE2 Gene from Tetranychus cinnabarinus (Boisduval) involved in Acaricide Resistance Shi L, Wei P, Wang X, Shen G, Zhang J, Xiao W, Xu Z, Xu Q, He L Ref: Sci Rep, 6:18646, 2016 : PubMed ESTHER: Shi_2016_Sci.Rep_6_18646 PubMedSearch: Shi 2016 Sci.Rep 6 18646 PubMedID: 26725309 Gene_locus related to this paper: 9acar-q5s1p7, tetur-t1kx09 Abstract The carmine spider mite, Tetranychus cinnabarinus is an important pest of crops and vegetables worldwide, and it has the ability to develop resistance against acaricides rapidly. Our previous study identified an esterase gene (designated TCE2) over-expressed in resistant mites. To investigate this gene's function in resistance, the expression levels of TCE2 in susceptible, abamectin-, fenpropathrin-, and cyflumetofen-resistant strains were knocked down (65.02%, 63.14%, 57.82%, and 63.99%, respectively) via RNA interference. The bioassay data showed that the resistant levels to three acaricides were significantly decreased after the down-regulation of TCE2, indicating a correlation between the expression of TCE2 and the acaricide-resistance in T. cinnabarinus. TCE2 gene was then re-engineered for heterologous expression in Escherichia coli. The recombinant TCE2 exhibited alpha-naphthyl acetate activity (483.3 +/- 71.8 nmol/mg pro. min(-1)), and the activity of this enzyme could be inhibited by abamectin, fenpropathrin, and cyflumetofen, respectively. HPLC and GC results showed that 10 mug of the recombinant TCE2 could effectively decompose 21.23% fenpropathrin and 49.70% cyflumetofen within 2 hours. This is the first report of a successful heterologous expression of an esterase gene from mites. This study provides direct evidence that TCE2 is a functional gene involved in acaricide resistance in T. cinnabarinus. Title: Characteristics of carboxylesterase genes and their expression-level between acaricide-susceptible and resistant Tetranychus cinnabarinus (Boisduval) Wei P, Shi L, Shen G, Xu Z, Liu J, Pan Y, He L Ref: Pestic Biochem Physiol, 131:87, 2016 : PubMed ESTHER: Wei_2016_Pestic.Biochem.Physiol_131_87 PubMedSearch: Wei 2016 Pestic.Biochem.Physiol 131 87 PubMedID: 27265830 Gene_locus related to this paper: tetur-t1jth5, tetur-t1kth5, tetur-t1kwe1, tetur-t1kx09, tetur-t1kxr8, tetur-t1l430, tetur-t1kgp1, tetur-t1l0m8, tetur-t1knw0, tetur-t1kgp7, tetur-t1l013, tetur-t1jz51, tetur-t1kg31, tetur-t1knv9, tetur-t1jrz3, tetur-t1k786, tetur-t1jth6, tetur-t1jtg9, tetur-t1kpg7, tetur-t1jvb8, tetur-t1kvj7 Abstract Carboxylesterases (CarEs) play important roles in metabolism and detoxification of dietary and environmental xenobiotics in insects and mites. On the basis of the Tetranychuscinnabarinus transcriptome dataset, 23 CarE genes (6 genes are full sequence and 17 genes are partial sequence) were identified. Synergist bioassay showed that CarEs were involved in acaricide detoxification and resistance in fenpropathrin- (FeR) and cyflumetofen-resistant (CyR) strains. In order to further reveal the relationship between CarE gene's expression and acaricide-resistance in T. cinnabarinus, we profiled their expression in susceptible (SS) and resistant strains (FeR, and CyR). There were 8 and 4 over-expressed carboxylesterase genes in FeR and CyR, respectively, from which the over-expressions were detected at mRNA level, but not DNA level. Pesticide induction experiment elucidated that 4 of 8 and 2 of 4 up-regulated genes were inducible with significance in FeR and CyR strains, respectively, but they could not be induced in SS strain, which indicated that these genes became more enhanced and effective to withstand the pesticides' stress in resistant T. cinnabarinus. Most expression-changed and all inducible genes possess the Abhydrolase_3 motif, which is a catalytic domain for hydrolyzing. As a whole, these findings in current study provide clues for further elucidating the function and regulation mechanism of these carboxylesterase