Author Report for: Sun YNo contact information in database for Sun Y
Cao Y, Zhang Y, Jia Z, Jia H, Sun Y, Yuan H, Bian Y, Xu B, Fu J, Qin F Ref: Physiol Behav, :114077, 2023 : PubMed ESTHER: Cao_2023_Physiol.Behav__114077 PubMedSearch: Cao 2023 Physiol.Behav 114077 PubMedID: 36638877 Abstract Age-related neurodegenerative diseases accompanied by learning and memory deficits are growing in prevalence due to population aging. Cellular oxidative stress is a common pathomechanism in multiple age-related disorders, and various antioxidants have demonstrated therapeutic efficacy in patients or animal models. Many plants and plant extracts possess potent antioxidant activity, but the compounds responsible are frequently unknown. Identification and evaluation of these phytochemicals is necessary for optimal targeted therapy. A recent study identified theaflavin-3,3'-digallate (TFDG) as the most potent among a large series of phytochemical antioxidants. Here we examined if TFDG can mitigate learning and memory impairments in the D-galactose model of age-related neurodegeneration. Experimental mice were injected subcutaneously with D-galactose (120 mg/kg) for 56 days. In treatment groups, different doses of TFDG were administered daily by gavage starting on day 29 of D-galactose injection. Model mice exhibited poor learning and memory in the novel object recognition and Y-maze tests, reduced brain/body mass ratio, increased brain glutamate concentration and acetylcholinesterase activity, decreased brain acetylcholine concentration, and lower choline acetyltransferase, glutaminase, and glutamine synthetase activities. Activities of antioxidant enzymes glutathione peroxidase and superoxide dismutase were also reduced, while the concentration of malondialdehyde, a lipid peroxidation product, was elevated. Further, antioxidant genes Nrf2, Prx2, Gsh-px1, and Sod1 were downregulated in brain. Each one of these changes was dose-dependently reversed by TFDG. TFDG is an effective antioxidant response inducer and neuroprotectant that can restore normal neurotransmitter metabolism and ameliorate learning and memory dysfunction in the D-galactose model of age-related cognitive decline. Title: Landscape of the gut archaeome in association with geography, ethnicity, urbanization, and diet in the Chinese population Bai X, Sun Y, Li Y, Li M, Cao Z, Huang Z, Zhang F, Yan P, Wang L and Zuo T <9 more author(s)> Bai X, Sun Y, Li Y, Li M, Cao Z, Huang Z, Zhang F, Yan P, Wang L, Luo J, Wu J, Fan D, Chen H, Zhi M, Lan P, Zeng Z, Wu X, Miao Y, Zuo T (- 9) Ref: Microbiome, 10:147, 2022 : PubMed ESTHER: Bai_2022_Microbiome_10_147 PubMedSearch: Bai 2022 Microbiome 10 147 PubMedID: 36100953 Abstract BACKGROUND AND AIMS: The human gut is home to a largely underexplored microbiome component, the archaeome. Little is known of the impact of geography, urbanization, ethnicity, and diet on the gut archaeome in association with host health. We aim to delineate the variation of the human gut archaeome in healthy individuals and its association with environmental factors and host homeostasis. METHODS: Using metagenomic sequencing, we characterized the fecal archaeomes of 792 healthy adult subjects from 5 regions in China, spanning 6 ethnicities (Han, Zang, Miao, Bai, Dai, and Hani), consisting of both urban and rural residents for each ethnicity. In addition, we sampled 119 host variables (including lifestyle, diet, and blood parameters) and interrogated the influences of those factors, individually and combined, on gut archaeome variations. RESULTS: Population geography had the strongest impact on the gut archaeome composition, followed by urbanization, dietary habit, and ethnicity. Overall, the metadata had a cumulative effect size of 11.0% on gut archaeome variation. Urbanization decreased both the alpha-diversity (intrinsic microbial diversity) and the beta-diversity (inter-individual dissimilarities) of the gut archaeome, and the archaea-to-bacteria ratios in feces, whereas rural residents were enriched for Methanobrevibacter smithii in feces. Consumption of buttered milk tea (a characteristic diet of the rural Zang population) was associated with increased abundance of M. smithii. M. smithii was at the central hub of archaeal-bacterial interactions in the gut microecology, where it was positively correlated with the abundances of a multitude of short chain fatty acid (SCFA)-producing bacteria (including Roseburia faecis, Collinsella aerofaciens, and Prevotella copri). Moreover, a decreased abundance of M. smithii was associated with increased human blood levels of cholinesterase in the urban population, coinciding with the increasing prevalence of noncommunicable diseases (such as dementia) during urbanization. CONCLUSIONS: Our data highlight marked contributions of environmental and host factors (geography, urbanization, ethnicity, and habitual diets) to gut archaeome variations across healthy individuals, and underscore the impact of urbanization on the gut archaeome in association with host health in modern society. Video Abstract. Title: Anti-Alzheimer's disease potential of traditional chinese medicinal herbs as inhibitors of BACE1 and AChE enzymes Dai R, Sun Y, Su R, Gao H Ref: Biomed Pharmacother, 154:113576, 2022 : PubMed ESTHER: Dai_2022_Biomed.Pharmacother_154_113576 PubMedSearch: Dai 2022 Biomed.Pharmacother 154 113576 PubMedID: 36007279 Abstract Alzheimer's disease (AD) is a common neurodegenerative disease that often occurs in the elderly population. At present, most drugs for AD on the market are single-target drugs, which have achieved certain success in the treatment of AD. However, the efficacy and safety of single-target drugs have not achieved the expected results because AD is a multifactorial disease. Multi-targeted drugs act on multiple factors of the disease network to improve efficacy and reduce adverse reactions. Therefore, the search for effective dual-target or even multi-target drugs has become a new research trend. Many of results found that the dual-target inhibitors of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) and acetylcholinesterase (AChE) found from traditional Chinese medicine have a good inhibitory effect on AD with fewer side effects. This article reviews sixty-six compounds extracted from Chinese medicinal herbs, which have inhibitory activity on BACE1 and AChE. This provides a theoretical basis for the further development of these compounds as dual-target inhibitors for the treatment of AD. Title: Identification and receptor mechanism of TIR-catalyzed small molecules in plant immunity Huang S, Jia A, Song W, Hessler G, Meng Y, Sun Y, Xu L, Laessle H, Jirschitzka J and Chai J <10 more author(s)> Huang S, Jia A, Song W, Hessler G, Meng Y, Sun Y, Xu L, Laessle H, Jirschitzka J, Ma S, Xiao Y, Yu D, Hou J, Liu R, Sun H, Liu X, Han Z, Chang J, Parker JE, Chai J (- 10) Ref: Science, :, 2022 : PubMed ESTHER: Huang_2022_Science__ PubMedSearch: Huang 2022 Science Gene_locus related to this paper: arath-eds1, arath-PAD4 Abstract Plant nucleotide-binding leucine-rich repeat-containing (NLR) receptors with an N-terminal Toll/interleukin-1 receptor (TIR) domain sense pathogen effectors to enable TIR-encoded NADase activity for immune signaling. TIR-NLR signaling requires helper NLRs N requirement gene 1 (NRG1) and Activated Disease Resistance 1 (ADR1), and Enhanced Disease Susceptibility 1 (EDS1) that forms a heterodimer with each of its paralogs Phytoalexin Deficient 4 (PAD4) and Senescence-Associated Gene101 (SAG101). Here, we show that TIR-containing proteins catalyze production of 2'-(5''-phosphoribosyl)-5'-adenosine mono-/di-phosphate (pRib-AMP/ADP) in vitro and in planta. Biochemical and structural data demonstrate that EDS1-PAD4 is a receptor complex for pRib-AMP/ADP, which allosterically promote EDS1-PAD4 interaction with ADR1-L1 but not NRG1A. Our study identifies TIR-catalyzed pRib-AMP/ADP as a missing link in TIR signaling via EDS1-PAD4 and as likely second messengers for plant immunity. Title: Integrative systems analysis identifies genetic and dietary modulators of bile acid homeostasis Li H, Perino A, Huang Q, Von Alvensleben GVG, Banaei-Esfahani A, Velazquez-Villegas LA, Gariani K, Korbelius M, Bou Sleiman M and Schoonjans K <9 more author(s)> Li H, Perino A, Huang Q, Von Alvensleben GVG, Banaei-Esfahani A, Velazquez-Villegas LA, Gariani K, Korbelius M, Bou Sleiman M, Imbach J, Sun Y, Li X, Bachmann A, Goeminne LJE, Gallart-Ayala H, Williams EG, Ivanisevic J, Auwerx J, Schoonjans K (- 9) Ref: Cell Metab, :, 2022 : PubMed ESTHER: Li_2022_Cell.Metab__ PubMedSearch: Li 2022 Cell.Metab PubMedID: 36099916 Abstract Bile acids (BAs) are complex and incompletely understood enterohepatic-derived hormones that control whole-body metabolism. Here, we profiled postprandial BAs in the liver, feces, and plasma of 360 chow- or high-fat-diet-fed BXD male mice and demonstrated that both genetics and diet strongly influence BA abundance, composition, and correlation with metabolic traits. Through an integrated systems approach, we mapped hundreds of quantitative trait loci that modulate BAs and identified both known and unknown regulators of BA homeostasis. In particular, we discovered carboxylesterase 1c (Ces1c) as a genetic determinant of plasma tauroursodeoxycholic acid (TUDCA), a BA species with established disease-preventing actions. The association between Ces1c and plasma TUDCA was validated using data from independent mouse cohorts and a Ces1c knockout mouse model. Collectively, our data are a unique resource to dissect the physiological importance of BAs as determinants of metabolic traits, as underscored by the identification of CES1C as a master regulator of plasma TUDCA levels. Title: Discovery of novel hybrids containing clioquinol-1-benzyl-1,2,3,6-tetrahydropyridine as multi-target-directed ligands (MTDLs) against Alzheimer's disease Li X, Li T, Zhang P, Lu L, Sun Y, Zhang B, Allen S, White L, Phillips J and Xu J <2 more author(s)> Li X, Li T, Zhang P, Lu L, Sun Y, Zhang B, Allen S, White L, Phillips J, Zhu Z, Yao H, Xu J (- 2) Ref: Eur Journal of Medicinal Chemistry, 244:114841, 2022 : PubMed ESTHER: Li_2022_Eur.J.Med.Chem_244_114841 PubMedSearch: Li 2022 Eur.J.Med.Chem 244 114841 PubMedID: 36257284 Abstract Based on the multitarget strategy, a series of novel clioquinol-1-benzyl-1,2,3,6-tetrahydropyridine hybrids were identified for the potential treatment of Alzheimer's disease (AD). Biological evaluation in vitro revealed that these hybrids exhibited significant inhibitory activities toward acetylcholinesterase (AChE). The optimal compound, 19n, exhibited excellent AChE inhibitory potency (IC(50) = 0.11 microM), appropriate metal chelating functions, modulation of AChE- and metal-induced Abeta aggregation, neuroprotection against okadaic acid-induced mitochondrial dysfunction and ROS damage, and interesting properties that reduced p-Tau levels in addition to no toxicity on SH-SY5Y cells observed at a concentration up to 50 microM. Most importantly, compound 19n was more well tolerated (>1200 mg/kg) than donepezil (LD(50) = 28.124 mg/kg) in vivo. Moreover, compound 19n demonstrated marked improvements in cognitive and spatial memory in two AD mice models (scopolamine-induced and Abeta(1-42)-induced) and suppressed inflammation induced by Abeta(1-42) in the cortex. The multifunctional profiles of compound 19n demonstrate that it deserves further investigation as a promising lead in the development of innovatively multifunctional drugs for Alzheimer's disease. Title: Identification and characterization of two types of triacylglycerol lipase genes from Neocaridina denticulata sinensis Liang M, Ma L, Li X, Feng D, Zhang J, Sun Y Ref: Fish Shellfish Immunol, :, 2022 : PubMed ESTHER: Liang_2022_Fish.Shellfish.Immunol__ PubMedSearch: Liang 2022 Fish.Shellfish.Immunol PubMedID: 36379446 Abstract Triacylglycerol lipases (TGLs) can catalyze the hydrolysis reaction of triacylglycerol serving multiple functions in most organisms. Based on the genomic and transcriptomic databases of Neocaridina denticulata sinensis, two TGL genes from N. denticulata sinensis designated NdTGL1 and NdTGL2 were identified and characterized. NdTGL1 showed the highest expression in the stomach, followed by the testis and hepatopancreas, and NdTGL2 exhibited the maximum expression in the hepatopancreas, followed by the stomach and heart. Under the stimulation of copper ion, the expression of NdTGL1 peaked at 12h and the expression of NdTGL2 elevated significantly at 24h after stimulation (P<0.05). It is speculated that NdTGLs may play an important role in the stress response of N. denticulata sinensis. Challenged with Vibrio parahaemolyticus, the expression profiles of NdTGL1 and NdTGL2 in the hepatopancreas was different, which indicates that the immune response of the V. parahaemolyticus challenge might lead to changes in triglyceride metabolism. The recombinant NdTGL (recNdTGL1 and recNdTGL2) were obtained and the enzymatic characterization of recNdTGL1 and recNdTGL2 were determined. The common maximum activity and stability of the recNdTGL1 and recNdTGL2 were observed at 45C and 10C, respectively. Both recNdTGL1 and recNdTGL2 exhibited the highest activity at pH 10.0. Furthermore, the recNdTGL1 and recNdTGL2 displayed the maximum stability at pH 5.0 and pH 8.0, respectively. In presence of different metal ions, the enzyme activity of recNdTGL1 and recNdTGL2 were inhibited by Cu(2+) and Zn(2+), and decreased by about 25%. Studies on the triacylglycerol lipases of N. denticulata sinensis provide theoretical support for studies related to fat metabolism in crustaceans and studies on response mechanism of digestive enzymes to microbial pathogens. Title: Surface Modification of Magnetic ZIF-90 Nanoparticles Improves the Microenvironment of Immobilized Lipase and Its Application in Esterification Suo H, Geng X, Sun Y, Zhang L, Yang J, Yang F, Yan H, Hu Y, Xu L Ref: Langmuir, :, 2022 : PubMed ESTHER: Suo_2022_Langmuir__ PubMedSearch: Suo 2022 Langmuir PubMedID: 36448653 Abstract Interactions of enzymes with supports significantly affect the activity and stability of immobilized enzymes. Herein, amino-functionalized ionic liquid (IL)-grafted magnetic zeolitic imidazolate framework-90 (MZIF-90) was prepared and used to immobilize porcine pancreatic lipase (PPL). The nanocomposites were fully characterized; meanwhile, the interactions between ILs and ZIF-90 were calculated based on density functional theory. The prepared biocatalyst (PPL-ILs/MZIF-90) had a lipase loading of 178.3 mg/g and hydrolysis activity up to 287.5 U/g. When the biocatalyst was used to synthesize isoamyl acetate, the reaction media, molar ratio of alcohol/acid, temperature, and reaction time were optimized. Under the optimized reaction conditions (in hexane, alcohol/acid = 3:1, under 45 degreesC, reacted for 9 h), the ester yield reached 85.5%. The results of the stability test showed that PPL-ILs/MZIF-90 retained 88.7% of the initial activity after storing for 35 days and 92.5% of the initial activity after reusing for seven cycles for synthesizing isoamyl acetate. Moreover, the secondary structure analysis showed that the synthesized supports protected the active conformation of immobilized lipase, which lead to the enhanced catalytic performance. Additionally, the biocatalyst can be easily separated with a magnet, which facilitated the reusability. This study provides insights regarding the application of metal organic framework composites in the field of enzyme catalysis. Title: Synthesis and biological