Author Report for: Zhang KNo contact information in database for Zhang K
Ang S, Liang J, Zheng W, Zhang Z, Li J, Yan Z, Wong WL, Zhang K, Chen M, Wu P Ref: Molecules, 28:, 2023 : PubMed ESTHER: Ang_2023_Molecules_28_ PubMedSearch: Ang 2023 Molecules 28 PubMedID: 37049799 Abstract A large number of studies have shown that matrine (MA) possesses various pharmacological activities and is one of the few natural, plant-derived pesticides with the highest prospects for promotion and application. Fifty-eight MA derivatives were prepared, including 10 intermediates and 48 target compounds in 3 series, to develop novel mosquitocidal agents. Compounds 4b, 4e, 4f, 4m, 4n, 6e, 6k, 6m, and 6o showed good larvicidal activity against Aedes albopictus, which is both a highly aggressive mosquito and an important viral vector that can transmit a wide range of pathogens. Dipping methods and a bottle bioassay were used for insecticidal activity evaluation. The LC(50) values of 4e, 4m, and 6m reached 147.65, 140.08, and 205.79 microg/mL, respectively, whereas the LC(50) value of MA was 659.34 microg/mL. Structure-activity relationship analysis demonstrated that larvicidal activity could be improved by the unsaturated heterocyclic groups introduced into the carboxyl group after opening the D ring. The MA derivatives with oxidized N-1 lost their mosquitocidal activities, indicating that the bareness of N-1 is crucial to maintain their anti-mosquito activity. However, the activity was not greatly influenced by introducing a cyan group at C-6 or a benzene sulfonyl group at N-16. Additionally, compounds 4e and 4m exhibited good inhibitory activities against acetylcholinesterase with inhibitory rates of 59.12% and 54.30%, respectively, at a concentration of 250 microg/mL, whereas the inhibitory rate of MA was 9.88%. Therefore, the structural modification and mosquitocidal activity of MA and its derivatives obtained here pave the way for those seeking strong mosquitocidal agents of plant origin. Title: Novel Sophoridine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, Acetylcholinesterase Inhibition, and Morphological Study Ang S, Cao N, Zheng W, Zhang Z, Li J, Yan Z, Su K, Wong WL, Zhang K and Wu P <1 more author(s)> Ang S, Cao N, Zheng W, Zhang Z, Li J, Yan Z, Su K, Wong WL, Zhang K, Hong WD, Wu P (- 1) Ref: Insects, 14:, 2023 : PubMed ESTHER: Ang_2023_Insects_14_ PubMedSearch: Ang 2023 Insects 14 PubMedID: 37103214 Abstract Two series of novel sophoridine derivatives were designed, synthesized, and evaluated for their anti-mosquito activity. SOP-2g, SOP-2q, and SOP-2r exhibited potential larvicidal activity against Aedes albopictus larva with LC(50) values of 330.98, 430.53, and 411.09 ppm, respectively. Analysis of structure-activity relationships indicated that the oxime ester group was beneficial for improving the larvicidal biological activity, whereas the long-chain aliphatic group and fused-ring group were introduced. Furthermore, the larvicidal mechanism was also investigated based on the inhibition assay of acetylcholinesterase (AChE) and the morphological observation of dead larva treated with derivatives. Results indicated that the AChE inhibitory activity of the preferred three derivatives were 63.16%, 46.67%, and 35.11%, respectively, at 250 ppm concentration. Additionally, morphological evidence demonstrated that SOP-2q and SOP-2r induced changes in the larva's intestinal cavity, caudal gill, and tail, thereby displaying larvicidal action against Ae. albopictus together with AChE inhibition. Therefore, this study implied that sophoridine and its novel derivatives could be used to control the population of mosquito larva, which may also be effective alkaloids to reduce the mosquito population density. Title: Inulin reduces liver triacylglycerol by increasing lipid droplet lipolysis in fat-loaded mice Chen B, Shi Y, Zhang K, Chang Y, Fu P, Liu P, Zhang S Ref: Food Res Int, 163:112226, 2023 : PubMed ESTHER: Chen_2023_Food.Res.Int_163_112226 PubMedSearch: Chen 2023 Food.Res.Int 163 112226 PubMedID: 36596155 Abstract Increased consumption of high-fat low-fiber foods has been shown to contribute to the development of metabolic syndromes, such as fatty liver, obesity, diabetes, et al. Fermentable dietary fiber, such as inulin, is broadly used to mitigate host metabolic abnormalities. In this work, we studied systematically the effect of inulin on mice with metabolic disorders, induced by either short- or long-term high-fat feeding. As expected, inulin reduced the body weight of mice in both groups. However, it was found that inulin feeding could only increase energy expenditure, alleviate adiposity, and improve glucose intolerance in mice fed with high-fat diet (HFD) for 1smonth but not for 4smonths. Surprisingly, inulin supplementation could alleviate HFD-induced hepatic steatosis, mediated through increasing adipose triglyceride lipase (ATGL) on liver lipid droplets, in both groups. Gut microbiota in the short- and long-term fat-loaded mice were shown to be modulated differently, which may mediate the differential effects of inulin. These results may help in understanding the role and mechanism of fermentable fiber regulating host metabolism. Title: Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe 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: A hepatokine derived from the ER protein CREBH promotes triglyceride metabolism by stimulating lipoprotein lipase activity Kim H, Song Z, Zhang R, Davies BSJ, Zhang K Ref: Sci Signal, 16:eadd6702, 2023 : PubMed ESTHER: Kim_2023_Sci.Signal_16_eadd6702 PubMedSearch: Kim 2023 Sci.Signal 16 eadd6702 PubMedID: 36649378 Abstract The endoplasmic reticulum (ER)-tethered, liver-enriched stress sensor CREBH is processed in response to increased energy demands or hepatic stress to release an amino-terminal fragment that functions as a transcription factor for hepatic genes encoding lipid and glucose metabolic factors. Here, we discovered that the carboxyl-terminal fragment of CREBH (CREBH-C) derived from membrane-bound, full-length CREBH was secreted as a hepatokine in response to fasting or hepatic stress. Phosphorylation of CREBH-C mediated by the kinase CaMKII was required for efficient secretion of CREBH-C through exocytosis. Lipoprotein lipase (LPL) mediates the lipolysis of circulating triglycerides for tissue uptake and is inhibited by a complex consisting of angiopoietin-like (ANGPTL) 3 and ANGPTL8. Secreted CREBH-C blocked the formation of ANGPTL3-ANGPTL8 complexes, leading to increased LPL activity in plasma and metabolic tissues in mice. CREBH-C administration promoted plasma triglyceride clearance and partitioning into peripheral tissues and mitigated hypertriglyceridemia and hepatic steatosis in mice fed a high-fat diet. Individuals with obesity had higher circulating amounts of CREBH-C than control individuals, and human CREBH loss-of-function variants were associated with dysregulated plasma triglycerides. These results identify a stress-induced, secreted protein fragment derived from CREBH that functions as a hepatokine to stimulate LPL activity and triglyceride homeostasis. Title: Broad-Specificity Screening of Pyrethroids Enabled by the Catalytic Function of Human Serum Albumin on Coumarin Hydrolysis Liang Z, Sun Y, Zeng H, Qin H, Yang R, Qu L, Zhang K, Li Z Ref: Analytical Chemistry, :, 2023 : PubMed ESTHER: Liang_2023_Anal.Chem__ PubMedSearch: Liang 2023 Anal.Chem PubMedID: 36952638 Abstract Sensing systems based on cholinesterase and carboxylesterase coupled with different transduction technologies have emerged for pesticide screening owing to their simple operation, fast response, and suitability for on-site analysis. However, the broad spectrum and specificity screening of pyrethroids over organophosphates and carbamates remains an unmet challenge for current enzymatic sensors. Human serum albumin (HSA), a multifunctional protein, can promote various chemical transformations and show a high affinity for pyrethroids, which offer a route for specific and broad-spectrum pyrethroid screening. Herein, for the first time, we evaluated the catalytic hydrolysis function of human serum albumin (HSA) on the coumarin lactone bond and revealed that HSA can act as an enzyme to catalyze the hydrolysis of the coumarin lactone bond. Molecular docking and chemical modifications indicate that lysine 199 and tyrosine 411 serve as the catalytic general base and contribute to most of the catalytic activity. Utilizing this enzymatic activity, a broad specific ratiometric fluorescence pyrethroids sensing system was developed. The binding energetics and binding constants of pesticides and HSA show that pyrethroids bind to HSA more easily than organophosphates and carbamates, which is responsible for the specificity of the sensing system. This study provides a general sensor platform and strategy for screening pesticides and reveals the catalytic activity of HSA on the hydrolysis of the coumarin lactone bond, which may open innovative horizons for the chemical sensing and biomedical applications of HSA. Title: Clinical profile, genetic spectrum and therapy evaluation of 19 Chinese pediatric patients with lipoprotein lipase deficiency Xia Y, Zheng W, Du T, Gong Z, Liang L, Wang R, Yang Y, Zhang K, Lu D and Qiu W <3 more author(s)> Xia Y, Zheng W, Du T, Gong Z, Liang L, Wang R, Yang Y, Zhang K, Lu D, Chen X, Sun Y, Xiao B, Qiu W (- 3) Ref: J Clin Lipidol, :, 2023 : PubMed ESTHER: Xia_2023_J.Clin.Lipidol__ PubMedSearch: Xia 2023 J.Clin.Lipidol PubMedID: 37858495 Gene_locus related to this paper: human-LPL Abstract BACKGROUND: Lipoprotein lipase (LPL) deficiency, the most common familial chylomicronemia syndrome (FCS), is a rare autosomal recessive disease characterized by chylomicronemia and severe hypertriglyceridemia (HTG), with limited clinical and genetic characterization. OBJECTIVE: To describe the manifestations and management of 19 pediatric patients with LPL-FCS. METHODS: LPL-FCS patients from 2014 to 2022 were divided into low-fat (LF), very-low-fat (VLF) and medium-chain-triglyceride (MCT) groups. Their clinical data were evaluated to investigate the effect of different diets. The genotype-phenotype relationship was assessed. Linear regression comparing long-chain triglyceride (LCT) intake and TG levels was analyzed. RESULTS: Nine novel LPL variants were identified in 19 LPL-FCS pediatric patients. At baseline, eruptive xanthomas occurred in 3/19 patients, acute pancreatitis in 2/19, splenomegaly in 6/19 and hepatomegaly in 3/19. The median triglyceride (TG) level (30.3mmol/L) was markedly increased. The MCT group and VLF group with LCT intakes <20 en% (energy percentage) had considerably lower TG levels than the LF group (both p<0.05). The LF group presented with severe HTG and significantly decreased TG levels after restricting LCT intakes to <20 en% (p<0.05). Six infants decreased TG levels to <10 mmol/L by keeping LCT intake <10 en%. TG levels and LCT intake were positively correlated in both patients under 2 years (r=0.84) and those aged 2-9 years (r=0.89). No genotype-phenotype relationship was observed. CONCLUSIONS: This study broadens the clinical and genetic spectra of LPL-FCS. The