genes in T. cinnabarinus' resistance formation. Title: Identification of Differentially Expressed microRNAs between the Fenpropathrin Resistant and Susceptible Strains in Tetranychus cinnabarinus Zhang Y, Xu Z, Wu Q, Peng M, Liu Y, Liu X, Shi L, Shen G, Pan Y, He L Ref: PLoS ONE, 11:e0152924, 2016 : PubMed ESTHER: Zhang_2016_PLoS.One_11_e0152924 PubMedSearch: Zhang 2016 PLoS.One 11 e0152924 PubMedID: 27050424 Abstract The carmine spider mite (Tetranychus cinnabarinus) is one of the most serious pests on crops and its control mainly depends on chemical acaricides. The excessive and improper acaricides use has resulted in mite resistance to many acaricides, including fenpropathrin. Previous studies have indicated fenpropathrin resistance is a complex development process involving many genes, but information on resistance mechanism of post-transcription regulation is rare. Using Illumina sequencing, several categories of sRNAs were identified from susceptible (TS) and fenpropathrin-resistant strains (TR) of T. cinnabarinus, including 75 known microRNAs (miRNAs) and 64 novel miRNAs, whose target genes containing 78592 miRNA-target pairs were predicted by 6 algorithms. Also, 12 significantly differently expressed miRNAs were identified between the TS and TR libraries and RT-qPCR validation also performed a well consistency with sequencing. The targets of significantly differentially expressed miRNAs included 7 glutathione S-transferase, 7 cytochrome P450 and 16 carboxyl/choline esterase genes, their function in fenpropathrin resistance were further analyzed. The present study provides the firstly large-scale characterization of miRNAs in T. cinnabarinus and the comparison between TS and TR strains gives a clue on how miRNA involves in fenpropathrin resistance. Title: No Association Between CEL-HYB Hybrid Allele and Chronic Pancreatitis in Asian Populations Zou WB, Boulling A, Masamune A, Issarapu P, Masson E, Wu H, Sun XT, Hu LH, Zhou DZ and Liao Z <16 more author(s)> Zou WB, Boulling A, Masamune A, Issarapu P, Masson E, Wu H, Sun XT, Hu LH, Zhou DZ, He L, Fichou Y, Nakano E, Hamada S, Kakuta Y, Kume K, Isayama H, Paliwal S, Mani KR, Bhaskar S, Cooper DN, Ferec C, Shimosegawa T, Chandak GR, Chen JM, Li ZS, Liao Z (- 16) Ref: Gastroenterology, 150:1558, 2016 : PubMed ESTHER: Zou_2016_Gastroenterology_150_1558 PubMedSearch: Zou 2016 Gastroenterology 150 1558 PubMedID: 26946345 Abstract A hybrid allele between the carboxyl ester lipase gene (CEL) and its pseudogene, CELP (called CEL-HYB), generated by nonallelic homologous recombination between CEL intron 10 and CELP intron 10', was found to increase susceptibility to chronic pancreatitis in a case-control study of patients of European ancestry. We attempted to replicate this finding in 3 independent cohorts from China, Japan, and India, but failed to detect the CEL-HYB allele in any of these populations. The CEL-HYB allele might therefore be an ethnic-specific risk factor for chronic pancreatitis. An alternative hybrid allele (CEL-HYB2) was identified in all 3 Asian populations (1.7% combined carrier frequency), but was not associated with chronic pancreatitis. Title: The Effect of Rifampin on the Pharmacokinetics of Edoxaban in Healthy Adults Mendell J, Chen S, He L, Desai M, Parasramupria DA Ref: Clin Drug Investig, 35:447, 2015 : PubMed ESTHER: Mendell_2015_Clin.Drug.Investig_35_447 PubMedSearch: Mendell 2015 Clin.Drug.Investig 35 447 PubMedID: 26068927 Abstract BACKGROUND AND OBJECTIVE: The oral direct factor Xa inhibitor edoxaban is a P-glycoprotein (P-gp) substrate metabolized via carboxylesterase-1 and cytochrome P450 (CYP) 3A4/5. The effect of rifampin-induced induction of P-gp and CYP3A4/5 on transport and metabolism of edoxaban through the CYP3A4/5 pathway was investigated in a single-dose edoxaban study. Title: Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6 Qiu S, Feng Y, LeSage G, Zhang