evaluation of new series of benzamide derivatives containing urea moiety as sEH inhibitors Tian Y, Li S, Yang P, Su X, Liu J, Lv X, Dong K, Yang T, Duan M and Zhao Y <9 more author(s)> Tian Y, Li S, Yang P, Su X, Liu J, Lv X, Dong K, Yang T, Duan M, Hu G, Yue H, Sun Y, Zhang H, Du Z, Miao Z, Tong M, Hou Y, Gao Z, Zhao Y (- 9) Ref: Bioorganic & Medicinal Chemistry Lett, 70:128805, 2022 : PubMed ESTHER: Tian_2022_Bioorg.Med.Chem.Lett_70_128805 PubMedSearch: Tian 2022 Bioorg.Med.Chem.Lett 70 128805 PubMedID: 35598794 Abstract The pharmacological inhibition of soluble epoxide hydrolase (sEH) was shown to reduce inflammation and pain. Herein, we described a series of newly synthesized sEH inhibitors with the trident-shaped skeleton. Intensive structural modifications led to the identification of compound B15 as a potent sEH inhibitor with an IC(50) value of 0.03 +/- 0.01 nM. Furthermore, compound B15 showed satisfactory metabolic stability in human liver microsomes with a half-time of 197 min. In carrageenan-induced inflammatory pain rat model, compound B15 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib, which demonstrated the proof of potential as anti-inflammatory agents for pain relief. Title: Discovery of benzamide derivatives containing urea moiety as soluble epoxide hydrolase inhibitors Tian Y, Li S, Dong K, Su X, Fu S, Lv X, Duan M, Yang T, Han Y and Zhao Y <13 more author(s)> Tian Y, Li S, Dong K, Su X, Fu S, Lv X, Duan M, Yang T, Han Y, Hu G, Liu J, Sun Y, Yue H, Zhang H, Du Z, Miao Z, Tong M, Liu Y, Qin M, Gong P, Hou Y, Gao Z, Zhao Y (- 13) Ref: Bioorg Chem, 127:105898, 2022 : PubMed ESTHER: Tian_2022_Bioorg.Chem_127_105898 PubMedSearch: Tian 2022 Bioorg.Chem 127 105898 PubMedID: 35792317 Abstract The elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) is efficient for the treatment of inflammatory and pain-related diseases. Herein, we reported the discovery of a series of benzamide derivatives containing urea moiety as sEH inhibitors. Intensive structural modifications led to the identification of compound A34 as a potent sEH inhibitor with good physicochemical properties. Molecular docking revealed an additional hydrogen-bonding interaction between the unique amide scaffold and Phe497, contributing to sEH inhibition potency enhancement. Compound A34 exhibited outstanding inhibitory activity against human sEH, with an IC(50) value of 0.04 +/- 0.01 nM and a K(i) value of 0.2 +/- 0.1 nM. It also showed moderate systemic drug exposure and oral bioavailability in vivo metabolism studies. In carrageenan-induced inflammatory pain rat model, compound A34 exhibited a better therapeutic effect compared to t-AUCB and Celecoxib. Metabolism studies in vivo together with an inflammatory pain evaluation suggest that A34 may be a viable lead compound for the development of highly potent sEH inhibitors. Title: Altereporenes A-E, five epoxy octa-hydronaphthalene polyketides produced by an endophytic fungus Alternaria sp. YUD20002 Xia DD, Duan HJ, Xie F, Xie TP, Zhang Y, Sun Y, Lu JM, Gao YH, Zhou H, Ding ZT Ref: RSC Adv, 12:22295, 2022 : PubMed ESTHER: Xia_2022_RSC.Adv_12_22295 PubMedSearch: Xia 2022 RSC.Adv 12 22295 PubMedID: 36043060 Abstract Five previously undescribed epoxy octa-hydronaphthalene polyketides, altereporenes A-E (1-5) were isolated from rice culture of the endophytic fungus Alternaria sp. YUD20002 derived from the tubers of Solanum tuberosum. Their structures were determined on the basis of comprehensive spectroscopic analyses, while the absolute configurations were elucidated by the comparison of experimental and calculated specific rotations. Meanwhile, the antimicrobial, cytotoxic, anti-inflammatory and acetylcholinesterase inhibitory activities of compounds 1-5 were also investigated. Title: Activation of cholinergic basal forebrain neurons improved cognitive functions in adult-onset hypothyroid mice Xu YX, Wang C, Li XD, Guo WL, Liu GY, Zhang HB, Sun Y, Zhu DF, Xu Q Ref: Biomed Pharmacother, 153:113495, 2022 : PubMed ESTHER: Xu_2022_Biomed.Pharmacother_153_113495 PubMedSearch: Xu 2022 Biomed.Pharmacother 153 113495 PubMedID: 36076509 Abstract Cognitive dysfunction is common in hypothyroid patients, even after undergoing sufficient levothyroxine (LT4) replacement therapy for euthyroid. Our previous studies indicated that cholinergic neurons might contribute to the decline of cognition in adult-onset hypothyroidism. Nevertheless, the role of the cellular and neural control of basal forebrain (BF) cholinergic neurons in hypothyroidism-induced cognitive impairments is unknown. Using transgenic mice that specifically expressed chemogenetic activators in their BF cholinergic neurons, we systematically investigated the role of BF cholinergic neurons in hypothyroidism-induced cognitive dysfunction by the combined approaches of patch clamp electrophysiology, behavioral testing, and immunohistochemistry. The results showed that LT4 treatment in the adult-onset hypothyroid mice reversed only 78 % of the BF cholinergic neurons to their normal values of electrophysiological properties. LT4 monotherapy did not rehabilitate cognitive function in the hypothyroid mice. Chemogenetic selective activation of the BF cholinergic neurons combined with LT4 treatment significantly improved learning and memory functions in the hypothyroid mice. In addition, chemogenetic activation of the cholinergic neurons induced the robust expression of c-Fos protein in the BF, prefrontal cortex (PFC), and hippocampus. This indicated that the BF cholinergic neurons improved learning and memory functions in the hypothyroid mice via the BF-PFC and BF-hippocampus pathways. In the hypothyroid C57BL/6 J mice, combined treatment via LT4 and donepezil, a cholinesterase inhibitor, significantly increased cognitive functions. The results suggested that the BF cholinergic neurons are critical for regulating learning and memory and reveal a novel pathophysiological mechanism for hypothyroidism-induced cognitive impairments. Title: Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents Gao H, Jiang Y, Zhan J, Sun Y Ref: Bioorg Chem, 114:105149, 2021 : PubMed ESTHER: Gao_2021_Bioorg.Chem_114_105149 PubMedSearch: Gao 2021 Bioorg.Chem 114 105149 PubMedID: 34252860 Abstract For the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in the future. The best 3D-QSAR acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors pharmacophore hypotheses Hypo1 A and Hypo1 B were generated and validated by HypoGen program in Discovery Studio 2016 based on the training set of flavonoids, and then they were used as 3D query for screening the ZINC database. Next, the hit molecules were then subjected to the ADMET and molecular docking study to prioritize the compounds. Finally, 6 compounds showed good estimated activities and promising ADMET properties. The result of best compound ZINC08751495 with AChE estimate activity (0.028), BChE estimate activity (1.55), AChE fit value (9.369), BChE fit value (8.415), AChE -CDOCKER ENERGY (30.22), BChE -CDOCKER ENERGY (33.13) has the potential for further development as a supplement to treat Alzheimer's disease. Title: Nutritional Status and Body Composition in Wilson Disease: A Cross-Sectional Study From China Geng H, Wang S, Jin Y, Cheng N, Song B, Shu S, Li B, Han Y, Gao L and Sun Y <4 more author(s)> Geng H, Wang S, Jin Y, Cheng N, Song B, Shu S, Li B, Han Y, Gao L, Ding Z, Xu Y, Wang X, Ma Z, Sun Y (- 4) Ref: Front Nutr, 8:790520, 2021 : PubMed ESTHER: Geng_2021_Front.Nutr_8_790520 PubMedSearch: Geng 2021 Front.Nutr 8 790520 PubMedID: 35036410 Abstract Background: Abnormal nutritional status is frequently seen in patients with chronic diseases. To date, no study has investigated the detailed characteristics of abnormal nutritional status among Wilson's disease (WD) patients in the Chinese cohort. This study aimed to describe the nutritional status of WD patients, with a particular focus on the differences between patients with different phenotypes. Methods: The study subjects comprised 119 healthy controls, 129 inpatients (hepatic subtype, n = 34; neurological subtype, n = 95) who were being treated at the affiliated hospital of the Institute of Neurology, Anhui University of Chinese Medicine. All of the subjects were assessed for body composition by using bioelectrical impedance analysis. All WD patients received anthropometry, nutritional risk screening 2002 (NRS2002), and laboratory test (hemocyte and serum biomarkers) additionally. Results: Compared with healthy controls, the fat mass and rate of total body and trunk were significantly higher in WD patients (P < 0.001), the muscle and skeletal muscle mass of total body and trunk were significantly lower in WD patients (P < 0.001). Compared with hepatic subtype patients, the fat mass and rate of total body, trunk, and limbs were significantly lower in neurological subtype patients (P<0.01); while there were no significant differences in muscle and skeletal muscle between these two subtypes. The overall prevalence of abnormal nutritional status in WD patients was 43.41% (56/129). The prevalence of high-nutritional risk and overweight in WD patients was 17.83% (23 of 129) and 25.58% (33 of 129), respectively. Compare with patients with high nutritional risk, macro platelet ratio, alkaline phosphatase, the basal metabolic rate (p < 0.05), creatinine, trunk fat rate (p < 0.01) and appendicular skeletal muscle mass (p < 0.001) were significantly higher in patients without nutritional risk (p < 0.001). Patients with a high nutritional risk tend to have a lower cholinesterase concentration (x (2) = 4.227, p < 0.05). Conclusion: Both patients with H-subtype and N-subtype are prone to have an abnormal nutritional status. Longitudinal studies are required to investigate if nutritional status and body composition could reflect prognosis in WD patients, and which of these body composition indexes contribute to malnutrition and worse prognosis. Title: Multienzyme-Targeted Fluorescent Probe as a Biosensing Platform for Broad Detection of Pesticide Residues Guo WY, Fu YX, Liu SY, Mei LC, Sun Y, Yin J, Yang WC, Yang GF Ref: Analytical Chemistry, :, 2021 : PubMed ESTHER: Guo_2021_Anal.Chem__ PubMedSearch: Guo 2021 Anal.Chem PubMedID: 33906355 Abstract Pesticide residues, significantly hampering the overall environmental and human health, have become an increasingly severe issue. Thus, developing rapid, cost-effective, and sensitive tools for monitoring the pesticide residues in food and water is extremely important. Compared to the conventional and chromatographic techniques, enzyme inhibition-based biosensors conjugated with the fluorogenic probes provide effective alternative methods for detecting pesticide residues due to the inherent advantages including high selectivity and sensitivity, simple operation, and capability of providing in situ and real-time information. However, the detection efficiency of a single enzyme-targeted biosensor in practical samples is strongly impeded by the structural diversity of pesticides and their distinct targets. In this work, we developed a strategy of multienzyme-targeted fluorescent probe design and accordingly obtained a novel fluorescent probe (named as 3CP) for detecting the presence of wide variety of pesticides. The designed probe 3CP, targeting cholinesterases, carboxylesterases, and chymotrypsin simultaneously, yielded intense fluorescence in the solid state upon the enzyme-catalyzed hydrolysis. It showed excellent sensitivity against organophosphorus and carbamate pesticides, and the detection limit for dichlorvos achieved 1.14 pg/L. Moreover, it allowed for the diffusion-resistant in situ visualization of pesticides in live cells and zebrafish and the sensitive measurement of organophosphorus pesticides in fresh vegetables, demonstrating the promising potential for tracking the pesticide residues in environment and biological systems. Title: Pyridostigmine ameliorates preeclamptic features in pregnant rats by inhibiting tumour necrosis factor-alpha synthetsis and antagonizing tumour necrosis factor-alpha-related effects Issotina Zibrila A, Wang Z, Ali MA, Osei JA, Sun Y, Zafar S, Liu K, Li C, Kang Y, Liu J Ref: J Hypertens, :, 2021 : PubMed ESTHER: Issotina_2021_J.Hypertens__ PubMedSearch: Issotina 2021 J.Hypertens PubMedID: 34232157 Abstract OBJECTIVE: Preeclampsia is a hypertensive disorder of pregnancy marked by an excessive inflammatory response. The anti-inflammatory effect of pyridostigmine (PYR) was previously reported; however, its role in hypertensive pregnancies remains unclear. We hypothesized that PYR could attenuate increased blood pressure and other pathological features in preeclampsia models. METHODS: The expression of tumour necrosis factor (TNF)-alpha was evaluated in normal and preeclampsia pregnant women. PYR (20mg/kg) was administered daily to reduced uterine perfusion pressure (RUPP) and TNF-alpha (150ng/day) infused rats from gestation day 14 to GD19. In a cell culture experiment, the effect of acetylcholine (ACh) on TNF-alpha-stimulated primary human umbilical endothelial cells (HUVEC) was assessed. RESULTS: Preeclampsia women had higher placental TNF-alpha expression than normal pregnant women. Mean arterial pressure (MAP) in the RUPP group was higher than in the Sham group. PYR inhibited serum and placental acetylcholinesterase activity in rats, and reduced MAP, placental oxidative stress, apoptosis and inflammation in the RUPP group but not in the Sham group. In addition, PYR significantly attenuated the TNF-alpha-induced increase in MAP, placental oxidative stress and apoptosis. Moreover, TNF-alpha decreased cell viability and increased the number of TUNEL-positive nuclei of HUVEC, which could largely be abolished by ACh treatment. CONCLUSION: Collectively, PYR ameliorated hypertension and other preeclampsia-like symptoms in rat models of preeclampsia not only by inhibiting the synthesis of TNF-alpha but also by acting against TNF-alpha-induced detrimental effects directly, which is worthy of further investigation and may be used as a potential agent for preeclampsia management. Title: Isoleucine increases muscle mass through promoting myogenesis and intramyocellular fat deposition Liu S, Sun Y, Zhao R, Wang Y, Zhang W, Pang W Ref: Food Funct, 12:144, 2021 : PubMed ESTHER: Liu_2021_Food.Funct_12_144 PubMedSearch: Liu 2021 Food.Funct 12 144 PubMedID: 33289736 Abstract Isoleucine (Ile), as a branched-chain amino acid (BCAA), has a vital role in regulating body weight and muscle protein synthesis. However, the regulatory effect of Ile on muscle mass under high-fat diet (HFD) conditions and intramyocellular lipid deposition remains largely unclear. In this study, a feeding experiment with HFD with or without 25 g L-1 Ile was performed using 32 wild male C57BL/6J mice randomly divided into two groups. The results showed that Ile significantly increased both muscle and fat mass, as well as causing insulin resistance and meanwhile upregulating the levels of key adipogenic and myogenic proteins. More importantly, Ile damaged the mitochondrial function by vacuolation, swelling and cristae fracture in the gastrocnemius (GAS) and tibialis anterior (TA) with downregulation of mitochondrial function-related genes. Furthermore, Ile promoted myogenesis and more lipid droplet accumulation in myotubes. Compared with the control, the protein levels of myosin heavy chain (MyHC), myoblast determination protein 1 (MyoD), myogenin (MyoG), peroxisome proliferator-activated receptor gamma (PPARg) and fatty acid synthase (FAS) were upregulated in