Author Report for: Wu QNo contact information in database for Wu Q
Liu Y, Tang S, Wang X, Tang X, Wu Q, Huang Z, Ding J Ref: J Hazard Mater, 451:131128, 2023 : PubMed ESTHER: Liu_2023_J.Hazard.Mater_451_131128 PubMedSearch: Liu 2023 J.Hazard.Mater 451 131128 PubMedID: 36893599 Gene_locus related to this paper: 9actn-EstGS1 Abstract The long-term and excessive use of pyrethroid pesticides poses substantial health risks and ecosystem concerns. Several bacteria and fungi have been reported that could degrade pyrethroids. The ester-bond hydrolysis using hydrolases is the initial regulatory metabolic reaction of pyrethroids. However, the thoroughly biochemical characterization of hydrolases involved in this process is limited. Here, a novel carboxylesterase, designated as EstGS1 that could hydrolyze pyrethroid pesticides was characterized. EstGS1 showed low sequence identity (<27.03%) compared to other reported pyrethroid hydrolases and belonged to the hydroxynitrile lyase family that preferred short short-chain acyl esters (C2 to C8). EstGS1 displayed the maximal activity of 213.38 U/mg at 60 degreesC and pH 8.5 using pNPC2 as substrate, with K(m) and V(max) were 2.21 +/- 0.72 mM and 212.90 +/- 41.78 microM/min, respectively. EstGS1 is a halotolerant esterase and remains stable in 5.1 M NaCl. Based on molecular docking and mutational analysis, the catalytic triad of S(74)-D(181)-H(212) and three other substrate-binding residues I(108), S(159), and G(75) are critical for the enzymatic activity of EstGS1. Additionally, 61 and 40 mg/L of deltamethrin and lambda-cyhalothrin were hydrolyzed by 20 U of EstGS1 in 4 h. This work presents the first report on a pyrethroid pesticide hydrolase characterized from a halophilic actinobacteria. Title: Cholinergic drugs reduce metabolic inflammation and diabetic myocardial injury by regulating the gut bacterial component lipopolysaccharide-induced ERK/Egr-1 pathway Wu Q, Zhao M, Li D, He X, Zang W Ref: FASEB Journal, 37:e22917, 2023 : PubMed ESTHER: Wu_2023_FASEB.J_37_e22917 PubMedSearch: Wu 2023 FASEB.J 37 e22917 PubMedID: 37039813 Abstract Autonomic imbalance and metabolic inflammation are important pathological processes in diabetic cardiomyopathy. Gut microbiota dysbiosis and increased levels of bacterial component lipopolysaccharide (LPS) are associated with diabetic myocardial injury, but the mechanism by which gut microbes affect metabolic inflammation and cardiac injury remains unclear. We determined whether pyridostigmine (PYR), which inhibits cholinesterase to improve vagal activity, could regulate the disordered gut microbiota and attenuate gut barrier dysfunction, metabolic endotoxemia, and inflammation in diabetes. Db/db mice exhibited high blood glucose levels, insulin resistance, low vagal activity, and diabetic myocardial injury. Db/db mice also exhibited gut microbiota perturbations and subsequent disruption of gut barrier function, resulting in an influx of LPS, metabolic endotoxemia, and inflammation. PYR ameliorated the dysregulated glucose and lipid metabolism, modulated the overall structure of the gut microbiota, selectively enhanced the abundance of anti-inflammatory bacteria, and reduced the abundance of proinflammatory and potentially pathogenic bacteria in db/db mice. Importantly, PYR enhanced vagal activity, restored gut microbiota homeostasis, and alleviated gut barrier dysfunction. Therefore, the LPS-induced extracellular signal-regulated kinase (ERK)/early growth response-1 (Egr-1) pathway and consequent metabolic inflammation were inhibited, and eventually, cardiac hypertrophy, fibrosis, oxidative stress, and dysfunction were ameliorated in db/db mice. In vitro cardiomyocyte injury was induced by exposing primary neonatal rat ventricular cardiomyocytes to high glucose (HG) and LPS. In vitro analyses showed that HG + LPS induced ERK1/2 phosphorylation, Egr-1 expression, inflammation, and cell apoptosis, which were inhibited by acetylcholine (ACh). Alpha 7 nicotinic ACh receptor but not muscarinic 2 ACh receptor plays an important role in ACh-mediated anti-inflammatory effects and inhibiting the ERK/Egr-1 pathway in HG + LPS-administered neonatal rat ventricular cardiomyocytes. PYR and ACh ameliorated diabetic myocardial injury by inhibiting the LPS-induced ERK/Egr-1 pathway and metabolic inflammation. The vagus-gut-heart axis has provided new insights into the complex mechanisms of diabetes and offers novel therapeutic targets. Title: Chromium exposure altered metabolome and microbiome-associated with neurotoxicity in zebrafish Yan T, Xu Y, Zhu Y, Jiang P, Zhang Z, Li L, Wu Q Ref: J Appl Toxicol, :, 2023 : PubMed ESTHER: Yan_2023_J.Appl.Toxicol__ PubMedSearch: Yan 2023 J.Appl.Toxicol PubMedID: 36727205 Abstract In recent years, chromium (Cr) has been found to induce neurotoxicity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of chromium exposure on the metabolome and microbiome that may contribute to neurotoxicity in juvenile zebrafish. Zebrafish embryos were exposed to 1mg/L Cr (III) and 1mg/L Cr (VI) for seven days, respectively. Swimming distance and locomotor behavior was decreased, and acetylcholinesterase activity was reduced in Cr-exposed groups. Total cholesterol levels were decreased in Cr-exposed groups. The differential-expressed metabolites due to Cr exposure were mainly enriched in primary bile acid biosynthesis, which indicated that Cr exposure may promote cholesterol conversion. The abundance of Bacteroidetes decreased and the abundance of Actinomycetes increased in Cr- exposed groups, as compared to that in the control group. At the genus level, the abundance of Acinetobacter, Acidophorax, Mycobacterium, Aeromonas, Hydrophagophaga and Brevundimonas increased, whereas Chryseobacterium, Pseudomonas, Delftia and Ancylobacter decreased in the Cr-exposed groups. Analysis of the correlation between gut microbiota and bile acid metabolites showed that changes of gut microbial community due to Cr exposure may be related to secondary bile acid metabolism. Collectively, chromium exposure may disturb cholesterol metabolism, including primary bile acid and microbiota-related secondary bile acid metabolism. This study provides potential mechanism of the effects of chromium on neurotoxicity based on modulation of metabolome and gut microbiota diversity, which needs further verification. Title: Serum cholinesterase is associated with incident diabetic retinopathy: the Shanghai Nicheng cohort study Yu R, Ye X, Wang X, Wu Q, Jia L, Dong K, Zhu Z, Bao Y, Hou X, Jia W Ref: Nutr Metab (Lond), 20:26, 2023 : PubMed ESTHER: Yu_2023_Nutr.Metab.(Lond)_20_26 PubMedSearch: Yu 2023 Nutr.Metab.(Lond) 20 26 PubMedID: 37138337 Abstract BACKGROUND: Serum cholinesterase (ChE) is positively associated with incident diabetes and dyslipidemia. We aimed to investigate the relationship between ChE and the incidence of diabetic retinopathy (DR). METHODS: Based on a community-based cohort study followed for 4.6 years, 1133 participants aged 55-70 years with diabetes were analyzed. Fundus photographs were taken for each eye at both baseline and follow-up investigations. The presence and severity of DR were categorized into no DR, mild non-proliferative DR (NPDR), and referable DR (moderate NPDR or worse). Binary and multinomial logistic regression models were used to estimate the risk ratio (RR) and 95% confidence interval (CI) between ChE and DR. RESULTS: Among the 1133 participants, 72 (6.4%) cases of DR occurred. The multivariable binary logistic regression showed that the highest tertile of ChE (<= 422 U/L) was associated with a 2.01-fold higher risk of incident DR (RR 2.01, 95%CI 1.01-4.00; P for trend < 0.05) than the lowest tertile (< 354 U/L). The multivariable binary and multinomial logistic regression showed that the risk of DR increased by 41% (RR 1.41, 95%CI 1.05-1.90), and the risk of incident referable DR was almost 2-fold higher than no DR (RR 1.99, 95%CI 1.24-3.18) with per 1-SD increase of log(e)-transformed ChE. Furthermore, multiplicative interactions were found between ChE and elderly participants (aged 60 and older; P for interaction = 0.003) and men (P for interaction = 0.044) on the risk of DR. CONCLUSIONS: In this study, ChE was associated with the incidence of DR, especially referable DR. ChE was a potential biomarker for predicting the incident DR. Title: Identification of Novel Dipeptidyl Peptidase-IV Inhibitory Peptides in Chickpea Protein Hydrolysates Zan R, Wu Q, Chen Y, Wu G, Zhang H, Zhu L Ref: Journal of Agricultural and Food Chemistry, :, 2023 : PubMed ESTHER: Zan_2023_J.Agric.Food.Chem__ PubMedSearch: Zan 2023 J.Agric.Food.Chem PubMedID: 37191584 Abstract Dipeptidyl peptidase-IV (DPP-IV) is one of the main targets for blood sugar control. Some food protein-derived peptides are thought to have DPP-IV inhibitory (DPP-IVi) activity. In this study, chickpea protein hydrolysates (CPHs) obtained through Neutrase hydrolysis for 60 min (CPHs-Pro-60) exhibited the highest DPP-IVi activity. DPP-IVi activity after simulated in vitro gastrointestinal digestion was maintained at >60%. Peptide libraries are established after the identification of peptide sequences. Molecular docking verified that the four screened peptides (AAWPGHPEF, LAFP, IAIPPGIPYW, and PPGIPYW) could bind to the active center of DPP-IV. Notably, IAIPPGIPYW exhibited the most potent DPP-IVi activity (half maximal inhibitory concentration (IC(50)): 12.43 microM). Both IAIPPGIPYW and PPGIPYW exhibited excellent DPP-IVi activity in Caco-2 cells. These results indicated that chickpea could be used as a source of natural hypoglycemic peptides for food and nutritional applications. Title: The UV-induced uptake of melanosome by skin keratinocyte is triggered by alpha7 nicotinic acetylcholine receptor-mediated phagocytosis Guo MSS, Wu Q, Dong TT, Tsim KWK Ref: Febs J, :, 2022 : PubMed ESTHER: Guo_2022_FEBS.J__ PubMedSearch: Guo 2022 FEBS.J PubMedID: 36048140 Abstract The melanosome is an organelle that produces melanin for skin pigmentation, which is synthesized by epidermal melanocytes, subsequently transported, and internalized by epidermal keratinocytes. Exposure to ultraviolet (UV) from sunlight radiation is a major stimulator of melanosome uptake by keratinocytes. Acetylcholine (ACh) is known to be released by keratinocytes under UV exposure, which regulates melanin production in melanocytes by participating in which has been named as "skin synapse". Here, the role of cholinergic molecules, i.e., ACh and alpha7 nicotinic acetylcholine receptor (nAChR), in regulating melanosome uptake through phagocytosis by keratinocytes was illustrated. In cultured keratinocytes (HaCaT cells), the fluorescent beads at different sizes imitating melanosomes, or melanosomes, were phagocytosed under UV exposure. The UV-induced phagocytosis in keratinocytes was markedly increased by applied ACh, an acetylcholinesterase (AChE) inhibitor, or an alpha7 nAChR agonist. In contrast, the antagonist of alpha7 nAChR was able to fully block the UV-induced phagocytosis, suggesting the role of alpha7 nAChR in this event. The intracellular Ca(++) mobilization was triggered by UV exposure, accounting for the initiation of phagocytosis. The blockage of UV-mediated Ca(++) mobilization, triggered by BAPTA-AM or alpha7 nAChR antagonist, resulted in a complete termination of phagocytosis. Besides, the phosphorylation of cofilin, as well as expression and activation of RhoA, accounting for phagocytosis was induced by UV exposure: the phosphorylation was blocked by BAPTA-AM or alpha7 nAChR antagonist. The result suggests that cholinergic system, especially alpha7 nAChR, is playing a regulatory role in modulating melanosome uptake in keratinocytes being induced by UV exposure. Title: Two New Picoline-Derived Meroterpenoids with Anti-Acetylcholinesterase Activity from Ascidian-Derived Fungus Amphichorda felina Jiang M, Guo H, Wu Q, Yuan S, Liu L Ref: Molecules, 27:, 2022 : PubMed ESTHER: Jiang_2022_Molecules_27_ PubMedSearch: Jiang 2022 Molecules 27 PubMedID: 36014315 Abstract Amphichoterpenoids D (1) and E (2), two new picoline-derived meroterpenoids with a rare 6/6/6 tricyclic pyrano[3,2-c]pyridinyl-gamma-pyranone scaffold, were isolated from the ascidian-derived fungus Amphichorda felina SYSU-MS7908. Their structures, including the absolute configurations, were established by extensive spectroscopic methods (1D and 2D NMR and high-resolution mass spectrometry) and ECD calculations. Compounds 1 and 2 showed anti-acetylcholinesterase (anti-AChE) activities with IC(50) values of 12.5 microM and 11.6 microM, respectively. The binding interactions between 1, 2, and AChE were investigated using molecular docking analyses. Title: Display of a novel carboxylesterase CarCby on Escherichia coli cell surface for carbaryl pesticide bioremediation Liu Y, Wang X, Nong S, Bai Z, Han N, Wu Q, Huang Z, Ding J Ref: Microb Cell Fact, 21:97, 2022 : PubMed ESTHER: Liu_2022_Microb.Cell.Fact_21_97 PubMedSearch: Liu 2022 Microb.Cell.Fact 21 97 PubMedID: 35643494 Gene_locus related to this paper: baca2-a7z924 Inhibitor(s) related to this paper: Carbaryl Abstract BACKGROUND: Carbamate pesticides have been widely used in agricultural and forestry pest control. The large-scale use of carbamates has caused severe toxicity in various systems because of their toxic environmental residues. Carbaryl is a representative carbamate pesticide and hydrolase/carboxylesterase is the initial and critical enzyme for its degradation. Whole-cell biocatalysts have become a powerful tool for environmental bioremediation. Here, a whole cell biocatalyst was constructed by displaying a novel carboxylesterase/hydrolase on the surface of Escherichia coli cells for carbaryl bioremediation. RESULTS: The carCby gene, encoding a protein with carbaryl hydrolysis activity was cloned and characterized. Subsequently, CarCby was displayed on the outer membrane of E. coli BL21(DE3) cells using the N-terminus of ice nucleation protein as an anchor. The surface localization of CarCby was confirmed by SDS-PAGE and fluorescence microscopy. The optimal temperature and pH of the engineered E. coli cells were 30 degreesC and 7.5, respectively, using pNPC4 as a substrate. The whole cell biocatalyst exhibited better stability and maintained approximately 8-fold higher specific enzymatic activity than purified CarCby when incubated at 30 degreesC for 120 h. In addition, ~ 100% and 50% of the original activity was retained when incubated with the whole cell biocatalyst at 4 degC and 30 degreesC for 35 days, respectively. However, the purified CarCby lost almost 100% of its activity when incubated at 30 degreesC for 134 h or 37 degreesC for 96 h, respectively. Finally, approximately 30 mg/L of carbaryl was hydrolyzed by 200 U of the engineered E. coli cells in 12 h. CONCLUSIONS: Here, a carbaryl hydrolase-containing surface-displayed system was first constructed, and the whole cell biocatalyst displayed better stability and maintained its catalytic activity. This surface-displayed strategy provides a new solution for the cost-efficient bioremediation of carbaryl and could also have the potential to be used to treat other carbamates in environmental bioremediation. Title: A Novel Multifunctional 5,6-Dimethoxy-Indanone-Chalcone-Carbamate Hybrids Alleviates Cognitive Decline in Alzheimer's Disease by Dual Inhibition of Acetylcholinesterase and Inflammation Liu C, Sang Z, Pan H, Wu Q, Qiu Y, Shi J Ref: Front Aging Neurosci, 14:922650, 2022 : PubMed ESTHER: Liu_2022_Front.Aging.Neurosci_14_922650 PubMedSearch: Liu 2022 Front.Aging.Neurosci 14 922650 PubMedID: 35860673 Abstract BACKGROUNDS: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease. The treatment of AD through multiple pathological targets may generate therapeutic efficacy better. The multifunctional molecules that simultaneously hit several pathological targets have been of great interest in the intervention of AD. METHODS: Here, we combined the chalcone scaffold with carbamate moiety and 5,6-dimethoxy-indanone moiety to generate a novel multi-target-directed ligand (MTDL) molecule (E)-3-((5,6-dimethoxy-1-oxo-1,3-dihydro-2H-inden-2-ylidene)-methyl)phenylethyl(methyl) carbamate (named AP5). In silico approaches were used to virtually predict the binding interaction of AP5 with AChE, the drug-likeness, and BBB penetrance, and later validated by evaluation of pharmacokinetics (PK) in vivo by LC-MS/MS. Moreover, studies were conducted to examine the potential of AP5 for inhibiting AChE and AChE-induced amyloid-beta (Abeta) aggregation, attenuating neuroinflammation, and providing neuroprotection in the APP/PS1 model of AD. RESULTS: We found that AP5 can simultaneously bind to the peripheral and catalytic sites of AChE by molecular docking. AP5 exhibited desirable pharmacokinetic (PK) characteristics including oral bioavailability (67.2%), >10% brain penetrance, and favorable drug-likeness. AP5 inhibited AChE activity and AChE-induced Abeta aggregation in vivo and in vitro. Further, AP5 lowered Abeta plaque deposition and insoluble Abeta levels in APP/PS1 mice. Moreover, AP5 exerted anti-inflammatory responses by switching microglia to a disease-associated microglia (DAM) phenotype and preventing A1 astrocytes formation. The phagocytic activity of microglial cells to Abeta was recovered upon AP5 treatment. Importantly, chronic