Y, Stuart C, He L, Li Y, Caudle Y, Peng Y, Yin D Ref: J Immunol, 194:1021, 2015 : PubMed ESTHER: Qiu_2015_J.Immunol_194_1021 PubMedSearch: Qiu 2015 J.Immunol 194 1021 PubMedID: 25539811 Abstract Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects including immunosuppression. However, the mechanisms are unclear. TLRs and acetylcholine are widely expressed in the immune and nervous systems, and play critical roles in immune responses. In this article, we show that morphine suppresses the innate immunity in microglia and bone marrow-derived macrophages through differential regulation of TLRs and acetylcholinesterase. Either morphine or inhibition of acetylcholine significantly promotes upregulation of microRNA-124 (miR-124) in microglia, bone marrow-derived macrophages, and the mouse brain, where miR-124 mediates morphine inhibition of the innate immunity by directly targeting a subunit of NF-kappaB p65 and TNFR-associated factor 6 (TRAF6). Furthermore, transcription factors AP-1 and CREB inhibited miR-124, whereas p65 bound directly to promoters of miR-124, thereby enhancing miR-124 transcription. Moreover, acute morphine treatment transiently upregulated the expression of p65 and phospho-p65 in both nucleus and cytoplasm priming the expression of miR-124, whereas long exposure of morphine maintained miR-124 expression, which inhibited p65- and TRAF6-dependent TLR signaling. These data suggest that modulation of miRs is capable of preventing opioid-induced damage to microglia. Title: Synthesis, biological activity, and biopharmaceutical characterization of tacrine dimers as acetylcholinesterase inhibitors Qian S, He L, Mak M, Han Y, Ho CY, Zuo Z Ref: Int J Pharm, 477:442, 2014 : PubMed ESTHER: Qian_2014_Int.J.Pharm_477_442 PubMedSearch: Qian 2014 Int.J.Pharm 477 442 PubMedID: 25445524 Inhibitor(s) related to this paper: Bis7-tacrine Abstract Tacrine (THA), as the first approved acetylcholinesterase (AChE) inhibitors for the treatment of Alzheimer's disease (AD), has been extensively investigated in last seven decades. After dimerization of THA via a 7-carbon alkyl spacer, bis(7)-tacrine (B7T) showed much potent anti-AChE activity than THA. We here report synthesis, biological evaluation and biopharmaceutical characterization of six THA dimers referable to B7T. According to IC50 values, the in vitro anti-AChE activities of THA dimers were up to 300-fold more potent and 200-fold more selective than that of THA. In addition, the anti-AChE activities of THA dimers were found to be associated with the type and length of the linkage. All studied THA dimers showed much lower cytotoxicity than B7T, but like B7T, they demonstrated much lower absorptive permeabilities than that of THA on Caco-2 monolayer model. In addition, all THA dimers demonstrated significant efflux transport (efflux ratio >4), indicating that the limited permeability could be associated with the efflux transport during absorption process. Moreover, the dimer with higher Log P value was accompanied with higher permeability but lower aqueous solubility. A balanced consideration of activity, solubility, cytotoxicity and permeability should be conducted in selection of the potential candidates for further in vivo investigation. Title: Resistance selection and biochemical mechanism of resistance against cyflumetofen in Tetranychus cinnabarinus (Boisduval) Wang Y, Zhao S, Shi L, Xu Z, He L Ref: Pestic Biochem Physiol, 111:24, 2014 : PubMed ESTHER: Wang_2014_Pestic.Biochem.Physiol_111_24 PubMedSearch: Wang 2014 Pestic.Biochem.Physiol 111 24 PubMedID: 24861930 Abstract The carmine spider mite, Tetranychus cinnabarinus is an important crop and vegetable plants pest mite. As a novel acaricide, cyflumetofen is effective against Tetranychus and Panonychus mites, but its risk and biochemical mechanism of resistance in mites is not clear. In this study, the resistance against cyflumetofen was selected