the Ile group, whereas the protein levels of adipose triglyceride lipase (ATGL) and lipoprotein lipase (LPL) were downregulated. Collectively, Ile increased muscle mass through myogenesis and intramyocellular lipid deposition. Our findings provide a new perspective for not only improving the lean juiciness of farm animals by increasing intramyocellular lipid accumulation, but also modulating myopathies under obesity. Title: Early enteral nutrition combined with PSS-based nursing in the treatment of organophosphorus pesticide poisoning Sun Y, Yang Y, Zhang Z, Li Y, Hu Y, Wang N Ref: Am J Transl Res, 13:9315, 2021 : PubMed ESTHER: Sun_2021_Am.J.Transl.Res_13_9315 PubMedSearch: Sun 2021 Am.J.Transl.Res 13 9315 PubMedID: 34540048 Abstract OBJECTIVE: To investigate the administration of early enteral nutrition combined with poisoning severity score (PSS)-based nursing in the treatment of organophosphorus pesticide poisoning (OPP). METHODS: A total of 99 OPP patients treated in our hospital between June 2019 and June 2020 were enrolled in this study and were divided into the conventional group (n=46, early enteral nutrition support + routine care) and the combined group (n=53, PSS-based nursing + early enteral nutrition support + routine care). The nutritional status indicators, the hemoglobin (Hb) and blood glucose levels, the Glasgow coma scale (GCS) scores, and the complications were compared between the two groups. RESULTS: The total protein (TP), albumin (ALB), and prealbumin (PAB) levels were reduced in the conventional group after the intervention (P<0.05) but were significantly lower than they were in the combined group (P<0.05). The Hb and blood glucose levels were decreased in the conventional group after the intervention (P<0.05) and were significantly higher than they were in the combined group (P<0.05). The GCS scores increased significantly as the treatment progressed (P<0.05), and the GCS scores in the combined group were significantly higher than the GCS scores in the conventional group at 3 and 5 days after the treatment (P<0.05). The time to the recovery of 60% cholinesterase (CHE) activity, the durations of the mechanical ventilation, the lengths of the hospital stays, and the hospital costs in the combined group were significantly lower than they were in the conventional group (P<0.05). The complication rate in the combined group (9.43%) was significantly lower than the complication rate in the conventional group (32.61%) (P<0.05). CONCLUSION: Early enteral nutrition combined with PSS-based nursing can effectively control the blood glucose, improve the nutritional disorders, promote recovery, and reduce complications in OPP patients. Title: Clinical Relevance and Prognostic Value of the Neuronal Protein Neuroligin 2 in Breast Cancer Zhang G, Sun Y, Wu ZS, Huang X Ref: Front Oncol, 11:630257, 2021 : PubMed ESTHER: Zhang_2021_Front.Oncol_11_630257 PubMedSearch: Zhang 2021 Front.Oncol 11 630257 PubMedID: 34804909 Abstract Neuroligin 2 (NLGN2) is a well-recognized transmembrane scaffolding protein that functions in synapse development and neuronal signal transduction. It has recently been implicated in multiple diseases of peripheral ectodermal origin. However, the potential roles of NLGN2 in tumors remain ill-defined. The aim of this study was to determine the clinical relevance and prognostic value of NLGN2 in breast cancer. To this end, breast cancer datasets were extracted from TCGA and other public databases, and subjected to Kaplan-Meier potter for survival analysis, GEPIA2 for assessing the immunological relevance of NLGN2 and THPA for identifying its subcellular localization. The in-silico results were further validated by immunohistochemistry analysis of in-house tumor tissue specimens. NLGN2 was identified as a prognostic factor in breast cancer subtypes, and its high expression correlated to a favorable survival outcome. Moreover, NLGN2 overexpression in breast cancer was significantly associated with large tumor size, lymph node metastasis, late TNM stage, and high histological grade. Interestingly, there was a significant correlation between the expression level of NLGN2 and the immunomodulatory molecules, along with increased interstitial infiltration of lymphocytes. Furthermore, NLGN2 was predominantly localized in the mitochondria of breast cancer cells. In conclusion, NLGN2 has a prognostic role and immunoregulatory potential in breast cancer, and its functions likely have a mitochondrial basis. It is a promising therapeutic target in breast cancer and should be explored further. Title: CRISPR-Cas9 Editing of CAFFEOYL SHIKIMATE ESTERASE 1 and 2 Shows Their Importance and Partial Redundancy in Lignification in Populus tremula x P. alba de Vries L, Brouckaert M, Chanoca A, Kim H, Regner MR, Timokhin VI, Sun Y, De Meester B, Van Doorsselaere J and Boerjan W <6 more author(s)> de Vries L, Brouckaert M, Chanoca A, Kim H, Regner MR, Timokhin VI, Sun Y, De Meester B, Van Doorsselaere J, Goeminne G, Chiang VL, Wang JP, Ralph J, Morreel K, Vanholme R, Boerjan W (- 6) Ref: Plant Biotechnol J, :, 2021 : PubMed ESTHER: de Vries_2021_Plant.Biotechnol.J__ PubMedSearch: de Vries 2021 Plant.Biotechnol.J PubMedID: 34160888 Abstract Lignins are cell-wall-located aromatic polymers that provide strength and hydrophobicity to woody tissues. Lignin monomers are synthesized via the phenylpropanoid pathway, wherein CAFFEOYL SHIKIMATE ESTERASE (CSE) converts caffeoyl shikimate into caffeic acid. Here, we explored the role of the two CSE homologs in poplar (Populus tremula x P. alba). Reporter lines showed that the expression conferred by both CSE1 and CSE2 promoters is similar. CRISPR-Cas9-generated cse1 and cse2 single mutants had a wild-type lignin level. Nevertheless, CSE1 and CSE2 are not completely redundant, as both single mutants accumulated caffeoyl shikimate. In contrast, the cse1 cse2 double mutants had a 35% reduction in lignin and associated growth penalty. The reduced lignin content translated into a four-fold increase in cellulose-to-glucose conversion upon limited saccharification. Phenolic profiling of the double mutants revealed large metabolic shifts, including an accumulation of p-coumaroyl, 5-hydroxyferuloyl, feruloyl and sinapoyl shikimate, in addition to caffeoyl shikimate. This indicates that the CSEs have a broad substrate specificity, which was confirmed by in vitro enzyme kinetics. Taken together, our results suggest an alternative path within the phenylpropanoid pathway at the level of the hydroxycinnamoyl shikimates, and show that CSE is a promising target to improve plants for the biorefinery. Title: miR-448-3p alleviates diabetic vascular dysfunction by inhibiting endothelial-mesenchymal transition through DPP-4 dysregulation Guan GY, Wei N, Song T, Zhao C, Sun Y, Pan RX, Zhang LL, Xu YY, Dai YM, Han H Ref: Journal of Cellular Physiology, 235:10024, 2020 : PubMed ESTHER: Guan_2020_J.Cell.Physiol_235_10024 PubMedSearch: Guan 2020 J.Cell.Physiol 235 10024 PubMedID: 32542696 Abstract Diabetes mellitus (DM) often causes vascular endothelial damage and alters vascular microRNA (miR) expression. miR-448-3p has been reported to be involved in the development of DM, but whether miR-448-3p regulates diabetic vascular endothelial dysfunction remains unclear. To investigate the molecular mechanism of diabetic vascular endothelial dysfunction and the role of miR-448-3p therein, Sprague-Dawley rats were injected with streptozotocin (STZ) to establish diabetic animal model and the rat aortic endothelial cells were treated with high glucose to establish diabetic cell model. For the treatment group, after the induction of diabetes, the miR-448-3p levels in vivo and in vitro were upregulated by adeno-associated virus serotype 2 (AAV2)-miR-448-3p injection and miR-448-3p mimic transfection, respectively. Our results showed that AAV2-miR-448-3p injection alleviated the body weight loss and blood glucose level elevation induced by STZ injection. The miR-448-3p level was significantly decreased and the dipeptidyl peptidase-4 (DPP-4) messenger RNA level was increased in diabetic animal and cell models, which was reversed by miR-448-3p treatment. Moreover, the diabetic rats exhibited endothelial damage and endothelial-mesenchymal transition (EndMT), while AAV2-miR-448-3p injection relieved those situations. In vitro experiments demonstrated that miR-448-3p overexpression in endothelial cells alleviated endothelial damage by inhibiting EndMT through blocking the transforming growth factor-beta/Smad pathway. We further proved that miR-448-3p negatively regulated DPP-4 by binding to its 3'-untranslated region, and DPP-4 overexpression reversed the effect of miR-448-3p overexpression on EndMT. Overall, we conclude that miR-448-3p overexpression inhibits EndMT via targeting DPP-4 and further ameliorates diabetic vascular endothelial dysfunction, indicating that miR-448-3p may serve as a promising therapeutic target for diabetic endothelial dysfunction. Title: Ligand-based optimization to identify novel 2-aminobenzo[d]thiazole derivatives as potent sEH inhibitors with anti-inflammatory effects Han Y, Huang D, Xu S, Li L, Tian Y, Li S, Chen C, Li Y, Sun Y and Zhao Y <4 more author(s)> Han Y, Huang D, Xu S, Li L, Tian Y, Li S, Chen C, Li Y, Sun Y, Hou Y, Qin M, Gong P, Gao Z, Zhao Y (- 4) Ref: Eur Journal of Medicinal Chemistry, :113028, 2020 : PubMed ESTHER: Han_2020_Eur.J.Med.Chem__113028 PubMedSearch: Han 2020 Eur.J.Med.Chem 113028 PubMedID: 33248848 Abstract Inhibition of the soluble epoxide hydrolase (sEH) is a promising new therapeutic approach in the treatment of inflammation. Driven by the in-house database product lead 1, a hybridization strategy was utilized for the design of a series of novel benzo [d]thiazol derivatives. To our delight, D016, a byproduct of compound 9, was obtained with an extraordinarily low IC(50) value of 0.1 nM but poor physical and chemical properties. After removal of a non-essential urea moiety or replacement of the urea group by an amide group, compounds 15a, 17p, and 18d were identified as promising sEH inhibitors, and their molecular binding modes to sEH were constructed. Furthermore, compounds 15a and 18d exhibited more effective in vivo anti-inflammatory effect than t-AUCB in carrageenan-induced mouse paw edema. Compound 15a also showed moderate metabolic stability with a half-time of 34.7 min. Although 18d was unstable in rat liver microsomes, it might be a "prodrug". In conclusion, this study could provide valuable insights into discovery of new sEH inhibitors, and compounds 15a and 18d were worthy of further development as potential drug candidates to treat inflammation. Title: Reasonably activating Nrf2: A long-term, effective and controllable strategy for neurodegenerative diseases Li Q, Xing S, Chen Y, Liao Q, Liu Y, He S, Feng F, Zhang J, Liu W and Sun H <2 more author(s)> Li Q, Xing S, Chen Y, Liao Q, Liu Y, He S, Feng F, Zhang J, Liu W, Guo Q, Sun Y, Sun H (- 2) Ref: Eur Journal of Medicinal Chemistry, 185:111862, 2020 : PubMed ESTHER: Li_2020_Eur.J.Med.Chem_185_111862 PubMedSearch: Li 2020 Eur.J.Med.Chem 185 111862 PubMedID: 31735576 Abstract Neurodegenerative diseases are a variety of debilitating and fatal disorder in central nervous system (CNS). Besides targeting neuronal activity by influencing neurotransmitters or their corresponding receptors, modulating the underlying processes that lead to cell death, such as oxidative stress and mitochondrial dysfunction, should also be emphasized as an assistant strategy for neurodegeneration therapy. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) has been closely verified to be related to anti-inflammation and oxidative stress, rationally regulating its belonging pathway and activating Nrf2 is emphasized to be a potential treatment approach. There have existed multiple Nrf2 activators with different mechanisms and diverse structures, but those applied for neuro-disorders are still limited. On the basis of research arrangement and compound summary, we put forward the limitations of existing Nrf2 activators for neurodegenerative diseases and their future developing directions in enhancing the blood-brain barrier permeability to make Nrf2 activators function in CNS and designing Nrf2-based multi-target-directed ligands to affect multiple nodes in pathology of neurodegenerative diseases. Title: Identification of Oliver-McFarlane syndrome caused by novel compound heterozygous variants of PNPLA6 Liu F, Ji Y, Li G, Xu C, Sun Y Ref: Gene, :145027, 2020 : PubMed ESTHER: Liu_2020_Gene__145027 PubMedSearch: Liu 2020 Gene 145027 PubMedID: 32758583 Abstract OBJECTIVES: Oliver-McFarlane syndrome (OMCS) is an autosomal recessive inherited disease resulting from PNPLA6 mutations that results in intellectual impairment and profound short stature. To obtain a better understanding of the genotype-phenotype correlations for PNPLA6-related disorders, we reported the 14th OMCS case and summarized all the reported cases of OMCS. METHODS: We collected clinical biochemical and data and brain MRI data and used whole-exon gene detection and analysis tools to evaluate the pathogenicity of the variants, including PolyPhen-2 and Mutation Taster, and we also generated three-dimensional protein structures and visualized the effects of altered residues with I-TASSER and PyMOL Viewer software. RESULTS: The patient presented with trichomegaly and multiple pituitary hormone deficiencies. Brain MRI showed small pituitary and bilateral paraventricular leukomalacia. Novel variants (c.1491G>T and c.3367G>A) in the PNPLA6 gene were detected in the proband and verified by direct sequencing. Amino acid residues of Gln497 and Gly1123 are predicted to be damaging and destroy the three-dimensional protein structures of the protein. In follow-up, this patient could neither walk nor hold his head erect and had not spoken one word at the age of one year and ten months. Moreover, there is no obvious hot spot mutation in any of the reported allelic variants. Interestingly, the majority of mutations are located in the phospholipid esterase domain, which is responsible for esterase activity. CONCLUSIONS: We identified two novel variants of the PNPLA6 gene in an OMCS patient, which will help to better understand the function of PNPLA6 and genotype-phenotype correlations for PNPLA6-related disorders. Title: An Activity-Based Fluorogenic Probe Enables Cellular and in Vivo Profiling of Carboxylesterase Isozymes Liu SY, Qu RY, Li RR, Yan YC, Sun Y, Yang WC, Yang GF Ref: Analytical Chemistry, 92:9205, 2020 : PubMed ESTHER: Liu_2020_Anal.Chem_92_9205 PubMedSearch: Liu 2020 Anal.Chem 92 9205 PubMedID: 32512997 Abstract Carboxylesterases (CEs) exist as multiple types of isomers in humans, and two major types are CE1 and CE2. They are widely distributed in human tissues and well-known for their important roles in drug metabolism and pathology of various diseases. Thus, the detection of CEs in living systems could provide efficient proof in disease diagnostics, as well as important information regarding chemotherapeutic effects of antitumor drugs and prognosis. To develop a specific probe to discriminate CEs from other hydrolases, especially cholinesterases, is quite challenging due to their structural similarities and substrate specificity. To date, almost all of the fluorescent probes developed for CEs have been constructed with an acetyl group as the recognition unit. Herein we proposed a new design strategy of probe-cavity matching, which led to the identification of a new fluorogenic substrate (termed