AP5 treatment significantly prevented neuronal and synaptic damage and memory deficits in AD mice. CONCLUSION: Together, our work demonstrated that AP5 inhibited the AChE activity, decreased Abeta plaque deposition by interfering Abeta aggregation and promoting microglial Abeta phagocytosis, and suppressed inflammation, thereby rescuing neuronal and synaptic damage and relieving cognitive decline. Thus, AP5 can be a new promising candidate for the treatment of AD. Title: Fosthiazate exposure induces oxidative stress, nerve damage, and reproductive disorders in nontarget nematodes Liu BD, Dong HT, Rong HW, Zhang RJ, Liu S, Wu Q, Zhong Y, He Z, Wang Z and Wang M <1 more author(s)> Liu BD, Dong HT, Rong HW, Zhang RJ, Liu S, Wu Q, Zhong Y, He Z, Wang Z, Li R, Wang M (- 1) Ref: Environ Sci Pollut Res Int, :, 2022 : PubMed ESTHER: Liu_2022_Environ.Sci.Pollut.Res.Int__ PubMedSearch: Liu 2022 Environ.Sci.Pollut.Res.Int PubMedID: 35796928 36112285 Abstract As a forceful nematicide, fosthiazate has been largely applied in the management of root-knot nematodes and other herbivorous nematodes. However, the toxicity of fosthiazate to nontarget nematodes is unclear. To explore the toxicity and the mechanisms of fosthiazate in nontarget nematodes, Caenorhabditis elegans was exposed to 0.01-10 mg/L fosthiazate. The results implied that treatment with fosthiazate at doses above 0.01 mg/L could cause injury to the growth, locomotion behavior, and reproduction of the nematodes. Moreover, L1 larvae were more vulnerable to fosthiazate exposure than L4 larvae. Reactive oxygen species (ROS) production and lipofuscin accumulation were fairly increased in 1 mg/L fosthiazate-exposed nematodes. Treatment with 0.1 mg/L fosthiazate significantly inhibited the activity of acetylcholinesterase (p < 0.01). Furthermore, subacute exposure to 10 mg/L fosthiazate strongly influenced the expression of genes related to oxidative stress, reproduction, and nerve function (e.g., gst-1, sod-1, puf-8, wee-1.3, and ace-1 genes). These findings suggested that oxidative stress, reproduction and nerve disorders could serve as key endpoints of toxicity induced by fosthiazate. The cyp-35a family gene was the main metabolic fosthiazate in C. elegans, and the cyp-35a5 subtype was the most sensitive, with a change in expression level of 2.11-fold compared with the control. These results indicate that oxidative stress and neurological and reproductive disorders played fundamental roles in the toxicity of fosthiazate in C. elegans and may affect the abundance and function of soil nematodes. Title: Discovery of novel beta-carboline-1,2,3-triazole hybrids as AChE/GSK-3beta dual inhibitors for Alzheimer's disease treatment Liu W, Tian L, Wu L, Chen H, Wang N, Liu X, Zhao C, Wu Z, Jiang X and Zhao Q <2 more author(s)> Liu W, Tian L, Wu L, Chen H, Wang N, Liu X, Zhao C, Wu Z, Jiang X, Wu Q, Xu Z, Zhao Q (- 2) Ref: Bioorg Chem, 129:106168, 2022 : PubMed ESTHER: Liu_2022_Bioorg.Chem_129_106168 PubMedSearch: Liu 2022 Bioorg.Chem 129 106168 PubMedID: 36191431 Inhibitor(s) related to this paper: ZTL-11 Abstract Alzheimer's disease (AD) is characterized by progressive cognitive impairment and mental behavior. The combination inhibition of two essential AD targets, acetylcholinesterase (AChE) and glycogen synthase kinase-3beta (GSK-3beta), might be a breakthrough in the discovery of therapeutic success. Herein, 17 beta-carboline-1,2,3-triazole hybrids were designed, synthesized, and evaluated for their AChE and GSK-3beta inhibitory potential. The results indicated that compound 21 has the most potent inhibition against eeAChE (IC(50) = 0.20 +/- 0.02 microM), hAChE (IC(50) = 0.34 +/- 0.01 microM) and GSK-3beta (IC(50) = 1.14 +/- 0.05 microM) among these compounds. In addition, it inhibited hAChE in a mixed type manner and could occupy the binding pocket forming diverse interactions with the target of AChE and GSK-3beta. Moreover, compound 21 showed low cytotoxicity against SH-SY5Y and HepG2 cell lines and good BBB permeability. Compound 21 also attenuated the tau hyperphosphorylation in the Tau (P301L) 293T cell model. The ADME projection exhibited that compound 21 has acceptable physicochemical characteristics. This study provides new leads for the assessment of AChE and GSK-3beta dual inhibition as a promising strategy for AD treatment. Title: Novel Bisamide Alkaloids Enantiomers from Pepper Roots (Piper nigrum L.) with Acetylcholinesterase Inhibitory and Anti-Neuroinflammatory Effects Wang Z, Li R, Wu Q, Duan J, Tan Y, Sun X, Chen R, Shi H, Wang M and Song SJ <7 more author(s)> Wang Z, Li R, Wu Q, Duan J, Tan Y, Sun X, Chen R, Shi H, Wang M, Wang YX, Xu ZY, Qin SY, Du NN, Yao GD, Lin B, Huang XX, Song SJ (- 7) Ref: Journal of Agricultural and Food Chemistry, :, 2022 : PubMed ESTHER: Wang_2022_J.Agric.Food.Chem__ PubMedSearch: Wang 2022 J.Agric.Food.Chem PubMedID: 35184556 36450093 Abstract The roots of Piper nigrum L., a seasoning for cooking various types of broths, are renowned for their high nutritional content and potential medicinal benefits. In this study, nine pairs of novel cyclohexene-type bisamide alkaloids (1a/1b-9a/9b) were isolated from the pepper roots using molecular network analysis strategies. Their structures were determined by extensive spectroscopic data, electronic circular dichroism (ECD) calculations, and X-ray diffraction analyses. Using an intermolecular Diels-Alder reaction, a strategy for the synthesis of bisamide alkaloids from different monomeric amide alkaloids was developed. Furthermore, these compounds were chirally separated for the first time, and compounds 3a and 5a/5b showed significant anti-neuroinflammation effects in the models of lipopolysaccharide(LPS)-induced BV2 microglial cells. Meanwhile, compounds 6b and 7a displayed concentration-dependent inhibitory activities against acetylcholinesterase with IC(50) values of 6.05 +/- 1.10 and 3.81 +/- 0.10 microM, respectively. These findings confirmed that these bisamide alkaloids could be applied in functional food formulations and pharmaceutical products as well as facilitate the further development and usage of pepper roots. Title: TPPU Downregulates Oxidative Stress Damage and Induces BDNF Expression in PC-12 Cells Wu Q, Lin M, Wu P, Zhao C, Yang S, Yu H, Xian W, Song J Ref: Comput Math Methods Med, 2022:7083022, 2022 : PubMed ESTHER: Wu_2022_Comput.Math.Methods.Med_2022_7083022 PubMedSearch: Wu 2022 Comput.Math.Methods.Med 2022 7083022 PubMedID: 35872930 Abstract OBJECTIVE: Ischemia-reperfusion is an ongoing clinical challenge that can lead to a series of pathological changes including oxidative stress. The inhibition of soluble epoxide hydrolase inhibitor (sEH) by 1-(1-propanoylpiperidin-4-yl)-3-[4-(trifluoromethoxy)phenyl]urea (TPPU) results in an anti-inflammatory, cardioprotective, and blood vessel growth-promoting effects. Therefore, this study focused on the protective effect of TPPU on a rat pheochromocytoma (PC-12) cell oxidative stress model induced by H(2)O(2). METHODS: CCK-8 and Hoechst 33342 were used to evaluate cell apoptosis and western blot to detect the apoptotic proteins and brain-derived neurotrophic factor (BDNF) expression. RESULT: The incubation with 100 microM, 50 microM, and 25 microM TPPU significantly increased PC-12 cell viability. Epoxyeicosatrienoic acid (EET) pretreatment also protected PC-12 cells from oxidative stress. In addition, TPPU reduced caspase-3 and Bax expression and induced Bcl-2 expression, and EETs exerted the same effect on caspase-3 expression as TPPU. A positive relationship was found between TPPU or EET incubation and BDNF expression. CONCLUSION: These results revealed that TPPU reduced PC-12 cell oxidative stress injury induced by H(2)O(2) and promoted BDNF expression. Title: Development and structure-activity relationship of tacrine derivatives as highly potent CDK2/9 inhibitors for the treatment of cancer Wu L, Liu W, Huang Y, Zhu C, Ma Q, Wu Q, Tian L, Feng X, Liu M and Zhao Q <6 more author(s)> Wu L, Liu W, Huang Y, Zhu C, Ma Q, Wu Q, Tian L, Feng X, Liu M, Wang N, Xu X, Liu X, Xu C, Qiu J, Xu Z, Zhao Q (- 6) Ref: Eur Journal of Medicinal Chemistry, 242:114701, 2022 : PubMed ESTHER: Wu_2022_Eur.J.Med.Chem_242_114701 PubMedSearch: Wu 2022 Eur.J.Med.Chem 242 114701 PubMedID: 36054949 Abstract CDK2/9 are members of the CDKs family, which play key roles in the occurrence and development of many cancers by regulating cell cycle and transcriptional prolongation, respectively. To further optimize and discuss the structure-activity relationships (SARs), a series of tacrine-based compounds were designed and synthesized from the compound ZLWT-37, which was studied by our group previously but no detailed SARs study was conducted on CDK2/9. Among this series, compounds ZLMT-12 (35) exhibited the most potent antiproliferative activity (GI(50) = 0.006 microM for HCT116) and superior CDK2/9 inhibitory properties (CDK2: IC(50) = 0.011 microM, CDK9: IC(50) = 0.002 microM). Meanwhile, ZLMT-12 showed a weak inhibitory effect on acetylcholinesterase (AChE, IC(50) = 19.023 microM) and butyrylcholinesterase (BuChE, IC(50) = 2.768 microM). In addition, ZLMT-12 can suppress colony formation and migration in HCT116 cells, as well as induce the apoptosis and arrest the cell cycle in the S phase and G2/M phase. In vivo investigations revealed that ZLMT-12 inhibits tumor growth in the HCT116 xenograft tumor model at a low dose of 10 mg/kg without causing hepatotoxicity. The acute toxicity test showed low toxicity with a median lethal dosage (LD(50)) of 104.417 mg/kg. These findings showed that ZLMT-12 might be used as a drug candidate by targeting CDK2/9. Title: Regulation of acetylcholinesterase during the lipopolysaccharide-induced inflammatory responses in microglial cells Xia Y, Wu Q, Mak S, Liu EYL, Zheng BZY, Dong TTX, Pi R, Tsim KWK Ref: FASEB Journal, 36:e22189, 2022 : PubMed ESTHER: Xia_2022_FASEB.J_36_e22189 PubMedSearch: Xia 2022 FASEB.J 36 e22189 PubMedID: 35129858 Abstract The non-classical function of acetylcholine (ACh) has been reported in neuroinflammation that represents the modulating factor in immune responses via activation of alpha7 nicotinic acetylcholine receptor (alpha7 nAChR), i.e., a cholinergic anti-inflammatory pathway (CAP). Acetylcholinesterase (AChE), an enzyme for ACh hydrolysis, has been proposed to have a non-classical function in immune cells. However, the involvement of AChE in neuroinflammation is unclear. Here, cultured BV2 cell, a microglial cell line, and primary microglia from rats were treated with lipopolysaccharide (LPS) to induce inflammation and to explore the regulation of AChE during this process. The expression profiles of AChE, alpha7 nAChR, and choline acetyltransferase (ChAT) were revealed in BV2 cells. The expression of AChE (G4 form) was induced significantly in LPS-treated BV2 cells: the induction was triggered by NF-kappaB and cAMP signaling. Moreover, ACh or alpha7 nAChR agonist suppressed the LPS-induced production of pro-inflammatory cytokines, as well as the phagocytosis of microglia, by activating alpha7 nAChR and followed by the regulation of NF-kappaB and CREB signaling. The ACh-induced suppression of inflammation was abolished in AChE overexpressed cells, but did not show a significant change in AChE mutant (enzymatic activity knockout) transfected cells. These results indicate that the neuroinflammation-regulated function of AChE may be mediated by controlling the ACh level in the brain system. Title: SARM1 deletion in parvalbumin neurons is associated with autism-like behaviors in mice Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J and Huang Z <13 more author(s)> Xiang L, Wu Q, Sun H, Miao X, Lv Z, Liu H, Chen L, Gu Y, Chen J, Zhou S, Jiang H, Du S, Zhou Y, Dong H, Fan Y, Miao S, Lu Q, Chang L, Wang H, Lu Y, Xu X, Wang W, Huang Z (- 13) Ref: Cell Death Dis, 13:638, 2022 : PubMed ESTHER: Xiang_2022_Cell.Death.Dis_13_638 PubMedSearch: Xiang 2022 Cell.Death.Dis 13 638 PubMedID: 35869039 Abstract Autism spectrum disorder (ASD), a group of neurodevelopmental disorder diseases, is characterized by social deficits, communication difficulties, and repetitive behaviors. Sterile alpha and TIR motif-containing 1 protein (SARM1) is known as an autism-associated protein and is enriched in brain tissue. Moreover, SARM1 knockdown mice exhibit autism-like behaviors. However, its specific mechanism in ASD pathogenesis remains unclear. Here we generated parvalbumin-positive interneurons (PVI)-specific conditional SARM1 knockout (SARM1(PV)-CKO) mice. SARM1(PV)-CKO male mice showed autism-like behaviors, such as mild social interaction deficits and repetitive behaviors. Moreover, we found that the expression level of parvalbumin was reduced in SARM1(PV)-CKO male mice, together with upregulated apoptosis-related proteins and more cleaved-caspase-3-positive PVIs, suggesting that knocking out SARM1 may cause a reduction in the number of PVIs due to apoptosis. Furthermore, the expression of c-fos was shown to increase in SARM1(PV)-CKO male mice, in combination with upregulation of excitatory postsynaptic proteins such as PSD-95 or neuroligin-1, indicating enhanced excitatory synaptic input in mutant mice. This notion was further supported by the partial rescue of autism-like behavior deficits by the administration of GABA receptor agonists in SARM1(PV)-CKO male mice. In conclusion, our findings suggest that SARM1 deficiency in PVIs may be involved in the pathogenesis of ASD. 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: Fine mapping of powdery mildew resistance gene MlWE74 derived from wild emmer wheat (Triticum turgidum ssp. dicoccoides) in an NBS-LRR gene cluster Zhu K, Li M, Wu H, Zhang D, Dong L, Wu Q, Chen Y, Xie J, Lu P and Hua W <13 more author(s)> Zhu K, Li M, Wu H, Zhang D, Dong L, Wu Q, Chen Y, Xie J, Lu P, Guo G, Zhang H, Zhang P, Li B, Li W, Wang Q, Zhu J, Hu W, Guo L, Wang R, Yuan C, Li H, Liu Z, Hua W (- 13) Ref: Theor Appl Genet, :, 2022 : PubMed ESTHER: Zhu_2022_Theor.Appl.Genet__ PubMedSearch: Zhu 2022 Theor.Appl.Genet PubMedID: 35006335 Abstract Powdery mildew resistance gene MlWE74, originated from wild emmer wheat accession G-748-M, was mapped in an NBS-LRR gene cluster of chromosome 2BS. Wheat powdery mildew, caused by Blumeria graminis f. sp. tritici (Bgt), is a globally devastating disease. Wild emmer wheat (Triticum turgidum var. dicoccoides) is a valuable genetic resource for improving disease resistance in common wheat. A powdery mildew resistance gene was transferred to hexaploid wheat line WE74 from wild emmer accession G-748-M. Genetic analysis revealed that the powdery mildew resistance in WE74 is controlled by a single dominant gene, herein temporarily designated MlWE74. Bulked segregant analysis (BSA) and molecular mapping delimited MlWE74 to the terminal region of chromosome 2BS flanking by markers WGGBD412 and WGGBH346 within a genetic interval of 0.25 cM and corresponding to 799.9 kb genomic region in the Zavitan reference sequence. Sequence annotation revealed two phosphoglycerate mutase-like genes, an alpha/beta-hydrolases gene, and five NBS-LRR disease resistance genes that could serve as candidates for map-based cloning of MlWE74. The geographical location analysis indicated that MlWE74 is mainly distributed in Rosh Pinna and Amirim regions, in the northern part of Israel, where environmental conditions are favorable to the occurrence of powdery mildew. Moreover, the co-segregated marker WGGBD425 is helpful in marker-assisted transfer of MlWE74 into elite cultivars. Title: Synthesis of highly active enzyme-metal nanohybrids and uncovering the design rules Cheng G, Wu Q, Jiang C Ref: Enzyme Microb Technol, 154:109962, 2021 : PubMed ESTHER: Cheng_2021_Enzyme.Microb.Technol_154_109962 PubMedSearch: Cheng 2021 Enzyme.Microb.Technol 154 109962 PubMedID: 34915246 Abstract Nanobiohybrid CAL-B/MNPs were synthesized through enzyme in situ reduction of metal ions, including noble and non-noble metals. Lipase CAL-B acted as multifunctional reagents (reducing and supporting agents). The hybrid catalysts were systematically characterized by HRTEM, EDX, MALDI-TOF-MS, and XPS analysis, confirming that highly dispersed 3-5 nm nanoparticles were evenly dispersed on lipase matrix without agglomeration. The mechanism of CAL-B reducing metal ions was investigated, revealing that AGLFFSSKDL in the amino acid sequence of CAL-B from 111 to 128 formed a stable spatial structure through hydrogen bonding, which was the key factor for enzyme in situ reduction of metal ions into highly dispersed nanoparticles. Title: Biodegradation of lambda-cyhalothrin through cell surface display of bacterial carboxylesterase Ding J, Liu Y, Gao Y, Zhang C, Wang Y, Xu B, Yang Y, Wu Q, Huang Z Ref: Chemosphere, 289:133130, 2021 : PubMed ESTHER: Ding_2021_Chemosphere_289_133130 PubMedSearch: Ding 2021 Chemosphere 289 133130 PubMedID: 34863720 Gene_locus related to this paper: 9baci-MW588803 Abstract Pyrethroids are the third widespread used insecticides globally which have been extensively applied in agricultural or household environments. Due to continuous applications, pyrethroids have been detected both in living cells and environments. The permanent exposure to pyrethroids have caused substantial health risks and ecosystem concerns. In this work, a lambda-cyhalothrin (one kind of pyrethroid insecticides) degrading bacterium Bacillus velezensis sd was isolated and a carboxylesterase gene, CarCB2 was characterized. A whole cell biocatalyst was developed for lambda-cyhalothrin biodegradation by displaying CarCB2 on the surface of Escherichia coli cells. CarCB2 was successfully displayed and functionally expressed on E. coli cells with optimal pH and temperature of 7.5 and 30 degreesC, using p-NPC(4) as substrate, respectively. The whole cell biocatalyst exhibited better stability than the purified CarCB2, and approximately 120%, 60% or 50% of its original activity at 4 degreesC, 30 degreesC or 37 degreesC over a period of 35 d was retained, respectively. No enzymatic activity was detected when incubated the purified CarCB2 at 30 degreesC for 120 h, or 37 degreesC for 72 h, respectively. Additionally, 30 mg/L of lambda-cyhalothrin was degraded in citrate-phosphate buffer by 10 U of the whole cell biocatalyst in 150 min. This work reveals that the whole cell biocatalyst affords a promising approach for efficient biodegradation of lambda-cyhalothrin, and might have the potential to be applied in further environmental bioremediation of other different kinds of pyrethroid insecticides. Title: A GRN Autocrine-Dependent FAM135B/AKT/mTOR Feedforward Loop Promotes Esophageal Squamous Cell Carcinoma Progression Dong D, Zhang W, Xiao W, Wu Q, Cao Y, Gao X, Huang L, Wang Y, Chen J and Zhan Q <1 more author(s)> Dong D, Zhang W, Xiao W, Wu Q, Cao Y, Gao X, Huang L, Wang Y, Chen J, Wang W, Zhan Q (- 1) Ref: Cancer Research, 81:910, 2021 : PubMed ESTHER: Dong_2021_Cancer.Res_81_910 PubMedSearch: Dong 2021 Cancer.Res 81 910 PubMedID: 33323378 Gene_locus related to this paper: human-FAM135B Abstract Esophageal squamous cell carcinoma (ESCC) is one of the most common and deadly diseases. In our previous comprehensive genomics study, we found that family with sequence similarity 135 member B (FAM135B) was a novel cancer-related gene, yet its biological functions and molecular mechanisms remain unclear. In this study, we demonstrate that the protein levels of FAM135B are significantly higher in ESCC tissues than in precancerous tissues, and high expression of FAM135B correlates with poorer clinical prognosis. Ectopic expression of FAM135B promoted ESCC cell proliferation in vitro and in vivo, likely through its direct interaction with growth factor GRN, thus forming a feedforward loop with AKT/mTOR signaling. Patients with ESCC with overexpression of both FAM135B and GRN had worse prognosis; multivariate Cox model analysis indicated that high expression of both FAM135B and GRN was an independent prognostic factor for patients with ESCC. FAM135B transgenic mice bore heavier tumor burden than wild-type mice and survived a relatively shorter lifespan after 4-nitroquinoline 1-oxide treatment. In addition, serum level of GRN in transgenic mice was higher than in wild-type mice, suggesting that serum GRN levels might provide diagnostic discrimination for patients with ESCC. These findings suggest that the interaction between FAM135B and GRN plays critical roles in the regulation of ESCC progression and both FAM135B and GRN might be potential therapeutic targets and prognostic factors in ESCC. SIGNIFICANCE: These findings investigate the mechanisms of FAM135B in promoting ESCC progression and suggest new potential prognostic biomarkers and therapeutic targets in patients with ESCC. Title: Effects of perioperative interventions for preventing postoperative delirium: A protocol for systematic review and meta-analysis of randomized controlled trials Li X, Wang Y, Liu J, Xiong Y, Chen S, Han J, Xie W, Wu Q Ref: Medicine (Baltimore), 100:e26662, 2021 : PubMed ESTHER: Li_2021_Medicine.(Baltimore)_100_e26662 PubMedSearch: Li 2021 Medicine.(Baltimore) 100 e26662 PubMedID: 34398027 Abstract BACKGROUND: Postoperative delirium (POD) not only increases the medical burden but also adversely affects patient prognosis. Although some cases of delirium can be avoided by early intervention, there is no clear evidence indicating whether any of these measures can effectively prevent POD in specific patient groups. OBJECTIVE: The aim of this meta-analysis was to compare the efficacy and safety of the existing preventive measures for managing POD. METHODS: The PubMed, OVID (Embase and MEDLINE), Web of Science, and the Cochrane Library databases were searched for articles published before January 2020. The relevant randomized controlled trials (RCTs) were selected based on the inclusion and exclusion criteria. Data extraction and methodological quality assessment were performed according to a predesigned data extraction form and scoring system, respectively. The interventions were compared on the basis of the primary outcome like incidence of POD, and secondary outcomes like duration of delirium and the length of intensive care unit and hospital stay. RESULTS: Sixty-three RCTs were included in the study, covering interventions like surgery, anesthesia, analgesics, intraoperative blood glucose control, cholinesterase inhibitors, anticonvulsant drugs, antipsychotic drugs, sleep rhythmic regulation, and multi-modal nursing. The occurrence of POD was low in 4 trials that monitored the depth of anesthesia with bispectral index during the operation (P<.0001). Two studies showed that supplementary analgesia was useful for delirium prevention (P=.002). Seventeen studies showed that perioperative sedation with alpha2-adrenergic receptor agonists prevented POD (P=.0006). Six studies showed that both typical and atypical antipsychotic drugs can reduce the incidence of POD (P=.002). Multimodal nursing during the perioperative period effectively reduced POD in 6 studies (P<.00001). Furthermore, these preventive measures can reduce the duration of delirium, as well as the total and postoperative length of hospitalized stay for non-cardiac surgery patients. For patients undergoing cardiac surgery, effective prevention can only reduce the length of intensive care unit stay. CONCLUSION: Measures including intraoperative monitoring of bispectral index, supplemental analgesia, alpha2-adrenergic receptor agonists, antipsychotic drugs, and multimodal care are helpful to prevent POD effectively. However, larger, high-quality RCTs are needed to verify these findings and develop more interventions and drugs for preventing postoperative delirium. Title: Effect of Selenium on Brain Injury in Chickens with Subacute Arsenic Poisoning Ren Z, Deng H, Wu Q, Jia G, Wen N, Deng Y, Zhu L, Zuo Z, Deng J Ref: Biol Trace Elem Res, :, 2021 : PubMed ESTHER: Ren_2021_Biol.Trace.Elem.Res__ PubMedSearch: Ren 2021 Biol.Trace.Elem.Res PubMedID: 33594525 Abstract The aim of this study was to investigate the effects of different doses of selenium (Se) on oxidative damage and neurotransmitter-related parameters in arsenic (As)-induced broiler brain tissue damage. Two hundred 1-day-old avian broilers were randomly divided into five groups and fed the following diets: control group (As 0.1 mg/kg + Se 0.2 mg/kg), As group (As 3 mg/kg + Se 0.2 mg/kg), low-Se group (As 3 mg/kg + Se 5 mg/kg), medium-Se group (As 3 mg/kg + Se 10 mg/kg), and high-Se group (As 3 mg/kg + Se 15 mg/kg). Glutathione (GSH), glutathione peroxidase (GSH-PX), nitric oxide (NO), nitric oxide synthase (NOS) activity, glutamate (Glu) concentration, glutamine synthetase (GS) activity, acetylcholinesterase (TchE) activity, and the apoptosis rate of brain cells were measured. The results showed that 3 mg/kg dietary As could induce oxidative damage and neurotransmitter disorder of brain tissue, increase the apoptosis rate of brain cells and cause damage to brain tissue, decrease activities of GSH and GSH-PX, decrease the contents of NO, decrease the activities of iNOS and tNOS, increase contents of Glu, and decrease activities of Gs and TchE. Compared with the As group, the Se addition of the low-Se and medium-Se groups protected against As-induced oxidative damage, neurotransmitter disorders, and the apoptosis rate of brain cells, with the addition of 10 mg/kg Se having the best effect. However, 15 mg/kg Se not only did not produce a protective effect against As damage but actually caused similar or severe damage. Title: Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice Tian Y, Yuan X, Wang Y, Wu Q, Fang Y, Zhu Z, Song G, Xu L, Wang W, Xie M Ref: Neurochem Int, 150:105197, 2021 : PubMed ESTHER: Tian_2021_Neurochem.Int_150_105197 PubMedSearch: Tian 2021 Neurochem.Int 150 105197 PubMedID: 34592333 Abstract Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity. Soluble epoxide hydrolase (sEH) is the key enzyme in the epoxyeicosatrienoic acids (EETs) signaling. sEH inhibition has been demonstrated to have neuroprotective effects against multiple brain injuries. However, its role in the secondary injuries after ICH has not been fully elucidated. Here we tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and the secondary injuries after ICH. Adult male C57BL/6 mice were subjected to a collagenase-induced ICH model. TPPU alleviated blood-brain barrier damage, inhibited inflammatory response, increased M2 polarization of microglial cells, reduced the infiltration of peripheral neutrophils. In addition, TPPU attenuated neuronal injury and promoted functional recovery. The results suggest that sEH may represent a potential therapeutic target for the treatment of ICH. Title: Pyridostigmine Protects Against Diabetic Cardiomyopathy by Regulating Vagal Activity, Gut Microbiota, and Branched-Chain Amino Acid Catabolism in Diabetic Mice Yang Y, Zhao M, He X, Wu Q, Li DL, Zang WJ Ref: Front Pharmacol, 12:647481, 2021 : PubMed ESTHER: Yang_2021_Front.Pharmacol_12_647481 PubMedSearch: Yang 2021 Front.Pharmacol 12 647481 PubMedID: 34084135 Abstract The disruption of gut microbes is associated with diabetic cardiomyopathy, but the mechanism by which gut microbes affect cardiac damage remains unclear. We explored gut microbes and branched-chain amino acid (BCAA) metabolite catabolism in diabetic cardiomyopathy mice and investigated the cardioprotective effect of pyridostigmine. The experiments were conducted using a model of diabetic cardiomyopathy induced by a high-fat diet + streptozotocin in C57BL/6 mice. The results of high-throughput sequencing showed that diabetic cardiomyopathy mice exhibited decreased gut microbial diversity, altered abundance of the diabetes-related microbes, and increased abundance of the BCAA-producing microbes Clostridiales and Lachnospiraceae. In addition, diabetes downregulated tight junction proteins (ZO-1, occludin, and claudin-1) and increased intestinal permeability to impair the intestinal barrier. These impairments were accompanied by reduction in vagal activity that manifested as increased acetylcholinesterase levels, decreased acetylcholine levels, and heart rate variability, which eventually led to cardiac damage. Pyridostigmine enhanced vagal activity, restored gut microbiota homeostasis, decreased BCAA-producing microbe abundance, and improved the intestinal barrier to reduce circulating BCAA levels. Pyridostigmine also upregulated BCAT2 and PP2Cm and downregulated p-BCKDHA/BCKDHA and BCKDK to improve cardiac BCAA catabolism. Moreover, pyridostigmine alleviated abnormal mitochondrial structure; increased ATP production; decreased reactive oxygen species and mitochondria-related apoptosis; and attenuated cardiac dysfunction, hypertrophy, and fibrosis in diabetic cardiomyopathy mice. In conclusion, the gut microbiota, BCAA catabolism, and vagal activity were impaired in diabetic cardiomyopathy mice but were improved by pyridostigmine. These results provide novel insights for the development of a therapeutic strategy for diabetes-induced cardiac damage that targets gut microbes and BCAA catabolism. Title: Inverting the Enantiopreference of Nitrilase-Catalyzed Desymmetric Hydrolysis of Prochiral Dinitriles by Reshaping the Binding Pocket with a Mirror-Image Strategy Yu S, Li J, Yao P, Feng J, Cui Y, Liu X, Wu Q, Lin J, Zhu D Ref: Angew Chem Int Ed Engl, 60:3679, 2021 : PubMed ESTHER: Yu_2021_Angew.Chem.Int.Ed.Engl_60_3679 PubMedSearch: Yu 2021 Angew.Chem.Int.Ed.Engl 60 3679 PubMedID: 33141478 Abstract A mirror-image strategy, that is, symmetry analysis of the substrate-binding pocket, was applied to identify two key amino acid residues W170 and V198 that possibly modulate the enantiopreference of a nitrilase from Synechocystis sp. PCC6803 towards 3-isobutyl glutaronitrile (1a). Exchange of these two residues resulted in the enantiopreference inversion (S, 90% ee to R, 47% ee). By further reshaping the substrate-binding pocket via routine site-saturation and combinatorial mutagenesis, variant E8 with higher activity and stereoselectivity (99% ee, R) was obtained. The mutant enzyme was applied in the preparation of optically pure (R)-3-isobutyl-4-cyanobutanoic acid ((R)-2a) and showed similar stereopreference inversion towards a series of 3-substituted glutaronitriles. This study may offer a general strategy to switch the stereopreference of other nitrilases and other enzymes toward the desymmetric reactions of prochiral substrates with two identical reactive functional groups. Title: Substrate Engineering in Lipase-Catalyzed Selective Polymerization of d-/l-Aspartates and Diols to Prepare Helical Chiral Polyester Zhang Y, Xia B, Li Y, Lin X, Wu Q Ref: Biomacromolecules, :, 2021 : PubMed ESTHER: Zhang_2021_Biomacromolecules__ PubMedSearch: Zhang 2021 Biomacromolecules PubMedID: 33427463 Abstract The synthesis of optically pure polymers is one of the most challenging tasks in polymer chemistry. Herein, Novozym 435 (Lipase B from Candida antarctica, immobilized on Lewatit VP OC 1600)-catalyzed polycondensation between d-/l-aspartic acid (Asp) diester and diols for the preparation of helical chiral polyesters was reported. Compared with d-Asp diesters, the fast-reacting l-Asp diesters easily reacted with diols to provide a series of chiral polyesters containing N-substitutional l-Asp repeating units. Besides amino acid configuration, N-substituent side chains and the chain length of diols were also investigated and optimized. It was found that bulky acyl N-substitutional groups like N-Boc and N-Cbz were more favorable for this polymerization than small ones probably due to competitively binding of these small acyl groups into the active site of Novozym 435. The highest molecular weight can reach up to 39.5 x 10(3) g/mol (M(w,) D = 1.64). Moreover, the slow-reacting d-Asp diesters were also successfully polymerized by modifying the substrate structure to create a "nonchiral" condensation environment artificially. These enantiocomplementary chiral polyesters are thermally stable and have specific helical structures, which was confirmed by circular dichroism (CD) spectra, scanning electron microscope (SEM), and molecular calculation. Title: Focused rational iterative site-specific mutagenesis (FRISM) Li D, Wu Q, Reetz MT Ref: Methods Enzymol, 643:225, 2020 : PubMed ESTHER: Li_2020_Methods.Enzymol_643_225 PubMedSearch: Li 2020 Methods.Enzymol 643 225 PubMedID: 32896283 Abstract Directed evolution has emerged as the most productive enzyme engineering method, with stereoselectivity playing a crucial role when evolving mutants for application in synthetic organic chemistry and biotechnology. In order to reduce the screening effort (bottleneck of directed evolution), improved methods for the creation of small and smart mutant libraries have been developed, including the combinatorial active-site saturation test (CAST) which involves saturation mutagenesis at appropriate residues surrounding the binding pocket, and iterative saturation mutagenesis (ISM). Nevertheless, even CAST/ISM mutant libraries require a formidable screening effort. Thus far, rational design as the alternative protein engineering technique has had only limited success when aiming for stereoselectivity. Here, we highlight a recent methodology dubbed focused rational iterative site-specific mutagenesis (FRISM), in which mutant libraries are not involved. It makes use of the tools that were previously employed in traditional rational enzyme design, but, inspired by CAST/ISM, the process is performed in an iterative manner. Only a few predicted mutants need to be screened, a fast process which leads to the identification of highly enantioselective and sufficiently active mutants. Title: Solar light induces expression of acetylcholinesterase in skin keratinocytes: Signalling mediated by activator protein 1 transcription factor Wu Q, Bai P, Xia Y, Lai QWS, Guo MSS, Dai K, Zheng Z, Ling CSJ, Dong TTX and Tsim KWK <1 more author(s)> Wu Q, Bai P, Xia Y, Lai QWS, Guo MSS, Dai K, Zheng Z, Ling CSJ, Dong TTX, Pi R, Tsim KWK (- 1) Ref: Neurochem Int, 141:104861, 2020 : PubMed ESTHER: Wu_2020_Neurochem.Int_141_104861 PubMedSearch: Wu 2020 Neurochem.Int 141 104861 PubMedID: 33038610 Abstract Acetylcholinesterase (AChE) hydrolyses acetylcholine to choline and acetate, playing an important role in terminating the neurotransmission in brain and muscle. Recently, the non-neuronal functions of AChE have been proposed in different tissues, in which there are various factors to regulate the expression of AChE. In mammalian skin, AChE was identified in melanocytes and keratinocytes. Our previous study has indicated that AChE