and its biochemical mechanisms were studied in T. cinnabarinus. After selection the susceptibility and resistance against cyflumetofen in T. cinnabarinus, the final resistance ratio reached 21.33 at LC50 (CyR-43/CyS). All the collected field populations showed low resistance against cyflumetofen, although it had never been used in China. The activity of detoxifying enzymes CarE, MFO and GSTs were significantly increased in the final selected resistance strain (CyR-43), especially that for GSTs increased more than 7-folds after selection. The resistance against cyflumetofen developed slowly when selected from the susceptible strain in laboratory, but the resistant genes already existed in field populations, and the GSTs was the most important detoxifying enzyme conferring resistance against cyflumetofen in T. cinnabarinus. These results would provide the valuable information for designing appropriate strategies for the practical application of cyflumetofen in the field and delaying resistance development. 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: The MDGA1 gene confers risk to schizophrenia and bipolar disorder Li J, Liu J, Feng G, Li T, Zhao Q, Li Y, Hu Z, Zheng L, Zeng Z and Shi Y <2 more author(s)> Li J, Liu J, Feng G, Li T, Zhao Q, Li Y, Hu Z, Zheng L, Zeng Z, He L, Wang T, Shi Y (- 2) Ref: Schizophr Res, 125:194, 2011 : PubMed ESTHER: Li_2011_Schizophr.Res_125_194 PubMedSearch: Li 2011 Schizophr.Res 125 194 PubMedID: 21146959 Abstract OBJECTIVE: The structural, cytoarchitectural and functional brain abnormalities reported in patients with mental disorders may be due to aberrant neuronal migration influenced by cell adhesion molecules. MDGA1, like Ig-containing cell adhesion molecules, has several cell adhesion molecule-like domains. Moreover, Kahler et al. (2008) reported that the MDGA1 gene was a schizophrenia susceptibility gene in Scandinavian population. To further investigate whether the MDGA1 gene is a shared risk factor of schizophrenia, bipolar disorder and major depressive disorder in Chinese Han population, we conducted this study. Title: Facile, high efficiency immobilization of lipase enzyme on magnetic iron oxide nanoparticles via a biomimetic coating Ren Y, Rivera JG, He L, Kulkarni H, Lee DK, Messersmith PB Ref: BMC Biotechnol, 11:63, 2011 : PubMed ESTHER: Ren_2011_BMC.Biotechnol_11_63 PubMedSearch: Ren 2011 BMC.Biotechnol 11 63 PubMedID: 21649934 Abstract BACKGROUND: Immobilization of lipase on appropriate solid supports is one way to improve their stability and activity, and can be reused for large scale applications. A sample, cost- effective and high loading capacity method is still challenging. RESULTS: A facile method of lipase immobilization was developed in this study, by the use of polydopamine coated magnetic nanoparticles (PD-MNPs). Under optimal conditions, 73.9% of the available lipase was immobilized on PD-MNPs, yielding a lipase loading capacity as high as 429 mg/g. Enzyme assays revealed that lipase immobilized on PD-MNPs displayed enhanced pH and thermal stability compared to free lipase. Furthermore, lipase immobilized on PD-MNPs was easily isolated from the reaction medium by magnetic separation and retained more than 70% of initial activity after 21 repeated cycles of enzyme reaction followed by magnetic separation. CONCLUSIONS: Immobilization of enzyme onto magnetic iron oxide nanoparticles via poly-dopamine film is economical, facile and efficient. Title: Effects of subchronic exposure to benzo[a]pyrene (B[a]P) on learning and memory, and neurotransmitters in male Sprague-Dawley rat Xia Y, Cheng S, He J, Liu X, Tang Y, Yuan H, He L, Lu T, Tu B, Wang Y Ref: Neurotoxicology, 32:188, 2011 : PubMed ESTHER: Xia_2011_Neurotoxicol_32_188 PubMedSearch: Xia 2011 Neurotoxicol 32 188 PubMedID: 21216261 Abstract The harmful effects of the environmental carcinogen, benzo[a]pyrene (B[a]P), on mammalian neurodevelopment