as HBT-CE) with high specificity toward both CE isomers and improved sensitivity, considering the higher binding affinity and catalysis efficiency. The promising capability of HBT-CE was further demonstrated for endogenous CEs imaging in living cells, zebrafish, and nude mice. In addition, HBT-CE was successfully applied in kinetically monitoring drug-induced CE regulation in cancer cells. All of these findings suggest that HBT-CE is a valuable tool for tracking and imaging endogenous CEs in complex biological systems. Title: A Pharmacokinetic and Pharmacodynamic Evaluation of the Anti-Hepatocellular Carcinoma Compound 4-N-Carbobenzoxy-gemcitabine (Cbz-dFdC) Sun Y, Wang J, Hao K Ref: Molecules, 25:, 2020 : PubMed ESTHER: Sun_2020_Molecules_25_ PubMedSearch: Sun 2020 Molecules 25 PubMedID: 32397338 Abstract Gemcitabine (dFdC) demonstrates significant effectiveness against solid tumors in vitro and in vivo; however, its clinical application is limited because it tends to easily undergo deamination metabolism. Therefore, we synthesized 4-N-carbobenzoxy-gemcitabine (Cbz-dFdC) as a lead prodrug and conducted a detailed pharmacokinetic, metabolic, and pharmacodynamic evaluation. After intragastric Cbz-dFdC administration, the Cmax of Cbz-dFdC and dFdC was 451.1 +/- 106.7 and 1656.3 +/- 431.5 ng/mL, respectively. The Tmax of Cbz-dFdC and dFdC was 2 and 4 h, respectively. After intragastric administration of Cbz-dFdC, this compound was mainly distributed in the intestine due to low carboxylesterase-1 (CES1) activity. Cbz-dFdC is activated by CES1 in both humans and rats. The enzyme kinetic curves were well fitted by the Michaelis-Menten equation in rats' blood, plasma, and tissue homogenates and S9 of the liver and kidney, as well as human liver S9 and CES1 recombinase. The pharmacodynamic results showed that the Cbz-dFdC have a good antitumor effect in the HepG2 cell and in tumor-bearing mice, respectively. In general, Cbz-dFdC has good pharmaceutical characteristics and is therefore a good candidate for a potential prodrug. Title: Dl-3-n-butylphthalide regulates cholinergic dysfunction in chronic cerebral hypoperfusion rats Sun Y, Zhao Z, Li Q, Wang C, Ge X, Wang X, Wang G, Qin Y Ref: J Internal Medicine Res, 48:300060520936177, 2020 : PubMed ESTHER: Sun_2020_J.Int.Med.Res_48_300060520936177 PubMedSearch: Sun 2020 J.Int.Med.Res 48 300060520936177 PubMedID: 32644834 Abstract OBJECTIVES: To investigate whether dl-3-n-butylphthalide (NBP) affects cholinergic system function and ameliorates cognitive decline in a rat model of vascular dementia (VaD). METHODS: The VaD rat model was established by bilateral common carotid artery ligation (two-vessel occlusion, 2VO). Rats were divided into five groups: control, sham, 2VO, 2VO+NBP (80 mg/kg; intragastric), and 2VO+donepezil (1 mg/kg; intragastric). Treatments were administered once daily for 2 weeks from day 21 post-surgery. Spatial learning and memory were evaluated by Morris water maze performance. Hippocampal choline acetyltransferase (ChAT), acetylcholinesterase (AChE), vesicular acetylcholine transporter (VAChT), vascular endothelial growth factor (VEGF), and brain-derived neurotrophic factor (BDNF) expressions were detected using immunohistochemistry, immunofluorescence, and real-time polymerase chain reaction methods. RESULTS: The daily escape latency was significantly longer in 2VO rats than in the sham or control groups, while the time spent in the target quadrant was significantly shorter. The daily escape latency of the 2VO+NBP group was significantly shorter compared with the 2VO group. Following NBP treatment, ChAT, AChE, VAChT, and BDNF expressions were significantly upregulated in the hippocampus. CONCLUSIONS: Central cholinergic dysfunction may be involved in VaD pathogenesis. NBP treatment significantly improved spatial learning and memory in VaD rats, and may enhance cholinergic system function via BDNF-mediated neuroprotection. Title: Ultrasensitive split-type electrochemical sensing platform for sensitive determination of organophosphorus pesticides based on MnO(2) nanoflower-electron mediator as a signal transduction system Sun Y, Xiong P, Tang J, Zeng Z, Tang D Ref: Anal Bioanal Chem, 412:6939, 2020 : PubMed ESTHER: Sun_2020_Anal.Bioanal.Chem_412_6939 PubMedSearch: Sun 2020 Anal.Bioanal.Chem 412 6939 PubMedID: 32691085 Abstract Organophosphorus pesticides (OPs) are extensively used worldwide as agrochemicals; however, excess use may threaten the health of humans. Thus, it is an urgent need to develop a sensitive method for determination of OPs. Herein, a simple and sensitive split-type electrochemical method was developed by using MnO(2) nanoflower-electron mediator as a signal transduction element. The MnO(2) nanoflower-electron mediator was synthesized and shows an excellent electrochemical signal attributed to the high specific surface area of MnO(2) nanoflower. Meanwhile, the inhibition of OPs on butyrylcholinesterase (BChE) was carried out in the homogeneous system. In the absence of target molecule, a large number of thiocholines (TCh) were yielded from hydrolysis of acetylthiocholine (ATCh) by BChE. The MnO(2) nanoflower was cracked, and subsequently, multiple electron mediator molecules were released from the platform after treated with TCh, thus decreasing the electrochemical response. Furthermore, the inhibition of OPs on BChE resulted in the reduced generation of TCh, thus inducing the recovery of electrochemical signal. Under the optimal experimental, dichlorvos can be detected in a wide range of 10(-6)-10(-10) M, with a detection limit of 3x10(-10) M. Moreover, the assay was successfully used to analyze dichlorvos in cucumber juice and pear juice, showing a great promising potential for detecting organophosphorus pesticides in complex samples. Graphical abstract In this assay, a split-type electrochemical biosensor was proposed for the ultrasensitive determination of organophosphorus pesticides based on the MnO(2) nanoflower-electron mediator as an electrochemical signal component. Title: Rolling circle amplification promoted magneto-controlled photoelectrochemical biosensor for organophosphorus pesticides based on dissolution of core-shell MnO(2) nanoflower@CdS mediated by butyrylcholinesterase Tang J, Li J, Xiong P, Sun Y, Zeng Z, Tian X, Tang D Ref: Mikrochim Acta, 187:450, 2020 : PubMed ESTHER: Tang_2020_Mikrochim.Acta_187_450 PubMedSearch: Tang 2020 Mikrochim.Acta 187 450 PubMedID: 32676787 Abstract A photoelectrochemical (PEC) aptasensing platform is devised for sensitive detection of an organophosphorus pesticide based on dissolution of core-shell MnO(2) nanoflower@CdS (MnO(2) NF@CdS) by thiocholine (TCh). TCH is produced from the butyrylcholinesterase-acetylthiocholine system, accompanied by target-triggered rolling circle amplification (RCA). The core-shell MnO(2) NF@CdS with excellent PEC performance was synthesized and employed as a photo-sensing platform. The target was detected on a functionalized magnetic probe with the corresponding aptamer. Upon malathion introduction, the aptamer was detached from the magnetic beads, while capture DNA (cDNA, with primer fragment) remained on the beads. The primer fragment in cDNA can trigger the RCA reaction to form a long single-stranded DNA (ssDNA). Furthermore, a large number of butyrylcholinesterase (BChE) were assembled on the long ssDNA strands through the hybridization with the S(2)-Au-BChE probe. Thereafter, TCh generated from hydrolysis of ATCh by BChE can reduce MnO(2) NF (core) to Mn(2+) and release the CdS nanoparticles (shell) from the platform electrode, significantly enhancing the PEC signal. Under optimal conditions, the proposed aptasensor exhibited high sensitivity for malathion with a low detection limit of 0.68 pg mL(-1). Meanwhile, it also presents outstanding specificity, reproducibility, and stability. Importantly, the sensing platform provides a new concept for detection of pesticide. Graphical abstract Herein, this work devised a photoelectrochemical (PEC) aptasensing platform for sensitive detection of organophosphorus pesticide based on dissolution of core-shell MnO(2) nanoflower@CdS (MnO(2) NF@CdS) by the as-produced thiocholine (TCh) from the butyrylcholinesterase-acetylthiocholine system, accompanying with the target-triggered rolling circle amplification (RCA). Title: Soluble epoxide hydrolase inhibitor protects against blood-brain barrier dysfunction in a mouse model of type 2 diabetes via the AMPK/HO-1 pathway Wu J, Zhao Y, Fan Z, Chen Q, Chen J, Sun Y, Jiang X, Xiao Q Ref: Biochemical & Biophysical Research Communications, :, 2020 : PubMed ESTHER: Wu_2020_Biochem.Biophys.Res.Commun__ PubMedSearch: Wu 2020 Biochem.Biophys.Res.Commun PubMedID: 32001002 Abstract Diabetes mellitus is a metabolic disorder that can lead to blood-brain barrier (BBB) disruption and cognitive decline. However, the mechanisms of BBB breakdown in diabetes are still unclear. Soluble epoxide hydrolase (sEH) is an enzyme that degrades epoxyeicosatrienoic acids (EETs), which have multiple protective effects on vascular structure and functions. In the current study, we showed increased vascular permeability of the BBB, which was accompanied by upregulation of sEH and downregulation of 14,15-EET. Moreover, the sEH inhibitor t-AUCB restored diabetic BBB integrity in vivo, and 14,15-EET prevented ROS accumulation and MEC injury in vitro. t-AUCB or 14,15-EET treatment provoked AMPK/HO-1 activation under diabetic conditions in vivo and in vitro. Thus, we suggest that decreased EET degradation by sEH inhibition might be a potential therapeutic approach to attenuate the progression of BBB injury in diabetic mice via AMPK/HO-1 pathway activation. Title: Overexpressed CES2 has prognostic value in CRC and knockdown CES2 reverses L-OHP-resistance in CRC cells by inhibition of the PI3K signaling pathway Zhang Y, Sun L, Sun Y, Chen Y, Wang X, Xu M, Chi P, Xu Z, Lu X Ref: Experimental Cell Research, :111856, 2020 : PubMed ESTHER: Zhang_2020_Exp.Cell.Res__111856 PubMedSearch: Zhang 2020 Exp.Cell.Res 111856 PubMedID: 31981591 Gene_locus related to this paper: human-CES2 Abstract CES-2 (carboxylesterase-2) belongs to the carboxylesterase gene family, which plays crucial roles in lipid mobilization and chemosensitivity to irinotecan. However, its role in chemosensitivity to oxaliplatin (L-OHP) remains unclear. Herein, L-OHP-resistant cells (HCT-116L and RKOL) were established by increasing the concentration of L-OHP. The results showed that CES2 expression was upregulated in L-OHP-resistant tissues and cells lines (P<0.01). Low expression of CES2 correlated with a better survival, and the results were further confirmed in the R2 platform: a biologist friendly web-based genomics analysis and visualization application. Downregulation of CES2 suppressed cell proliferation, induced apoptosis and reversed L-OHP resistance by medicating the PI3K signaling pathway in L-OHP-resistant cells. However, both PI3K inhibitor (LY294002) and activator (IGF-1) could not medicate CES2 expression. These findings indicated that CES2 may be utilized as a novel biomarker and therapeutic target for L-OHP resistance in CRC treatment. Title: Optimization of chemoenzymatic Baeyer-Villiger oxidation of cyclohexanone to sigma-caprolactone using response surface methodology Zhang Y, Jiang W, Lv K, Sun Y, Gao X, Zhao Q, Ren W, Wang F, Liu J Ref: Biotechnol Prog, 36:e2901, 2020 : PubMed ESTHER: Zhang_2020_Biotechnol.Prog_36_e2901 PubMedSearch: Zhang 2020 Biotechnol.Prog 36 e2901 PubMedID: 31465150 Abstract sigma-Caprolactone (sigma-CL) has attracted a great deal of attention and a high product concentration is of great significance for reducing production cost. The optimization of sigma-CL synthesis through chemoenzymatic Baeyer-Villiger oxidation mediated by immobilized Trichosporon laibacchii lipase was studied using response surface methodology (RSM). The yield of sigma-CL was 98.06% with about 1.2 M sigma-CL concentration that has a substantial increase mainly due to both better stability of the cross-linked immobilized lipase used and the optimum reaction conditions in which the concentration of cyclohexanone was 1.22 M, the molar ratio of cyclohexanone:urea hydrogen peroxide (UHP) was 1:1.3, and the reaction temperature was 56.5 degreesC. Based on our experimental results, it can be safely concluded that there are three reactions in this reaction system, not just two reactions, in which the third reaction is that the acetic acid formed reacts with UHP to form peracetic acid in situ catalyzed by the immobilized lipase. A quadratic polynomial model based on RSM experimental results was developed and the R(2) value of the equation is 0.9988, indicating that model can predict the experimental results with high precision. The experimental results also show that the molar ratio of cyclohexanone to UHP has very significant impact on the yield of sigma-CL (p < .0006). Title: Circular RNA cMras Suppresses the Progression of Lung Adenocarcinoma Through ABHD5/ATGL Axis Using NF-B Signaling Pathway Zhou Q, Sun Y Ref: Cancer Biother Radiopharm, :, 2020 : PubMed ESTHER: Zhou_2020_Cancer.Biother.Radiopharm__ PubMedSearch: Zhou 2020 Cancer.Biother.Radiopharm PubMedID: 32822232 Gene_locus related to this paper: human-ABHD5 Abstract Background: Lung adenocarcinoma (LAC) is a common malignancy worldwide. Emerging findings indicated that circular RNAs possess complex capacities of gene modulation in tumorigenesis and metastasis. Nevertheless, the role of circular RNA in LAC is still largely unknown. Methods: The level of circular RNA cMras (circ_cMras), alpha-beta hydrolase domain 5 (ABHD5), and adipose triglyceride lipase (ATGL) was determined by quantitative real-time polymerase chain reaction assay. Protein levels of ABHD5, ATGL, p53, p65, and phospho-p65 (p-p65) were examined by western blot. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) was used to detect cell proliferation in vitro. Cell apoptosis was estimated using flow cytometry. Transwell assay was used to measure cell migration and invasion in A549 and HCC827 cells. Finally, the role of circ_cMras was explored using xenograft tumor model. Results: Low levels of circ_cMras, ABHD5, and ATGL were observed in LAC tissues and cells. Upregulation of circ_cMras could hamper tumor aggression in vitro and in vivo, exhibiting as the inhibition of cell proliferation, migration, invasion, and promotion of cell apoptosis, as well as the inhibition on tumor growth in vivo. Moreover, ABHD5 deletion could overturn the effects of circ_cMras overexpression on cell behaviors in LAC cells. Furthermore, the inhibiting effects of ABHD5 on cell aggression were reversed by ATGL deficiency in vitro. Mechanically, circ_cMras/ABHD5/ATGL axis exerted its role through NF-kappaB signaling pathway in LAC cells. Conclusion: Circ_cMras exerted its function through ABHD5/ATGL axis using NF-kappaB signaling pathway in LAC, which might provide a novel insight for the diagnosis and prognosis of LAC. Title: Liver Function of Male Rats Exposed to Manganese at Different Time Points Zhu X, Yang L, He Y, Sun Y, Shi W, Ou C Ref: Biol Trace Elem Res, :, 2020 : PubMed ESTHER: Zhu_2020_Biol.Trace.Elem.Res__ PubMedSearch: Zhu 2020 Biol.Trace.Elem.Res PubMedID: 32100273 Abstract As an essential trace element in the human body, manganese (Mn) is involved in many important biochemical reactions. However, excessive exposure to manganese can cause multiple systematic damages to the body. This study aims to investigate the effects of manganese exposure on serum hepatic enzymes in male rats at different time points. After adaptive feeding for 7 days, male Sprague-Dawley (SD) rats were injected intraperitoneally with 30 mg/kg MnCl2.4H2O once a day for 21 days at zeitgeber time point 2 (ZT2), ZT8, ZT14, and ZT20, respectively. We found that short-term repeated exposure to manganese caused slower body weight gain and increased relative liver and spleen weight index in male rats at different time points. Moreover, serum total bile acid (TBA) increased while aspartate aminotransferase (AST) decreased at ZT2, ZT8, and ZT20. Cholinesterase (ChE) decreased at ZT2 and ZT20, lactic dehydrogenase (LDH) decreased at ZT2, ZT14, and ZT20, and acid phosphatase (ACP) decreased at ZT2 and ZT14. Alkaline phosphatase (ALP) decreased at ZT2, ZT14, and ZT20, but increased at ZT8. Alanine amino transferase (ALT) decreased at ZT2 and ZT20, but increased at ZT8. There was a negative correlation between relative liver weight index with AST, ACP, ALP, and LDH, while a positive correlation with TBA. However, relative spleen weight index had a positive correlation with relative liver weight index and TBA, while a negative correlation with ALT, AST, ACP, ALP, LDH, and ChE. Our study shows that the injury of liver function is caused by short-term repeated manganese exposure at different time points. The time effect should be considered in manganese toxicity evaluation. Title: The effect of anti-dementia drugs on Alzheimer disease-induced cognitive impairment: A network meta-analysis Cui CC, Sun Y, Wang XY, Zhang Y, Xing Y Ref: Medicine (Baltimore), 98:e16091, 2019 : PubMed ESTHER: Cui_2019_Medicine.