primary therapy for LPL-FCS pediatric patients is restricting dietary LCTs to <10 en% or <20 en% depending on different ages. MCTs potentially provide extra energy. Title: Design, synthesis and evaluation of OA-tacrine hybrids as cholinesterase inhibitors with low neurotoxicity and hepatotoxicity against Alzheimer's disease Yang H, Jia H, Deng M, Zhang K, Liu Y, Cheng M, Xiao W Ref: J Enzyme Inhib Med Chem, 38:2192439, 2023 : PubMed ESTHER: Yang_2023_J.Enzyme.Inhib.Med.Chem_38_2192439 PubMedSearch: Yang 2023 J.Enzyme.Inhib.Med.Chem 38 2192439 PubMedID: 36950955 Abstract A series of OA-tacrine hybrids with the alkylamine linker was designed, synthesized, and evaluated as effective cholinesterase inhibitors for the treatment of Alzheimer's disease (AD). Biological activity results demonstrated that some hybrids possessed significant inhibitory activities against acetylcholinesterase (AChE). Among them, compounds B4 (hAChE, IC(50) = 14.37 +/- 1.89 nM; SI > 695.89) and D4 (hAChE, IC(50) = 0.18 +/- 0.01 nM; SI = 3374.44) showed excellent inhibitory activities and selectivity for AChE as well as low nerve cell toxicity. Furthermore, compounds B4 and D4 exhibited lower hepatotoxicity than tacrine in cell viability, apoptosis, and intracellular ROS production for HepG2 cells. These properties of compounds B4 and D4 suggest that they deserve further investigation as promising agents for the prospective treatment of AD. Title: Antinociceptive Effects and Interaction Mechanisms of Intrathecal Pentazocine and Neostigmine in Two Different Pain Models in Rats Huang H, Bai X, Zhang K, Guo J, Wu S, Ouyang H Ref: Pain Res Manag, 2022:4819910, 2022 : PubMed ESTHER: Huang_2022_Pain.Res.Manag_2022_4819910 PubMedSearch: Huang 2022 Pain.Res.Manag 2022 4819910 PubMedID: 35646201 Abstract BACKGROUND: Pentazocine produces a wide variety of actions in the treatment of perioperative analgesia. Neostigmine is a cholinesterase inhibitor used to antagonize the residual effects of muscle relaxants and also produces an analgesic effect. OBJECTIVES: To investigate the analgesic effects of intrathecally injected pentazocine and neostigmine and their interaction. METHODS: Sprague-Dawley rats were used to test the analgesic effect of pentazocine and neostigmine using the paw formalin pain model and the incision mechanical allodynia model. Pentazocine (3, 10, 30, and 100 microg), neostigmine (0.3, 1, 3, and 10 microg) or a pentazocine-neostigmine mixture were separately injected to evaluate their antinociceptive effects alone on the treatment groups. The corresponding control group received an intrathecal injection containing the same volume of saline. The formalin pain test, or the plantar incision pain behavior test were performed 30 minutes later. Isobolographic analysis was used to evaluate the interaction between pentazocine and neostigmine. Intrathecally administered selective mu-opioid receptor antagonist CTAP, selective kappa-opioid receptor antagonist nor-Binaltorphimine (nor-BNI), nonselective opioid receptor antagonist naloxone, and muscarinic acetylcholine receptor antagonist atropine were also used to test the possible interaction mechanism. These antagonists were used 30 minutes before the pentazocine and neostigmine mixtures which were intrathecally injected. RESULTS: Intrathecally administered pentazocine (3, 10, 30, and 100 microg) and neostigmine (0.3, 1, 3, and 10 microg) alone had a marked dose-related impact on suppressing the biphasic responses in the formalin test. Pentazocine (3, 10, 30, and 100 microg) and neostigmine (0.3, 1, 3, and 10 microg) alone attenuated the mechanical allodynia in a plantar incision model in a dose-dependent manner. Isobolographic analysis revealed that the mixture of intrathecal pentazocine and neostigmine synergistically decreased both phase I and II activity in the formalin test and mechanical allodynia in the plantar incision model. Pretreatment of intrathecally administered nor-BNI, naloxone, atropine, but not CTAP, antagonized the analgesic effect of the pentazocine-neostigmine mixture. CONCLUSIONS: All of these results suggest that the combined application of pentazocine and neostigmine is an effective way to relieve pain from formalin and acute incision mechanical allodynia. The synergistic effect between pentazocine and neostigmine is mostly attributed to the kappa-opioid receptor and the cholinergic receptor in the spinal cord. Title: Effects of Lipase and Xylanase Pretreatment on the Structure and Pulping Properties of Wheat Straw Jia Q, Chen J, Yang G, Liu K, Wang Y, Zhang K Ref: Polymers (Basel), 14:, 2022 : PubMed ESTHER: Jia_2022_Polymers.(Basel)_14_ PubMedSearch: Jia 2022 Polymers.(Basel) 14 PubMedID: 36501524 Abstract Based on the reduction of environmental pollution, a biological enzyme assisted alkali-oxygen pulping method was explored to improve the delignification efficiency and fiber accessibility of wheat straw and improve the properties of wheat straw pulp. In this paper, lipase and xylanase were used to pretreat wheat straw and the effects of different enzyme types and enzyme dosage on the microstructure and pulp properties of wheat straw were investigated and experimented. The results showed that the lipase can remove fat and wax on the surface of wheat straw, while xylanase degraded the hemicellulose components, such as xylan, of wheat straw fiber, destroyed the structure of the lignin-carbohydrate complex, increasing lignin removal as a result and enhancing the impregnating, diffusion and penetration of alkali. Compared with wheat straw without enzyme pretreatment, the skeleton of wheat straw pretreated by enzyme became looser, the internal cavity appeared and the wall cavity became thin and transparent. The fines decreased obviously and the length of fibers increased. After combined pretreatment with lipase (15 U.g(-1)) and xylanase (15 U.g(-1)), the pulping performance of wheat straw was improved and the tensile index (97.37 N.m.g(-1)), brightness (40.9% ISO) and yield (58.10%) of the pulp increased by 12.9%, 19.9% and 9.9%, respectively. It can be seen that enzyme pretreatment is a green and effective approach to improving the alkali-oxygen pulping performance of wheat straw. Title: Semaglutide May Alleviate Hepatic Steatosis in T2DM Combined with NFALD Mice via miR-5120/ABHD6 Li R, Ye Z, She D, Fang P, Zong G, Hu K, Kong D, Xu W, Li L and Xue Y <2 more author(s)> Li R, Ye Z, She D, Fang P, Zong G, Hu K, Kong D, Xu W, Li L, Zhou Y, Zhang K, Xue Y (- 2) Ref: Drug Des Devel Ther, 16:3557, 2022 : PubMed ESTHER: Li_2022_Drug.Des.Devel.Ther_16_3557 PubMedSearch: Li 2022 Drug.Des.Devel.Ther 16 3557 PubMedID: 36238196 Abstract OBJECTIVE: Although the pathogenesis of non-alcoholic fatty liver disease (NAFLD) has been extensively studied, the role of its underlying pathogenesis remains unclear, and there is currently no approved therapeutic strategy for NAFLD. The purpose of this study was to observe the beneficial effects of Semaglutide on NAFLD in vivo and in vitro, as well as its potential molecular mechanisms. METHODS: Semaglutide was used to treat type 2 diabetes mellitus (T2DM) combined with NAFLD mice for 12 weeks. Hepatic function and structure were evaluated by liver function, blood lipids, liver lipids, H&E staining, oil red staining and Sirius staining. The expression of alpha/beta hydrolase domain-6 (ABHD6) was measured by qPCR and Western blotting in vivo and in vitro. Then, dual-luciferase reporter assay was performed to verify the regulation of the upstream miR-5120 on ABHD6. RESULTS: Our data revealed that Semaglutide administration significantly improved liver function and hepatic steatosis in T2DM combined with NAFLD mice. Furthermore, compared with controls, up-regulation of ABHD6 and down-regulation of miR-5120 were found in the liver of T2DM+NAFLD mice and HG+FFA-stimulated Hepa 1-6 hepatocytes. Interestingly, after Semaglutide intervention, ABHD6 expression was significantly decreased in the liver of T2DM+NAFLD mice and in HG+FFA-stimulated Hepa 1-6 hepatocytes, while miR-5120 expression was increased. We also found that miR-5120 could regulate the expression of ABHD6 in hepatocytes, while Semaglutide could modulate the expression of ABHD6 through miR-5120. In addition, GLP-1R was widely expressed in mouse liver tissues and Hepa 1-6 cells. Semaglutide could regulate miR-5120/ABHD6 expression through GLP-1R. CONCLUSION: Our data revealed the underlying mechanism by which Semaglutide improves hepatic steatosis in T2DM+NAFLD, and might shed new light on the pathological role of miR-5120/ABHD6 in the pathogenesis of T2DM+NAFLD. Title: Esterase-Activated Precipitating Strategy to Achieve Highly Specific Detection and Long-Term Imaging of Calcium Ions by Aggregation-Induced Phosphorescence Probe Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K and Qian Z <1 more author(s)> Wang Z, Xiong Z, Liu W, Zhu Q, Zhang X, Ding Y, Huang C, Feng H, Zhang K, Zhu E, Qian Z (- 1) Ref: Analytical Chemistry, :, 2022 : PubMed ESTHER: Wang_2022_Anal.Chem__ PubMedSearch: Wang 2022 Anal.Chem PubMedID: 35315662 Abstract Spatial and temporal monitoring of bioactive targets such as calcium ions is vitally significant for their essential roles in physiological and biochemical functions. Herein, we proposed an esterase-activated precipitating strategy to achieve highly specific identification and long-term bioimaging of calcium ions via lighting up the calcium ions by precipitation using a water-soluble aggregation-induced phosphorescence (AIP) probe. The designed probe CaP2 has an AIP behavior and can be efficiently aggregated by calcium ions through the coupling coordination of carboxylic acid and cyanide groups, which enables it to light up Ca(2+) by precipitating-triggered phosphorescence. Four hydrophilic groups of tetraethylene glycol were introduced to endow the resulting probe CaP3 with extraordinary water solubility as well as excellent cellular penetration. Only when the probe CaP3 penetrates inside the live cells the existing esterase in cells can activate the probe to be transformed active CaP2 probe selectively binding with calcium ion in the surroundings. The probe was used to further evaluate the imaging of intracellular calcium ions in model organisms. The excellent imaging performance of CaP3 in Arabidopsis thaliana seedling roots demonstrates that CaP3 has the excellent capability of monitoring calcium ions in live-cell imaging, and furthermore CaP3 exhibits much better photostability and thereby greater potential in long-term imaging. This work established a general esterase-activated precipitating strategy to achieve specific detection and bioimaging in situ triggered by esterase in live cells, and established a water-soluble aggregation-induced phosphorescence probe with high selectivity to achieve specific sensing and long-term imaging of calcium ions in live cells. Title: Response of xenobiotic biodegradation and metabolic genes in Tribolium castaneum following eugenol exposure Zhang Y, Gao S, Zhang P, Sun H, Lu R, Yu R, Li Y, Zhang K, Li B Ref: Mol Genet Genomics, :, 2022 : PubMed ESTHER: Zhang_2022_Mol.Genet.Genomics__ PubMedSearch: Zhang 2022 Mol.Genet.Genomics