and behavior as yet remain unclear. Several studies have suggested that B[a]P impairs learning and memory. In the present investigation, we investigated the effects of subchronic exposure to B[a]P on rats. Male rats received daily injection of B[a]P (0, 1.0, 2.5, and 6.25 mg/kg, i.p.) or vehicle for 13 weeks. Employing the Morris water maze (MWM) test, we observed that rats exposed to either 2.5 mg/kg or 6.25 mg/kg B[a]P had modified behavior compared to controls as indicated by the increased mean latencies, the decreased number of crossing platform and the decreased swimming time in the target area. B[a]P treatment decreased the levels of malondialdehyde (MDA), nitric oxide (NO), nitric oxide synthase (NOS), superoxide dismutase (SOD), acetylcholine (ACh), choline acetyltransferase (ChAT), and increased the activity of acetylcholinesterase (AChE). Endogenous monoamine levels, norepinephrine (NE), adrenaline (A), dopamine (DA) and 5-hydroxytryptamine (5-HT) and their selected metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in hippocampus were measured using high performance liquid chromatography (HPLC). B[a]P at both doses, 2.5 and 6.25 mg/kg, increased NE, DA, DOPAC and 5-HT content in the hippocampus. Our results suggested a close link between the modified levels of neurotransmitters in the hippocampus and the impaired behavioral performance, indicating that B[a]P is a potential neurotoxic pollutant. Title: The sequence and de novo assembly of the giant panda genome Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B and Yang H <103 more author(s)> Li R, Fan W, Tian G, Zhu H, He L, Cai J, Huang Q, Cai Q, Li B, Bai Y, Zhang Z, Zhang Y, Wang W, Li J, Wei F, Li H, Jian M, Nielsen R, Li D, Gu W, Yang Z, Xuan Z, Ryder OA, Leung FC, Zhou Y, Cao J, Sun X, Fu Y, Fang X, Guo X, Wang B, Hou R, Shen F, Mu B, Ni P, Lin R, Qian W, Wang G, Yu C, Nie W, Wang J, Wu Z, Liang H, Min J, Wu Q, Cheng S, Ruan J, Wang M, Shi Z, Wen M, Liu B, Ren X, Zheng H, Dong D, Cook K, Shan G, Zhang H, Kosiol C, Xie X, Lu Z, Li Y, Steiner CC, Lam TT, Lin S, Zhang Q, Li G, Tian J, Gong T, Liu H, Zhang D, Fang L, Ye C, Zhang J, Hu W, Xu A, Ren Y, Zhang G, Bruford MW, Li Q, Ma L, Guo Y, An N, Hu Y, Zheng Y, Shi Y, Li Z, Liu Q, Chen Y, Zhao J, Qu N, Zhao S, Tian F, Wang X, Wang H, Xu L, Liu X, Vinar T, Wang Y, Lam TW, Yiu SM, Liu S, Huang Y, Yang G, Jiang Z, Qin N, Li L, Bolund L, Kristiansen K, Wong GK, Olson M, Zhang X, Li S, Yang H (- 103) Ref: Nature, 463:311, 2010 : PubMed ESTHER: Li_2010_Nature_463_311 PubMedSearch: Li 2010 Nature 463 311 PubMedID: 20010809 Gene_locus related to this paper: ailme-ABH15, ailme-ACHE, ailme-BCHE, ailme-d2gtv3, ailme-d2gty9, ailme-d2gu87, ailme-d2gu97, ailme-d2gve7, ailme-d2gwu1, ailme-d2gx08, ailme-d2gyt0, ailme-d2gz36, ailme-d2gz37, ailme-d2gz38, ailme-d2gz39, ailme-d2gz40, ailme-d2h5r9, ailme-d2h7b7, ailme-d2h9c9, ailme-d2h794, ailme-d2hau7, ailme-d2hau8, ailme-d2hcd9, ailme-d2hdi6, ailme-d2heu6, ailme-d2hga4, ailme-d2hqw5, ailme-d2hs98, ailme-d2hsx4, ailme-d2hti6, ailme-d2htv3, ailme-d2htz6, ailme-d2huc7, ailme-d2hwj8, ailme-d2hwy7, ailme-d2hxm1, ailme-d2hyc8, ailme-d2hyv2, ailme-d2hz11, ailme-d2hza3, ailme-d2hzr4, ailme-d2i1l4, ailme-d2i2g8, ailme-g1l7m3, ailme-g1lu36, ailme-g1m769, ailme-g1mc29, ailme-g1mdj8, ailme-g1mdr5, ailme-g1mfp4, ailme-g1mfx5, ailme-g1lj41, ailme-g1lm28, ailme-g1l3u1, ailme-g1l7l1, ailme-g1m5i3, ailme-g1l2f6, ailme-g1lji5, ailme-g1lqk3, ailme-g1l8s9, ailme-d2h717, ailme-d2h718, ailme-d2h719, ailme-d2h720, ailme-g1m5v0, ailme-g1m5y7, ailme-g1lkt7, ailme-g1l2a1, ailme-g1lsc8, ailme-g1lrp4, ailme-d2gv02, ailme-g1mik5, ailme-g1ljr1, ailme-g1lxw7, ailme-d2h8b5, ailme-d2h2r2, ailme-d2h9w7, ailme-g1meh3, ailme-g1m719 Abstract Using next-generation sequencing technology alone, we have successfully generated and assembled a draft sequence of the giant panda genome. The assembled contigs (2.25 gigabases (Gb)) cover