(Baltimore)_98_e16091 PubMedSearch: Cui 2019 Medicine.(Baltimore) 98 e16091 PubMedID: 31277107 Abstract BACKGROUND: Cognitive impairment is a principal manifestation of Alzheimer disease (AD). To provide a clinical reference for the treatment of AD, a network meta-analysis (NMA) was performed to evaluate the effects of different anti-dementia drugs on the cognitive impairment exhibited by patients with AD. METHODS: Relevant randomized controlled trials are found through the Pubmed database, Web of Science, Clinical Trials, Embase, Cohranne library, Chinese National Knowledge Infrastructure database, CBM databases, and Wanfang among others. A total of 33 articles were collected, with the earliest document collected having been published in February 2017. The included reports were screened for quality of papers by using strict inclusion and exclusion criteria. All analyses were based on previously published studies reporting de-identified data; thus, no ethical approval or patient consent were required. The Mini-Mental State Examination scores informed the classification of the 33 articles into a mild subgroup, which featured 11 articles, and 12 drugs (besides a placebo); a moderate subgroup, which featured 17 articles and 15 drugs (besides a placebo); and a severe subgroup, which featured 5 articles and 3 drugs (besides a placebo). RESULTS: While donepezil, galanthamine, and huperzine demonstrated the highest efficacy in the mild cognitive dysfunction subgroup (mean difference = 5.2, 2.5, and 2.4, respectively). Donepezil, huperzine A, and rivastigmine achieved the most significant effects in the moderate cognitive dysfunction subgroup (MD = 3.8, 2.9, and 3.0 respectively). In the severe subgroup, donepezil was demonstrably superior to memantine. Donepezil was thus found to effectively address cognitive impairment in patients with AD regardless of the degrees of cognitive decline. CONCLUSIONS: Evaluation of the clinically common anti-dementia drugs using NMA affirmed the utility of cholinesterase inhibitors, especially donepezil, in alleviating cognitive dysfunction of patients with AD. This study may therefore help to inform the clinical selection of pharmacotherapeutic interventions addressing cognitive dysfunction in patients with AD. Title: High-level expression of Humicola insolens cutinase in Pichia pastoris without carbon starvation and its use in cotton fabric bioscouring Hong R, Sun Y, Su L, Gu L, Wang F, Wu J Ref: J Biotechnol, 304:10, 2019 : PubMed ESTHER: Hong_2019_J.Biotechnol_304_10 PubMedSearch: Hong 2019 J.Biotechnol 304 10 PubMedID: 31400343 Abstract Huimcola insolens cutinase (HiC) was heterologously expressed in Pichia pastoris. To avoid a carbon starvation step, fermentation was conducted using combinations of sorbitol with glycerol and methanol in the cell growth and induction phases, respectively. The cutinase productivity (27.71 U mL(-1) h(-1)) was 9.93 U mL(-1) h(-1) greater than that achieved using traditional two-phase methods, and a cutinase activity of 2660 U mL(-1), using p-nitrophenyl butyrate as substrate, was achieved after only 96 h in a 3-L bioreactor. Subsequently, the combination of HiC with Thermobifida fusca cutinase (TfC) in cotton fabric bioscouring was evaluated by monitoring the wettability and dyeability of the fabric. Treatment with 20 U mL(-1) of HiC at 80 degrees C for 5 min followed by 30 U mL(-1) of TfC at 50 degrees C for 1 h gave the best results. The total treatment time was shorter and performance was better than those seen with the alkali method. Title: Lipase member H is a downstream molecular target of hypoxia inducible factor-1alpha and promotes papillary thyroid carcinoma cell migration in BCPAP and KTC-1 cell lines Li Y, Zhou X, Zhang Q, Chen E, Sun Y, Ye D, Wang O, Zhang X, Lyu J Ref: Cancer Manag Res, 11:931, 2019 : PubMed ESTHER: Li_2019_Cancer.Manag.Res_11_931 PubMedSearch: Li 2019 Cancer.Manag.Res 11 931 PubMedID: 30774423 Abstract Background: Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma, which is associated with a high incidence of lymph-node metastasis. Multiple biomarkers have been identified for the precise diagnosis of PTC at an early stage. However, their role in PTC remains poorly elucidated. Previously, we reported that lipase H (LIPH), a membrane-bound protein, was highly expressed in PTC. This study aimed to fully elucidate the causal role of LIPH in the development of PTC and investigated its relationship with lymph-node metastasis in PTC. Materials and methods: Quantitative reverse transcription PCR and immunohistochemistry were used to measure the mRNA and protein expression levels of LIPH in 45 and 6 pairs of PTC tissues and adjacent normal tissues, respectively. Clinical tissue data of 504 PTC tissues and 60 normal thyroid tissues from The Cancer Genome Atlas database were used to analyze the correlation between LIPH expression level and clinical features in PTC. siRNAs were used to knock down genes, while plasmids were used to overexpress genes. Two PTC cell lines (KTC-1 and BCPAP) were used in subsequent cytological function studies. In addition, a hypoxia stress model was constructed using cobaltous chloride hexahydrate reagent, and the protein expression level of the corresponding biomarkers was measured by Western blotting. Results: This study revealed that high expression of LIPH in PTC was closely associated with lymph-node metastasis. Our cellular function experiments indicated that LIPH positively correlated with the malignant behavior of PTC cell lines. We further confirmed the role of LIPH in hypoxia and its relationship with the epithelial-mesenchymal transition pathway in PTC. Conclusion: LIPH plays an important role in PTC oncogenesis and development, especially in lymph-node metastasis. It can be regarded as a biomarker for the diagnosis and treatment of PTC in the near future. Title: Metal coordination polymer induced perylene probe excimer fluorescence and its application in acetylcholinesterase sensing and alpha-fetoprotein immunoassay Li Y, Yin S, Hou J, Meng L, Gao M, Sun Y, Zhang C, Bai S, Ren J, Yu C Ref: Analyst, 144:2034, 2019 : PubMed ESTHER: Li_2019_Analyst_144_2034 PubMedSearch: Li 2019 Analyst 144 2034 PubMedID: 30702092 Abstract A novel sensing strategy for acetylcholinesterase (AChE) and alpha-fetoprotein (AFP) is developed, based on the perylene probe monomer to excimer fluorescence transformation induced by the in situ generation of a metal coordination polymer. In the presence of AChE, acetylthiocholine chloride was hydrolyzed to thiocholine. Ag(+) and the produced thiocholine formed a positively charged metal coordination polymer, which induced the aggregation of a negatively charged perylene probe and the formation of probe excimer emission. The intensity ratio of excimer to monomer emission was proportional to the AChE concentration. A sensing method for AChE was thus established with a detection limit of 0.02 mU mL(-1). The excimer emission with a large Stokes shift could avoid the interference of background fluorescence from complex biological samples, and thus achieved selective and sensitive detection of AChE. In addition, a fluorescence immunoassay strategy for AFP was then developed. Gold nanoparticles (AuNPs) co-immobilized with acetylcholinesterase and the AFP antibody as the capture and amplification probe were first prepared. In the presence of AFP, the sandwich structure was formed by immunological recognition. The hydrolysis of acetylthiocholine was catalyzed by AChE on the AuNPs, and the metal coordination polymer was then formed which resulted in the aggregation of the perylene probe and the formation of the excimer emission. The proposed sensing method offers a new strategy for the detection of other biomarkers. Title: Distribution characteristics of sweat gland nerve fibres in normal humans identified by acetylcholinesterase histochemical staining Ling L, Liu Y, Sun Y, Cai Y, Jiang Y, Chen L, He L, Xue J Ref: Clin Neurol Neurosurg, 189:105620, 2019 : PubMed ESTHER: Ling_2019_Clin.Neurol.Neurosurg_189_105620 PubMedSearch: Ling 2019 Clin.Neurol.Neurosurg 189 105620 PubMedID: 31812030 Abstract OBJECTIVE: To quantitatively analyze distribution characteristics of sweat gland nerve fibres (SGNF) in normal Chinese individuals for obtaining a reference for early diagnosis of peripheral neuropathy. PATIENTS AND METHODS: Skin biopsy samples were collected from 192 normal Chinese individuals and divided into six, four and two groups according to anatomic sites, age and gender, respectively. SGNF morphology was observed and SGNF density (SGNFD) was determined. RESULTS: There was a significant difference in SGNFD among different anatomic sites, age and gender. A degressive tendency was observed from proximal to distal anatomic sites. SGNFD was the lowest in subjects in the 21-40-year-old age group, but was the highest in subjects in the >61-year-old age group. Overall, SGNFD fluctuated with age. SGNFD in males was significantly higher than that in females. CONCLUSIONS: Distribution characteristics of SGNF in normal individuals may serve as a reference for early diagnosis of nerve fibre damage. Title: Donepezil decreases heart rate in elderly patients with Alzheimer's disease Pu Z, Xu W, Lin Y, Shen J, Sun Y Ref: Int J Clinical Pharmacology & Therapeutics, 57:94, 2019 : PubMed ESTHER: Pu_2019_Int.J.Clin.Pharmacol.Ther_57_94 PubMedSearch: Pu 2019 Int.J.Clin.Pharmacol.Ther 57 94 PubMedID: 30378536 Abstract OBJECTIVE: Donepezil is an acetylcholinesterase inhibitor (AChI) that improves cognitive function in Alzheimer's disease (AD) patients. However, AChIs are usually associated with peripheral adverse reactions. Here, we investigated the cardiac outcomes in elderly AD patients treated with donepezil. MATERIALS AND METHODS: A total of 82 AD patients (age, 75.47 +/- 6.53 years) received 5 mg or 10 mg donepezil (n = 41/group) once daily for 12 weeks. Next, we examined the heart rate (HR), cardiac rhythm, and PR, QRS, and QTc intervals. RESULTS: Compared to the 5-mg donepezil-treated group, the HR was slower in the 10-mg donepezil-treated group at the 4(th), 8(th), and 12(th) weeks of treatment (p = 0.041, 0.026, 0.008, respectively). The PR interval was longer in the 10-mg donepezil-treated group at the 12(th) week of treatment (p = 0.022). Compared to the pretreatment values, the post-treatment HR and PR interval in the 10-mg donepezil-treated group were significantly slower and longer, respectively (p = 0.002, p = 0.005). Further, the HR was significantly correlated to the donepezil dosage (p = 0.014). Similarly, donepezil dosage and treatment interval were significantly correlated (p = 0.048). CONCLUSION: Taken together, our findings suggest that 10 mg donepezil decreased the HR of elderly AD patients without inducing severe cardiac outcomes. Therefore, AD patients receiving donepezil should undergo regular cardiovascular monitoring.. Title: Plasma levels of soluble ST2, but not IL-33, correlate with the severity of alcoholic liver disease Sun Z, Chang B, Huang A, Hao S, Gao M, Sun Y, Shi M, Jin L, Zhang W and Zou Z <6 more author(s)> Sun Z, Chang B, Huang A, Hao S, Gao M, Sun Y, Shi M, Jin L, Zhang W, Zhao J, Teng G, Han L, Tian H, Liang Q, Zhang JY, Zou Z (- 6) Ref: J Cell Mol Med, 23:887, 2019 : PubMed ESTHER: Sun_2019_J.Cell.Mol.Med_23_887 PubMedSearch: Sun 2019 J.Cell.Mol.Med 23 887 PubMedID: 30478965 Abstract Alcoholic liver disease (ALD) is a complication that is a burden on global health and economy. Interleukin-33 (IL-33) is a newly identified member of the IL-1 cytokine family and is released as an "alarmin" during inflammation. Soluble suppression of tumourigenicity 2 (sST2), an IL-33 decoy receptor, has been reported as a new biomarker for the severity of systemic and highly inflammatory diseases. Here, we found the levels of plasma sST2, increased with the disease severity from mild to severe ALD. Importantly, the plasma sST2 levels in ALD patients not only correlated with scores for prognostic models (Maddrey's discriminant function, model for end-stage liver disease and Child-Pugh scores) and indexes for liver function (total bilirubin, international normalized ratio, albumin, and cholinesterase) but also correlated with neutrophil-associated factors as well as some proinflammatory cytokines. In vitro, lipopolysaccharide-activated monocytes down-regulated transmembrane ST2 receptor but up-regulated sST2 mRNA and protein expression and produced higher levels of tumour necrosis factor-alpha (TNF-alpha). By contrast, monocytes pretreated with recombinant sST2 showed decreased TNF-alpha production. In addition, although plasma IL-33 levels were comparable between healthy controls and ALD patients, we found the IL-33 expression in liver tissues from ALD patients was down-regulated at both RNA and protein levels. Immunohistochemical staining further showed that the decreased of IL-33-positive cells were mainly located in liver lobule area. These results suggested that sST2, but not IL-33, is closely related to the severity of ALD. Consequently, sST2 could be used as a potential biomarker for predicting the prognosis of ALD. Title: Noninvasive Evaluation of Liver Fibrosis Reverse Using Artificial Neural Network Model for Chronic Hepatitis B Patients Wei W, Wu X, Zhou J, Sun Y, Kong Y, Yang X Ref: Comput Math Methods Med, 2019:7239780, 2019 : PubMed ESTHER: Wei_2019_Comput.Math.Methods.Med_2019_7239780 PubMedSearch: Wei 2019 Comput.Math.Methods.Med 2019 7239780 PubMedID: 31428186 Abstract The diagnostic performance of an artificial neural network model for chronic HBV-induced liver fibrosis reverse is not well established. Our research aims to construct an ANN model for estimating noninvasive predictors of fibrosis reverse in chronic HBV patients after regular antiviral therapy. In our study, 141 consecutive patients requiring liver biopsy at baseline and 1.5 years were enrolled. Several serum biomarkers and liver