PubMedID: 35419714 Abstract Eugenol, a plant-derived component possessing small side effects, has an insecticidal activity to Tribolium castaneum; however, the underlying molecular mechanisms of eugenol acting on T. castaneum are currently unclear. Here, a nerve conduction carboxylesterase and a detoxifying glutathione S-transferase were significantly inhibited after eugenol exposure, resulting in the paralysis or death of beetles. Then, RNA-sequencing of eugenol-exposed and control samples identified 362 differentially expressed genes (DEGs), containing 206 up-regulated and 156 down-regulated genes. RNA-seq data were validated further by qRT-PCR. GO analysis revealed that DEGs were associated with 1308 GO terms of which the most enriched GO terms were catalytic activity, and integral component of membrane; KEGG pathway analysis showed that these DEGs were distributed in 151 different pathways, of which some pathways associated with metabolism of xenobiotics or drug were significantly enriched, which indicated that eugenol most likely disturbed the processes of metabolism, and detoxication. Moreover, several DEGs including Hexokinase type 2, Isocitrate dehydrogenase, and Cytochrome b-related protein, might participate in the respiratory metabolism of eugenol-exposed beetles. Some DEGs encoding CYP, UGT, GST, OBP, CSP, and ABC transporter were involved in the xenobiotic or drug metabolism pathway, which suggested that these genes of T. castaneum participated in the response to eugenol exposure. Additionally, TcOBPC11/ TcGSTs7, detected by qRT-PCR and RNA-interference against these genes, significantly increased the mortality of eugenol-treated T. castaneum, providing further evidence for the involvement of OBP/GST in eugenol metabolic detoxification in T. castaneum. These results aid eugenol insecticidal mechanisms and provide the basis of insect control. Title: Biodegradation of polyester polyurethane by the marine fungus Cladosporium halotolerans 6UPA1 Zhang K, Hu J, Yang S, Xu W, Wang Z, Zhuang P, Grossart HP, Luo Z Ref: J Hazard Mater, 437:129406, 2022 : PubMed ESTHER: Zhang_2022_J.Hazard.Mater_437_129406 PubMedSearch: Zhang 2022 J.Hazard.Mater 437 129406 PubMedID: 35753302 Abstract Lack of degradability and the accumulation of polymeric wastes increase the risk for the health of the environment. Recently, recycling of polymeric waste materials becomes increasingly important as raw materials for polymer synthesis are in short supply due to the rise in price and supply chain disruptions. As an important polymer, polyurethane (PU) is widely used in modern life, therefore, PU biodegradation is desirable to avoid its accumulation in the environment. In this study, we isolated a fungal strain Cladosporium halotolerans from the deep sea which can grow in mineral medium with a polyester PU (Impranil DLN) as a sole carbon source. Further, we demonstrate that it can degrade up to 80% of Impranil PU after 3 days of incubation at 28 degC by breaking the carbonyl groups (1732 cm(-1)) and C-N-H bonds (1532 cm(-1) and 1247 cm(-1)) as confirmed by Fourier-transform infrared (FTIR) spectroscopy analysis. Gas chromatography-mass spectrometry (GC-MS) analysis revealed polyols and alkanes as PU degradation intermediates, indicating the hydrolysis of ester and urethane bonds. Esterase and urease activities were detected in 7 days-old cultures with PU as a carbon source. Transcriptome analysis showed a number of extracellular protein genes coding for enzymes such as cutinase, lipase, peroxidase and hydrophobic surface binding proteins A (HsbA) were expressed when cultivated on Impranil PU. The yeast two-hybrid assay revealed that the hydrophobic surface binding protein ChHsbA1 directly interacts with inducible esterases, ChLip1 (lipase) and ChCut1 (cutinase). Further, the KEGG pathway for "fatty acid degradation" was significantly enriched in Impranil PU inducible genes, indicating that the fungus may use the degradation intermediates to generate energy via this pathway. Taken together, our data indicates secretion of both esterase and hydrophobic surface binding proteins by C. halotolerans plays an important role in Impranil PU absorption and subsequent degradation. Our study provides a mechanistic insight into Impranil PU biodegradation by deep sea fungi and provides the basis for future development of biotechnological PU recycling. Title: FAM135B sustains the reservoir of Tip60-ATM assembly to promote DNA damage response Zhang K, Wu Q, Liu W, Wang Y, Zhao L, Chen J, Liu H, Liu S, Li J and Zhan Q <1 more author(s)> Zhang K, Wu Q, Liu W, Wang Y, Zhao L, Chen J, Liu H, Liu S, Li J, Zhang W, Zhan Q (- 1) Ref: Clin Transl Med, 12:e945, 2022 : PubMed ESTHER: Zhang_2022_Clin.Transl.Med_12_e945 PubMedSearch: Zhang 2022 Clin.Transl.Med 12 e945 PubMedID: 35979619 Gene_locus related to this paper: human-FAM135B Abstract BACKGROUND: Recently, the mechanism by which cells adapt to intrinsic and extrinsic stresses has received considerable attention. Tat-interactive protein 60-kDa/ataxia-telangiectasia-mutated (TIP60/ATM) axis-mediated DNA damage response (DDR) is vital for maintaining genomic integrity. METHODS: Protein levels were detected by western blot, protein colocalisation was examined by immunofluorescence (IF) and protein interactions were measured by co-immunoprecipitation, proximity ligation assay and GST pull-down assays. Flow cytometry, comet assay and IF assays were used to explore the biological functions of sequence similarity 135 family member B (FAM135B) in DDR. Xenograft tumour, FAM135B transgenic mouse models and immunohistochemistry were utilised to confirm in vitro observations. RESULTS: We identified a novel DDR regulator FAM135B which could protect cancer cells from genotoxic stress in vitro and in vivo. The overexpression of FAM135B promoted the removal of gammaH2AX and 53BP1 foci, whereas the elimination of FAM135B attenuated these effects. Consistently, our findings revealed that FAM135B could promote homologous recombination and non-homologous end-joining repairs. Further study demonstrated that FAM135B physically bound to the chromodomain of TIP60 and improved its histone acetyltransferase activity. Moreover, FAM135B enhanced the interactions between TIP60 and ATM under resting conditions. Intriguingly, the protein levels of FAM135B dramatically decreased following DNA damage stress but gradually increased during the DNA repair period. Thus, we proposed a potential DDR mechanism where FAM135B sustains a reservoir of pre-existing TIP60-ATM assemblies under resting conditions. Once cancer cells suffer DNA damage, FAM135B is released from TIP60, and the functioning pre-assembled TIP60-ATM complex participates in DDR. CONCLUSIONS: We characterised FAM135B as a novel DDR regulator and further elucidated the role of the TIP60-ATM axis in response to DNA damage, which suggests that targeting FAM135B in combination with radiation therapy or chemotherapy could be a potentially effective approach for cancer treatment. Title: Analysis of virulence proteins in pathogenic Acinetobacter baumannii to provide early warning of zoonotic risk Zou D, Chang J, Lu S, Xu J, Hu P, Zhang K, Sun X, Guo W, Li Y and Ren H <1 more author(s)> Zou D, Chang J, Lu S, Xu J, Hu P, Zhang K, Sun X, Guo W, Li Y, Liu Z, Ren H (- 1) Ref: Microbiol Res, 266:127222, 2022 : PubMed ESTHER: Zou_2022_Microbiol.Res_266_127222 PubMedSearch: Zou 2022 Microbiol.Res 266 127222 PubMedID: 36306681 Gene_locus related to this paper: aciba-YdeN Abstract Acinetobacter baumannii is a ubiquitous opportunistic pathogen usually with low virulence. In recent years, reports of increased pathogenicity of A. baumannii in livestock due to the migratory behaviour of wildlife have attracted public health attention. Our previous study reported that an A. baumannii strain isolated from dead chicks, CCGGD201101, showed enhanced pathogenicity, but the mechanism for increased virulence is not understood. Here, to screen potential virulence factors, the proteomes of the isolated strain CCGGD201101 and the standard strain ATCC19606 of A. baumannii were compared, and the possible virulence-enhancing mechanisms were further analysed. The 50 % lethal dose (LD(50)) values of CCGGD201101 and standard strain ATCC19606 in ICR mice were determined to verify their bacterial toxicity. 2D fluorescence difference gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF/TOF-MS) and quantitative real-time PCR (RTqPCR) were applied to screen and identify differentially expressed proteins or genes that may be related to virulence enhancement. Bioinformatics analyses based on proteinprotein interaction (PPI) networks were used to explore the function of potential virulence proteins. The pathogenicity of potential virulence factors was assessed by phylogenetic analyses and an animal infection model. The results showed that the LD(50) of CCGGD201101 for mice was 1.186 x 10(6) CFU/mL, and the virulence was increased by 180.5-fold compared to ATCC19606. Forty-seven protein spots were significantly upregulated for the A. baumannii CCGGD201101 strain (fold change <=1.5, p < 0.05). In total, 14 upregulated proteins were identified using proteomic analysis, and the mRNA expression levels of these proteins were nearly identical, with few exceptions. According to the PPI network and phylogenetic analyses, the I78 family peptidase inhibitor, 3-oxoacyl-ACP reductase FabG, and glycine zipper were screened as being closely related to the pathogenicity of bacteria. Furthermore, the I78 overexpression strains exhibited higher lethality in mouse infection models, which indicated that the I78 family peptidase inhibitor was a potential new virulence factor to enhance the pathogenicity of the A. baumannii CCGGD201101 strain. The present study helped us to better understand the mechanisms of virulence enhancement and provided a scientific basis for establishing an early warning system for enhanced virulence of A. baumannii from animals. Title: Mapping the catalytic conformations of an assembly-line polyketide synthase module Cogan DP, Zhang K, Li X, Li S, Pintilie GD, Roh SH, Craik CS, Chiu W, Khosla C Ref: Science, 374:729, 2021 : PubMed ESTHER: Cogan_2021_Science_374_729 PubMedSearch: Cogan 2021 Science 374 729 PubMedID: 34735239 Gene_locus related to this paper: sacer-ery3 Abstract Assembly-line polyketide synthases, such as the 6-deoxyerythronolide B synthase (DEBS), are large enzyme factories prized for their ability to produce specific and complex polyketide products. By channeling protein-tethered substrates across multiple active sites in a defined linear sequence, these enzymes facilitate programmed small-molecule syntheses that could theoretically be harnessed to access countless polyketide product structures. Using cryogenic electron microscopy to study DEBS module 1, we present a structural model describing this substrate-channeling phenomenon. Our 3.2- to 4.3-angstrom-resolution structures of the intact module reveal key domain-domain interfaces and highlight an unexpected module asymmetry. We also present the structure of a product-bound module that shines light on a recently described ""turnstile"" mechanism for