in keratinocyte affects the process of solar light-induced skin pigmentation; however, the expression of AChE in keratinocytes in responding to sunlight remains unknown. Here, we provided several lines of evidence to support a notion that AChE could be upregulated at transcriptional and translational levels in keratinocytes when exposed to solar light. The light-mediated AChE expression was triggered by Ca(2+), supported by an induction of Ca(2+) ionophore A23187 and a blockage by Ca(2+) chelator BAPTA-AM. In addition, this increase on AChE transcriptional expression was eliminated by mutagenesis on the activating protein 1 (AP1) site in ACHE gene. Hence, the solar light-induced AChE expression is mediated by Ca(2+) signalling through AP1 site. This finding supports the role of solar light in affecting the cholinergic system in skin cells, and which may further influence the dermatological function. Title: Patatin primary structural properties and effects on lipid metabolism Wu J, Wu Q, Yang D, Zhou M, Xu J, Wen Q, Cui Y, Bai Y, Xu S and Wang S <1 more author(s)> Wu J, Wu Q, Yang D, Zhou M, Xu J, Wen Q, Cui Y, Bai Y, Xu S, Wang Z, Wang S (- 1) Ref: Food Chem, :128661, 2020 : PubMed ESTHER: Wu_2020_Food.Chem__128661 PubMedSearch: Wu 2020 Food.Chem 128661 PubMedID: 33272761 Abstract Patatin, the major protein found in potatoes, was purified and shows several isoforms. The essential amino acid content of patatin was ashighas 76%, indicating that it is a valuable protein source. Patatin was an O-linked glycoprotein that contained fucose monosaccharides, as well as mannose, rhamnose, glucose, galactose, xylose, and arabinose. Patatin had a fucosylated glycan structural feature, which strongly bound AAL (Aleuria aurantia Leukoagglutinin), a known fucose binding lectin. Moreover, thelipid metabolism regulatory effects of patatin on the fat catabolism, fat absorption, and inhibition of lipase activity were measured after high-fat feeding of zebrafish larvae. Results revealed that 37.0 g/mL patatin promoted 23% lipid decomposition metabolism. Meanwhile patatin could inhibite lipase activity and fat absorption, whose effects accounted for half that of a positive control drug. Our findings suggest that patatin, a fucosylated glycoprotein, could potentially be used as a naturalactiveconstituent with anti-obesity effects. Title: An update on T-2 toxin and its modified forms: metabolism, immunotoxicity mechanism, and human exposure assessment Wu Q, Qin Z, Kuca K, You L, Zhao Y, Liu A, Musilek K, Chrienova Z, Nepovimova E and Wang X <2 more author(s)> Wu Q, Qin Z, Kuca K, You L, Zhao Y, Liu A, Musilek K, Chrienova Z, Nepovimova E, Oleksak P, Wu W, Wang X (- 2) Ref: Archives of Toxicology, 94:3645, 2020 : PubMed ESTHER: Wu_2020_Arch.Toxicol_94_3645 PubMedSearch: Wu 2020 Arch.Toxicol 94 3645 PubMedID: 32910237 Abstract T-2 toxin is the most toxic trichothecene mycotoxin, and it exerts potent toxic effects, including immunotoxicity, neurotoxicity, and reproductive toxicity. Recently, several novel metabolites, including 3',4'-dihydroxy-T-2 toxin and 4',4'-dihydroxy-T-2 toxin, have been uncovered. The enzymes CYP3A4 and carboxylesterase contribute to T-2 toxin metabolism, with 3'-hydroxy-T-2 toxin and HT-2 toxin as the corresponding primary products. Modified forms of T-2 toxin, including T-2-3-glucoside, exert their immunotoxic effects by signaling through JAK/STAT but not MAPK. T-2-3-glucoside results from hydrolyzation of the corresponding parent mycotoxin and other metabolites by the intestinal microbiota, which leads to enhanced toxicity. Increasing evidence has shown that autophagy, hypoxia-inducible factors, and exosomes are involved in T-2 toxin-induced immunotoxicity. Autophagy promotes the immunosuppression induced by T-2 toxin, and a complex crosstalk between apoptosis and autophagy exists. Very recently, "immune evasion" activity was reported to be associated with this toxin; this activity is initiated inside cells and allows pathogens to escape the host immune response. Moreover, T-2 toxin has the potential to trigger hypoxia in cells, which is related to activation of hypoxia-inducible factor and the release of exosomes, leading to immunotoxicity. Based on the data from a series of human exposure studies, free T-2 toxin, HT-2 toxin, and HT-2-4-glucuronide should be considered human T-2 toxin biomarkers in the urine. The present review focuses on novel findings related to the metabolism, immunotoxicity, and human exposure assessment of T-2 toxin and its modified forms. In particular, the immunotoxicity mechanisms of T-2 toxin and the toxicity mechanism of its modified form, as well as human T-2 toxin biomarkers, are discussed. This work will contribute to an improved understanding of the immunotoxicity mechanism of T-2 toxin and its modified forms. Title: Solar light induces the release of acetylcholine from skin keratinocytes affecting melanogenesis Wu Q, Xia Y, Dai K, Bai P, Kwan KKL, Guo MSS, Dong TTX, Tsim KWK Ref: FASEB Journal, 34:8941, 2020 : PubMed ESTHER: Wu_2020_FASEB.J_34_8941 PubMedSearch: Wu 2020 FASEB.J 34 8941 PubMedID: 32519787 Abstract Cholinergic system conducts signal transmission in brain and muscle. Besides nervous system, the nonneuronal functions of cholinergic system have been proposed in various tissues. The expression of cholinergic proteins and release of acetylcholine in human skin have been reported, but its mechanism and influence on dermatological functions is not elucidated. Here, the expression profile of cholinergic markers was further investigated in skin and keratinocyte. The expression levels of choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), and synaptophysin, were upregulated during differentiation of keratinocytes. In cultured keratinocytes, a transient exposure of solar light induced the release of acetylcholine, which was mediated by intracellular Ca(2+) mobilization. The light-induced acetylcholine release was mediated by the present of opsin. The light-induced melanogenesis was inhibited by acetylcholine or AChE inhibitor in melanocyte in vitro and mouse skin ex vivo. These results indicated that the potential role of cholinergic system could be a negative regulator in skin pigmentation. Title: Artificial cysteine-lipases with high activity and altered catalytic mechanism created by laboratory evolution Cen Y, Singh W, Arkin M, Moody TS, Huang M, Zhou J, Wu Q, Reetz MT Ref: Nat Commun, 10:3198, 2019 : PubMed ESTHER: Cen_2019_Nat.Commun_10_3198 PubMedSearch: Cen 2019 Nat.Commun 10 3198 PubMedID: 31324776 Gene_locus related to this paper: canar-LipB Abstract Engineering artificial enzymes with high activity and catalytic mechanism different from naturally occurring enzymes is a challenge in protein design. For example, many attempts have been made to obtain active hydrolases by introducing a Ser --> Cys exchange at the respective catalytic triads, but this generally induced a breakdown of activity. We now report that this long-standing dogma no longer pertains, provided additional mutations are introduced by directed evolution. By employing Candida antarctica lipase B (CALB) as the model enzyme with the Ser-His-Asp catalytic triad, a highly active cysteine-lipase having a Cys-His-Asp catalytic triad and additional mutations W104V/A281Y/A282Y/V149G can be evolved, showing a 40-fold higher catalytic efficiency than wild-type CALB in the hydrolysis of 4-nitrophenyl benzoate, and tolerating bulky substrates. Crystal structures, kinetics, MD simulations and QM/MM calculations reveal dynamic features and explain all results, including the preference of a two-step mechanism involving the zwitterionic pair Cys105(-)/His224(+) rather than a concerted process. Title: Identification and characterization of an acetyl esterase from Paenibacillus sp. XW-6-66 and its novel function in 7-aminocephalosporanic acid deacetylation Ding J, Zhou Y, Zhu H, Deng M, Long L, Yang Y, Wu Q, Huang Z Ref: Biotechnol Lett, 41:1059, 2019 : PubMed ESTHER: Ding_2019_Biotechnol.Lett_41_1059 PubMedSearch: Ding 2019 Biotechnol.Lett 41 1059 PubMedID: 31302814 Gene_locus related to this paper: 9bacl-7ACAaes Abstract OBJECTIVES: To obtain a new acetyl esterase from Paenibacillus sp. XW-6-66 and apply the enzyme to 7-aminocephalosporanic acid (7-ACA) deacetylation. RESULTS: The acetyl esterase AesZY was identified from Paenibacillus sp. XW-6-66, and its enzymatic properties were investigated. With the putative catalytic triad Ser114-Asp203-His235, AesZY belongs to the Acetyl esterase (Aes) family which is included in the alpha/beta hydrolase superfamily and contains the consensus Gly-X-Ser-X-Gly motif. The maximum activity of AesZY was detected at pH 8.0 and 40 degrees C. AesZY was stable at different pH values ranging from 5.0 to 12.0, and was tolerant to several metal ions. Furthermore, the deacetylation activity of AesZY toward 7-ACA was approximately 7.5 U/mg, and the Kcat/Km value was 2.04 s(-1) mM(-1). CONCLUSIONS: Our results demonstrate the characterization of a new acetyl esterase belonging to the Aes family with potential biotechnological applications. Title: TPPU, a sEH Inhibitor, Attenuates Corticosterone-Induced PC12 Cell Injury by Modulation of BDNF-TrkB Pathway Wu Q, Song J, Meng D, Chang Q Ref: Journal of Molecular Neuroscience, 67:364, 2019 : PubMed ESTHER: Wu_2019_J.Mol.Neurosci_67_364 PubMedSearch: Wu 2019 J.Mol.Neurosci 67 364 PubMedID: 30644034 Inhibitor(s) related to this paper: TPPU Abstract High level of corticosterone (CORT) is toxic to neurons and plays an important role in depression-like behavior and chronic stress. Our previous study showed that TPPU, a soluble epoxide hydrolase (sEH) inhibitor (sEHI), induces an antidepressant effect in animal models. However, the underlying mechanism is not clear. In this study, we investigated the protective effect of TPPU on PC12 cells against CORT-induced cytotoxicity and its underlying mechanism. We found that TPPU and the sEH substrate epoxyeicosatrienoic acids (EETs) protected PC12 cells from the CORT-induced injury by increasing cell viability and inhibiting apoptosis. Furthermore, TPPU and EETs also blocked the CORT-mediated downregulation of BDNF. Blocking the BDNF-TrkB pathway by the TrkB inhibitor K252a abolished the protective effect of TPPU. Taken together, our results suggest that sEHI could protect PC12 cells against the CORT-induced cytotoxicity via the BDNF-TrkB signaling pathway. Title: Traditional Chinese Medicine Shenmayizhi Decoction Ameliorates Memory And Cognitive Impairment Induced By Scopolamine Via Preventing Hippocampal Cholinergic Dysfunction In Rats Wu Q, Cao Y, Liu M, Liu F, Brantner AH, Yang Y, Wei Y, Zhou Y, Wang Z and Li H <3 more author(s)> Wu Q, Cao Y, Liu M, Liu F, Brantner AH, Yang Y, Wei Y, Zhou Y, Wang Z, Ma L, Wang F, Pei H, Li H (- 3) Ref: Neuropsychiatr Dis Treat, 15:3167, 2019 : PubMed ESTHER: Wu_2019_Neuropsychiatr.Dis.Treat_15_3167 PubMedSearch: Wu 2019 Neuropsychiatr.Dis.Treat 15 3167 PubMedID: 31814724 Abstract Purpose: Clinical trials have illustrated that Shenmayizhi decoction (SMYZ) could improve the cognitive functions in patients with dementia. However, the mechanism needs to be explored. Methods: Fifty adult male rats (Wistar strain) were divided into five groups equally and randomly, including control, model, and SMYZ of low dose, medium dose and high dose. Rats in each group received a daily gavage of respective treatment. Rats in control and model group were administrated by the same volume of distilled water. Memory impairment was induced by intraperitoneal administration of scopolamine (0.7 mg/kg) for 5 continuous days. Four weeks later, Morris water maze (MWM) was performed to evaluate the spatial memory in all rats. Then, rats were sacrificed and the hippocampus was removed for further tests. Furthermore, Western blot analysis was employed to assess the levels of acetylcholine M1 receptor (M1), acetylcholine M2 receptor (M2), acetylcholinesterase (AChE) and cholineacetyltransferase (ChAT). AChE and ChAT activities were determined. Results: The SMYZ decoction significantly improved behavioral performance of rats in high dose. The SMYZ decoction in three doses exhibited anti-acetylcholinesterase activity. In addition, a high dose of SMYZ promoted ChAT activity. Moreover, a high dose of SMYZ increased the level of ChAT and declined the level of AChE assessed by Western blotting. Besides, an increased level of M1 receptor was found after treatment. Conclusion: Shenmayizhi decoction could mitigate scopolamine-induced cognitive deficits through the preventative effect on cholinergic system dysfunction. Title: Stereodivergent Protein Engineering of a Lipase To Access All Possible Stereoisomers of Chiral Esters with Two Stereocenters Xu J, Cen Y, Singh W, Fan J, Wu L, Lin X, Zhou J, Huang M, Reetz MT, Wu Q Ref: Journal of the American Chemical Society, 141:7934, 2019 : PubMed ESTHER: Xu_2019_J.Am.Chem.Soc_141_7934 PubMedSearch: Xu 2019 J.Am.Chem.Soc 141 7934 PubMedID: 31023008 Gene_locus related to this paper: canar-LipB Inhibitor(s) related to this paper: 6J1T-B7U Abstract Enzymatic stereodivergent synthesis to access all possible product stereoisomers bearing multiple stereocenters is relatively undeveloped, although enzymes are being increasingly used in both academic and industrial areas. When two stereocenters and thus four stereoisomeric products are involved, obtaining stereodivergent enzyme mutants for individually accessing all four stereoisomers would be ideal. Although significant success has been achieved in directed evolution of enzymes in general, stereodivergent engineering of one enzyme into four highly stereocomplementary variants for obtaining the full complement of stereoisomers bearing multiple stereocenters remains a challenge. Using Candida antarctica lipase B (CALB) as a model, we report the protein engineering of this enzyme into four highly stereocomplementary variants needed for obtaining all four stereoisomers in transesterification reactions between racemic acids and racemic alcohols in organic solvents. By generating and screening less than 25 variants of each isomer, we achieved >90% selectivity for all of the four possible stereoisomers in the model reaction. This difficult feat was accomplished by developing a strategy dubbed "focused rational iterative site-specific mutagenesis" (FRISM) at sites lining the enzyme's binding pocket. The accumulation of single mutations by iterative site-specific mutagenesis using a restricted set of rationally chosen amino acids allows the formation of ultrasmall mutant libraries requiring minimal screening for stereoselectivity. The crystal structure of all stereodivergent CALB variants, flanked by MD simulations, uncovered the source of selectivity. Title: Pyridostigmine alleviates cardiac dysfunction via improving mitochondrial cristae shape in a mouse model of metabolic syndrome Xue RQ, Yu XJ, Zhao M, Xu M, Wu Q, Cui YL, Yang S, Li DL, Zang WJ Ref: Free Radic Biol Med, 134:119, 2019 : PubMed ESTHER: Xue_2019_Free.Radic.Biol.Med_134_119 PubMedSearch: Xue 2019 Free.Radic.Biol.Med 134 119 PubMedID: 30633969 Inhibitor(s) related to this paper: Pyridostigmine Abstract Insulin resistance and autonomic imbalance are important pathological processes in metabolic syndrome-induced cardiac remodeling. Recent studies determined that disruption of mitochondrial cristae shape is associated with myocardial ischemia; however, the change in cristae shape in metabolic syndrome-induced cardiac remodeling remains unclear. This study determined the effect of pyridostigmine (PYR), which reversibly inhibits cholinesterase to improve autonomic imbalance, on high-fat diet (HFD)-induced cardiac insulin resistance and explored the potential effect on the shape of mitochondrial cristae. Feeding of a HFD for 22 weeks led to an irregular and even lysed cristae structure in cardiac mitochondria, which contributed to decreased mitochondrial content and ATP production and increased oxygen species production, ultimately impairing insulin signaling and lipid metabolism. Interestingly, PYR enhanced vagal activity by increasing acetylcholine production and exerted mito-protective effects by activating the LKB1/AMPK/ACC signal pathway. Specifically, PYR upregulated OPA1 and Mfn1/2 expression, promoted the formation of the mitofilin/CHCHD3/Sam50 complex, and decreased p-Drp1 and Fis1 expression, resulting in tight and parallel cristae and increasing cardiac mitochondrial complex subunit expression and ATP generation as well as decreasing release of cytochrome C from mitochondria and oxidative damage. Furthermore, PYR improved glucose and insulin tolerance and insulin-stimulated Akt phosphorylation, decreased lipid toxicity, and ultimately ameliorated HFD-induced cardiac remodeling and dysfunction. In conclusion, PYR prevented cardiac and insulin insensitivity and remodeling by stimulating vagal activity to regulate mitochondrial cristae shape and function in HFD-induced metabolic syndrome in mice. These results provide novel insights for the development of a therapeutic strategy for obesity-induced cardiac dysfunction that targets mitochondrial cristae. Title: Graphene oxide disrupts the protein-protein interaction between Neuroligin/NLG-1 and DLG-1 or MAGI-1 in nematode Caenorhabditis elegans Zhao Y, Chen H, Yang Y, Wu Q, Wang D Ref: Sci Total Environ, 700:134492, 2019 : PubMed ESTHER: Zhao_2019_Sci.Total.Environ_700_134492 PubMedSearch: Zhao 2019 Sci.Total.Environ 700 134492 PubMedID: 31627046 Gene_locus related to this paper: caeel-NLGN1, human-NLGN1 Abstract Graphene oxide (GO) is a carbon-based engineered nanomaterial (ENM). Using Caenorhabditis elegans as an animal model, we investigated the effect of GO exposure on protein-protein interactions. In nematodes, NLG-1/Neuroligin, a postsynaptic protein, acted only in the neurons to regulate the GO toxicity. In the neurons, DLG-1, a PSD-95 protein, and MAGI-1, a S-SCAM protein, were identified as the downstream targets of NLG-1 in the regulation of GO toxicity. PKC-1, a serine/threonine protein kinase C, further acted downstream of neuronal DLG-1 and MAGI-1 to regulate the GO toxicity. Co-immunoprecipitation analysis demonstrated the protein-protein interaction between NLG-1 and DLG-1 or MAGI-1. After GO expression, this protein-protein interaction between NLG-1 and DLG-1 or MAGI-1 was significantly inhibited. Therefore, our data raised the evidence to suggest the potential of GO exposure in disrupting protein-protein interactions in organisms. Title: Perfluorododecanoic acid exposure induced developmental neurotoxicity in zebrafish embryos Guo X, Zhang S, Lu S, Zheng B, Xie P, Chen J, Li G, Liu C, Wu Q and Sang N <1 more author(s)> Guo X, Zhang S, Lu S, Zheng B, Xie P, Chen J, Li G, Liu C, Wu Q, Cheng H, Sang N (- 1) Ref: Environ Pollut, 241:1018, 2018 : PubMed ESTHER: Guo_2018_Environ.Pollut_241_1018 PubMedSearch: Guo 2018 Environ.Pollut 241 1018 PubMedID: 30029309 Abstract Perfluorododecanoic acid (PFDoA), an artificial perfluorochemical, has been widely distributed in different ambient media and has been reported to have the potential to cause developmental neurotoxicity. However, the specific mechanism is largely unknown. In the current study, zebrafish embryos were treated with 0, 0.24, 1.2, and 6mg/L PFDoA for 120h. Exposure to PFDoA causes serious decreases in hatching delay, body length, as well as decreased locomotor speed in zebrafish larvae. Additionally, the acetylcholine (ACh) content as well as acetylcholinesterase (AChE) activity were determined to be significantly downregulated in PFDoA treatment groups. The level of dopamine was upregulated significantly after treating with 1.2 and 6mg/L of PFDoA. Gene expressions related to the nervous system development were also analyzed, with the exception of the gene mesencephalic astrocyte-derived neurotrophic factor (manf), which is upregulated in the 6mg/L treatment group. All other genes were significantly downregulated in larvae in the PFDoA group in different degrees. In general, the results demonstrated that PFDoA exposure could result in the disruption of the cholinergic system, dopaminergic signaling, and the central nervous system. Title: Synthesis, Biological Evaluation, and Docking Studies of Novel Bisquaternary Aldoxime Reactivators on Acetylcholinesterase and Butyrylcholinesterase Inhibited by Paraoxon Kuca K, Jun D, Junova L, Musilek K, Hrabinova M, da Silva JAV, Ramalho TC, Valko M, Wu Q and Franca TCC <1 more author(s)> Kuca K, Jun D, Junova L, Musilek K, Hrabinova M, da Silva JAV, Ramalho TC, Valko M, Wu Q, Nepovimova E, Franca TCC (- 1) Ref: Molecules, 23:, 2018 : PubMed ESTHER: Kuca_2018_Molecules_23_ PubMedSearch: Kuca 2018 Molecules 23 PubMedID: 29735900 Abstract Nerve agents and oxon forms of organophosphorus pesticides act as strong irreversible inhibitors of two cholinesterases in the human body: acetylcholinesterase (AChE; EC 3.1.1.7) and butyrylcholinesterase (BChE; EC 3.1.1.8), and are therefore highly toxic compounds. For the recovery of inhibited AChE, antidotes from the group of pyridinium or bispyridinium aldoxime reactivators (pralidoxime, obidoxime, HI-6) are used in combination with anticholinergics and anticonvulsives. Therapeutic efficacy of reactivators (called “oximes”) depends on their chemical structure and also the type of organophosphorus inhibitor. Three novel oximes (K131, K142, K153) with an oxime group in position four of the pyridinium ring were designed and then tested for their potency to reactivate human (Homo sapiens sapiens) AChE (HssACHE) and BChE (HssBChE) inhibited by the pesticide paraoxon (diethyl 4-nitrophenyl phosphate). According to the obtained results, none of the prepared oximes were able to satisfactorily reactivate paraoxon-inhibited cholinesterases. On the contrary, extraordinary activity of obidoxime in the case of paraoxon-inhibited HssAChE reactivation was confirmed. Additional docking studies pointed to possible explanations for these results. Title: Pyridostigmine protects against cardiomyopathy associated with adipose tissue browning and improvement of vagal activity in high-fat diet rats Lu Y, Wu Q, Liu LZ, Yu XJ, Liu JJ, Li MX, Zang WJ Ref: Biochimica & Biophysica Acta, 1864:1037, 2018 : PubMed ESTHER: Lu_2018_Biochim.Biophys.Acta_1864_1037 PubMedSearch: Lu 2018 Biochim.Biophys.Acta 1864 1037 PubMedID: 29309922 Inhibitor(s) related to this paper: Pyridostigmine Abstract Obesity, a major contributor to the development of cardiovascular diseases, is associated with an autonomic imbalance characterized by sympathetic hyperactivity and diminished vagal activity. Vagal activation plays important roles in weight loss and improvement of cardiac function. Pyridostigmine is a reversible acetylcholinesterase inhibitor, but whether it ameliorates cardiac lipid accumulation and cardiac remodeling in rats fed a high-fat diet has not been determined. This study investigated the effects of pyridostigmine on high-fat diet-induced cardiac dysfunction and explored the potential mechanisms. Rats were fed a normal or high-fat diet and treated with pyridostigmine. Vagal discharge was evaluated using the BL-420S system, and cardiac function by echocardiograms. Lipid deposition and cardiac remodeling were determined histologically. Lipid utility was assessed by qPCR. A high-fat diet led to a significant reduction in vagal discharge and lipid utility and a marked increase in lipid accumulation, cardiac remodeling, and cardiac dysfunction. Pyridostigmine improved vagal activity and lipid metabolism disorder and cardiac remodeling, accompanied by an improvement of cardiac function in high-fat diet-fed rats. An increase in the browning of white adipose tissue in pyridostigmine-treated rats was also observed and linked to the expression of UCP-1 and CIDEA. Additionally, pyridostigmine facilitated activation of brown adipose tissue via activation of the SIRT-1/AMPK/PGC-1alpha pathway. In conclusion, a high-fat diet resulted in cardiac lipid accumulation, cardiac remodeling, and a significant decrease in vagal discharge. Pyridostigmine ameliorated cardiomyopathy, an effect related to reduced cardiac lipid accumulation, and facilitated the browning of white adipose tissue while activating brown adipose tissue. Title: Studies on the lipid-regulating mechanism of alisol-based compounds on lipoprotein lipase Xu F, Lu C, Wu Q, Gu W, Chen J, Fang F, Zhao B, Du W, You M Ref: Bioorg Chem, 80:347, 2018 : PubMed ESTHER: Xu_2018_Bioorg.Chem_80_347 PubMedSearch: Xu 2018 Bioorg.Chem 80 347 PubMedID: 29986183 Abstract Studies on the lipid-regulating effects of alisol compounds are reported that include alisol B, alisol A 24-acetate (24A), alisol A and an alisol B - 24A - alisol A mixture (content ratio=1:1:1). The effects on the activity of lipoprotein lipase (LPL), a key lipid-modulating enzyme, were studied to investigate the molecular mechanism of lipid-regulating activity of alisols. The effects of alisols on regulating blood lipids and the activities of LPL were determined using a reagent kit method. The structure of LPL was obtained by homology modeling and the interactive mechanism of alisol monomers and the mixture with LPL was investigated by molecular simulation. The alisol monomer and mixture were shown to regulate blood lipids, suggesting that alisols may decrease the level of triglyceride (TG) by improving the activity of LPL. The order of intensity was: mixture>alisol A>alisol B>24A, indicating that alisols of alismatis rhizoma feature a synergistic effect on LPL. The N- and C-terminus of LPL both represented the catalytic active domains of this lipid-regulating effect. Cys306, Gln129 and Ser166 were the key amino acid residues resulting in the lipid-regulating effect of the alisol monomer while Ser166 and Arg18 were found to be responsible for the lipid-regulating effect of the mixture. The C-terminus of LPL was indirectly involved in the enzymatic process. A folded side chain of alisols or the parent ring was found to bind somewhat weaker to LPL than an open side chain or parent ring. The hydroxyl groups on the C14-, C22-, C28-, C30- and C31-terminus in the side chain, the ring ether structure in C23-position, and the acetyl group in C29-position represented the key sites for the lipid-regulating action of alisols. Meanwhile, the C30-site hydroxyl group played an important role in the synergistic effect of the alisol mixture. Title: Enhanced catalytic efficiency and enantioselectivity of epoxide hydrolase from Agrobacterium radiobacter AD1 by iterative saturation mutagenesis for (R)-epichlorohydrin synthesis Zou SP, Zheng YG, Wu Q, Wang ZC, Xue YP, Liu ZQ Ref: Applied Microbiology & Biotechnology, 102:733, 2018 : PubMed ESTHER: Zou_2018_Appl.Microbiol.Biotechnol_102_733 PubMedSearch: Zou 2018 Appl.Microbiol.Biotechnol 102 733 PubMedID: 29151159 Gene_locus related to this paper: agrra-echA Abstract Enantioselective hydrolysis of epoxides by epoxide hydrolase (EH) is one of the most attractive approaches for the synthesis of chiral epoxides. So far, attempts to develop an efficient epoxide hydrolase -mediated biotransformation have been limited by either the low activity or insufficient enantioselectivity of epoxide hydrolase. In this study, iterative saturation mutagenesis (ISM) of epoxide hydrolase from Agrobacterium radiobacter AD1 (ArEH) was performed for efficient production of (R)-epichlorohydrin. Six amino acid residues, I108, A110, D131, I133, T247, and G245, were selected for site saturation mutagenesis, and a sequential combination of positive mutants using ISM was constructed. Targeted mutagenesis generated five mutants (T247K, I108L, D131S, T247K/I108L, and T247K/I108L/D131S) with improved activity and enantioselectivity. Kinetics analysis showed that the best mutant, T247K/I108L/D131S, exhibited a 4.5-fold higher catalytic efficiency (k (cat)/K (m)) value and a 2.1-fold higher enantioselectivity (E value) towards epichlorohydrin than the wild-type (WT) enzyme. Molecular docking computations support the source of notably improved enantioselectivity. In addition, the triple mutant also displayed a significantly enhanced thermostability, with > 8-fold longer half-life at 50 degreesC than WT. A gram-scale kinetic resolution of (R,S)-epichlorohydrin was performed using T247K/I108L/D131S mutant as biocatalyst, affording a (R)-epichlorohydrin yield of 40.2% (> 99.9% enantiomeric excess) and an average productivity of 1410 g L(-1) d(-1). The engineered T247K/I108L/D131S variant is a promising biocatalyst for the enzymatic synthesis of (R)-epichlorohydrin. Title: Online Monitoring of Enzymatic Reactions Using Time-Resolved Desorption Electrospray Ionization Mass Spectrometry Cheng S, Wu Q, Xiao H, Chen H Ref: Analytical Chemistry, 89:2338, 2017 : PubMed ESTHER: Cheng_2017_Anal.Chem_89_2338 PubMedSearch: Cheng 2017 Anal.Chem 89 2338 PubMedID: 28192910 Abstract Electrospray ionization mass spectrometry (ESI-MS) is powerful for determining enzymatic reaction kinetics because of its soft ionization nature. However, it is limited to use ESI-favored solvents containing volatile buffers (e.g., ammonium acetate). In addition, lack of a quenching step for online ESI-MS reaction monitoring might introduce inaccuracy, due to the possible acceleration of reaction in the sprayed microdroplets. To overcome these issues, this study presents a new approach for online measuring enzymatic reaction kinetics using desorption electrospray ionization mass spectrometry (DESI-MS). By using DESI-MS, enzymatic reaction products in a buffered aqueous media (e.g., a solution containing Tris buffer or high concentration of inorganic salts) could be directly detected. Furthermore, by adjusting the pH and solvent composition of the DESI spray, reaction can be online quenched to avoid the postionization reaction event, leading to fast and accurate measurement of kinetic constants. Reaction time control can be obtained simply by adjusting the injection flow rates of enzyme and substrate solutions. Enzymatic reactions examined in this study include hydrolysis of 2-nitrophenyl-beta-D-galactopyranoside by beta-galactosidase and hydrolysis of acetylcholine by acetylcholinesterase. Derived Michaelis-Menten constants Km for these two reactions were determined to be 214 muM and 172 muM, respectively, which are in good agreement with the values of 300 muM and 230 muM reported in literature, validating the DESI-MS approach. Furthermore, this time-resolved DESI-MS also allowed us to determine Km and turnover number kcat for trypsin digestion of angiotensin II (Km and kcat are determined to be 6.4 mM and 1.3 s-1, respectively). Title: Expression and evolutionary analyses of three acetylcholinesterase genes (Mi-ace-1, Mi-ace-2, Mi-ace-3) in the root-knot nematode Meloidogyne incognita Cui R, Zhang L, Chen Y, Huang W, Fan C, Wu Q, Peng D, da Silva W, Sun X Ref: Experimental Parasitology, 176:75, 2017 : PubMed ESTHER: Cui_2017_Exp.Parasitol_176_75 PubMedSearch: Cui 2017 Exp.Parasitol 176 75 PubMedID: 28238686 Gene_locus related to this paper: melin-ACHE1, melin-ACHE2, melic-a0a0m5m7r8 Abstract The full cDNA of Mi-ace-3 encoding an acetylcholinesterase (AChE) in Meloidogyne incognita was cloned and characterized. Mi-ace-3 had an open reading frame of 1875 bp encoding 624 amino acid residues. Key residues essential to AChE structure and function were conserved. The deduced Mi-ACE-3 protein sequence had 72% amino acid similarity with that of Ditylenchus destructor Dd-AChE-3. Phylogenetic analyses using 41 AChEs from 24 species showed that Mi-ACE-3 formed a cluster with 4 other nematode AChEs. Our results revealed that the Mi-ace-3 cloned in this study, which is orthologous to Caenorhabditis elegans AChE, belongs to the nematode ACE-3/4 subgroup. There was a significant reduction in the number of galls in transgenic tobacco roots when Mi-ace-1, Mi-ace-2, and Mi-ace-3 were knocked down simultaneously, whereas little or no effect were observed when only one or two of these genes were knocked down. This is an indication that the functions of these three genes are redundant. Title: Parental transfer of microcystin-LR induced transgenerational effects of developmental neurotoxicity in zebrafish offspring Wu Q, Yan W, Cheng H, Liu C, Hung TC, Guo X, Li G Ref: Environ Pollut, 231:471, 2017 : PubMed ESTHER: Wu_2017_Environ.Pollut_231_471 PubMedSearch: Wu 2017 Environ.Pollut 231 471 PubMedID: 28837927 Abstract Microcystin-LR (MCLR) has been reported to cause developmental neurotoxicity in zebrafish, but there are few studies on the mechanisms of MCLR-induced transgenerational effects of developmental neurotoxicity. In this study, zebrafish were exposed to 0, 1, 5, and 25 mug/L MCLR for 60 days. The F1 zebrafish embryos from the above-mentioned parents were collected and incubated in clean water for 120 h for hatching. After examining the parental zebrafish and F1 embryos, MCLR was detected in the gonad of adults and F1 embryos, indicating MCLR could potentially be transferred from parents to offspring. The larvae also showed a serious hypoactivity. The contents of dopamine, dihydroxyphenylacetic acid (DOPAC), serotonin, gamma-aminobutyric acid (GABA) and acetylcholine (ACh) were further detected, but only the first three neurotransmitters showed significant reduction in the 5 and 25 mug/L MCLR parental exposure groups. In addition, the acetylcholinesterase (AChE) activity was remarkably decreased in MCLR parental exposure groups, while the expression levels of manf, bdnf, ache, htr1ab, htr1b, htr2a, htr1aa, htr5a, DAT, TH1 and TH2 genes coincided with the decreased content of neurotransmitters (dopamine, DOPAC and serotonin) and the activity of AChE. Neuronal development related genes, alpha1-tubulin, syn2a, mbp, gfap, elavl3, shha and gap43 were also measured, but gap43 was the gene only up-regulated. Our results demonstrated MCLR could be transferred to offspring, and subsequently induce developmental neurotoxicity in F1 zebrafish larvae by disturbing the neurotransmitter systems and neuronal development. Title: Stereoselectivity-Tailored, Metal-Free Hydrolytic Dynamic Kinetic Resolution of Morita-Baylis-Hillman Acetates Using an Engineered Lipase-Organic Base Cocatalyst Xia B, Xu J, Xiang Z, Cen Y, Hu Y, Lin X, Wu Q Ref: ACS Catal, 7:4542, 2017 : PubMed ESTHER: Xia_2017_ACS.Catal_7_4542 PubMedSearch: Xia 2017 ACS.Catal 7 4542 Gene_locus related to this paper: canar-LipB Abstract Metal-free enantiocomplementary hydrolytic dynamic kinetic resolution of Morita-Baylis-Hillman (MBH) acetates was developed using triethylamine (TEA) as a racemization catalyst and wild-type or engineered lipase B from Candida antarctica (CALB) as stereoselectivity-determining catalyst, leading to chiral MBH alcohols with tailor-made R or S configurations on an optional basis. In the TEA-WT CALB catalysis system, WT CALB displays excellent S enantioselectivity for a series of MBH acetates tested (up to 96% ee and 98% conversion). Reversal of enantioselectivity in favor of (R)-MBH alcohols (95% ee; 95% conversion) was achieved by generating a focused site-specific mutagenesis library composed of less than 20 variants. Molecular modeling explains the origin of stereoselectivity. Title: Kinetic resolution of racemic styrene oxide at a high concentration by recombinant Aspergillus usamii epoxide hydrolase in an n-hexanol/buffer biphasic system Hu D, Wang R, Shi XL, Ye HH, Wu Q, Wu MC, Chu JJ Ref: J Biotechnol, 236:152, 2016 : PubMed ESTHER: Hu_2016_J.Biotechnol_236_152 PubMedSearch: Hu 2016 J.Biotechnol 236 152 PubMedID: 27546798 Gene_locus related to this paper: aspng-q1ktb5 Abstract Using the cell-free extract of engineered E. coli/Aueh2, expressing the recombinant Aspergillus usamii epoxide hydrolase (reAuEH2), as a biocatalyst, the kinetic resolution technique of racemic styrene oxide (rac-SO) was examined. In a phosphate buffer system (50mM, pH 7.0), 200mM rac-SO was efficiently resolved, obtaining (S)-SO with 98.1% enantiomeric excess (e.e.), whereas (S)-SO only with 45.2% e.e. was obtained from 750mM rac-SO. The analytical results verified that reAuEH2 shows tolerance towards high substrate concentration but is inactivated at a product concentration of 300mM. To produce (S)-SO with the high concentration, e.e. and volumetric productivity, n-hexanol was selected from a variety of water-miscible and water-immiscible organic solvents to construct an n-hexanol/buffer biphasic system. The optimal phase volume ratio, substrate over enzyme ratio and temperature were 1:1 (v/v), 6:1 (w/w) and 25 degrees C, respectively. In an optimized biocatalytic system, a gram-scale resolution of rac-SO at a high concentration of 1M (120g/L) was performed at 25 degrees C for 2h, obtaining (S)-SO with 98.2% e.e., 34.3% yield (maximum yield of 50%). The substrate concentration and volumetric productivity (1M, 20.6g/L/h) in a biphasic system significantly increased compared with those (0.2M, 3.1g/L/h) in a phosphate buffer system. The efficient resolution of rac-SO at a high concentration in a biphasic system makes it a promising technique for preparing a highly value-added enantiopure (S)-SO with high volumetric productivity. Title: Fumonisins: oxidative stress-mediated toxicity and metabolism in vivo and in vitro Wang X, Wu Q, Wan D, Liu Q, Chen D, Liu Z, Martinez-Larranaga MR, Martinez MA, Anadon A, Yuan Z Ref: Archives of Toxicology, 90:81, 2016 : PubMed ESTHER: Wang_2016_Arch.Toxicol_90_81 PubMedSearch: Wang 2016 Arch.Toxicol 90 81 PubMedID: 26419546 Abstract Fumonisins (FBs) are widespread Fusarium toxins commonly found as corn contaminants. FBs could cause a variety of diseases in animals and humans, such as hepatotoxic, nephrotoxic, hepatocarcinogenic and cytotoxic effects in mammals. To date, almost no review has addressed the toxicity of FBs in relation to oxidative stress and their metabolism. The focus of this article is primarily intended to summarize the progress in research associated with oxidative stress as a plausible mechanism for FB-induced toxicity as well as the metabolism. The present review showed that studies have been carried out over the last three decades to elucidate the production of reactive oxygen species (ROS) and oxidative stress as a result of FBs treatment and have correlated them with various types of FBs toxicity, indicating that oxidative stress plays critical roles in the toxicity of FBs. The major metabolic pathways of FBs are hydrolysis, acylation and transamination. Ceramide synthase, carboxylesterase FumD and aminotransferase FumI could degrade FB1 and FB2. The cecal microbiota of pigs and alkaline processing such as nixtamalization can also transform FB1 into metabolites. Most of the metabolites of FB1 were less toxic than FB1, except its partial (pHFB1) metabolites. Further understanding of the role of oxidative stress in FB-induced toxicity will throw new light on the use of antioxidants, scavengers of ROS, as well as on the blind spots of metabolism and the metabolizing enzymes of FBs. The present review might contribute to reveal the toxicity of FBs and help to protect against their oxidative damage. Title: Microcystin-LR exposure induces developmental neurotoxicity in zebrafish embryo Wu Q, Yan W, Liu C, Li L, Yu L, Zhao S, Li G Ref: Environ Pollut, 213:793, 2016 : PubMed ESTHER: Wu_2016_Environ.Pollut_213_793 PubMedSearch: Wu 2016 Environ.Pollut 213 793 PubMedID: 27038211 Abstract Microcystin-LR (MCLR) is a commonly acting potent hepatotoxin and has been pointed out of potentially causing developmental neurotoxicity, but the exact mechanism is little known. In this study, zebrafish embryos were exposed to 0, 0.8, 1.6 or 3.2 mg/L MCLR for 120 h. MCLR exposure through submersion caused serious hatching delay and body length decrease. The content of MCLR in zebrafish larvae was analyzed and the results demonstrated that MCLR can accumulate in zebrafish larvae. The locomotor speed of zebrafish larvae was decreased. Furthermore, the dopamine and acetylcholine (ACh) content were detected to be significantly decreased in MCLR exposure groups. And the acetylcholinesterase (AChE) activity was significantly increased after exposure to 1.6 and 3.2 mg/L MCLR. The transcription pattern of manf, chrnalpha7 and ache gene was consistent with the change of the dopamine content, ACh content and AChE activity. Gene expression involved in the development of neurons was also measured. a1-tubulin and shha gene expression were down-regulated, whereas mbp and gap43 gene expression were observed to be significantly up-regulated upon exposure to MCLR. The above results indicated that MCLR-induced developmental toxicity might attribute to the disorder of cholinergic system, dopaminergic signaling, and the development of neurons. Title: Identification and Characterization of a New Alkaline SGNH Hydrolase from a Thermophilic Bacterium Bacillus sp. K91 Yu T, Ding J, Zheng Q, Han N, Yu J, Yang Y, Li J, Mu Y, Wu Q, Huang Z Ref: J Microbiol Biotechnol, 26:730, 2016 : PubMed ESTHER: Yu_2016_J.Microbiol.Biotechnol_26_730 PubMedSearch: Yu 2016 J.Microbiol.Biotechnol 26 730 PubMedID: 26699742 Abstract est19 is a gene from Bacillus sp. K91 that encodes a new esterase. A comparison of the amino acid sequence showed that Est19 has typical Ser-Gly-Asn-His (SGNH) family motifs and could be grouped into the SGNH hydrolase family. The Est19 protein was functionally cloned, and expressed and purified from Escherichia coli BL21(DE3). The enzyme activity was optimal at 60 degrees C and pH 9.0, and displayed esterase activity towards esters with short-chain acyl esters (C(2)-C(6)). A structural model of Est19 was constructed using phospholipase A1 from Streptomyces albidoflavus NA297 as a template. The structure showed an alpha/beta-hydrolase fold and indicated the presence of the typical catalytic triad Ser49-Asp227-His230, which were further investigated by site-directed mutagenesis. To the best of our knowledge, Est19 is a new member of the SGNH hydrolase family identified from thermophiles, which may be applicable in the industrial production of semisynthetic beta-lactam antibiotics after modification. 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: Overexpression of miR-155 in the Liver of Transgenic Mice Alters the Expression Profiling of Hepatic Genes Associated with Lipid Metabolism Lin X, Jia J, Du T, Li W, Wang X, Wei J, Zeng H, Yao L, Chen X and Xiao D <8 more author(s)> Lin X, Jia J, Du T, Li W, Wang X, Wei J, Zeng H, Yao L, Chen X, Zhuang J, Weng J, Liu Y, Lin J, Wu Q, Wang W, Yao K, Xu K, Xiao D (- 8) Ref: PLoS ONE, 10:e0118417, 2015 : PubMed ESTHER: Lin_2015_PLoS.One_10_e0118417 PubMedSearch: Lin 2015 PLoS.One 10 e0118417 PubMedID: 25799309 Abstract Hepatic expression profiling has revealed miRNA changes in liver diseases, while hepatic miR-155 expression was increased in murine non-alcoholic fatty liver disease, suggesting that miR-155 might regulate the biological process of lipid metabolism. To illustrate the effects of miR-155 gain of function in transgenic mouse liver on lipid metabolism, transgenic mice (i.e., Rm155LG mice) for the conditional overexpression of mouse miR-155 transgene mediated by Cre/lox P system were firstly generated around the world in this study. Rm155LG mice were further crossed to Alb-Cre mice to realize the liver-specific overexpression of miR-155 transgene in Rm155LG/Alb-Cre double transgenic mice which showed the unaltered body weight, liver weight, epididymal fat pad weight and gross morphology and appearance of liver. Furthermore, liver-specific overexpression of miR-155 transgene resulted in significantly reduced levels of serum total cholesterol, triglycerides (TG) and high-density lipoprotein (HDL), as well as remarkably decreased contents of hepatic lipid, TG, HDL and free fatty acid in Rm155LG/Alb-Cre transgenic mice. More importantly, microarray data revealed a general downward trend in the expression profile of hepatic genes with functions typically associated with fatty acid, cholesterol and triglyceride metabolism, which is likely at least partially responsible for serum cholesterol and triglyceride lowering observed in Rm155LG/Alb-Cre mice. In this study, we demonstrated that hepatic overexpression of miR-155 alleviated nonalcoholic fatty liver induced by a high-fat diet. Additionally, carboxylesterase 3/triacylglycerol hydrolase (Ces3/TGH) was identified as a direct miR-155 target gene that is potentially responsible for the partial liver phenotypes observed in Rm155LG/Alb-Cre mice. Taken together, these data from miR-155 gain of function study suggest, for what we believe is the first time, the altered lipid metabolism and provide new insights into the metabolic state of the liver in Rm155LG/Alb-Cre mice. Title: Soluble Epoxide Hydrolase Deficiency or Inhibition Attenuates MPTP-Induced Parkinsonism Qin X, Wu Q, Lin L, Sun A, Liu S, Li X, Cao X, Gao T, Luo P and Wang X <1 more author(s)> Qin X, Wu Q, Lin L, Sun A, Liu S, Li X, Cao X, Gao T, Luo P, Zhu X, Wang X (- 1) Ref: Molecular Neurobiology, 52:187, 2015 : PubMed ESTHER: Qin_2015_Mol.Neurobiol_52_187 PubMedSearch: Qin 2015 Mol.Neurobiol 52 187 PubMedID: 25128026 Abstract Soluble epoxide hydrolase (sEH) inhibition has been demonstrated to have beneficial effects on various diseases, such as hypertension, diabetes, and brain ischemia. However, whether sEH inhibition has therapeutic potential in Parkinson's disease is still unknown. In this paper, we found that sEH expression is increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP)-treated mice, and sEH deficiency and inhibition significantly attenuated tyrosine hydroxylase (TH)-positive cell loss and improved rotarod performance. The substrate of sEH, 14,15-epoxyeicosatrienoic acid (14,15-EET), protected TH-positive cells and alleviated the rotarod performance deficits of wild-type mice but not sEH-knockout mice. Moreover, the 14,15-EET antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE) abolished the neuronal protective effects of sEH deficiency. In primary cultured cortical neurons, MPP(+) induced significant Akt inactivation in neurons from sEH wild-type mice, and this effect was not observed in neurons from knockout mice. Our data indicate that sEH deficiency and inhibition increased 14,15-EET in MPTP-treated mice, which activated the Akt-mediated protection of TH-positive neurons and behavioral functioning. We also found that sEH deficiency attenuated TH-positive cell loss in a paraquat-induced mouse model of Parkinson's. Our data suggest that sEH inhibition might be a powerful tool to protect dopaminergic neurons in Parkinson's disease. Title: Improvement in the thermostability of a type A feruloyl esterase, AuFaeA, from Aspergillus usamii by iterative saturation mutagenesis Yin X, Li JF, Wang CJ, Hu D, Wu Q, Gu Y, Wu MC Ref: Applied Microbiology & Biotechnology, 99:10047, 2015 : PubMed ESTHER: Yin_2015_Appl.Microbiol.Biotechnol_99_10047 PubMedSearch: Yin 2015 Appl.Microbiol.Biotechnol 99 10047 PubMedID: 26266754 Gene_locus related to this paper: aspni-FAEA Abstract Feruloyl or ferulic acid esterase (Fae, EC 3.1.1.73) catalyzes the hydrolysis of ester bonds between polysaccharides and phenolic acid compounds in xylan side chain. In this study, the thermostability of a type A feruloyl esterase (AuFaeA) from Aspergillus usamii was increased by iterative saturation mutagenesis (ISM). Two amino acids, Ser33 and Asn92, were selected for saturation mutagenesis according to the B-factors analyzed by B-FITTER software and DeltaDeltaG values predicted by PoPMuSiC algorithm. After screening the saturation mutagenesis libraries constructed in Pichia pastoris, 15 promising variants were obtained. The best variant S33E/N92-4 (S33E/N92R) produced a T m value of 44.5 degrees C, the half-lives (t 1/2) of 35 and 198 min at 55 and 50 degrees C, respectively, corresponding to a 4.7 degrees C, 2.33- and 3.96-fold improvement compared to the wild type. Additionally, the best S33 variant S33-6 (S33E) was thermostable at 50 degrees C with a t 1/2 of 82 min, which was 32 min longer than that of the wild type. All the screened S33E/N92 variants were more thermostable than the best S33 variant S33-6 (S33E). This work would contribute to the further studies on higher thermostability modification of type A feruloyl esterases, especially those from fungi. The thermostable feruloyl esterase variants were expected to be potential candidates for industrial application in prompting the enzymic degradation of plant biomass materials at elevated temperatures. Title: Oil accumulation mechanisms of the oleaginous microalga Chlorella protothecoides revealed through its genome, transcriptomes, and proteomes Gao C, Wang Y, Shen Y, Yan D, He X, Dai J, Wu Q Ref: BMC Genomics, 15:582, 2014 : PubMed ESTHER: Gao_2014_BMC.Genomics_15_582 PubMedSearch: Gao 2014 BMC.Genomics 15 582 PubMedID: 25012212 Gene_locus related to this paper: auxpr-a0a087suf4, auxpr-a0a087sif8, auxpr-a0a087srm3 Abstract BACKGROUND: Microalgae-derived biodiesel is a promising substitute for conventional fossil fuels. In particular, the green alga Chlorella protothecoides sp. 0710 is regarded as one of the best candidates for commercial manufacture of microalgae-derived biofuel. This is due not only to its ability to live autotrophically through photosynthesis, but also to its capacity to produce a large amount of biomass and lipid through fermentation of glucose. However, until the present study, neither its genome sequence nor the platform required for molecular manipulations were available. Title: Detoxification enzymes of Bemisia tabaci B and Q: biochemical characteristics and gene expression profiles Guo L, Xie W, Wang S, Wu Q, Li R, Yang N, Yang X, Pan H, Zhang Y Ref: Pest Manag Sci, 70:1588, 2014 : PubMed ESTHER: Guo_2014_Pest.Manag.Sci_70_1588 PubMedSearch: Guo 2014 Pest.Manag.Sci 70 1588 PubMedID: 24488614 Abstract BACKGROUND: The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is one of the most invasive and destructive pests of field crops worldwide. The sibling species B and Q are the two most damaging members of the B. tabaci species complex. That Q is more resistant than B to many insecticides has been well documented. Over the last decade, Q has gradually displaced B and has become the dominant form of B. tabaci in field agricultural systems in most parts of China. To help understand the differences in insecticide resistance, the activities and gene expression profiles of detoxification enzymes in B. tabaci B and Q were investigated. Title: Two Enzyme Cooperatively Catalyzed Tandem Polymerization for the Synthesis of Polyester Containing Chiral (R)- or (S)-Ibuprofen Pendants Qian X, Wang J, Li Y, Lin X, Wu Q Ref: Macromol Rapid Commun, 35:1788, 2014 : PubMed ESTHER: Qian_2014_Macromol.Rapid.Commun_35_1788 PubMedSearch: Qian 2014 Macromol.Rapid.Commun 35 1788 PubMedID: 25200738 Abstract An interesting cooperation between Candida antarctica Lipase B (CAL-B) and alkaline protease from Bacillus subtilis (BSP) in the copolymerization of bulky ibuprofen-containing hydroxyacid methyl ester (HAEP) and sigma-caprolactone (sigma-CL) is observed. This cooperation improved the Mn of the polymers from 3130 (CAL-B) to 9200 g mol(-1) (CAL-B/BSP). Experimental results clearly indicate that CAL-B mainly catalyzes the ring-opening polymerization (ROP) of sigma-CL under the initiation of HAEP to form the homopolymer of sigma-CL, while BSP catalyzes the subsequent polycondensation of the ROP product to yield the copolymer with increased molecular weight. Furthermore, using suitable chemo-enzymatic methods, valuable polyesters with chiral (R)- or (S)-ibuprofen pendants can be tailor-made. Title: Lactobacillus casei-01 Facilitates the Ameliorative Effects of Proanthocyanidins Extracted from Lotus Seedpod on Learning and Memory Impairment in Scopolamine-Induced Amnesia Mice Xiao J, Li S, Sui Y, Wu Q, Li X, Xie B, Zhang M, Sun Z Ref: PLoS ONE, 9:e112773, 2014 : PubMed ESTHER: Xiao_2014_PLoS.One_9_e112773 PubMedSearch: Xiao 2014 