stiffness were measured during antiviral therapy in both reverse and nonreverse groups. Statistically significant variables between two groups were selected to form an input layer of the ANN model. The ROC (receiver-operating characteristic) curve and AUC (area under the curve) were calculated for comparison of effectiveness of the ANN model and logistic regression model in predicting HBV-induced liver fibrosis reverse. The prevalence of fibrosis reverse of HBV patients was about 39% (55/141) after 78-week antiviral therapy. The Ishak scoring system was used to assess fibrosis reverse. Our study manifested that AST (aspartate aminotransferase; importance coefficient = 0.296), PLT (platelet count; IC = 0.159), WBC (white blood cell; IC = 0.142), CHE (cholinesterase; IC = 0.128), LSM (liver stiffness measurement; IC = 0.125), ALT (alanine aminotransferase; IC = 0.110), and gender (IC = 0.041) were the most crucial predictors of reverse. The AUC of the ANN model and logistic model was 0.809 +/- 0.062 and 0.756 +/- 0.059, respectively. In our study, we concluded that the ANN model with variables consisting of AST, PLT, WBC, CHE, LSM, ALT, and gender may be useful in diagnosing liver fibrosis reverse for chronic HBV-induced liver fibrosis patients. Title: The genome of broomcorn millet Zou C, Li L, Miki D, Li D, Tang Q, Xiao L, Rajput S, Deng P, Peng L and Zhu JK <14 more author(s)> Zou C, Li L, Miki D, Li D, Tang Q, Xiao L, Rajput S, Deng P, Peng L, Jia W, Huang R, Zhang M, Sun Y, Hu J, Fu X, Schnable PS, Chang Y, Li F, Zhang H, Feng B, Zhu X, Liu R, Schnable JC, Zhu JK (- 14) Ref: Nat Commun, 10:436, 2019 : PubMed ESTHER: Zou_2019_Nat.Commun_10_436 PubMedSearch: Zou 2019 Nat.Commun 10 436 PubMedID: 30683860 Gene_locus related to this paper: panmi-a0a3l6qvl9, 9poal-a0a2s3hbt0, panmi-a0a3l6sxg5, 9poal-a0a2t7cdl4, panmi-a0a3l6ta96, panmi-a0a3l6qv47 Abstract Broomcorn millet (Panicum miliaceum L.) is the most water-efficient cereal and one of the earliest domesticated plants. Here we report its high-quality, chromosome-scale genome assembly using a combination of short-read sequencing, single-molecule real-time sequencing, Hi-C, and a high-density genetic map. Phylogenetic analyses reveal two sets of homologous chromosomes that may have merged ~5.6 million years ago, both of which exhibit strong synteny with other grass species. Broomcorn millet contains 55,930 protein-coding genes and 339 microRNA genes. We find Paniceae-specific expansion in several subfamilies of the BTB (broad complex/tramtrack/bric-a-brac) subunit of ubiquitin E3 ligases, suggesting enhanced regulation of protein dynamics may have contributed to the evolution of broomcorn millet. In addition, we identify the coexistence of all three C4 subtypes of carbon fixation candidate genes. The genome sequence is a valuable resource for breeders and will provide the foundation for studying the exceptional stress tolerance as well as C4 biology. Title: Guided Evolution of Recombinant Bombyx mori Acetylcholinesterase II by Homology Modeling to Change Pesticide Sensitivity Cai J, Wang B, Li J, Chen Z, Rao M, Muyldermans S, Hua X, Xie X, Wang H and Sun Y <3 more author(s)> Cai J, Wang B, Li J, Chen Z, Rao M, Muyldermans S, Hua X, Xie X, Wang H, Yang J, Xu Z, Shen Y, Sun Y (- 3) Ref: Int J Mol Sci, 19:, 2018 : PubMed Title: Biopanning of allergens from wasp sting patients Chai L, Yang X, Liu M, Liu C, Han L, Guo H, Li C, Sun Y, Li X and Fang Z <1 more author(s)> Chai L, Yang X, Liu M, Liu C, Han L, Guo H, Li C, Sun Y, Li X, Xiao M, Fang Z (- 1) Ref: Bioscience Reports, 38:, 2018 : PubMed ESTHER: Chai_2018_Biosci.Rep_38_ PubMedSearch: Chai 2018 Biosci.Rep 38 PubMedID: 30249752 Abstract OBJECTIVE: Wasp venom is a potentially important natural drug, but it can cause hypersensitivity reactions. The purpose of the present study was to systematically study the epitopes of wasp venom. METHODS: Using a random 12-peptide phage library, we performed antibody-binding epitope panning on ten serum samples from wasp sting victims at 3 h and 4 days after the sting. The panning epitopes were identified by high-throughput sequencing and matched with wasp venom proteins by BLAST. The panned antibody-binding epitopes were verified by ELISA. RESULTS: A total of 35 specific potential wasp venom epitopes in 4 days were identified. Amongst them, twelve peptide epitopes were matched with nine wasp venom proteins, namely, vitellogenin precursor, hexamerin 70b precursor, venom carboxylesterase-6 precursor, MRJP5, major royal jelly protein 8 precursor, venom acid phosphatase Acph-1 precursor, phospholipase A2, venom serine protease 34 precursor, and major royal jelly protein 9 precursor. The changes in serum IgM antibodies induced by wasp venom were confirmed by ELISA based on the 12 peptide epitopes. CONCLUSION: The nine wasp venom proteins are potential allergens, which should be excluded or modified in the potential biomedical applications of wasp venom. Title: Protein Surface Structural Recognition in Inactive Areas: A New Immobilization Strategy for Acetylcholinesterase Diao J, Yu X, Ma L, Li Y, Sun Y Ref: Bioconjug Chem, 29:1703, 2018 : PubMed ESTHER: Diao_2018_Bioconjug.Chem_29_1703 PubMedSearch: Diao 2018 Bioconjug.Chem 29 1703 PubMedID: 29617563 Abstract This work reported a new method of design for the immobilization of acetylcholinesterase (AChE) based on its molecular structure to improve its sensitivity and stability. The immobilization binding site on the surface of AChE was determined using MOLCAD's multi-channel functionality. Then, 11 molecules ((+)-catechin, (-)-epicatechin, (-)-gallocatechin, hesperetin, naringenin, quercetin, taxifolin, (-)-epicatechin gallate, flupirtine, atropine, and hyoscyamine) were selected from the ZINC database (about 50000 molecules) as candidate affinity ligands for AChE. The fluorescence results showed that the binding constant Kb between AChE and the ligands ranged from 0.01344 x 10(4) to 4.689 x 10(4) M(-1) and there was one independent class of binding site for the ligands on AChE. The AChE-ligand binding free energy ranged from -12.14 to -26.65 kJ mol(-1). Naringenin, hesperetin, and quercetin were the three most potent immobilized affinity ligands. In addition, it was confirmed that the binding between the immobilized ligands only occurred at a single site, located in an inactive area on the surface of AChE, and did not affect the enzymatic activity as shown through a competition experiment and enzyme assay. This method based on protein surface structural recognition with high sensitivity and stability can be used as a generic approach for design of the enzyme immobilization and biosensor development. Title: Increased Neuroligin 2 Levels in the Postsynaptic Membrane in Spinal Dorsal Horn may Contribute to Postoperative Pain Guo R, Li H, Li X, Sun Y, Miao H, Ma D, Hong F, Zhang Y, Guan Y and Wang Y <2 more author(s)> Guo R, Li H, Li X, Sun Y, Miao H, Ma D, Hong F, Zhang Y, Guan Y, Li J, Tian M, Wang Y (- 2) Ref: Neuroscience, 382:14, 2018 : PubMed ESTHER: Guo_2018_Neurosci_382_14 PubMedSearch: Guo 2018 Neurosci 382 14 PubMedID: 29715511 Abstract Neuroligin 2 is a synaptic cell adhesion molecule that is mainly located in inhibitory synapses and is crucial in the regulation of synapse function through protein-protein interactions. However, researchers have not clearly determined whether neuroligin 2 is involved in the development of postoperative pain. In the current study, Western blot, immunofluorescence staining and co-immunoprecipitation were used to examine the critical role of neuroligin 2 in postoperative pain hypersensitivity. A small interfering ribonucleic acid (siRNA)-targeting neuroligin 2 was used to inhibit neuroligin 2 expression. Our data found that plantar incision induced postoperative pain hypersensitivity, which was characterized by paw withdrawal threshold and cumulative pain score. The upregulation of neuroligin 2 and GluR1 expression in the postsynaptic membranes of ipsilateral spinal dorsal horn was observed at 3h and 1day after plantar incision. Additionally, at 3h after plantar incision, the amount of PSD-95 that was co-immunoprecipitated with neuroligin 2 antibody was significantly increased in the ipsilateral dorsal horn, as compared to that of the control group. Intrathecal pretreatment of siRNA-targeting neuroligin 2 to reduce the neuroligin 2 expression in the spinal cord significantly inhibited the pain hypersensitivity and reduced the synaptic targeting of GluR1 in ipsilateral dorsal horns. Our study indicates that the incision-induced interaction between neuroligin 2 and PSD-95 and subsequent synaptic targeting of GluR1 in ipsilateral dorsal horns contribute to postoperative pain hypersensitivity. Title: Coumarin-dithiocarbamate hybrids as novel multitarget AChE and MAO-B inhibitors against Alzheimer's disease: Design, synthesis and biological evaluation He Q, Liu J, Lan JS, Ding J, Sun Y, Fang Y, Jiang N, Yang Z, Sun L and Xie SS <1 more author(s)> He Q, Liu J, Lan JS, Ding J, Sun Y, Fang Y, Jiang N, Yang Z, Sun L, Jin Y, Xie SS (- 1) Ref: Bioorg Chem, 81:512, 2018 : PubMed ESTHER: He_2018_Bioorg.Chem_81_512 PubMedSearch: He 2018 Bioorg.Chem 81 512 PubMedID: 30245233 Abstract A series of new coumarin-dithiocarbamate hybrids were designed and synthesized as multitarget agents for the treatment of Alzheimer's disease. Most of them showed potent and clearly selective inhibition towards AChE and MAO-B. Among these compounds, compound 8f demonstrated the most potent inhibition to AChE with IC50 values of 0.0068muM and 0.0089muM for eeAChE and hAChE, respectively. Compound 8g was identified as the most potent inhibitor to hMAO-B, and it is also a good and balanced inhibitor to both hAChE and hMAO-B (0.114microM for hAChE; 0.101microM for hMAO-B). Kinetic and molecular modeling studies revealed that 8g was a dual binding site inhibitor for AChE and a competitive inhibitor for MAO-B. Further studies indicated that 8g could penetrate the BBB and exhibit no toxicity on SH-SY5Y neuroblastoma cells. More importantly, 8g did not display any acute toxicity in mice at doses up to 2500mg/kg and could reverse the cognitive dysfunction of scopolamine-induced AD mice. Overall, these results highlighted 8g as a potential multitarget agent for AD treatment and offered a starting point for design of new multitarget AChE/MAO-B inhibitors based on dithiocarbamate scaffold. Title: Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding Lau SKP, Zhang L, Luk HKH, Xiong L, Peng X, Li KSM, He X, Zhao PS, Fan RYY and Woo PCY <11 more author(s)> Lau SKP, Zhang L, Luk HKH, Xiong L, Peng X, Li KSM, He X, Zhao PS, Fan RYY, Wong ACP, Ahmed SS, Cai JP, Chan JFW, Sun Y, Jin D, Chen H, Lau TCK, Kok RKH, Li W, Yuen KY, Woo PCY (- 11) Ref: J Infect Dis, 218:197, 2018 : PubMed ESTHER: Lau_2018_J.Infect.Dis_218_197 PubMedSearch: Lau 2018 J.Infect.Dis 218 197 PubMedID: 29346682 Abstract Although bats are known to harbor Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses, the role of bats in the evolutionary origin and pathway remains obscure. We identified a novel MERS-CoV-related betacoronavirus, Hp-BatCoV HKU25, from Chinese pipistrelle bats. Although it is closely related to MERS-CoV in most genome regions, its spike protein occupies a phylogenetic position between that of Ty-BatCoV HKU4 and Pi-BatCoV HKU5. Because Ty-BatCoV HKU4 but not Pi-BatCoV HKU5 can use the MERS-CoV receptor human dipeptidyl peptidase 4 (hDPP4) for cell entry, we tested the ability of Hp-BatCoV HKU25 to bind and use hDPP4. The HKU25-receptor binding domain (RBD) can bind to hDPP4 protein and hDPP4-expressing cells, but it does so with lower efficiency than that of MERS-RBD. Pseudovirus assays showed that HKU25-spike can use hDPP4 for entry to hDPP4-expressing cells, although with lower efficiency than that of MERS-spike and HKU4-spike. Our findings support a bat origin of MERS-CoV and suggest that bat CoV spike proteins may have evolved in a stepwise manner for binding to hDPP4. Title: A colorimetric assay for acetylcholinesterase activity and inhibitor screening based on the thiocholine-induced inhibition of the oxidative power of MnO2 nanosheets on 3,3',5,5'-tetramethylbenzidine Sun Y, Tan H, Li Y Ref: Mikrochim Acta, 185:446, 2018 : PubMed ESTHER: Sun_2018_Mikrochim.Acta_185_446 PubMedSearch: Sun 2018 Mikrochim.Acta 185 446 PubMedID: 30187211 Abstract The authors describe a colorimetric method for the determination of the activity of acetylcholinesterase (AChE). Manganese dioxide (MnO2) nanosheets directly reacts with 3,3',5,5'-tetramethylbenzidine (TMB) in the absence of hydrogen peroxide (H2O2). This leads to the formation of a blue product (oxTMB) with an absorption peak at 652 nm. If AChE hydrolyzes its substrate acetylthiocholine chloride, thiocholine is formed which blocks the oxidative power of the MnO2 nanosheets. Hence, oxTMB will not be formed. The decreased absorbance is directly related to the AChE activity in the 0.01-1.0 mU.mL(-1) range. The detection limit is 0.01 mU.mL(-1) and the relative standard deviation is 1.2% (for n = 11 at 0.5 mU.mL(-1)). The method was also applied to screen for inhibitors of AChE. Graphical abstract Based on the oxidizing properties of manganese dioxide nanosheets (MnO2 nanosheets), we report a colorimetric method for determining acetylcholinesterase activity with the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB). Title: Computational evidence for the degradation mechanism of haloalkane dehalogenase LinB and mutants of Leu248 to 1-chlorobutane Wang J, Tang X, Li Y, Zhang R, Zhu L, Chen J, Sun Y, Zhang Q, Wang W Ref: Phys Chem Chem Phys, 20:20540, 2018 : PubMed ESTHER: Wang_2018_Phys.Chem.Chem.Phys_20_20540 PubMedSearch: Wang 2018 Phys.Chem.Chem.Phys 20 20540 PubMedID: 30051124 Abstract The catalytic degradation ability of the haloalkane dehalogenase LinB toward 1-chlorobutane (1-CB) was studied using a combined quantum mechanics/molecular mechanics (QM/MM) approach. Two major processes are involved in the LinB-catalyzed removal of halogens: dechlorination and hydrolyzation. The present study confirmed the experimentally proposed reaction path at the molecular level. Moreover, based on nucleophilic substitution mechanism (SN2 reaction), dechlorination was found to be the rate-determining step of the entire reaction process. In this study, the Boltzmann-weighted average barrier for dechlorination was determined to be 17.0 kcal mol-1, which is fairly close to the experimental value (17.4 kcal mol-1). The state of His107 and the influence of Leu248 on the dechlorination process were also explored. In addition, an intriguing phenomenon was discovered: the potential energy barrier decreased by 7.5 kcal mol-1 when the Leu248 residue was mutated into Phe248. This discovery might be of great help to design new mutant enzymes or novel biocatalysts. Title: Neurexin-Neuroligin 1 regulates synaptic morphology and function via the WAVE regulatory complex in Drosophila neuromuscular junction Xing G, Li M, Sun Y, Rui M, Zhuang Y, Lv H, Han J, Jia Z, Xie W Ref: Elife, 7:, 2018 : PubMed ESTHER: Xing_2018_Elife_7_ PubMedSearch: Xing 2018 Elife 7 PubMedID: 29537369 Abstract Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of Neuroligin functions remain unclear. We found that Drosophila Neuroligin1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner Neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 knockout mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction. Title: Improvement of Learning and Memory Induced by Cordyceps Polypeptide Treatment and the Underlying Mechanism Yuan G, An L, Sun Y, Xu G, Du P Ref: Evid Based Complement Alternat Med, 2018:9419264, 2018 : PubMed ESTHER: Yuan_2018_Evid.Based.Complement.Alternat.Med_2018_9419264 PubMedSearch: Yuan 2018 Evid.Based.Complement.Alternat.Med 2018 9419264 PubMedID: 29736181 Abstract Our previous research revealed that Cordyceps militaris can improve the learning and memory, and although the main active ingredient should be its polypeptide complexes, the underlying mechanism of its activity remains poorly understood. In this study, we explored the mechanisms by which Cordyceps militaris improves learning and memory in a mouse model. Mice were given scopolamine hydrobromide intraperitoneally to establish a mouse model of learning and memory impairment. The effects of Cordyceps polypeptide in this model were tested using the Morris water maze test; serum superoxide dismutase activity; serum malondialdehyde levels; activities of acetyl cholinesterase, Na+-k+-ATPase, and nitric oxide synthase; and gamma aminobutyric acid and glutamate contents in brain tissue. Moreover, differentially expressed genes and the related cellular signaling pathways were screened using an mRNA expression profile chip. The results showed that the genes Pik3r5, Il-1beta, and Slc18a2 were involved in the effects of Cordyceps polypeptide on the nervous system of these mice. Our findings suggest that Cordyceps polypeptide may improve learning and memory in the scopolamine-induced mouse model of learning and memory impairment by scavenging oxygen free radicals, preventing oxidative damage, and protecting the nervous system. Title: The Impairment of Trans Fatty Acids on Learning, Memory and Brain Amino Acid Neurotransmitters in Mice Zhang T, Liu P, Sun Y, Ren N, Nie S Ref: J Nutr Sci Vitaminol (Tokyo), 64:63, 2018 : PubMed ESTHER: Zhang_2018_J.Nutr.Sci.Vitaminol.