transient gating of active sites along the assembly line. Title: Deletion of soluble epoxide hydrolase suppressed chronic kidney disease-related vascular calcification by restoring Sirtuin 3 expression He W, Huang J, Liu Y, Xie C, Zhang K, Zhu X, Chen J, Huang H Ref: Cell Death Dis, 12:992, 2021 : PubMed ESTHER: He_2021_Cell.Death.Dis_12_992 PubMedSearch: He 2021 Cell.Death.Dis 12 992 PubMedID: 34689162 Abstract Vascular calcification is common in chronic kidney disease (CKD) and contributes to cardiovascular disease (CVD) without any effective therapies available up to date. The expression of soluble epoxide hydrolase (sEH) is different in patients with and without vascular calcification. The present study investigates the role of sEH as a potential mediator of vascular calcification in CKD. Both Ephx2(-)(/-) and wild-type (WT) mice fed with high adenine and phosphate (AP) diet were used to explore the vascular calcification in CKD. Compared with WT, deletion of sEH inhibited vascular calcification induced by AP. sEH deletion also abolished high phosphorus (Pi)-induced phenotypic transition of vascular smooth muscle cells (VSMCs) independent of its epoxyeicosatrienoic acids (EETs) hydrolysis. Further gene expression analysis identified the potential role of Sirtuin 3 (Sirt3) in the sEH-regulated VSMC calcification. Under high Pi treatment, sEH interacted with Sirt3, which might destabilize Sirt3 and accelerate the degradation of Sirt3. Deletion of sEH may preserve the expression of Sirt3, and thus maintain the mitochondrial adenosine triphosphate (ATP) synthesis and morphology, significantly suppressing VSMC calcification. Our data supported that sEH deletion inhibited vascular calcification and indicated a promising target of sEH inhibition in vascular calcification prevention. Title: Insecticidal Activity of Artemisia vulgaris Essential Oil and Transcriptome Analysis of Tribolium castaneum in Response to Oil Exposure Gao S, Zhang K, Wei L, Wei G, Xiong W, Lu Y, Zhang Y, Gao A, Li B Ref: Front Genet, 11:589, 2020 : PubMed ESTHER: Gao_2020_Front.Genet_11_589 PubMedSearch: Gao 2020 Front.Genet 11 589 PubMedID: 32670352 Abstract Red flour beetle (Tribolium castaneum) is one of the most destructive pests of stored cereals worldwide. The essential oil (EO) of Artemisia vulgaris (mugwort) is known to be a strong toxicant that inhibits the growth, development, and reproduction of T. castaneum. However, the molecular mechanisms underlying the toxic effects of A. vulgaris EO on T. castaneum remain unclear. Here, two detoxifying enzymes, carboxylesterase (CarEs) and cytochrome oxidase P450 (CYPs), were dramatically increased in red flour beetle larvae when they were exposed to A. vulgaris EO. Further, 758 genes were differentially expressed between EO treated and control samples. Based on Gene Ontology (GO) analysis, numerous differentially expressed genes (DEGs) were enriched for terms related to the regulation of biological processes, response to stimulus, and antigen processing and presentation. Our results indicated that A. vulgaris EO disturbed the antioxidant activity in larvae and partially inhibited serine protease (SP), cathepsin (CAT), and lipase signaling pathways, thus disrupting larval development and reproduction as well as down-regulating the stress response. Moreover, these DEGs showed that A. vulgaris indirectly affected the development and reproduction of beetles by inducing the expression of genes encoding copper-zinc-superoxide dismutase (CuZnSOD), heme peroxidase (HPX), antioxidant enzymes, and transcription factors. Moreover, the majority of DEGs were mapped to the drug metabolism pathway in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Notably, the following genes were detected: 6 odorant binding proteins (OBPs), 5 chemosensory proteins (CSPs), 14 CYPs, 3 esterases (ESTs), 5 glutathione S-transferases (GSTs), 6 UDP-glucuronosyltransferases (UGTs), and 2 multidrug resistance proteins (MRPs), of which 8 CYPs, 2 ESTs, 2 GSTs, and 3 UGTs were up-regulated dramatically after exposure to A. vulgaris EO. The residual DEGs were significantly down-regulated in EO exposed larvae, implying that partial compensation of metabolism detoxification existed in treated beetles. Furthermore, A. vulgaris EO induced overexpression of OBP/CYP, and RNAi against these genes significantly increased mortality of larvae exposed to EO, providing further evidence for the involvement of OBP/CYP in EO metabolic detoxification in T. castaneum. Our results provide an overview of the transcriptomic changes in T. castaneum in response to A. vulgaris EO. Title: Improved production of recombinant Rhizomucor miehei lipase by coexpressing protein folding chaperones in Pichia pastoris, which triggered ER stress Huang J, Zhao Q, Chen L, Zhang C, Bu W, Zhang X, Zhang K, Yang Z Ref: Bioengineered, 11:375, 2020 : PubMed ESTHER: Huang_2020_Bioengineered_11_375 PubMedSearch: Huang 2020 Bioengineered 11 375 PubMedID: 32175802 Gene_locus related to this paper: rhimi-lipas Abstract Rhizomucor miehei lipase (RML) is a biocatalyst that widely used in laboratory and industrial. Previously, RML with a 70-amino acid propeptide (pRML) was cloned and expressed in P. pastoris. Recombinant strains with (strain containing 4-copy prml) and without ER stress (strain containing 2-copy prml) were obtained. However, the effective expression of pRML in P. pastoris by coexpressing ER-related elements in pRML-produced strain with or without ER stress has not been reported to date. In this study, an efficient way to produce functional pRML was explored in P. pastoris. The coexpression of protein folding chaperones, including PDI and ERO1, in different strains with or without ER stress, was investigated. PDI overexpression only increased pRML production in 4-copy strain from 705 U/mL to 1430 U/mL because it alleviated the protein folded stress, increased the protein concentration from 0.56 mg/mL to 0.65 mg/mL, and improved enzyme-specific activity from 1238 U/mg to 2186 U/mg. However, PDI coexpression could not improve pRML production in the 2-copy strain because it increased protein folded stress, while ERO1 coexpression in the two strains all had a negative effect on pRML expression. We also investigated the effect of the propeptide on the substrate specificity and the condition for pRML enzyme powder preparation. Results showed that the relative activity exceeded 80% when the substrates C8-C10 were detected at 35 degrees C and pH 6, and C8-C12 at 45 degrees C and pH 8. The optimal enzyme powder preparation pH was 7, and the maximum recovery rate for pRML was 73.19%. Title: Maternal glyphosate exposure causes autism-like behaviors in offspring through increased expression of soluble epoxide hydrolase Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y and Hashimoto K <6 more author(s)> Pu Y, Yang J, Chang L, Qu Y, Wang S, Zhang K, Xiong Z, Zhang J, Tan Y, Wang X, Fujita Y, Ishima T, Wan D, Hwang SH, Hammock BD, Hashimoto K (- 6) Ref: Proc Natl Acad Sci U S A, :, 2020 : PubMed ESTHER: Pu_2020_Proc.Natl.Acad.Sci.U.S.A__ PubMedSearch: Pu 2020 Proc.Natl.Acad.Sci.U.S.A PubMedID: 32398374 Abstract Epidemiological studies suggest that exposure to herbicides during pregnancy might increase risk for autism spectrum disorder (ASD) in offspring. However, the precise mechanisms underlying the risk of ASD by herbicides such as glyphosate remain unclear. Soluble epoxide hydrolase (sEH) in the metabolism of polyunsaturated fatty acids is shown to play a key role in the development of ASD in offspring after maternal immune activation. Here, we found ASD-like behavioral abnormalities in juvenile offspring after maternal exposure to high levels of formulated glyphosate. Furthermore, we found higher levels of sEH in the prefrontal cortex (PFC), hippocampus, and striatum of juvenile offspring, and oxylipin analysis showed decreased levels of epoxy-fatty acids such as 8 (9)-EpETrE in the blood, PFC, hippocampus, and striatum of juvenile offspring after maternal glyphosate exposure, supporting increased activity of sEH in the offspring. Moreover, we found abnormal composition of gut microbiota and short-chain fatty acids in fecal samples of juvenile offspring after maternal glyphosate exposure. Interestingly, oral administration of TPPU (an sEH inhibitor) to pregnant mothers from E5 to P21 prevented ASD-like behaviors such as social interaction deficits and increased grooming time in the juvenile offspring after maternal glyphosate exposure. These findings suggest that maternal exposure to high levels of glyphosate causes ASD-like behavioral abnormalities and abnormal composition of gut microbiota in juvenile offspring, and that increased activity of sEH might play a role in ASD-like behaviors in offspring after maternal glyphosate exposure. Therefore, sEH may represent a target for ASD in offspring after maternal stress from occupational exposure to contaminants. Title: The genome evolution and low-phosphorus adaptation in white lupin Xu W, Zhang Q, Yuan W, Xu F, Muhammad Aslam M, Miao R, Li Y, Wang Q, Li X and Cheng F <3 more author(s)> Xu W, Zhang Q, Yuan W, Xu F, Muhammad Aslam M, Miao R, Li Y, Wang Q, Li X, Zhang X, Zhang K, Xia T, Cheng F (- 3) Ref: Nat Commun, 11:1069, 2020 : PubMed ESTHER: Xu_2020_Nat.Commun_11_1069 PubMedSearch: Xu 2020 Nat.Commun 11 1069 PubMedID: 32103018 Gene_locus related to this paper: lupal-a0a6a5lz53, lupal-a0a6a5mjk3 Abstract White lupin (Lupinus albus) is a legume crop that develops cluster roots and has high phosphorus (P)-use efficiency (PUE) in low-P soils. Here, we assemble the genome of white lupin and find that it has evolved from a whole-genome triplication (WGT) event. We then decipher its diploid ancestral genome and reconstruct the three sub-genomes. Based on the results, we further reveal the sub-genome dominance and the genic expression of the different sub-genomes varying in relation to their transposable element (TE) density. The PUE genes in white lupin have been expanded through WGT as well as tandem and dispersed duplications. Furthermore, we characterize four main pathways for high PUE, which include carbon fixation, cluster root formation, soil-P remobilization, and cellular-P reuse. Among these, auxin modulation may be important for cluster root formation through involvement of potential genes LaABCG36s and LaABCG37s. These findings provide insights into the genome evolution and low-P adaptation of white lupin. Title: Key role of soluble epoxide hydrolase in the neurodevelopmental disorders of offspring after maternal immune activation Ma M, Ren Q, Yang J, Zhang K, Xiong Z, Ishima T, Pu Y, Hwang SH, Toyoshima M and Hashimoto K <4 more author(s)> Ma M, Ren Q, Yang J, Zhang K, Xiong Z, Ishima T, Pu Y, Hwang SH, Toyoshima M, Iwayama Y, Hisano Y, Yoshikawa T, Hammock BD, Hashimoto K (- 4) Ref: Proc Natl Acad Sci U S A, 116:7083, 2019 : PubMed ESTHER: Ma_2019_Proc.Natl.Acad.Sci.U.S.A_116_7083 PubMedSearch: Ma 2019 Proc.Natl.Acad.Sci.U.S.A 116 7083 PubMedID: 30890645 Abstract Maternal infection during pregnancy increases risk of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder (ASD) in offspring. In rodents, maternal immune activation (MIA) yields offspring with schizophrenia- and ASD-like behavioral abnormalities. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with neurodevelopmental disorders. Here we found higher levels of sEH in the prefrontal cortex (PFC) of juvenile offspring after MIA. Oxylipin analysis showed decreased levels of epoxy fatty acids in the PFC of juvenile offspring after MIA, supporting increased activity of sEH in the PFC of juvenile offspring. Furthermore, expression of sEH (or EPHX2) mRNA in induced pluripotent stem cell-derived neurospheres from schizophrenia patients with the 22q11.2 deletion was higher than that of healthy controls. Moreover, the expression of EPHX2 mRNA in postmortem brain samples (Brodmann area 9 and 40) from ASD patients was higher than that of controls. Treatment with 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent sEH inhibitor, in juvenile offspring from prenatal day (P) 28 to P56 could prevent cognitive deficits and loss of parvalbumin (PV) immunoreactivity in the medial PFC of adult offspring after MIA. In addition, dosing of TPPU to pregnant mothers from E5 to P21 could prevent cognitive deficits, and social interaction deficits and PV immunoreactivity in the medial prefrontal cortex of juvenile offspring after MIA. These findings suggest that increased activity of sEH in the PFC plays a key role in the etiology of neurodevelopmental disorders in offspring after MIA. Therefore, sEH represents a promising prophylactic or therapeutic target for neurodevelopmental disorders in offspring after MIA. Title: Fascaplysin Derivatives Are Potent Multitarget Agents against Alzheimer's Disease: in Vitro and in Vivo Evidence Pan H, Qiu H, Zhang K, Zhang P, Liang W, Yang M, Mou C, Lin M, He M and Cui W <8 more author(s)> Pan H, Qiu H, Zhang K, Zhang P, Liang W, Yang M, Mou C, Lin M, He M, Xiao X, Zhang D, Wang H, Liu F, Li Y, Jin H, Yan X, Liang H, Cui W (- 8) Ref: ACS Chem Neurosci, 10:4741, 2019 : PubMed ESTHER: Pan_2019_ACS.Chem.Neurosci_10_4741 PubMedSearch: Pan 2019 ACS.Chem.Neurosci 10 4741 PubMedID: 31639294 Abstract Alzheimer's disease (AD) is characterized by progressive neurodegeneration and impaired cognitive functions. Fascaplysin is a beta-carboline alkaloid isolated from marine sponge Fascaplysinopsis bergquist in 1988. Previous studies have shown that fascaplysin might act on acetylcholinesterase and beta-amyloid (Abeta) to produce anti-AD properties. In this study, a series of fascaplysin derivatives were synthesized. The cholinesterase inhibition activities, the neuronal protective effects, and the toxicities of these compounds were evaluated in vitro. Compounds 2a and 2b, the two most powerful compounds in vitro, were further selected to evaluate their cognitive-enhancing effects in animals. Both 2a and 2b could ameliorate cognitive dysfunction induced by scopolamine or Abeta oligomers without affecting locomotor functions in mice. We also found that 2a and 2b could prevent cholinergic dysfunctions, decrease pro-inflammatory cytokine expression, and inhibit Abeta-induced tau hyperphosphorylation in vivo. Most importantly, pharmacodynamics studies suggested that 2b could penetrate the blood-brain barrier and be retained in the central nervous system. All these results suggested that fascaplysin derivatives are potent multitarget agents against AD and might be clinical useful for AD treatment. Title: A Unique Role of Carboxylesterase 3 (Ces3) in beta-Adrenergic Signaling-Stimulated Thermogenesis Yang L, Li X, Tang H, Gao Z, Zhang K, Sun K Ref: Diabetes, 68:1178, 2019 : PubMed ESTHER: Yang_2019_Diabetes_68_1178 PubMedSearch: Yang 2019 Diabetes 68 1178 PubMedID: 30862682 Gene_locus related to this paper: human-CES3, mouse-Ces1d Inhibitor(s) related to this paper: WWL229, WWL113 Abstract Carboxylesterase 3 (Ces3) is a hydrolase with a wide range of activities in liver and adipose tissue. In this study, we identified Ces3 as a major lipid droplet surface-targeting protein in adipose tissue upon cold exposure by liquid chromatography-tandem mass spectrometry. To investigate the function of Ces3 in the beta-adrenergic signaling-activated adipocytes, we applied WWL229, a specific Ces3 inhibitor, or genetic inhibition by siRNA to Ces3 on isoproterenol (ISO)-treated 3T3-L1 and brown adipocyte cells. We found that blockage of Ces3 by WWL229 or siRNA dramatically attenuated the ISO-induced lipolytic effect in the cells. Furthermore, Ces3 inhibition led to impaired mitochondrial function measured by Seahorse. Interestingly, Ces3 inhibition attenuated an ISO-induced thermogenic program in adipocytes by downregulating Ucp1 and Pgc1alpha genes via peroxisome proliferator-activated receptor gamma. We further confirmed the effects of Ces3 inhibition in vivo by showing that the thermogenesis in adipose tissues was significantly attenuated in WWL229-treated or adipose tissue-specific Ces3 heterozygous knockout (Adn-Cre-Ces3(flx/wt)) mice. As a result, the mice exhibited dramatically impaired ability to defend their body temperature in coldness. In conclusion, our study highlights a lipolytic signaling induced by Ces3 as a unique process to regulate thermogenesis in adipose tissue. Title: Soluble epoxide hydrolase inhibitor, TUPS, attenuates isoproterenol/angiotensin II-induced cardiac hypertrophy through mammalian target of rapamycin-mediated autophagy inhibition Zhang H, Zhang K, Liang J, Yan W, Wu F, Xu W, Wu Z, Chen Y, Pan R, Wu G Ref: J Pharm Pharmacol, 71:1291, 2019 : PubMed ESTHER: Zhang_2019_J.Pharm.Pharmacol_71_1291 PubMedSearch: Zhang 2019 J.Pharm.Pharmacol 71 1291 PubMedID: 31215026 Inhibitor(s) related to this paper: TUPS Abstract OBJECTIVES: To investigate the potential role and mechanism of TUPS, a soluble epoxide hydrolase inhibitor, in cardiac hypertrophy. METHODS: Rat and H9C2 cell models of cardiac hypertrophy were induced by isoproterenol and angiotensin II, respectively, followed by TUPS treatment. The expression of hypertrophic markers, ANP and BNP, was determined by quantitative real-time PCR. The abundance of Beclin-1, LC3, p-AMPK and phosphorylated-mammalian target of rapamycin (p-mTOR) proteins was analysed by Western blot and immunohistocytology. Cell morphology and viability were evaluated by F-actin staining and MTS. H9C2 cells were transfected with GFP-LC3 to evaluate autophagy flux. KEY FINDINGS: TUPS significantly inhibited rat heart size, heart weight-to-body weight ratio, heart wall thickness, hypertrophic H9C2 cell swelling and viability suppression as well as the expression of ANP and BNP genes in hypertrophic models. In addition, autophagic markers Beclin-1 and LC3 were elevated in both cellular and animal models, which were suppressed by TUPS, with corresponding changes of autophagy flux. The abundance of p-AMPK was increased, while p-mTOR was decreased in hypertrophic cells, which were abolished by TUPS. Rapamycin decreased p-mTOR level, increased Beclin-1 and LC3 expression and induced cell size enlargement and cell viability inhibition in hypertrophic H9C2 cells treated with TUPS. CONCLUSIONS: TUPS inhibits cardiac hypertrophy by regulating mTOR/autophagy axis. Title: Tacrine(10)-Hupyridone Prevents Post-operative Cognitive Dysfunction via the Activation of BDNF Pathway and the Inhibition of AChE in Aged Mice Chen H, Wu X, Gu X, Zhou Y, Ye L, Zhang K, Pan H, Wang J, Wei H and Han YF <5 more author(s)> Chen H, Wu X, Gu X, Zhou Y, Ye L, Zhang K, Pan H, Wang J, Wei H, Zhu B, Naman CB, Mak SH, Carlier PR, Cui W, Han YF (- 5) Ref: Front Cell Neurosci, 12:396, 2018 : PubMed ESTHER: Chen_2018_Front.Cell.Neurosci_12_396 PubMedSearch: Chen 2018 Front.Cell.Neurosci 12 396 PubMedID: 30483056 Inhibitor(s) related to this paper: Hupyridone Abstract Post-operative cognitive dysfunction (POCD) could cause short-term or long-term cognitive disruption lasting weeks or months after anesthesia and surgery in elderly. However, no effective treatment of POCD is currently available. Previous studies indicated that the enhancement of brain-derived neurotrophic factor (BDNF) expression, and the elevation the cholinergic system, might be effective to prevent POCD. In this study, we have discovered that tacrine(10)-hupyridone (A10E), a novel acetylcholinesterase (AChE) inhibitor derived from tacrine and huperzine A, could prevent surgery-induced short-term and long-term impairments of recognition and spatial cognition, as evidenced by the novel object recognition test and Morris water maze (MWM) tests, in aged mice. Moreover, A10E significantly increased the expression of BDNF and activated the downstream Akt and extracellular regulated kinase (ERK) signaling in the surgery-treated mice. Furthermore, A10E substantially enhanced choline acetyltransferase (ChAT)-positive area and decreased AChE activity, in the hippocampus regions of surgery-treated mice, indicating that A10E could prevent surgery-induced dysfunction of cholinergic system, possibly via increasing the synthesis of acetylcholine and the inhibition of AChE. In conclusion, our results suggested that A10E might prevent POCD via the activation of BDNF pathway and the inhibition of AChE, concurrently, in aged mice. These findings also provided a support that A10E might be developed as a potential drug lead for POCD. Title: Kinetic resolution of sec-alcohols catalysed by Candida antarctica lipase B displaying Pichia pastoris whole-cell biocatalyst Zhang K, Pan Z, Diao Z, Liang S, Han S, Zheng S, Lin Y Ref: Enzyme Microb Technol, 110:8, 2018 : PubMed ESTHER: Zhang_2018_Enzyme.Microb.Technol_110_8 PubMedSearch: Zhang 2018 Enzyme.Microb.Technol 110 8 PubMedID: 29310860 Abstract Kinetic resolution of sec-alcohols is a green process with biocatalyst. Candida antarctica lipase B (CALB) displayed on Pichia pastoris cell-surface (Pp-CALB) was characterized in kinetic resolution of sec-alcohols with different structures. The reaction parameters including acyl donors, molar ratio of substrates, solvents and temperatures were examined with 2-octanol as model substrate. 