approximately 94% of the whole genome, and the remaining gaps (0.05 Gb) seem to contain carnivore-specific repeats and tandem repeats. Comparisons with the dog and human showed that the panda genome has a lower divergence rate. The assessment of panda genes potentially underlying some of its unique traits indicated that its bamboo diet might be more dependent on its gut microbiome than its own genetic composition. We also identified more than 2.7 million heterozygous single nucleotide polymorphisms in the diploid genome. Our data and analyses provide a foundation for promoting mammalian genetic research, and demonstrate the feasibility for using next-generation sequencing technologies for accurate, cost-effective and rapid de novo assembly of large eukaryotic genomes. Title: Identifying unexpected therapeutic targets via chemical-protein interactome Yang L, Chen J, Shi L, Hudock MP, Wang K, He L Ref: PLoS ONE, 5:e9568, 2010 : PubMed ESTHER: Yang_2010_PLoS.One_5_e9568 PubMedSearch: Yang 2010 PLoS.One 5 e9568 PubMedID: 20221449 Abstract Drug medications inevitably affect not only their intended protein targets but also other proteins as well. In this study we examined the hypothesis that drugs that share the same therapeutic effect also share a common therapeutic mechanism by targeting not only known drug targets, but also by interacting unexpectedly on the same cryptic targets. By constructing and mining an Alzheimer's disease (AD) drug-oriented chemical-protein interactome (CPI) using a matrix of 10 drug molecules known to treat AD towards 401 human protein pockets, we found that such cryptic targets exist. We recovered from CPI the only validated therapeutic target of AD, acetylcholinesterase (ACHE), and highlighted several other putative targets. For example, we discovered that estrogen receptor (ER) and histone deacetylase (HDAC), which have recently been identified as two new therapeutic targets of AD, might already have been targeted by the marketed AD drugs. We further established that the CPI profile of a drug can reflect its interacting character towards multi-protein sets, and that drugs with the same therapeutic attribute will share a similar interacting profile. These findings indicate that the CPI could represent the landscape of chemical-protein interactions and uncover "behind-the-scenes" aspects of the therapeutic mechanisms of existing drugs, providing testable hypotheses of the key nodes for network pharmacology or brand new drug targets for one-target pharmacology paradigm. Title: Genomic characterization of the Guillain-Barre syndrome-associated Campylobacter jejuni ICDCCJ07001 Isolate Zhang M, He L, Li Q, Sun H, Gu Y, You Y, Meng F, Zhang J Ref: PLoS ONE, 5:e15060, 2010 : PubMed ESTHER: Zhang_2010_PLoS.ONE_5_E15060 PubMedSearch: Zhang 2010 PLoS.ONE 5 E15060 PubMedID: 21124772 Gene_locus related to this paper: camjr-q5ht69 Abstract Campylobacter jejuni ICDCCJ07001 (HS:41, ST2993) was isolated from a Guillain-Barre syndrome (GBS) patient during a 36-case GBS outbreak triggered by C. jejuni infections in north China in 2007. Sequence analysis revealed that the ICDCCJ07001 genome consisted of 1,664,840 base pairs (bp) and one tetracycline resistance plasmid of 44,084 bp. The GC content was 59.29% and 1,579 and 37 CDSs were identified on the chromosome and plasmid, respectively. The ICDCCJ07001 genome was compared to C. jejuni subsp. jejuni strains 81-176, 81116, NCTC11168, RM1221 and C. jejuni subsp. doylei 269.97. The length and organization of ICDCCJ07001 was similar to that of NCTC11168, 81-176 and 81-116 except that CMLP1 had a reverse orientation in strain ICDCCJ07001. Comparative genomic analyses were also carried out between GBS-associated C. jejuni strains. Thirteen common genes were present in four GBS-associated strains and 9 genes mapped to the LOS cluster and the ICDCCJ07001_pTet (44 kb) plasmid was mosaic in structure. Thirty-seven