(Tokyo)_64_63 PubMedSearch: Zhang 2018 J.Nutr.Sci.Vitaminol.(Tokyo) 64 63 PubMedID: 29491274 Abstract The aim of the study was to demonstrate the impairment of trans fatty acids (TFAs) in neurological disorders in mice. Forty-eight male Kunming mice were randomly divided into four groups with twelve in each group, namely a control group (corn oil group), and TFA groups with low, middle and high dosages. The tested chemicals were given by gavage, once a day, for 12 wk in total, with the volume of the intragastric liquid as 0.1 mL/10 g of body weight. The mice in the control group were given corn oil only. The mice in the TFA groups were given TFA solution (doses were 25, 50 and 100 mg/kg of body weight, respectively). The Morris circle water maze was used to test learning and memory of mice. The activity of acetylcholinesterase (AChE), nitric oxide synthase (NOS) and the level of brain amino acid neurotransmitters were tested. In the Morris water maze task, and compared to the control group, TFAs showed no obvious effect on learning or memory. TFA intake led to a significant decrease of AChE in all TFA groups, and the increase in levels of NOS in the high-dose group. Meanwhile, intake of TFAs increased the levels of Asp, Glu, Gly, and Tau in all TFA groups. The results suggest that long-term intake of TFAs probably impairs learning, memory and brain neurotransmitters in mice. Title: Metabolic profiles of corydaline in rats by ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry Chai L, Donkor PO, Wang K, Sun Y, Oppong MB, Ding L, Qiu F Ref: Xenobiotica, :1, 2017 : PubMed ESTHER: Chai_2017_Xenobiotica__1 PubMedSearch: Chai 2017 Xenobiotica 1 PubMedID: 29235899 Abstract Corydaline, an isoquinoline alkaloid obtained from the rhizomes of Corydalis yanhusuo, exhibits anti-acetylcholinesterase, anti-angiogenic, anti-allergic and gastric emptying activities. In this study, a rapid and reliable ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS) method was developed and employed for the comprehensive study of the metabolites of corydaline in rats. Altogether, 43 metabolites were identified in the plasma (11), bile (9), urine (34) and feces (21) of rats after oral administration of corydaline at a dose of 4.5mg/kg. It was demonstrated that demethylation, hydroxylation, sulfation and glucuronidation were the major metabolic transformation pathways. Among these, two metabolites were identified as tetrahydropalmatine and isocorybulbine, and thirty-three (33) phase I and phase II products were inferred to be new metabolites arising from the in vivo metabolism of corydaline. Importantly, this research provides scientific and reliable support for full understanding of the metabolic profiles of corydaline and the results could help to elucidate its safety and efficacy. Title: Soluble epoxide hydrolase inhibitor AUDA decreases bleomycin-induced pulmonary toxicity in mice by inhibiting the p38/Smad3 pathways Dong XW, Jia YL, Ge LT, Jiang B, Jiang JX, Shen J, Jin YC, Guan Y, Sun Y, Xie QM Ref: Toxicology, 389:31, 2017 : PubMed ESTHER: Dong_2017_Toxicology_389_31 PubMedSearch: Dong 2017 Toxicology 389 31 PubMedID: 28694203 Inhibitor(s) related to this paper: AUDA Abstract Bleomycin (BLM) has potent tumor cell-killing properties that have given it an important place in cancer chemotherapy, but pulmonary toxicity is its major adverse effect. Soluble epoxide hydrolase (sEH) inhibitors have been reported to have protective effects in fibrosis models, but the effects of AUDA, an sEH inhibitor of BLM-induced pulmonary toxicity and fibrosis, remain to be researched. In this study, we assessed the effects of AUDA on the BLM-induced pulmonary fibrosis in a mouse model, and transforming growth factor (TGF)-beta1-induced epithelial proliferation and epithelial-mesenchymal transition (EMT) in vitro by monitoring changes in pulmonary function, inflammatory response, fibrotic remodeling, and signaling pathways. AUDA was administered by intragastric administration (i.g) daily for three weeks, starting at seven days after intratracheal instillation of BLM. All examinations were performed 24h after the last i.g. In vivo, AUDA significantly improved BLM-induced decline in lung function and body weight, and inhibited inflammatory cell accumulation and the mRNA and protein expression of interleukin (IL)-1beta, TGF-beta1, and matrix metalloproteinase 9 (MMP-9) in lung tissue. Moreover, AUDA attenuated BLM-induced deposition of collagen fibers, destruction of alveolar structures, and pulmonary parenchyma. Additionally, AUDA regulated the expression of alpha-smooth muscle actin (alpha-SMA) and E-cadherin by inhibiting the Smad3/p38 signaling pathway. In vitro, AUDA significantly inhibited TGF-beta1-induced epithelial cells and fibroblast proliferation, reduced sEH expression and alpha-SMA expression, and increased epoxyeicosatrienoic acid (EET) levels and E-cadherin expression in epithelial cells. These effects were blocked by AUDA by downregulating the Smad3 and p38 signaling pathways. Taken together, these data indicate that treatment with sEH inhibitors may improve BLM-induced pulmonary toxicity. Title: Disease spectrum of alcoholic liver disease in Beijing 302 Hospital from 2002 to 2013: A large tertiary referral hospital experience from 7422 patients Huang A, Chang B, Sun Y, Lin H, Li B, Teng G, Zou ZS Ref: Medicine (Baltimore), 96:e6163, 2017 : PubMed ESTHER: Huang_2017_Medicine.(Baltimore)_96_e6163 PubMedSearch: Huang 2017 Medicine.(Baltimore) 96 e6163 PubMedID: 28207552 Abstract Alcohol consumption in China has substantially increased over the last 3 decades and the number of patients with alcoholic liver disease (ALD) is rising at an alarming rate. However, accurate and representative data on time trends in its hospitalization rates are not available. The aim of this study is to assess the current status and burden of ALD in China by analyzing the data from a large tertiary referral hospital, Beijing 302 Hospital.Data were retrospectively recorded from patients diagnosed as ALD in Beijing 302 Hospital from 2002 to 2013. The disease spectrum and biochemical parameters of each patient were collected.The patients with ALD accounted for 3.93% (7422) of all patients (188,902) with liver diseases between 2002 and 2013. The number of patients hospitalized with ALD increased from 110 in 2002 to 1672 in 2013. The ratio of patients hospitalized with ALD to all patients hospitalized with liver diseases was rising almost continuously and increased from 1.68% in 2002 to 4.59% in 2013. Most patients with ALD were male. Age distribution of ALD hospitalization showed that the highest rate was in 40- to 49-year-old group in subjects. Notably, the annual proportion of severe alcoholic hepatitis (SAH) increased 2.43 times from 2002 to 2013. We found the highest levels of mean corpuscular volume, the aspartate aminotransferase/alanine aminotransferase ratio, total bilirubin, international normalized ratio, and alkaline phosphatase in SAH patients, while serum levels of hemoglobin, albumin, and cholinesterase were significantly decreased in SAH group. Among these ALD, the SAH patient population has the worst prognosis. Alcoholic cirrhosis (ALC) is the most common ALD, and annual admissions for ALC increased significantly during the analyzed period.The number of hospitalized patients with ALD and the annual hospitalization rate of ALD were increasing continuously in Beijing 302 Hospital from 2002 to 2013. More attention should be paid to develop population-based effective strategy to control ALD. Title: Can Persistence With Cholinesterase Inhibitor Treatment Lower Mortality and Health-Care Costs Among Patients With Alzheimer's Disease? A Population-Based Study in Taiwan Ku LE, Li CY, Sun Y Ref: Am J Alzheimers Dis Other Demen, :1533317517734639, 2017 : PubMed ESTHER: Ku_2017_Am.J.Alzheimers.Dis.Other.Demen__1533317517734639 PubMedSearch: Ku 2017 Am.J.Alzheimers.Dis.Other.Demen 1533317517734639 PubMedID: 29210284 Abstract Although cholinesterase inhibitors (ChEIs) have been proved to help reduce cognitive deterioration in patients with Alzheimer's disease (AD), their effects on survival remain inconclusive. This study aims to assess the effects of the persistent use of ChEIs on the risk of mortality in patients with AD. This population-based cohort study included 8614 patients having AD with ChEI prescription from 2002 to 2006 and followed until 2010. Kaplan-Meier curves and hazard ratios (HRs) of mortality were estimated in association with ChEI treatment duration and adherence. The average annual mortality rate per 100 person-years was 9.2 for the short-duration group (discontinued < 1 year) and 7.2 for the long-duration group (discontinued >/= 2 years). Compared to the short-duration group, the long-duration group had a lower mortality (HR = 0.76, 95% confidence interval: 0.69-0.84) and shorter annual inpatient days. But the annual health-care costs did not differ significantly between the 2 groups. Title: Neuroprotective Effects and Mechanisms of Action of Multifunctional Agents Targeting Free Radicals, Monoamine Oxidase B and Cholinesterase in Parkinson's Disease Model Liu Z, Cai W, Lang M, Yan R, Li Z, Zhang G, Yu P, Wang Y, Sun Y, Zhang Z Ref: Journal of Molecular Neuroscience, 61:498, 2017 : PubMed ESTHER: Liu_2017_J.Mol.Neurosci_61_498 PubMedSearch: Liu 2017 J.Mol.Neurosci 61 498 PubMedID: 28144826 Abstract Parkinson's disease (PD) is a complex neurodegenerative disorder with multifactorial pathologies, including progressive loss of dopaminergic (DA) neurons, oxidative stress, mitochondrial dysfunction, and increased monoamine oxidase (MAO) enzyme activity. There are currently only a few agents approved to ameliorate the symptoms of PD; however, no agent is able to reverse the progression of the disease. Due to the multifactorial pathologies, it is necessary to develop multifunctional agents that can affect more than one target involved in the disease pathology. We have designed and synthesized a series of new multifunctional anti-Parkinson's compounds which can protect cerebral granular neurons from 1-methyl-4-phenylpyridinium (MPP+) insult, scavenge free radicals, and inhibit monoamine oxidase (MAO)/cholinesterase (ChE) activities. Among them, MT-20R exhibited the most potent MAO-B inhibition both in vitro and in vivo. We further investigated the neuroprotective effects of MT-20R using a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model. In vivo, MT-20R alleviated MPTP-induced motor deficits, raised the striatal contents of dopamine and its metabolites, and restored the expression of tyrosine hydroxylase (TH) and the number of TH-positive DA neurons in the substantia nigra. Additionally, MT-20R enhanced the expression of Bcl-2, decreased the expression of Bax and Caspase 3, and activated the AKT/Nrf2/HO-1 signaling pathway. These findings suggest that MT-20R may be a novel therapeutic candidate for treatment of PD. Title: Scallop genome provides insights into evolution of bilaterian karyotype and development Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B and Bao Z <42 more author(s)> Wang S, Zhang J, Jiao W, Li J, Xun X, Sun Y, Guo X, Huan P, Dong B, Zhang L, Hu X, Sun X, Wang J, Zhao C, Wang Y, Wang D, Huang X, Wang R, Lv J, Li Y, Zhang Z, Liu B, Lu W, Hui Y, Liang J, Zhou Z, Hou R, Li X, Liu Y, Li H, Ning X, Lin Y, Zhao L, Xing Q, Dou J, Mao J, Guo H, Dou H, Li T, Mu C, Jiang W, Fu Q, Fu X, Miao Y, Liu J, Yu Q, Li R, Liao H, Kong Y, Jiang Z, Chourrout D, Bao Z (- 42) Ref: Nat Ecol Evol, 1:120, 2017 : PubMed ESTHER: Wang_2017_Nat.Ecol.Evol_1_120 PubMedSearch: Wang 2017 Nat.Ecol.Evol 1 120 PubMedID: 28812685 Gene_locus related to this paper: mizye-a0a210qls6, mizye-a0a210qis3, mizye-a0a210qg00, mizye-a0a210ped6, mizye-a0a210q4h5, mizye-a0a210q4h9, mizye-a0a210q4j1, mizye-a0a210qf86, mizye-a0a210q332, mizye-a0a210pqn0, mizye-a0a210q7t5, mizye-a0a210pij5, mizye-a0a210qyk8, mizye-a0a210pwl7, mizye-a0a210q8u5, mizye-a0a210r5n9, mizye-a0a210qbv2, mizye-a0a210pu25, mizye-a0a210pek1, mizye-a0a210pul3, mizye-a0a210pum3, mizye-a0a210ptr6, mizye-a0a210ptq5, mizye-a0a210ptc4.1, mizye-a0a210ptc4.2, mizye-a0a210ptv1, mizye-a0a210ptv7, mizye-a0a210qgl6, mizye-a0a210qg90, mizye-a0a210ptq0, mizye-a0a210qg72, mizye-a0a210ptb1, mizye-a0a210pjd3, mizye-a0a210qg92, mizye-a0a210q8v2, mizye-a0a210qg93, mizye-a0a210q160.1, mizye-a0a210q160.2, mizye-a0a210qes4, mizye-a0a210pk25, mizye-a0a210q1b8, mizye-a0a210q110, mizye-a0a210r503, mizye-P021348901.1, mizye-P021348901.2 Abstract Reconstructing the genomes of bilaterian ancestors is central to our understanding of animal evolution, where knowledge from ancient and/or slow-evolving bilaterian lineages is critical. Here we report a high-quality, chromosome-anchored reference genome for the scallop Patinopecten yessoensis, a bivalve mollusc that has a slow-evolving genome with many ancestral features. Chromosome-based macrosynteny analysis reveals a striking correspondence between the 19 scallop chromosomes and the 17 presumed ancestral bilaterian linkage groups at a level of conservation previously unseen, suggesting that the scallop may have a karyotype close to that of the bilaterian ancestor. Scallop Hox gene expression follows a new mode of subcluster temporal co-linearity that is possibly ancestral and may provide great potential in supporting diverse bilaterian body plans. Transcriptome analysis of scallop mantle eyes finds unexpected diversity in phototransduction cascades and a potentially ancient Pax2/5/8-dependent pathway for noncephalic eyes. The outstanding preservation of ancestral karyotype and developmental control makes the scallop genome a valuable resource for understanding early bilaterian evolution