47.4% molar conversion of 2-octanol and 99.7% eep were obtained after a 5h reaction with Pp-CALB, and 90% of its original activity still remained after being reused for 10 cycles. Pp-CALB was then used to several sec-alcohols and it showed great enzymatic activity and enantioselectivity to all tested sec-alcohols, more than 93.1% of eep. The enantioselective characteristics of Pp-CALB catalysed sec-alcohols with different structures were compared with Novozyme 435 which was almost the same. Solvent free system as one way of green chemistry was applied to Pp-CALB and Pp-CALB showed great catalytic activity and enantioselectivity. Pp-CALB was potential biocatalyst of high enzymatic activity and enantioselectivity using in resolution of sec-alcohols. Title: Downregulation of the N-myc downstream regulated gene 1 is related to enhanced proliferation, invasion and migration of pancreatic cancer Cen G, Zhang K, Cao J, Qiu Z Ref: Oncol Rep, 37:1189, 2017 : PubMed ESTHER: Cen_2017_Oncol.Rep_37_1189 PubMedSearch: Cen 2017 Oncol.Rep 37 1189 PubMedID: 28075464 Abstract The N-myc downstream regulated gene 1 (NDRG1) is differently expressed in human malignancies according to the tumor type. We investigated the expression of NDRG1 in pancreatic cancer tissues and cell lines as well as how it affects tumor growth, invasion and migration in pancreatic cancer cells. Experimental groups included NDRG1 overexpression and knockdown pancreatic cancer cell lines. Lentivirus-based empty vector transfected cells (NC group) were considered control groups. Proliferation, invasion and migration related proteins such as STAT3, MMPs, PTEN, PI3K/AKT were assessed by CCK-8, Transwell assay and western blotting. Efficient NDRG1 overexpression results in reduced cell proliferation, invasion and migration. Inversely, downregulation of NDRG1 promoted proliferation, invasion and migration. We also found NDRG1 could deactivate p-STAT3, PI3K, p-AKT, MMP2, MMP9 and activate PTEN. NDRG1 is a potential anti-oncogene. Its upregulation significantly decreases pancreatic cancer tumorigenesis, likely by inhibiting STAT3 and the PI3K/AKT signaling pathway. Title: Esterase D enhances type I interferon signal transduction to suppress foot-and-mouth disease virus replication Li W, Zhu Z, Cao W, Yang F, Zhang X, Li D, Zhang K, Li P, Mao R and Zheng H <1 more author(s)> Li W, Zhu Z, Cao W, Yang F, Zhang X, Li D, Zhang K, Li P, Mao R, Liu X, Zheng H (- 1) Ref: Mol Immunol, 75:112, 2016 : PubMed ESTHER: Li_2016_Mol.Immunol_75_112 PubMedSearch: Li 2016 Mol.Immunol 75 112 PubMedID: 27267271 Abstract The enzymatic activities of esterase D (ESD) are involved in many human diseases. However, no antiviral property of ESD has been described to date. Foot-and-mouth disease virus (FMDV) is the etiological agent of foot-and-mouth disease. In this study, we showed that FMDV infection triggered ESD expression. Overexpression of ESD significantly suppressed FMDV replication and knockdown of ESD expression enhanced virus replication, showing an essential antiviral role of ESD. Furthermore, we found that Sendai-virus-induced interferon (IFN) signaling was enhanced by upregulation of ESD, and ESD promoted activation of the IFN-beta promoter simulated by IFN regulatory factor (IRF)3 or its upstream molecules (retinoic acid-inducible gene-I, melanoma differentiation-associated protein 5, virus-induced signaling adaptor and TANK binding kinase 1). Detailed analysis revealed that ESD protein enhanced IRF3 phosphorylation during FMDV infection. Overexpression of ESD also promoted the expression of various antiviral interferon-stimulated genes (ISGs) and knockdown of ESD impaired the expression of these antiviral genes during FMDV infection. Our findings demonstrate a new mechanism evolved by ESD to enhance type I IFN signal transduction and suppress viral replication during FMDV infection. Title: Design, synthesis and bioactivity of novel phthalimide derivatives as acetylcholinesterase inhibitors Si W, Zhang T, Zhang L, Mei X, Dong M, Zhang K, Ning J Ref: Bioorganic & Medicinal Chemistry Lett, 26:2380, 2016 : PubMed ESTHER: Si_2016_Bioorg.Med.Chem.Lett_26_2380 PubMedSearch: Si 2016 Bioorg.Med.Chem.Lett 26 2380 PubMedID: 27017111 Abstract A series of novel phthalimide derivatives related to benzylpiperazine were synthesized and evaluated as cholinesterase inhibitors. The results showed that all compounds were able to inhibit acetylcholinesterase (AChE), with two of them dramatically inhibiting butyrylcholinesterase (BuChE). Most compounds exhibited potent anti-AChE activity in the range of nM concentrations. In particular, compounds 7aIII and 10a showed the most potent activity with the IC50 values of 18.44nM and 13.58nM, respectively. To understand the excellent activity of these compounds, the structure-activity relationship was further examined. The protein-ligand docking study demonstrated that the target compounds have special binding modes and these results are in agreement with the kinetic study. Title: Complete genome sequences of one human respiratory syncytial antigenic group a virus from china and its four mouse-adapted isolates Zhang K, He J, Li C, Bose ME, Henrickson KJ, Zhou J, Zheng BJ Ref: Genome Announc, 3:, 2015 : PubMed ESTHER: Zhang_2015_Genome.Announc_3_0 PubMedSearch: Zhang 2015 Genome.Announc 3 0 PubMedID: 25744999 Gene_locus related to this paper: 9noca-a0a0d5aa12, 9noca-a0a0d5abi2 Abstract In this study, one human respiratory syncytial antigenic group A virus (HRSV-A-GZ08-0) and its four BALB/c mouse-adapted isolates were sequenced and elucidated. Nineteen nucleotides were mutated between HRSV-A-GZ08-0 and the four mouse-adapted isolates. Title: Deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2 Zhang H, Wang T, Zhang K, Liu Y, Huang F, Zhu X, Wang MH, Tang W, Wang J, Huang H Ref: Critical Care Medicine, 42:e345, 2014 : PubMed ESTHER: Zhang_2014_Crit.Care.Med_42_e345 PubMedSearch: Zhang 2014 Crit.Care.Med 42 e345 PubMedID: 24448199 Abstract OBJECTIVE: Inhibition of soluble epoxide hydrolase (Ephx2) has been shown to play a protective role in cardiac hypertrophy, but the mechanism is not fully understood. We tested the hypothesis that deletion of soluble epoxide hydrolase attenuates cardiac hypertrophy via down-regulation of cardiac fibroblasts-derived fibroblast growth factor-2. DESIGN: Prospective, controlled, and randomized animal study. SETTING: University laboratory. SUBJECTS: Male wild-type C57BL/6 mice and Ephx2 (-/-) mice. INTERVENTIONS: Male wild-type or Ephx2 (-/-) mice were subjected to transverse aorta constriction surgery. MEASUREMENTS AND MAIN Title: Specific adaptation of Ustilaginoidea virens in occupying host florets revealed by comparative and functional genomics Zhang Y, Zhang K, Fang A, Han Y, Yang J, Xue M, Bao J, Hu D, Zhou B and Sun W <18 more author(s)> Zhang Y, Zhang K, Fang A, Han Y, Yang J, Xue M, Bao J, Hu D, Zhou B, Sun X, Li S, Wen M, Yao N, Ma LJ, Liu Y, Zhang M, Huang F, Luo C, Zhou L, Li J, Chen Z, Miao J, Wang S, Lai J, Xu JR, Hsiang T, Peng YL, Sun W (- 18) Ref: Nat Commun, 5:3849, 2014 : PubMed ESTHER: Zhang_2014_Nat.Commun_5_3849 PubMedSearch: Zhang 2014 Nat.Commun 5 3849 PubMedID: 24846013 Gene_locus related to this paper: ustvr-a0a063bxn3 Abstract Ustilaginoidea virens (Cooke) Takah is an ascomycetous fungus that causes rice false smut, a devastating emerging disease worldwide. Here we report a 39.4 Mb draft genome sequence of U. virens that encodes 8,426 predicted genes. The genome has ~25% repetitive sequences that have been affected by repeat-induced point mutations. Evolutionarily, U. virens is close to the entomopathogenic Metarhizium spp., suggesting potential host jumping across kingdoms. U. virens possesses reduced gene inventories for polysaccharide degradation, nutrient uptake and secondary metabolism, which may result from adaptations to the specific floret infection and biotrophic lifestyles. Consistent with their potential roles in pathogenicity, genes for secreted proteins and secondary metabolism and the pathogen-host interaction database genes are highly enriched in the transcriptome during early infection. We further show that 18 candidate effectors can suppress plant hypersensitive responses. Together, our analyses offer new insights into molecular mechanisms of evolution, biotrophy and pathogenesis of U. virens. Title: Association of LIPC and advanced age-related macular degeneration Lee J, Zeng J, Hughes G, Chen Y, Grob S, Zhao L, Lee C, Krupa M, Quach J and Zhang K <10 more author(s)> Lee J, Zeng J, Hughes G, Chen Y, Grob S, Zhao L, Lee C, Krupa M, Quach J, Luo J, Wei X, Zhang X, Zhu J, Duan Y, Ferreyra H, Goldbaum M, Haw W, Shaw PX, Tang L, Zhang K (- 10) Ref: Eye (Lond), 27:265, 2013 : PubMed ESTHER: Lee_2013_Eye.(Lond)_27_265 PubMedSearch: Lee 2013 Eye.(Lond) 27 265 PubMedID: 23348725 Abstract PURPOSE: To determine whether there is an association between hepatic lipase (LIPC) and age-related macular degeneration (AMD) in two independent Caucasian cohorts. Title: Draft genome of the wheat A-genome progenitor Triticum urartu Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L and Zhang A <39 more author(s)> Ling HQ, Zhao S, Liu D, Wang J, Sun H, Zhang C, Fan H, Li D, Dong L, Tao Y, Gao C, Wu H, Li Y, Cui Y, Guo X, Zheng S, Wang B, Yu K, Liang Q, Yang W, Lou X, Chen J, Feng M, Jian J, Zhang X, Luo G, Jiang Y, Liu J, Wang Z, Sha Y, Zhang B, Tang D, Shen Q, Xue P, Zou S, Wang X, Liu X, Wang F, Yang Y, An X, Dong Z, Zhang K, Luo MC, Dvorak J, Tong Y, Yang H, Li Z, Wang D, Zhang A (- 39) Ref: Nature, 496:87, 2013 : PubMed ESTHER: Ling_2013_Nature_496_87 PubMedSearch: Ling 2013 Nature 496 87 PubMedID: 23535596 Gene_locus related to this paper: triua-m8a764, triua-m8ag96, triua-m7zp69, wheat-w5d1z6, wheat-w5d232, wheat-w5bnf5, triua-t1nm05, wheat-w5cae4, triua-m7ytf7, wheat-w5f1j8, triua-m8ad49, wheat-a0a077s1q2, wheat-a0a3b6c2m6, triua-m7zi26, wheat-a0a3b6at77, wheat-a0a3b6atp7 Abstract Bread wheat (Triticum aestivum, AABBDD) is one of the most widely cultivated and consumed food crops in the world. However, the complex polyploid nature of its genome makes genetic and functional analyses extremely challenging. The A genome, as a basic genome of bread wheat and other polyploid wheats, for example, T. turgidum (AABB), T. timopheevii (AAGG) and T. zhukovskyi (AAGGA(m)A(m)), is central to wheat evolution, domestication and genetic improvement. The progenitor species of the A genome is the diploid wild einkorn wheat T. urartu, which resembles cultivated wheat more extensively than do Aegilops speltoides (the ancestor of the B genome) and Ae. tauschii (the donor of the D genome), especially in the morphology and development of spike and seed. Here we present the generation, assembly and analysis of a whole-genome shotgun draft sequence of the T. urartu genome. We identified protein-coding gene models, performed genome structure analyses and assessed its utility for analysing agronomically important genes and for developing molecular markers. Our T. urartu genome assembly provides a diploid reference for analysis of polyploid wheat genomes and is a valuable resource for the genetic improvement of wheat. Title: Systematic unraveling of the unsolved pathway of nicotine degradation in Pseudomonas Tang H, Wang L, Wang W, Yu H, Zhang K, Yao Y, Xu P Ref: PLoS Genet, 9:e1003923, 2013 : PubMed ESTHER: Tang_2013_PLoS.Genet_9_e1003923 PubMedSearch: Tang 2013 PLoS.Genet 9 e1003923 PubMedID: 24204321 Abstract Microorganisms such as Pseudomonas putida play important roles in the mineralization of organic wastes and toxic compounds. To comprehensively and accurately elucidate key processes of nicotine degradation in Pseudomonas putida, we measured differential protein abundance levels with MS-based spectral counting in P. putida S16 grown on nicotine or glycerol, a non-repressive carbon source. In silico analyses highlighted significant clustering of proteins involved in a functional pathway in nicotine degradation. The transcriptional regulation of differentially expressed genes was analyzed by using quantitative reverse transcription-PCR. We observed the following key results: (i) The proteomes, containing 1,292 observed proteins, provide a detailed view of enzymes involved in nicotine metabolism. These proteins could be assigned to the functional groups of transport, detoxification, and amino acid