predicted CDS in ICDCCJ07001_pTet were homologous to genes present in three virulence-associated plasmids in Campylobacter: 81-176_pTet, pCC31 and 81-176_pVir. Comparative analysis of virulence loci and virulence-associated genes indicated that the LOS biosynthesis loci of ICDCCJ07001 belonged to type A, previously reported to be associated with cases of GBS. The polysaccharide capsular biosynthesis (CPS) loci and the flagella modification (FM) loci of ICDCCJ07001 were similar to corresponding sequences of strain 260.94 of similar serotype as strain ICDCCJ07001. Other virulence-associated genes including cadF, peb1, jlpA, cdt and ciaB were conserved between the C. jejuni strains examined. Title: [Inhibitory effects of sinapine on activity of acetylcholinesterase in cerebral homogenate and blood serum of rats] He L, Li HT, Guo SW, Liu LF, Qiu JB, Li F, Cai BC Ref: Zhongguo Zhong Yao Za Zhi, 33:813, 2008 : PubMed ESTHER: He_2008_Zhongguo.Zhong.Yao.Za.Zhi_33_813 PubMedSearch: He 2008 Zhongguo.Zhong.Yao.Za.Zhi 33 813 PubMedID: 18589789 Abstract OBJECTIVE: The present study investigated the inhibitory effects of Chinese herb component sinapine on activity of acetylcholinesterase (AChE) in cerebral homogenate and blood serum of rats. METHOD: AChE was prepared from cerebral homogenate and blood serum of rats, respectively. Acetylcholinesterase activity assay kit and Chromatometry were used to detect the AChE activity. RESULT: Sinapine significantly inhibited AChE activity in vitro, with more effective on cerebral homogenate (IC50 3.66 micromol x L(-1)) than blood serum (IC50 22.1 micromol x L(-1)). CONCLUSION: Sinapine could significantly inhibit the cerebral AChE activity and may be a promising drug used for prevention and cure of Alzheimer's disease as a cholinesterase inhibitor. Title: Large-scale cDNA transfection screening for genes related to cancer development and progression Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X and Gu J <15 more author(s)> Wan D, Gong Y, Qin W, Zhang P, Li J, Wei L, Zhou X, Li H, Qiu X, Zhong F, He L, Yu J, Yao G, Jiang H, Qian L, Yu Y, Shu H, Chen X, Xu H, Guo M, Pan Z, Chen Y, Ge C, Yang S, Gu J (- 15) Ref: Proc Natl Acad Sci U S A, 101:15724, 2004 : PubMed ESTHER: Wan_2004_Proc.Natl.Acad.Sci.U.S.A_101_15724 PubMedSearch: Wan 2004 Proc.Natl.Acad.Sci.U.S.A 101 15724 PubMedID: 15498874 Abstract A large-scale assay was performed by transfecting 29,910 individual cDNA clones derived from human placenta, fetus, and normal liver tissues into human hepatoma cells and 22,926 cDNA clones into mouse NIH 3T3 cells. Based on the results of colony formation in hepatoma cells and foci formation in NIH 3T3 cells, 3,806 cDNA species (8,237 clones) were found to possess the ability of either stimulating or inhibiting cell growth. Among them, 2,836 (6,958 clones) were known genes, 372 (384 clones) were previously unrecognized genes, and 598 (895 clones) were unigenes of uncharacterized structure and function. A comprehensive analysis of the genes and the potential mechanisms for their involvement in the regulation of cell growth is provided. The genes were classified into four categories: I, genes related to the basic cellular mechanism for growth and survival; II, genes related to the cellular microenvironment; III, genes related to host-cell systemic regulation; and IV, genes of miscellaneous function. The extensive growth-regulatory activity of genes with such highly diversified functions suggests that cancer may be related to multiple levels of cellular and systemic controls. The present assay provides a direct genomewide functional screening method. It offers a better understanding of the basic machinery of oncogenesis, including previously undescribed systemic regulatory mechanisms, and also provides a tool for gene discovery with potential clinical applications. | |||||||
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