PLoS.One 9 e112773 PubMedID: 25396737 Abstract Learning and memory abilities are associated with alterations in gut function. The two-way proanthocyanidins-microbiota interaction in vivo enhances the physiological activities of proanthocyanidins and promotes the regulation of gut function. Proanthocyanidins extracted from lotus seedpod (LSPC) have shown the memory-enhancing ability. However, there has been no literature about whether Lactobacillus casei-01 (LC) enhances the ameliorative effects of LSPC on learning and memory abilities. In this study, learning and memory abilities of scopolamine-induced amnesia mice were evaluated by Y-maze test after 20-day administration of LC (109 cfu/kg body weight (BW)), LSPC (low dose was 60 mg/kg BW (L-LSPC) and high dose was 90 mg/kg BW (H-LSPC)), or LSPC and LC combinations (L-LSPC+LC and H-LSPC+LC). Alterations in antioxidant defense ability and oxidative damage of brain, serum and colon, and brain cholinergic system were investigated as the possible mechanisms. As a result, the error times of H-LSPC+LC group were reduced by 41.59% and 68.75% relative to those of H-LSPC and LC groups respectively. LSPC and LC combinations ameliorated scopolamine-induced memory impairment by improving total antioxidant capacity (TAOC) level, glutathione peroxidase (GSH-Px) and total superoxide dismutase (T-SOD) activities of brain, serum and colon, suppressing malondialdehyde (MDA) level of brain, serum and colon, and inhibiting brain acetylcholinesterase (AchE), myeloperoxidase, total nitric oxide synthase and neural nitric oxide synthase (nNOS) activities, and nNOS mRNA level. Moreover, LC facilitated the ameliorative effects of H-LSPC on GSH-Px activity of colon, TAOC level, GSH-Px activity and ratio of T-SOD to MDA of brain and serum, and the inhibitory effects of H-LSPC on serum MDA level, brain nNOS mRNA level and AchE activity. These results indicated that LC promoted the memory-enhancing effect of LSPC in scopolamine-induced amnesia mice. Title: A novel protein elicitor (SsCut) from Sclerotinia sclerotiorum induces multiple defense responses in plants Zhang H, Wu Q, Cao S, Zhao T, Chen L, Zhuang P, Zhou X, Gao Z Ref: Plant Mol Biol, 86:495, 2014 : PubMed ESTHER: Zhang_2014_Plant.Mol.Biol_86_495 PubMedSearch: Zhang 2014 Plant.Mol.Biol 86 495 PubMedID: 25149470 Abstract In this study, we report the cloning of the SsCut gene encoding cutinase from Sclerotinia sclerotiorum. We isolated a 609-bp cDNA encoding a polypeptide of 202 amino acids with a molecular weight of 20.4 kDa. Heterologous expression of SsCut in Escherichia coli (His-SsCut) caused the formation of lesions in tobacco that closely resembled hypersensitive response lesions. Mutational analysis identified the C-terminal-half peptide and the same amino acids indispensable for both enzyme and elicitor activity. His-SsCut was caused cell death in Arabidopsis, soybean (Glycine max), oilseed rape (Brassica napus), rice (Oryza sativa), maize (Zea mays), and wheat (Triticum aestivum), indicating that both dicot and monocot species are responsive to the elicitor. Furthermore, the elicitation of tobacco was effective in the induction of the activities of hydrogen peroxide, phenylalanine ammonia-lyase, peroxides, and polyphenol oxidase. His-SsCut-treated plants exhibited enhanced resistance as indicated by a significant reduction in the number and size of S. sclerotiorum, Phytophthora sojae, and P. nicotianae lesions on leaves relative to controls. Real-time PCR results indicated that the expression of defense-related genes and genes involved in signal transduction were induced by His-SsCut. Our results demonstrate that SsCut is an elicitor that triggers defense responses in plants and will help to clarify its relationship to downstream signaling pathways that induce defense responses. Title: Genomic study of polyhydroxyalkanoates producing Aeromonas hydrophila 4AK4 Gao X, Jian J, Li WJ, Yang YC, Shen XW, Sun ZR, Wu Q, Chen GQ Ref: Applied Microbiology & Biotechnology, 97:9099, 2013 : PubMed ESTHER: Gao_2013_Appl.Microbiol.Biotechnol_97_9099 PubMedSearch: Gao 2013 Appl.Microbiol.Biotechnol 97 9099 PubMedID: 24000047 Gene_locus related to this paper: aerme-a0a023rmd0, aervb-f4dgq1 Abstract The complete genome of Gram-negative Aeromonas hydrophila 4AK4 that has been used for industrial production of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) was sequenced and annotated. Its chromosome is 4,527,993 bp in size encoding 4,272 genes, including 28 rRNA genes and 104 tRNA genes. Comparative analysis indicated that genome of A. hydrophila 4AK4 was similar to that of the A. hydrophila ATCC 7966(T), an intensively studied aeromonad for its pathogenicity related to its genomic information. Genes possibly coming from other species or even other genus were identified in A. hydrophila 4AK4. A large number of putative virulent genes were predicted. However, a cytotonic enterotoxin (Ast) is absent in A. hydrophila 4AK4, allowing the industrial strain to be different from other A. hydrophila strains, indicating possible reduced virulence of strain 4AK4, which is very important for industrial fermentation. Genes involved in polyhydroxyalkanoate (PHA) metabolism were predicted and analyzed. The resulting genomic information is useful for improved production of PHA via metabolic engineering of A. hydrophila 4AK4. Title: Droplet-based microfluidics for dose-response assay of enzyme inhibitors by electrochemical method Gu S, Lu Y, Ding Y, Li L, Zhang F, Wu Q Ref: Anal Chim Acta, 796:68, 2013 : PubMed ESTHER: Gu_2013_Anal.Chim.Acta_796_68 PubMedSearch: Gu 2013 Anal.Chim.Acta 796 68 PubMedID: 24016585 Abstract A simple but robust droplet-based microfluidic system was developed for dose-response enzyme inhibition assay by combining concentration gradient generation method with electrochemical detection method. A slotted-vials array and a tapered tip capillary were used for reagents introduction and concentration gradient generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with microelectrodes was used for droplet generation and electrochemical detection. Effects of oil flow rate and surfactant on electrochemical sensing were investigated. This system was validated by measuring dose-response curves of three types of acetylcholinesterase (AChE) inhibitors, including carbamate pesticide, organophosphorus pesticide, and therapeutic drugs regulating Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model analytes, respectively, and their IC50 (half maximal inhibitory concentration) values were determined. A whole enzyme inhibition assay was completed in 6min, and the total consumption of reagents was less than 5muL. This microfluidic system is applicable to many biochemical reactions, such as drug screening and kinetic studies, as long as one of the reactants or products is electrochemically active. Title: Biocatalysts for cascade reaction: porcine pancreas lipase (PPL)-catalyzed synthesis of bis(indolyl)alkanes Xiang Z, Liu Z, Chen X, Wu Q, Lin X Ref: Amino Acids, 45:937, 2013 : PubMed ESTHER: Xiang_2013_Amino.Acids_45_937 PubMedSearch: Xiang 2013 Amino.Acids 45 937 PubMedID: 23860845 Abstract A cascade reaction between aldehydes and indole catalyzed by lipase from porcine pancreas Type II (PPL) in solvent mixture at 50 degrees C was reported for the first time. Some control experiments had been designed to demonstrate that the PPL was responsible for the cascade reaction. After the optimization of the stepwise process, a series of bis(indolyl)alkanes were prepared in moderate to excellent yields under the catalysis of PPL. Title: 3-Hydroxybutyrate methyl ester as a potential drug against Alzheimer's disease via mitochondria protection mechanism Zhang J, Cao Q, Li S, Lu X, Zhao Y, Guan JS, Chen JC, Wu Q, Chen GQ Ref: Biomaterials, 34:7552, 2013 : PubMed ESTHER: Zhang_2013_Biomaterials_34_7552 PubMedSearch: Zhang 2013 Biomaterials 34 7552 PubMedID: 23849878 Abstract Alzheimer's disease (AD) is induced by many reasons, including decreased cellular utilization of glucose and brain cell mitochondrial damages. Degradation product of microbially synthesized polyhydroxybutyrate (PHB), namely, 3-hydroxybutyrate (3HB), can be an alternative to glucose during sustained hypoglycemia. In this study, the derivative of 3HB, 3-hydroxybutyrate methyl ester (HBME), was used by cells as an alternative to glucose. HBME inhibited cell apoptosis under glucose deprivation, rescued activities of mitochondrial respiratory chain complexes that were impaired in AD patients and decreased the generation of ROS. Meanwhile, HBME stabilized the mitochondrial membrane potential. In vivo studies showed that HBME crossed the blood brain barrier easier compared with charged 3HB, resulting in a better bioavailability. AD mice treated with HBME performed significantly better (p < 0.05) in the Morris water maze compared with other groups, demonstrating that HBME has a positive in vivo pharmaceutical effect to improve the spatial learning and working memory of mice. A reduced amyloid-beta deposition in mouse brains after intragastric administration of HBME was also observed. Combined with the in vitro and in vivo results, HBME was proposed to be a drug candidate against AD, its working mechanism appeared to be mediated by various effects of protecting mitochondrial damages. Title: Complete genome sequence of Brucella melitensis biovar 3 strain NI, isolated from an aborted bovine fetus Liu W, Jing Z, Ou Q, Cui B, He Y, Wu Q Ref: Journal of Bacteriology, 194:6321, 2012 : PubMed ESTHER: Liu_2012_J.Bacteriol_194_6321 PubMedSearch: Liu 2012 J.Bacteriol 194 6321 PubMedID: 23105063 Gene_locus related to this paper: brume-PCAD Abstract From an aborted bovine fetus in China, a bacterial strain named NI was isolated and identified as Brucella melitensis by a PCR assay. Strain NI was further characterized as B. melitensis biovar 3 using biochemical assays. Here we report the complete genome sequence of strain NI. Title: Insights into pyrroindomycin biosynthesis reveal a uniform paradigm for tetramate/tetronate formation Wu Q, Wu Z, Qu X, Liu W Ref: Journal of the American Chemical Society, 134:17342, 2012 : PubMed ESTHER: Wu_2012_J.Am.Chem.Soc_134_17342 PubMedSearch: Wu 2012 J.Am.Chem.Soc 134 17342 PubMedID: 23062149 Gene_locus related to this paper: strrg-k7qrj3 Abstract The natural products pyrroindomycins (PYRs), active against various drug-resistant pathogens, possess a characteristic, cyclohexene ring spiro-linked tetramate moiety. In this study, investigation into PYR biosynthesis revealed two new proteins, both of which, phylogenetically distinct from but functionally substitutable to each other in vivo, individually catalyze a Dieckmann cyclization in vitro for converting an N-acetoacetyl-l-alanyl thioester into a tetramate. Their counterparts are commonly present in the biosynthetic pathways of spiro and polyether tetronates, supporting a uniform paradigm for tetronate/tetramate formation, which features an enzymatic way to generate the C-X (X = O or N) bond first and the C-C bond next in building of the 5-membered heterocycle. Title: Chlorpyrifos exposure causes alternation in dopamine metabolism in PC12 cells Xu F, Chang X, Lou D, Wu Q, Zhou Z Ref: Toxicol Mech Methods, 22:309, 2012 : PubMed ESTHER: Xu_2012_Toxicol.Mech.Methods_22_309 PubMedSearch: Xu 2012 Toxicol.Mech.Methods 22 309 PubMedID: 22356570 Abstract Chlorpyrifos (CPF) is one of the organophosphorus pesticides widely used around the world, especially in China. Acetylcholinesterase inhibition is the main effect of organophosphorus insecticides exposure. Studies showed that CPF may also interfere with the metabolism of monoamine transmitters. To investigate the effects of CPF on dopaminergic pathway, the dopamine content, gene expression of catechol-O-methyl- transferase (COMT), vesicular monoamine transporter-2 (VMAT-2), and monoamine oxidase (MAO) and its activity in PC12 cells exposed to CPF was determined. Results showed that cell viability was decreased and total dopamine concentration was increased with CPF administration in a dose-dependent pattern. Gene of MAO was significantly downregulated in PC12 cells, while genes of COMT and VMAT-2 in PC12 cells did not show any change after CPF exposure. The MAO activity was decreased following incubation exposed to CPF. These results suggest that CPF may interfere with dopaminergic pathway through inhibition on gene and protein expression of MAO in vitro. Title: A comparison of hepatic in vitro metabolism of T-2 toxin in rats, pigs, chickens, and carp Wu Q, Huang L, Liu Z, Yao M, Wang Y, Dai M, Yuan Z Ref: Xenobiotica, 41:863, 2011 : PubMed ESTHER: Wu_2011_Xenobiotica_41_863 PubMedSearch: Wu 2011 Xenobiotica 41 863 PubMedID: 21745144 Abstract T-2 toxin, a highly toxic member of the type-A trichothecenes, is produced by various Fusarium moulds that can potentially affect human health. It is strongly cytotoxic for human hematopoietic progenitors. Alimentary toxic aleukia (ATA), a disease typically associated with human, is primarily induced by T-2 toxin. A comparison of the metabolism of T-2 toxin incubated with hepatocytes of rats, piglets, chickens, and the hepatic subcellular fractions (microsomes and cytosol) of piglets, chickens, rats, and carp (common carp and grass carp) was carried out. The activities of the recombinant pig CYP3A29 on the transformation of T-2 and HT-2 toxins were preliminary studied. Metabolites were identified by novel LC/MS-IT-TOF. Qualitative similarities and differences across the species were observed. In liver microsomes, HT-2 toxin, neosolaniol (NEO), 3'-OH-T-2, and 3'-OH-HT-2 were detected in rats, chickens, and pigs. 3'-OH-HT-2 and HT-2 toxin was not detectable in common carp and grass crap, respectively. Moreover, in liver microsomes, the hydroxyl metabolites accounted for the largest percentage in carp, whereas the hydrolysis product, HT-2 toxin, was the major one for the land animals. Only hydrolysis products such as NEO and HT-2 toxin were detected in hepatocytes. Recombinant pig CYP3A29 was able to convert T-2 and HT-2 toxins to high rates of 3'-OH-T-2 and 3'-OH-HT-2, respectively. Both CYP450 and carboxylesterase enzymes have been found to play a role in the metabolism of T-2 toxin. Metabolism of T-2 toxin across species produces a similar spectrum of metabolites. Preliminary metabolic studies of carp reveal that ester hydrolysis of T-2 toxin in carp may not play as important a role as is the case with land animals. Title: Cross-resistance study and biochemical mechanisms of thiamethoxam resistance in B-biotype Bemisia tabaci (Hemiptera: Aleyrodidae) Feng Y, Wu Q, Wang S, Chang X, Xie W, Xu B, Zhang Y Ref: Pest Manag Sci, 66:313, 2010 : PubMed ESTHER: Feng_2010_Pest.Manag.Sci_66_313 PubMedSearch: Feng 2010 Pest.Manag.Sci 66 313 PubMedID: 19937914 Inhibitor(s) related to this paper: Diethyl-maleate Abstract BACKGROUND: B-biotype Bemisia tabaci (Gennadius) has invaded China over the past two decades. To understand the risks and to determine possible mechanisms of resistance to thiamethoxam in B. tabaci, a resistant strain was selected in the laboratory. Cross-resistance and the biochemical mechanisms of thiamethoxam resistance were investigated in the present study. RESULTS: A 66.3-fold thiamethoxam-resistant B. tabaci strain (TH-R) was established after selection for 36 generations. Compared with the susceptible strain (TH-S), the selected TH-R strain showed obvious cross-resistance to imidacloprid (47.3-fold), acetamiprid (35.8-fold), nitenpyram (9.99-fold), abamectin (5.33-fold) and carbosulfan (4.43-fold). No cross-resistance to fipronil, chlorpyrifos or deltamethrin was seen. Piperonyl butoxide (PBO) and triphenyl phosphate (TPP) exhibited significant synergism on thiamethoxam effects in the TH-R strain (3.14- and 2.37-fold respectively). However, diethyl maleate (DEM) did not act synergistically with thiamethoxam. Biochemical assays showed that cytochrome P450 monooxygenase activities increased 1.21- and 1.68-fold respectively, and carboxylesterase activity increased 2.96-fold in the TH-R strain. However, no difference was observed for glutathione S-transferase between the two strains. CONCLUSION: B-biotype B. tabaci develops resistance to thiamethoxam. Cytochrome P450 monooxygenase and carboxylesterase appear to be responsible for the resistance. Reasonable resistance management that avoids the use of cross-resistance insecticides may delay the development of resistance to thiamethoxam in this species. 