metabolism. There were significant differences in the cytosolic protein patterns of cells growing in a nicotine medium and those in a glycerol medium. (ii) The key step in the conversion of 3-succinoylpyridine to 6-hydroxy-3-succinoylpyridine was catalyzed by a multi-enzyme reaction consisting of a molybdopeterin binding oxidase (spmA), molybdopterin dehydrogenase (spmB), and a (2Fe-2S)-binding ferredoxin (spmC) with molybdenum molybdopterin cytosine dinucleotide as a cofactor. (iii) The gene of a novel nicotine oxidoreductase (nicA2) was cloned, and the recombinant protein was characterized. The proteins and functional pathway identified in the current study represent attractive targets for degradation of environmental toxic compounds. Title: Molecular characterization of two carboxylesterase genes of the citrus red mite, Panonychus citri (Acari: Tetranychidae) Zhang K, Niu JZ, Ding TB, Dou W, Wang JJ Ref: Archives of Insect Biochemistry & Physiology, 82:213, 2013 : PubMed ESTHER: Zhang_2013_Arch.Insect.Biochem.Physiol_82_213 PubMedSearch: Zhang 2013 Arch.Insect.Biochem.Physiol 82 213 PubMedID: 23404785 Gene_locus related to this paper: 9acar-k7pb99 Abstract The citrus red mite, Panonychus citri, is known for its ability to rapidly evolve resistance to insecticides/acaricides and to adapt to hosts that produce toxins. To get better insight into the detoxification mechanism of P. citri, two carboxylesterase (CarE) genes, PCE1 and PCE2, were isolated and characterized. PCE1 and PCE2 contained open reading frames of 1,653 and 1,392 nucleotides, encoding proteins of 550 and 463 amino acid residues, respectively. Phylogenetic analyses showed that PCE1 and PCE2 were most closely related to the CarE genes from other phytophagous mites. The transcriptional profiles of two CarE genes among developmental stages (egg, larva, nymph, adult female, and adult male), after exposing to four acaricides (avermectin, azocyclotin, pyridaben, and spirodiclofen) and acid rain were investigated using real-time quantitative PCR (qPCR). The results showed that during development, PCE1 was highly expressed at the egg stage, whereas PCE2 was abundantly expressed at the adult stage of males. The expression levels of PCE1 were highly induced upon exposure to acaricides and acid rain. On the other hand, the expression levels of PCE2 were increased after treatment with avermectin and pyridaben. These results suggest that PCE1 and PCE2 may have distinct roles in different developmental stages and participate in the detoxification of acaricides. Title: Leishmania parasites possess a platelet-activating factor acetylhydrolase important for virulence Pawlowic MC, Zhang K Ref: Molecular & Biochemical Parasitology, 186:11, 2012 : PubMed ESTHER: Pawlowic_2012_Mol.Biochem.Parasitol_186_11 PubMedSearch: Pawlowic 2012 Mol.Biochem.Parasitol 186 11 PubMedID: 22954769 Gene_locus related to this paper: leima-q4fwg8, tryb2-q38de4, trycr-q4dvp2 Abstract Leishmania parasites are intracellular protozoans capable of salvaging and remodeling lipids from the host. To understand the role of lipid metabolism in Leishmania virulence, it is necessary to characterize the enzymes involved in the uptake and turnover of phospholipids. This study focuses on a putative phospholipase A2 (PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) in Leishmania major. In mammals, PAF-AH is a subgroup of PLA2 catalyzing the hydrolysis/inactivation of platelet-activating factor (PAF), a potent mediator of many leukocyte functions. By immunofluorescence microscopy, L. major PLA2/PAF-AH is predominantly localized in the ER. While wild type L. major parasites are able to hydrolyze PAF, this activity is completely absent in the PLA2/PAF-AH-null mutants. Meanwhile, deletion of PLA2/PAF-AH had no significant effect on the turnover of common glycerophospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylglycerol. PLA2/PAF-AH is not required for the growth of L. major parasites in culture, or the production of GPI-anchored virulence factors. Nonetheless, it does play a key role in the mammalian host as the PLA2/PAF-AH null mutants exhibit attenuated virulence in BALB/c mice. In conclusion, these data suggest that Leishmania parasites possess a functional PAF-AH and the degradation of PAF or PAF-like lipids is an important step in infection. Title: Distribution of CuO nanoparticles in juvenile carp (Cyprinus carpio) and their potential toxicity Zhao J, Wang Z, Liu X, Xie X, Zhang K, Xing B Ref: J Hazard Mater, 197:304, 2011 : PubMed ESTHER: Zhao_2011_J.Hazard.Mater_197_304 PubMedSearch: Zhao 2011 J.Hazard.Mater 197 304 PubMedID: 22014442 Abstract Adverse effect of engineered nanoparticles (NPs) on the aquatic environment and organisms has recently drawn much attention. This paper reports on the toxicity of CuO NPs to juvenile carp (Cyprinus carpio) and their distribution in the fish. CuO NPs and its counterpart bulk particles (BPs) (10, 50, 100, 200, 300, 500 and 1000 mg L(-1)) exhibited no acute toxicity (96 h), while during the 30 day sub-acute toxicity test, carp growth was significantly inhibited by CuO NPs (100 mg L(-1)) in comparison to control, CuO BPs and Cu(2+) groups. CuO NPs (or released Cu(2+) ions inside the fish body) could distribute in various tissues/organs and followed an order: intestine>gill>muscle>skin and scale>liver>brain. For time-related distribution, Cu content (expressed on a dry mass basis) in intestine, gill and liver increased faster (within 1 day) and they had obviously higher Cu content than other tissues/organs at all exposure times. CuO NPs could be excreted by carp to lower their toxicity. Cholinesterase activity was inhibited during CuO NPs exposure, suggesting NPs exposure could have potential neurotoxicity, and free Cu(2+) ions dissolved inside the carp body was responsible for the cholinesterase inhibition. Finally, actual suspended NPs concentrations should be used instead of initially added concentrations whenever possible in nanotoxicity studies. Title: Crystal structure of a novel esterase Rv0045c from Mycobacterium tuberculosis Zheng X, Guo J, Xu L, Li H, Zhang D, Zhang K, Sun F, Wen T, Liu S, Pang H Ref: PLoS ONE, 6:e20506, 2011 : PubMed ESTHER: Zheng_2011_PLoS.ONE_6_e20506 PubMedSearch: Zheng 2011 PLoS.ONE 6 e20506 PubMedID: 21637775 Gene_locus related to this paper: myctu-RV0045C Abstract There are at least 250 enzymes in Mycobacterium tuberculosis (M. tuberculosis) involved in lipid metabolism. Some of the enzymes are required for bacterial survival and full virulence. The esterase Rv0045c shares little amino acid sequence similarity with other members of the esterase/lipase family. Here, we report the 3D structure of Rv0045c. Our studies demonstrated that Rv0045c is a novel member of alpha/beta hydrolase fold family. The structure of esterase Rv0045c contains two distinct domains: the alpha/beta fold domain and the cap domain. The active site of esterase Rv0045c is highly conserved and comprised of two residues: Ser154 and His309. We proposed that Rv0045c probably employs two kinds of enzymatic mechanisms when hydrolyzing C-O ester bonds within substrates. The structure provides insight into the hydrolysis mechanism of the C-O ester bond, and will be helpful in understanding the ester/lipid metabolism in M. tuberculosis. Title: Cellulosilyticum ruminicola, a newly described rumen bacterium that possesses redundant fibrolytic-protein-encoding genes and degrades lignocellulose with multiple carbohydrate- borne fibrolytic enzymes Cai S, Li J, Hu FZ, Zhang K, Luo Y, Janto B, Boissy R, Ehrlich G, Dong X Ref: Applied Environmental Microbiology, 76:3818, 2010 : PubMed ESTHER: Cai_2010_Appl.Environ.Microbiol_76_3818 PubMedSearch: Cai 2010 Appl.Environ.Microbiol 76 3818 PubMedID: 20400560 Gene_locus related to this paper: 9firm-d2kfj6, 9firm-d2kfp1, 9firm-d2kfp6 Abstract Cellulosilyticum ruminicola H1 is a newly described bacterium isolated from yak (Bos grunniens) rumen and is characterized by its ability to grow on a variety of hemicelluloses and degrade cellulosic materials. In this study, we performed the whole-genome sequencing of C. ruminicola H1 and observed a comprehensive set of genes encoding the enzymes essential for hydrolyzing plant cell wall. The corresponding enzymatic activities were also determined in strain H1; these included endoglucanases, cellobiohydrolases, xylanases, mannanase, pectinases, and feruloyl esterases and acetyl esterases to break the interbridge cross-link, as well as the enzymes that degrade the glycosidic bonds. This bacterium appears to produce polymer hydrolases that act on both soluble and crystal celluloses. Approximately half of the cellulytic activities, including cellobiohydrolase (50%), feruloyl esterase (45%), and one third of xylanase (31%) and endoglucanase (36%) activities were bound to cellulosic fibers. However, only a minority of mannase (6.78%) and pectinase (1.76%) activities were fiber associated. Strain H1 seems to degrade the plant-derived polysaccharides by producing individual fibrolytic enzymes, whereas the majority of polysaccharide hydrolases contain carbohydrate-binding module. Cellulosome or cellulosomelike protein complex was never isolated from this bacterium. Thus, the fibrolytic enzyme production of strain H1 may represent a different strategy in cellulase organization used by most of other ruminal microbes, but it applies the fungal mode of cellulose production. Title: Genome-wide association study of advanced age-related macular degeneration identifies a role of the hepatic lipase gene (LIPC) Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, Raychaudhuri S, Tan PL, Oh EC, Merriam JE and Seddon JM <16 more author(s)> Neale BM, Fagerness J, Reynolds R, Sobrin L, Parker M, Raychaudhuri S, Tan PL, Oh EC, Merriam JE, Souied E, Bernstein PS, Li B, Frederick JM, Zhang K, Brantley MA, Jr., Lee AY, Zack DJ, Campochiaro B, Campochiaro P, Ripke S, Smith RT, Barile GR, Katsanis N, Allikmets R, Daly MJ, Seddon JM (- 16) Ref: Proc Natl Acad Sci U S A, 107:7395, 2010 : PubMed ESTHER: Neale_2010_Proc.Natl.Acad.Sci.U.S.A_107_7395 PubMedSearch: Neale 2010 Proc.Natl.Acad.Sci.U.S.A 107 7395 PubMedID: 20385826 Abstract Advanced age-related macular degeneration (AMD) is the leading cause of late onset blindness. We present results of a genome-wide association study of 979 advanced AMD cases and 1,709 controls using the Affymetrix 6.0 platform with replication in seven additional cohorts (totaling 5,789 unrelated cases and 4,234 unrelated controls). We also present a comprehensive analysis of copy-number variations and polymorphisms for AMD. Our discovery data implicated the association between AMD and a variant in the hepatic lipase gene (LIPC) in the high-density lipoprotein cholesterol (HDL) pathway (discovery P = 4.53e-05 for rs493258). Our LIPC association was strongest for a functional promoter variant, rs10468017, (P = 1.34e-08), that influences LIPC expression and serum HDL levels with a protective effect of the minor T allele (HDL increasing) for advanced wet and dry AMD. The association we found with LIPC was corroborated by the Michigan/Penn/Mayo genome-wide association study; the locus near the tissue inhibitor of metalloproteinase 3 was corroborated by our replication cohort for rs9621532 with P = 3.71e-09. We observed weaker associations with other HDL loci (ABCA1, P = 9.73e-04; cholesterylester transfer protein, P = 1.41e-03; FADS1-3, P = 2.69e-02). Based on a lack of consistent association between HDL increasing alleles and AMD risk, the LIPC association may not be the result of an effect on HDL levels, but it could represent a pleiotropic effect of the same functional component. Results implicate different biologic pathways than previously reported and provide new avenues for prevention and treatment of AMD. Title: Adsorption and inhibition of butyrylcholinesterase by different engineered nanoparticles Wang Z, Zhang K, Zhao J, Liu X, Xing B Ref: Chemosphere, 79:86, 2010 : PubMed ESTHER: Wang_2010_Chemosphere_79_86 PubMedSearch: Wang 2010 Chemosphere 79 86 PubMedID: 20089293 Abstract Butyrylcholinesterase (BChE), an important enzyme present in brain, serum and nervous system, is sensitive to neurotoxin. Engineered nanoparticles (NPs) may enter the mammalian body and be toxic. To investigate the potential neurotoxicity of different NPs and the interaction between NPs and BChE, three metal NPs (Cu-C, Cu and Al), three oxides NPs (SiO(2), TiO(2) and Al(2)O(3)), two carbon nanotubes (MWCNT and SWCNT) and two micro-scaled particles (Cu and activated carbon) were used to test their adsorption and inhibition on human serum BChE. At 800mgL(-1), adsorption and inhibition of BChE by MWCNT were the highest, 97% and 96%, respectively, while Al NPs showed the lowest adsorption (6.8%) and inhibition rates (3.3%). Ions could be dissolved in all metal and oxide NPs suspensions except TiO(2) NPs. In comparison to other ions, Cu(2+) released in Cu and Cu-C suspensions had the highest BChE activity reduction, 39.1% and 42.6%, respectively. The contribution of dissolved ions to the total inhibition by NPs suspension followed a decreasing sequence of Al (66%)>Cu (46%)>Cu-C (45%)>Al(2)O(3) (44%)>SS1[SiO(2)] (25%)>SP1[SiO(2)] (4%), suggesting that the inhibition of BChE may partly result from ion dissolution from NPs. The inhibition of BChE by micro-scaled activated carbon and Cu particles was significantly lower than that of their nano-scaled particles. The inhibition of BChE by MWCNT, SWCNT, TiO(2) (HR3) and Cu NPs showed concentration-response relationships. Their median inhibitory concentrations (IC(50)) were 97, 49, 206 and 1.54mgL(-1), respectively. These results indicate that these four NPs may have neurotoxicity and BChE may be potentially used as a biomarker of NPs in the environment. Title: Gender differences in cognitive ability associated with genetic variants of NLGN4 Zhang K, Gao X, Qi H, Li J, Zheng Z, Zhang F Ref: Neuropsychobiology, 62:221, 2010 : PubMed ESTHER: Zhang_2010_Neuropsychobiology_62_221 PubMedSearch: Zhang 2010 Neuropsychobiology 62 221 PubMedID: 20714171 Abstract Neuroligin-4 (NL4), encoded by the NLGN4 gene on the X chromosome, is a neuronal-specific brain membrane protein which plays an important role in the formation of functional presynaptic elements and axon specialization. The genetic variants of NLGN4 affect the biological function of NL4, resulting in the manifestation of different psychiatric disorders. The present study investigates the influence of these genetic variants on cognitive performance. The cognitive abilities of 351 subjects were evaluated using the Chinese Wechsler Intelligence Scale Children. The haplotypes were assigned with the PHASE program. The ANOVA method was applied to investigate the relationship between single SNP, the identified target haplotypes and cognitive performance in a random sample. We observed that the X(C) allele of rs5916271 and X(A) allele of the re6638575 carriers had significantly higher cognitive ability performances than the noncarrier boys (p < 0.05). The target haplotype composed of 2 allele (X(CA+)) carriers also displayed a higher cognitive performance than that of the noncarriers boys. The genetic polymorphism of NLGN4 also had a significant effect on the boys' cognitive ability and other intelligence factors. Future research will involve determining the relationship between NLGN4 and personal cognitive ability. Title: Positive association of neuroligin-4 gene with nonspecific mental retardation in the Qinba Mountains Region of China Qi H, Xing L, Zhang K, Gao X, Zheng Z, Huang S, Guo Y, Zhang F Ref: Psychiatr Genet, 19:1, 2009 : PubMed ESTHER: Qi_2009_Psychiatr.Genet_19_1 PubMedSearch: Qi 2009 Psychiatr.Genet 19 1 PubMedID: 19125102 Abstract OBJECTIVE: Neuroligin-4 is essential for proper brain function. Some studies indicate a close relationship between neuroligin-4 and several human psychiatric conditions. METHODS: The case-control method was used to study the association between nonspecific mental retardation (NSMR) and genetic variants of neuroligin-4 gene (NLGN4). Five single nucleotide polymorphisms (SNPs: rs5916271, rs7049300, rs6638575, rs3810686, and rs1882260) were genotyped by PCR-RFLP/SSCP method in the NLGN4. RESULTS: Individual SNP analysis shows significant differences at SNPs rs3810686 and rs1882260 for allele frequency when NSMR cases and controls [odds ratio (OR)=1.589, 95% confidence interval (CI)=1.035-2.438, chi2=4.53, df=1, P=0.033; OR=2.050, 95% CI=1.211-3.470, chi2=7.38, df=1, P=0.007, respectively] were compared. Further haplotype analysis indicates that there are two haplotype sets, rs3810686-rs1882260 and rs6638575-rs3810686-rs1882260, which show statistical differences between NSMR cases and controls (chi2=6.79, df=2, global P=0.034; chi2=9.29, df=2, global P=0.0096, respectively). CONCLUSION: The results suggest a positive association between the genetic variants of the NLGN4 and NSMR in the Chinese children from Qinba Mountains Region. Title: Higher post-absorptive skeletal muscle LPL activity in African American vs. non-Hispanic White pre-menopausal women Berk ES, Johnson JA, Lee M, Zhang K, Boozer CN, Pi-Sunyer FX, Fried SK, Albu JB Ref: Obesity (Silver Spring), 16:199, 2008 : PubMed ESTHER: Berk_2008_Obesity.(Silver.Spring)_16_199 PubMedSearch: Berk 2008 Obesity.(Silver.Spring) 16 199 PubMedID: 18223635 Abstract OBJECTIVE: Higher post-absorptive post-heparin plasma lipoprotein lipase (LPL) activity has been reported in African Americans as compared to non-Hispanic whites but differences in tissue-specific LPL activity are unclear. METHODS AND PROCEDURES: Post-absorptive skeletal muscle (SM)-LPL (vastus lateralis ) and subcutaneous abdominal adipose tissue (AT)-LPL activity was measured in overweight, sedentary African American females (n = 11) as well as in their non-Hispanic white counterparts (n = 6) during a period of controlled low fat (30%) diet (for 10 days) combined with physical activity (for days 8-10). Post-absorptive substrate utilization was measured on day 10; fasting blood levels and SM and AT biopsies were obtained on day 11. Title: A phospholipase A1 platelet activator from the wasp venom of Vespa magnifica (Smith) Yang H, Xu X, Ma D, Zhang K, Lai R Ref: Toxicon, 51:289, 2008 : PubMed ESTHER: Yang_2008_Toxicon_51_289 PubMedSearch: Yang 2008 Toxicon 51 289 PubMedID: 18023835 Gene_locus related to this paper: vesmg-pa1 Abstract Wasp is an important venomous animal that can induce human fatalities. Aortic thrombosis and cerebral infarction are major clinical symptoms after massive wasp stings but the reason leading to the envenomation manifestation is still not known. In this paper, a toxin protein is purified and characterized by Sephadex G-75 gel filtration, CM-Sephadex C-25 cationic exchange and fast protein liquid chromatography (FPLC) from the venom of the wasp, Vespa magnifica (Smith). This protein, named magnifin, contains phospholipase-like activity and induces platelet aggregation. The cDNA encoding magnifin is cloned from the venom sac cDNA library of the wasp. The predicted protein was deduced from the cDNA with a sequence composed of 337 amino acid residues. Magnifin is very similar to other phospholipase A(1) (PLA(1)), especially to other wasp allergen PLA(1). Magnifin can activate platelet aggregation and induce thrombosis in vivo. The current results proved that PLA(1) in wasp venom could be contributable to aortic thrombosis after massive wasp stings. Title: [An experimental study of the effects of profenofos on antioxidase in rabbits] Lin L, Liu J, Zhang K, Chen Y Ref: Wei Sheng Yan Jiu, 32:434, 2003 : PubMed ESTHER: Lin_2003_Wei.Sheng.Yan.Jiu_32_434 PubMedSearch: Lin 2003 Wei.Sheng.Yan.Jiu 32 434 PubMedID: 14650183 Abstract In order to explore the effects of superoxide dismutase(SOD), catalase(CAT), glutathione-peroxidase (GSH-Px) in rabbits exposed by profenofos and its meaning. 18 rabbits were divided into three groups randomly: A group (high-dose group), B group(low-dose group), C group(control group), each group including 6 rabbits. The activities of SOD, CAT, GSH-Px in plasma, and cholinesterase(ChE) in blood were measured in different exposure period. The results showed that activities of SOD, CAT and GSH-Px increased, ChE decreased markedly compared with those in the same group before experiment and control group (P < 0.05, P < 0.01). The increase of antioxidase activities was earlier than the decease of ChE activity. It suggests that profenofos can result in the increases of the activities of SOD, CAT and GSH-Px, which may be earlier diagnostic index in profenofos poisoning. Title: Purification of an extracellular D-(-)-3-hydroxybutyrate oligomer hydrolase from Pseudomonas sp. strain A1 and cloning and sequencing of its gene Zhang K, Shiraki M, Saito T Ref: Journal of Bacteriology, 179:72, 1997 : PubMed ESTHER: Zhang_1997_J.Bacteriol_179_72 PubMedSearch: Zhang 1997 J.Bacteriol 179 72 PubMedID: 8981982 Abstract An extracellular D-(-)-3-hydroxybutyrate oligomer hydrolase was purified from a poly(3-hydroxybutyrate)-degrading bacterium, Pseudomonas sp. strain A1. The purified enzyme hydrolyzed the D-(-)-3-hydroxybutyrate dimer and trimer at similar rates. The enzyme activity was inhibited by a low concentration of diisopropylfluorophosphate. The molecular weight of the hydrolase was estimated to be about 70,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A 10-kbp DNA fragment of A1 was detected by hybridization with the gene (2 kbp) of an extracellular poly(3-hydroxybutyrate) depolymerase from Alcaligenes faecalis. Subsequent subcloning showed that a SmaI-KpnI fragment (2.8 kbp) was responsible for expression of the hydrolase in Escherichia coli and an in vitro transcription-translation system. The expressed protein detected by immunostaining had the same molecular weight as the purified enzyme from A1. The protein band detected in the in vitro transcription-translation system had a molecular size of 72 kDa. The nucleotide sequence of the SmaI-KpnI fragment was determined, and one open reading frame (2,112 nucleotides) was found. It specifies a protein with a deduced molecular weight of 72,876 (704 amino acids). In this sequence, the consensus sequence of serine-dependent hydrolysis, G-X-S-X-G, did not exist. | |||||||
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