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: Application of ultrasound-assisted surfactant-enhanced emulsification microextraction for the determination of some organophosphorus pesticides in water samples Wu C, Liu N, Wu Q, Wang C, Wang Z Ref: Anal Chim Acta, 679:56, 2010 : PubMed ESTHER: Wu_2010_Anal.Chim.Acta_679_56 PubMedSearch: Wu 2010 Anal.Chim.Acta 679 56 PubMedID: 20951857 Abstract An ultrasound-assisted surfactant-enhanced emulsification microextraction (UASEME) was developed as a new approach for the extraction of organophosphorus pesticides (OPs) in water samples prior to high-performance liquid chromatography with diode array detection (HPLC-DAD). The use of a surfactant as an emulsifier in the UASEME method could enhance the dispersion of water-immiscible extraction solvent into aqueous phase and is favorable for the mass-transfer of the analytes from aqueous phase to the organic phase. Several variables that affect the extraction efficiency, including the kind and volume of the extraction solvent, the type and concentration of the surfactant, salt addition, ultrasound emulsification time and temperature, were investigated and optimized. Under the optimum experimental conditions, the calibration curve was linear in the concentration range from 1 to 200 ng mL(-1) for the seven OPs (isocarbophos, phosmet, parathion, parathion-methyl, fenitrothion, fonofos and phoxim), with the correlation coefficients (r) varying from 0.9973 to 0.9998. High enrichment factors were achieved ranging from 210 to 242. The established UASEME-HPLC-DAD method has been successfully applied for the determination of the OPs in real water samples. The limits of detection were in the range between 0.1 and 0.3 ng mL(-1). The recoveries of the target analytes over the three spiked concentration levels of the compounds (10, 50, and 100 ng mL(-1), respectively) in rain, reservoir and well water samples were between 83% and 106% with the relative standard deviations varying from 3.3% to 5.6%. Title: Protective effects of icariin on cognitive deficits induced by chronic cerebral hypoperfusion in rats Xu RX, Wu Q, Luo Y, Gong QH, Yu LM, Huang XN, Sun AS, Shi JS Ref: Clinical & Experimental Pharmacology & Physiology, 36:810, 2009 : PubMed ESTHER: Xu_2009_Clin.Exp.Pharmacol.Physiol_36_810 PubMedSearch: Xu 2009 Clin.Exp.Pharmacol.Physiol 36 810 PubMedID: 19215241 Abstract 1. Icariin is a major constituent of flavonoids derived from the Chinese medicinal herb Epimedium revicornum Maxim. The aim of the present study was to investigate whether icariin has protective effects on learning ability and memory in a rat model of chronic cerebral hypoperfusion. 2. Chronic cerebral hypoperfusion was induced by permanent ligation of the common carotid artery in Wistar rats for 4 months. One month after permanent artery occlusion, rats were adminitered icariin at doses of 0, 30, 60 or 120 mg/kg per day, p.o., for 3 months. Neurobehavioural and neurobiochemical parameters were examined to evaluate the effects of icariin on cognitive deficits induced by chronic cerebral hypoperfusion. 3. The Morris water maze test revealed that learning ability and memory were severely impaired in untreated rats, but were significantly improved in icariin-treated rats. Icariin treatment also ameliorated chronic cerebral hypoperfusion-induced oxidative stress in the brain, as evidenced by reduced malondialdehyde formation and maintained superoxide dismutase activity. In addition, the decreased hippocampal levels of acetylcholine, acetylcholinesterase and choline acetyltransferase associated with chronic cerebral hypoperfusion were significantly prevented by icariin treatment. 4. In conclusion, icariin protects against cognitive deficits induced by chronic cerebral hypoperfusion in rats. These effects appear to be mediated through its anti-oxidant effects, as well as its effects on the circulatory and cholinergic systems. Title: NO-1886, a lipoprotein lipase activator, attenuates contraction of rat intestinal ring preparations Wu Q, Harada N, Nakamura A, Yoshida M, Mawatari K, Hattori A, Li Q, Shimohata T, Yinhua and Nakaya Y <4 more author(s)> Wu Q, Harada N, Nakamura A, Yoshida M, Mawatari K, Hattori A, Li Q, Shimohata T, Yinhua, Lian X, Nakano M, Hosaka T, Takahashi A, Nakaya Y (- 4) Ref: J Med Invest, 55:61, 2008 : PubMed ESTHER: Wu_2008_J.Med.Invest_55_61 PubMedSearch: Wu 2008 J.Med.Invest 55 61 PubMedID: 18319547 Abstract Various intestinal symptoms or diseases are closely associated with intestinal motility, which may be altered by metabolic disturbances associated with diabetes and obesity. It is therefore important that drugs used in the treatment of metabolic disorders should not have any adverse effects on the intestine. In the present study, we examined whether [4-(4-bromo-2-cyano-phenylcarbamoyl)-benzyl]-phosphonic acid diethyl ester (NO-1886), a lipoprotein lipase activator with anti-diabetic and/or anti-obese activity, affects stimulant-induced intestinal contractility. Administration of NO-1886 to intestinal ring preparations of ileum, rectum and colon isolated from Wistar rats attenuated or relaxed contraction induced by a high K+ environment or acetylcholine (ACh). This effect of NO-1886 was dependent on extracellular Ca(2+) and intracellular myosin light chain kinase activity. Our results also showed that ACh-induced colonic contraction was significantly higher in the obese Otsuka Long-Evans Tokushima Fatty (OLETF) than in the non-obese Long-Evans Tokushima Otsuka (LETO) rats. The hypercontractility observed in the colons of OLETF rats occurred concomitantly with an elevation in muscarinic M3 ACh receptor protein levels. Administration of NO-1886 attenuated the obesity-induced hypercontractility of the colonic rings of OLETF rats. Thus, intestinal contractile system would be a novel pharmacological target of the lipoprotein lipase activator NO-1886. Title: N-methylimidazole significantly improves lipase-catalysed acylation of ribavirin Liu BK, Wu Q, Xu JM, Lin XF Ref: Chem Commun (Camb), :295, 2007 : PubMed ESTHER: Liu_2007_Chem.Commun.(Camb)__295 PubMedSearch: Liu 2007 Chem.Commun.(Camb) 295 PubMedID: 17299644 Abstract N-methylimidazole, a molecular solvent, but also, in cationic form, a component of 1-alkyl-3-methylimidazolium ([C(n)MIM]+) ionic liquids, showed promise as an additive in accelerating remarkably transesterification catalyzed by lipase acrylic resin from Candida antarctica (CAL-B). Title: Protective effect of Ginkgo biloba leaf extract on learning and memory deficit induced by aluminum in model rats Gong QH, Wu Q, Huang XN, Sun AS, Nie J, Shi JS Ref: Chin J Integr Med, 12:37, 2006 : PubMed ESTHER: Gong_2006_Chin.J.Integr.Med_12_37 PubMedSearch: Gong 2006 Chin.J.Integr.Med 12 37 PubMedID: 16571282 Abstract OBJECTIVE: To examine the protective effect of Ginkgo biloba leaf extract (GbE) on learning and memory deficit induced by aluminum chloride (AlCl(3)), and explore its mechanisms. Title: Encapsulating drugs in biodegradable ultrafine fibers through co-axial electrospinning Huang ZM, He CL, Yang A, Zhang Y, Han XJ, Yin J, Wu Q Ref: J Biomed Mater Res A, 77:169, 2006 : PubMed ESTHER: Huang_2006_J.Biomed.Mater.Res.A_77_169 PubMedSearch: Huang 2006 J.Biomed.Mater.Res.A 77 169 PubMedID: 16392131 Abstract This article describes an electrospinning process to fabricate double-layered ultrafine fibers. A bioabsorbable polymer, Polycaprolactone (PCL), was used as the outer layer or the shell and two medically pure drugs, Resveratrol (RT, a kind of antioxidant) and Gentamycin Sulfate (GS, an antibiotic), were used as the inner layers or the cores. Morphology and microstructure of the ultrafine fibers were characterized by scanning electron microscope (SEM) and transmission electron microscopy (TEM), whereas mechanical performance of them was understood through tensile test. In vitro degradation rates of the nanofibrous membranes were determined by measuring their weight loss when immersed in pH 7.4 phosphate-buffered saline (PBS) mixed with certain amount of Pseudomonas lipase for a maximum of 7 days. The drug release behaviors of the RT and GS were measured using a high performance liquid chromatography (HPLC) and ultraviolet-visible (UV-vis) spectroscopy, respectively. It has been found that the drug solutions without any fiber-forming additive could be encapsulated in the PCL ultrafine fibers, although they alone cannot be made into a fiber form. Beads on the fiber surface influenced the tensile behavior of the ultrafine fibers remarkably. When the core solvent was miscible with the shell solvent, higher drug concentration decreased the bead formation and thus favored the mechanical performance. The situation, however, became different if the two solvents were immiscible with each other. The degradation rate was closely related to hydrophilicity of the drugs in the cores. Higher hydrophilicity apparently led to faster degradation. The release profiles of the RT and GS exhibited a sustained release characteristic, with no burst release phenomenon. Title: Controllable synthesis of polymerizable ester and amide prodrugs of acyclovir by enzyme in organic solvent Li X, Wu Q, Lv DS, Lin XF Ref: Bioorganic & Medicinal Chemistry, 14:3377, 2006 : PubMed ESTHER: Li_2006_Bioorg.Med.Chem_14_3377 PubMedSearch: Li 2006 Bioorg.Med.Chem 14 3377 PubMedID: 16431120 Abstract A facile control of the acylation position at the primary hydroxyl and amino of acyclovir, respectively, was achieved and five polymerizable acyclovir prodrugs were synthesized. Various reaction conditions were studied in detail. Thus, lipase acrylic resin from Candida antarctica (CAL-B) in pyridine or acetone showed high chemo-selectivity toward the primary hydroxyl of acyclovir. However, lipase PS 'Amano' (PS) in DMSO selectively acylated the amino group. The selectivity of PS could be adjusted by changing reaction solvents. The acyclovir vinyl derivatives obtained would be important monomers used for the preparation of macromolecular nucleoside drugs. Title: Markedly enhancing lipase-catalyzed synthesis of nucleoside drugs' ester by using a mixture system containing organic solvents and ionic liquid Liu BK, Wang N, Chen ZC, Wu Q, Lin XF Ref: Bioorganic & Medicinal Chemistry Lett, 16:3769, 2006 : PubMed ESTHER: Liu_2006_Bioorg.Med.Chem.Lett_16_3769 PubMedSearch: Liu 2006 Bioorg.Med.Chem.Lett 16 3769 PubMedID: 16682199 Abstract Eightfold higher yields and three times faster reaction rates were achieved by means of using a mixture solvent system composed of 90% acetone and 10% [BMIM]BF4 in the lipase-catalyzed regioselective synthesis of polymerizable ester of nucleoside drugs. Title: Molecular cloning and functional analysis of two polyhydroxyalkanoate synthases from two strains of Aeromonas hydrophila spp Lu X, Zhang W, Jian J, Wu Q, Chen GQ Ref: FEMS Microbiology Letters, 243:149, 2005 : PubMed ESTHER: Lu_2005_FEMS.Microbiol.Lett_243_149 PubMedSearch: Lu 2005 FEMS.Microbiol.Lett 243 149 PubMedID: 15668013 Gene_locus related to this paper: aerhy-PHAC Abstract Polyhydroxyalkanoate (PHA) synthase genes (phaC) were cloned from two Aeromonas hydrophila strains named WQ and 4AK5, respectively. Both strains are able to produce PHBHHx copolyesters consisting of 3-hydroxybutyrate (3HB) and 3-hydroxyhexanoate (3HHx). Sequence analysis showed that there was only 2 bp difference between these two PHA synthase genes, corresponding to two-amino acid difference at positions of 437 and 458 of the two synthases. PHA productivity and its monomer content produced by A. hydrophila WQ and A. hydrophila 4AK5 were quite different. A. hydrophila WQ accumulated 33% PHBHHx of its cell dry weight (CDW) with 5 mol% 3HHx in the copolyester when cultured in lauric acid for 48 h. Yet A. hydrophila 4AK5 was able to produce 43% PHBHHx of the CDW with 14 mol% 3HHx under the same condition. Hetero-expression of PHA synthase genes of A. hydrophila WQ and A. hydrophila 4AK5, respectively, in Escherichia coli XL1-Blue led to PHBHHx accumulation of 24% and 39% of the CDW and the 3HHx content in PHBHHx were 6 and 15 mol%, respectively. This indicated that the function of these two PHA synthases were different due to these two different residues at positions of 437 and 458. Site specific mutation was carried out to change these two amino acid residues. Results showed that the changes on either of the two amino acids negatively affected the PHA productivity. Title: The Genomes of Oryza sativa: a history of duplications Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S and Yang H <88 more author(s)> Yu J, Wang J, Lin W, Li S, Li H, Zhou J, Ni P, Dong W, Hu S, Zeng C, Zhang J, Zhang Y, Li R, Xu Z, Li X, Zheng H, Cong L, Lin L, Yin J, Geng J, Li G, Shi J, Liu J, Lv H, Li J, Deng Y, Ran L, Shi X, Wang X, Wu Q, Li C, Ren X, Li D, Liu D, Zhang X, Ji Z, Zhao W, Sun Y, Zhang Z, Bao J, Han Y, Dong L, Ji J, Chen P, Wu S, Xiao Y, Bu D, Tan J, Yang L, Ye C, Xu J, Zhou Y, Yu Y, Zhang B, Zhuang S, Wei H, Liu B, Lei M, Yu H, Li Y, Xu H, Wei S, He X, Fang L, Huang X, Su Z, Tong W, Tong Z, Ye J, Wang L, Lei T, Chen C, Chen H, Huang H, Zhang F, Li N, Zhao C, Huang Y, Li L, Xi Y, Qi Q, Li W, Hu W, Tian X, Jiao Y, Liang X, Jin J, Gao L, Zheng W, Hao B, Liu S, Wang W, Yuan L, Cao M, McDermott J, Samudrala R, Wong GK, Yang H (- 88) Ref: PLoS Biol, 3:e38, 2005 : PubMed ESTHER: Yu_2005_PLoS.Biol_3_e38 PubMedSearch: Yu 2005 PLoS.Biol 3 e38 PubMedID: 15685292 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q852M6, orysa-Q8GSE8, orysa-Q9S7P1, orysa-Q9FYP7, orysa-Q5ZBH3, orysa-Q5ZA26, orysa-Q5JLP6, orysa-Q8H5P9, orysa-Q8H5P5, orysa-Q7F1Y5, orysa-Q949C9, orysa-cbp1, orysa-cbp3, orysa-cbpx, orysa-Q33B71, orysa-Q8GSJ3, orysa-LPL1, orysa-Q6YSZ8, orysa-Q8S5X5, orysa-Q8LIG3, orysa-Q6K7F5, orysa-Q7F1B1, orysa-Q8H4S9, orysa-Q69UB1, orysa-Q9FW17, orysa-Q337C3, orysa-Q7F959, orysa-Q84QZ6, orysa-Q84QY7, orysa-Q851E3, orysa-Q6YTH5, orysa-Q0JK71, orysa-Q8S1D9, orysa-Q5N8V4, orysa-Q0JCY4, orysa-Q8GTK2, orysa-B9EWJ8, orysa-Q8H3K6, orysa-Q6ZDG8, orysa-Q6ZDG6, orysa-Q6ZDG5, orysa-Q6ZDG4, orysa-Q5NAI4, orysa-Q658B2, orysa-Q5JMQ8, orysa-Q5QMD9, orysa-Q5N7L1, orysa-Q8RYV9, orysa-Q8H3R3, orysa-Q5SNH3, orysa-Q8W0F0, orysa-pir7a, orysa-pir7b, orysa-q2qlm4, orysa-q2qm78, orysa-q2qm82, orysa-q2qn31, orysa-q2qnj4, orysa-q2qnt9, orysa-q2qur1, orysa-q2qx94, orysa-q2qyi1, orysa-q2qyj1, orysa-q2r051, orysa-q2r077, orysa-q2ram0, orysa-q2rat1, orysa-q2rbb3, orysa-Q4VWY7, orysa-q5na00, orysa-q5nbu1, orysa-Q5QLC0, orysa-q5smv5, orysa-Q5VP27, orysa-q5vrt2, orysa-q5w6c5, orysa-q5z5a3, orysa-q5z9i2, orysa-q5z417, orysa-q5z901, orysa-Q5ZAM8, orysa-Q5ZBI5, orysa-Q5ZCR3, orysa-q6atz0, orysa-q6ave2, orysa-q6f358, orysa-q6h6s1, orysa-q6h7i6, orysa-q6i5q3, orysa-q6i5u7, orysa-q6j657, orysa-q6k3d9, orysa-q6k4q2, orysa-q6k880, orysa-q6l5b6, orysa-Q6L5F5, orysa-q6l556, orysj-q6yse8, orysa-q6yy42, orysa-q6yzk1, orysa-q6z8b1, orysa-q6z995, orysa-q6zc62, orysa-q6zia4, orysa-q6zjq6, orysa-q7x7y5, orysa-Q7XC50, orysa-q7xej4, orysa-q7xem8, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-q7xts6, orysa-q7xv53, orysa-Q7XVB5, orysa-Q8L562, orysa-Q8LQS5, orysa-Q8RZ40, orysa-Q8RZ79, orysa-Q8S0U8, orysa-Q8S0V0, orysa-Q8S125, orysa-Q8SAY7, orysa-Q8SAY9, orysa-Q8W3C6, orysa-Q8W3F2, orysa-Q8W3F4, orysa-Q8W3F6, orysa-Q9LHX5, orysa-q33aq0, orysa-q53lh1, orysa-q53m20, orysa-q53nd8, orysa-q60e79, orysa-q60ew8, orysa-q67iz2, orysa-q67iz3, orysa-q67iz7, orysa-q67iz8, orysa-q67j02, orysa-q67j05, orysa-q67j07, orysa-q67j09, orysa-q67j10, orysa-q67tr6, orysa-q67tv0, orysa-q67uz1, orysa-q67v34, orysa-q67wz5, orysa-q69j38, orysa-q69k08, orysa-q69md7, orysa-q69me0, orysa-q69pf3, orysa-q69ti3, orysa-q69xr2, orysa-q69y12, orysa-q69y21, orysa-q75hy2, orysa-q75i01, orysa-Q94JD7, orysa-Q0J0A4, orysa-q651a8, orysa-q651z3, orysa-q652g4, orysa-q688m0, orysa-q688m8, orysa-q688m9, orysa-Q6H8G1, orysi-a2wn01, orysi-a2xc83, orysi-a2yh83, orysi-a2z179, orysi-a2zef2, orysi-b8a7e6, orysi-b8a7e7, orysi-b8bfe5, orysi-b8bhp9, orysj-a3b9l8, orysj-b9eub8, orysj-b9eya5, orysj-b9fi05, orysj-b9fkb0, orysj-b9fn42, orysj-b9gbb7, orysj-cgep, orysj-PLA7, orysj-q0d4u5, orysj-q0djj0, orysj-q0jaf0, orysj-q5jl22, orysj-q5jlw7, orysj-q5z419, orysj-q6h7q9, orysj-q6yvk6, orysj-q6z6i1, orysj-q7f8x1, orysj-q7xcx3, orysj-q9fwm6, orysj-q10j20, orysj-q10ss2, orysj-q69uw6, orysj-q94d71, orysj-q338c0, orysi-b8bly4, orysj-b9gbs4, orysi-a2zb88, orysj-b9gbs1, orysi-b8b698, orysj-pla4, orysj-pla1 Abstract We report improved whole-genome shotgun sequences for the genomes of indica and japonica rice, both with multimegabase contiguity, or almost 1,000-fold improvement over the drafts of 2002. Tested against a nonredundant collection of 19,079 full-length cDNAs, 97.7% of the genes are aligned, without fragmentation, to the mapped super-scaffolds of one or the other genome. We introduce a gene identification procedure for plants that does not rely on similarity to known genes to remove erroneous predictions resulting from transposable elements. Using the available EST data to adjust for residual errors in the predictions, the estimated gene count is at least 38,000-40,000. Only 2%-3% of the genes are unique to any one subspecies, comparable to the amount of sequence that might still be missing. Despite this lack of variation in gene content, there is enormous variation in the intergenic regions. At least a quarter of the two sequences could not be aligned, and where they could be aligned, single nucleotide polymorphism (SNP) rates varied from as little as 3.0 SNP/kb in the coding regions to 27.6 SNP/kb in the transposable elements. A more inclusive new approach for analyzing duplication history is introduced here. It reveals an ancient whole-genome duplication, a recent segmental duplication on Chromosomes 11 and 12, and massive ongoing individual gene duplications. We find 18 distinct pairs of duplicated segments that cover 65.7% of the genome; 17 of these pairs date back to a common time before the divergence of the grasses. More important, ongoing individual gene duplications provide a never-ending source of raw material for gene genesis and are major contributors to the differences between members of the grass family. | |||||||
|