and biology. Title: Sensitive inkjet printing paper-based colormetric strips for acetylcholinesterase inhibitors with indoxyl acetate substrate Wu Y, Sun Y, Xiao F, Wu Z, Yu R Ref: Talanta, 162:174, 2017 : PubMed ESTHER: Wu_2017_Talanta_162_174 PubMedSearch: Wu 2017 Talanta 162 174 PubMedID: 27837814 Abstract A new paper-based biosensing approach has been developed for sensitive and rapid detection of acetylcholinesterase (AChE) inhibitors. The biosensing zone of the paper strip is constructed with an inkjet printing method, and the biomolecule AChE is immobilized into two layers of biocompatible sol-gel-derived silica ink with a "sandwich" form. Indoxyl acetate (IDA) is used as a chromogenic substrate, which is colorless and can be catalytically hydrolyzed into blue-colored indigo dipolymer. When the enzymatic activity of AChE is inhibited after incubation with organophosphate pesticides (OPs), there is a decreased hydrolysis of IDA accompanying with a drop in color intensity. Paraoxon and trichlorfon are used as the representative OPs in the assay. Due to the low solubility and high molar absorption coefficient of the IDA dipolymer product, the paper-based strip can form a neat blue sensing zone and shows obviously improved sensitivity with a limit of detection (LOD) of 0.01ngmL-1 paraoxon and 0.04ngmL-1 trichlorfon (S/N=3) and the LODs for visual detection are 0.03ngmL-1 for paraoxon and 0.1ngmL-1 for trichlorfon comparing with the previously reported colorimetric methods. The concentrations of paraoxon in apple juice samples are also detected, and the results are in accord well with these results from high-performance liquid chromatography, showing great potential for on-site detection of OPs in practical application. The developed assay can be used to qualitatively and semiquantitatively estimate with naked eyes and quantitatively assess OPs through image analysis. Title: Effects of phoxim-induced hepatotoxicity on SD rats and the protection of vitamin E Zhang J, Song W, Sun Y, Shan A Ref: Environ Sci Pollut Res Int, 24:24916, 2017 : PubMed ESTHER: Zhang_2017_Environ.Sci.Pollut.Res.Int_24_24916 PubMedSearch: Zhang 2017 Environ.Sci.Pollut.Res.Int 24 24916 PubMedID: 28918601 Abstract Currently, public pay more attention to the adverse effect of organophosphate pesticides on human and animal health and on the environment in developing nations. Vitamin E may protect the hepatocyte and increase the function of liver. The study was to investigate the effects of phoxim-induced hepatotoxicity on Sprague Dawley (SD) rats and the protection of vitamin E. SD rats received by gavage 180 mg kg(-1) (per body weight) of phoxim, 200 mg kg(-1) (per body weight) of vitamin E, and phoxim + vitamin E. The results showed that exposure to phoxim elevated liver coefficient; glutamyl transpeptidase (GGT), aspartate aminotransferase, alkaline phosphatase, total bilirubin, total bile acid, and alanine aminotransferase in the serum; ROS in the liver; and the expression of p53, Bax, CYP2E1, ROS, caspase-9, caspase-8, and caspase-3, while phoxim caused a reduction of total protein, albumin, and cholinesterase in the serum; acetylcholinesterase, total antioxidant capacity, glutathione peroxidase, and glutathione in the liver; and the expression of Bcl-2. Vitamin E modified the phoxim-induced hepatotoxicity by reducing the GGT in the serum, malondialdehyde in the liver, and the expression of CYP2E1 significantly. There were no significant changes of globulin in the serum, the activity of catalase in the liver, as well as expression levels of Fas and Bad in the liver. Overall, subacute exposure to phoxim induced hepatic injury, oxidative stress damage, and cell apoptosis. Vitamin E modified phoxim-induced hepatotoxicity slightly. And, vitamin E minimized oxidative stress damage and ultrastructural changes in rat hepatocytes notably. Title: The sea cucumber genome provides insights into morphological evolution and visceral regeneration Zhang X, Sun L, Yuan J, Sun Y, Gao Y, Zhang L, Li S, Dai H, Hamel JF and Xiang J <21 more author(s)> Zhang X, Sun L, Yuan J, Sun Y, Gao Y, Zhang L, Li S, Dai H, Hamel JF, Liu C, Yu Y, Liu S, Lin W, Guo K, Jin S, Xu P, Storey KB, Huan P, Zhang T, Zhou Y, Zhang J, Lin C, Li X, Xing L, Huo D, Sun M, Wang L, Mercier A, Li F, Yang H, Xiang J (- 21) Ref: PLoS Biol, 15:e2003790, 2017 : PubMed ESTHER: Zhang_2017_PLoS.Biol_15_E2003790 PubMedSearch: Zhang 2017 PLoS.Biol 15 E2003790 PubMedID: 29023486 Gene_locus related to this paper: stija-a0a2g8k9s2, stija-a0a2g8ka54, stija-a0a2g8jd52, stija-a0a2g8l0w8 Abstract Apart from sharing common ancestry with chordates, sea cucumbers exhibit a unique morphology and exceptional regenerative capacity. Here we present the complete genome sequence of an economically important sea cucumber, A. japonicus, generated using Illumina and PacBio platforms, to achieve an assembly of approximately 805 Mb (contig N50 of 190 Kb and scaffold N50 of 486 Kb), with 30,350 protein-coding genes and high continuity. We used this resource to explore key genetic mechanisms behind the unique biological characters of sea cucumbers. Phylogenetic and comparative genomic analyses revealed the presence of marker genes associated with notochord and gill slits, suggesting that these chordate features were present in ancestral echinoderms. The unique shape and weak mineralization of the sea cucumber adult body were also preliminarily explained by the contraction of biomineralization genes. Genome, transcriptome, and proteome analyses of organ regrowth after induced evisceration provided insight into the molecular underpinnings of visceral regeneration, including a specific tandem-duplicated prostatic secretory protein of 94 amino acids (PSP94)-like gene family and a significantly expanded fibrinogen-related protein (FREP) gene family. This high-quality genome resource will provide a useful framework for future research into biological processes and evolution in deuterostomes, including remarkable regenerative abilities that could have medical applications. Moreover, the multiomics data will be of prime value for commercial sea cucumber breeding programs. Title: NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway Ai R, Sun Y, Guo Z, Wei W, Zhou L, Liu F, Hendricks DT, Xu Y, Zhao X Ref: Cancer Biol Ther, 17:943, 2016 : PubMed ESTHER: Ai_2016_Cancer.Biol.Ther_17_943 PubMedSearch: Ai 2016 Cancer.Biol.Ther 17 943 PubMedID: 27414086 Abstract N-myc down-regulated gene 1 (NDRG1) has been shown to regulate tumor growth and metastasis in various malignant tumors and also to be dysregulated in esophageal squamous cell carcinoma (ESCC). Here, we show that NDRG1 overexpression (91.9%, 79/86) in ESCC tumor tissues is associated with poor overall survival of esophageal cancer patients. When placed in stable transfectants of the KYSE 30 ESCC cell line generated by lentiviral transduction with the ectopic overexpression of NDRG1, the expression of transducin-like enhancer of Split 2 (TLE2) was decreased sharply, however beta-catenin was increased. Mechanistically, NDRG1 physically associates with TLE2 and beta-catenin to affect the Wnt pathway. RNA interference and TLE2 overexpression studies demonstrate that NDRG1 fails to active Wnt pathway compared with isogenic wild-type controls. Strikingly, NDRG1 overexpression induces the epithelial mesenchymal transition (EMT) through activating the Wnt signaling pathway in ESCC cells, decreased the expression of E-cadherin and enhanced the expression of Snail. Our study elucidates a mechanism of NDRG1-regulated Wnt pathway activation and EMT via affecting TLE2 and beta-catenin expression in esophageal cancer cells. This indicates a pro-oncogenic role for NDRG1 in esophageal cancer cells whereby it modulates tumor progression. Title: Identification of 4-aminoquinoline core for the design of new cholinesterase inhibitors Chen Y, Bian Y, Sun Y, Kang C, Yu S, Fu T, Li W, Pei Y, Sun H Ref: PeerJ, 4:e2140, 2016 : PubMed ESTHER: Chen_2016_PeerJ_4_e2140 PubMedSearch: Chen 2016 PeerJ 4 e2140 PubMedID: 27441112 Abstract Inhibition of acetylcholinesterase (AChE) using small molecules is still one of the most successful therapeutic strategies in the treatment of Alzheimer's disease (AD). Previously we reported compound T5369186 with a core of quinolone as a new cholinesterase inhibitor. In the present study, in order to identify new cores for the designing of AChE inhibitors, we screened different derivatives of this core with the aim to identify the best core as the starting point for further optimization. Based on the results, we confirmed that only 4-aminoquinoline (compound 04 and 07) had cholinesterase inhibitory effects. Considering the simple structure and high inhibitory potency against AChE, 4-aminoquinoline provides a good starting core for further designing novel multifunctional AChEIs. Title: Silibinin rescues learning and memory deficits by attenuating microglia activation and preventing neuroinflammatory reactions in SAMP8 mice Jin G, Bai D, Yin S, Yang Z, Zou D, Zhang Z, Li X, Sun Y, Zhu Q Ref: Neuroscience Letters, 629:256, 2016 : PubMed ESTHER: Jin_2016_Neurosci.Lett_629_256 PubMedSearch: Jin 2016 Neurosci.Lett 629 256 PubMedID: 27276653 Abstract Silibinin was reported to be effective in reversing the learning and memory deficits of several AD animal models. These improvements are thought to be regulated by various factors, including antioxidative stress, inhibition of acetylcholinesterase activity and Abeta aggregation. However, there are still no reports that demonstrate the effect of silibinin on microglia activation in vivo. Thus, in this study, we used the senescence-accelerated mouse (SAMP8) strain to test the effects of silibinin on behavioral impairments and microglia activation-induced neuroinflammation. Silibinin treatment significantly rescued memory deficits in novel object recognition test and Morris water maze test. Silibinin treatment significantly attenuated microglial activation; down-regulated the level of the proinflammatory cytokine IL-6, anti-inflammatory cytokine IL-4, and inflammation-associated proteins, iNOS and COX-2; and further modulated MAPK to protect neural cells. These results suggest that silibinin could be a potential candidate for the therapy of neurodegenerative disorders. Title: Design, synthesis and evaluation of novel dual monoamine-cholinesterase inhibitors as potential treatment for Alzheimer's disease Liu W, Lang M, Youdim MB, Amit T, Sun Y, Zhang Z, Wang Y, Weinreb O Ref: Neuropharmacology, 109:376, 2016 : PubMed ESTHER: Liu_2016_Neuropharmacol_109_376 PubMedSearch: Liu 2016 Neuropharmacol 109 376 PubMedID: 27318273 Inhibitor(s) related to this paper: MT-031 Abstract Current novel therapeutic approach suggests that multifunctional compounds with diverse biological properties and a single bioavailability and pharmacokinetic metabolism, will produce higher significant advantages in treatment of neurodegenerative diseases, such as Alzheimer's disease (AD). Based on this rational, a new class of cholinesterase (ChE)-monoamine oxidase (MAO) inhibitors were designed and synthesized by amalgamating the propargyl moiety of the irreversible selective MAO-B inhibitor, neuroprotective/neurorestorative anti-Parkinsonian drug, rasagiline, into the "N-methyl" position of the ChE inhibitor, anti-AD drug rivastigmine. Initially, we examined the MAO and ChE inhibitory effect of these novel compounds, MT series in vitro and in vivo. Among MT series, MT-031 exhibited higher potency as a dual MAO-A and ChE inhibitor compared to other compounds in acute-treated mice. Additionally, MT-031 was found to increase the striatal levels of dopamine (DA), serotonin (5-HT) and norepinephrine (NE), and prevent the metabolism of DA and 5-HT. Finally, we have demonstrated that MT-031 exerted neuroprotective effect against H2O2-induced neurotoxicity and reactive oxygen species generation in human neuroblastoma SH-SY5Y cells. These findings provide evidence that MT-031 is a potent brain permeable novel multifunctional, neuroprotective and MAO-A/ChE inhibitor, preserves in one molecule entity some of the beneficial properties of its parent drugs, rasagiline and rivastigmine, and thus may be indicated as novel therapeutic approach for AD. Title: Comparative transcriptome analyses of deltamethrin-susceptible and -resistant Culex pipiens pallens by RNA-seq Lv Y, Wang W, Hong S, Lei Z, Fang F, Guo Q, Hu S, Tian M, Liu B and Zhu C <5 more author(s)> Lv Y, Wang W, Hong S, Lei Z, Fang F, Guo Q, Hu S, Tian M, Liu B, Zhang D, Sun Y, Ma L, Shen B, Zhou D, Zhu C (- 5) Ref: Mol Genet Genomics, 291:309, 2016 : PubMed ESTHER: Lv_2016_Mol.Genet.Genomics_291_309 PubMedSearch: Lv 2016 Mol.Genet.Genomics 291 309 PubMedID: 26377942 Abstract The widespread and improper use of pyrethroid insecticides, such as deltamethrin, has resulted in the evolution of resistance in many mosquito species, including Culex pipiens pallens. With the development of high-throughput sequencing, it is possible to massively screen pyrethroid resistance-associated gene. In this study, we used Illumina-Solexa transcriptome sequencing to identify genes that are expressed differently in deltamethrin-susceptible and -resistant strains of Culex pipiens pallens as a critical knowledge base for further studies. A total of 4,961,197,620 base pairs and 55,124,418 reads were sequenced, mapped to the Culex quinquefasciatus genome and assembled into 17,679 known genes. We recorded 1826 significantly differentially expressed genes (DEGs). Among them, 1078 genes were up-regulated and 748 genes were down-regulated in the deltamethrin-resistant strain compared to -susceptible strain. These DEGs contained cytochrome P450 s, cuticle proteins, UDP-glucuronosyltransferases, lipases, serine proteases, heat shock proteins, esterases and others. Among the 1826 DEGs, we found that the transcriptional levels of CYP6AA9 in the laboratory populations was elevated as the levels of deltamethrin resistance increased. Moreover, the expression levels of the CYP6AA9 were significantly higher in the resistant strains than the susceptible strains in three different field populations. We further confirmed the association between the CYP6AA9 gene and deltamethrin resistance in mosquitoes by RNA interfering (RNAi). Altogether, we explored massive potential pyrethroid resistance-associated genes and demonstrated that CYP6AA9 participated in the pyrethroid resistance in mosquitoes. Title: Nitrous oxide emission by the non-denitrifying, nitrate ammonifier Bacillus licheniformis Sun Y, De Vos P, Heylen K Ref: BMC Genomics, 17:68, 2016 : PubMed ESTHER: Sun_2016_BMC.Genomics_17_68 PubMedSearch: Sun 2016 BMC.Genomics 17 68 PubMedID: 26786044 Gene_locus related to this paper: bacli-a0a0w8js59 Abstract BACKGROUND: Firmicutes have the capacity to remove excess nitrate from the environment via either denitrification, dissimilatory nitrate reduction to ammonium or both. The recent renewed interest in their nitrogen metabolism has revealed many interesting features, the most striking being their wide variety of dissimilatory nitrate reduction pathways. In the present study, nitrous oxide production from Bacillus licheniformis, a ubiquitous Gram-positive, spore-forming species with many industrial applications, is investigated. Title: Dual functional cholinesterase and MAO inhibitors for the treatment of Alzheimer's disease: synthesis, pharmacological analysis and molecular modeling of homoisoflavonoid derivatives Wang Y, Sun Y, Guo Y, Wang Z, Huang L, Li X Ref: J Enzyme Inhib Med Chem, 31:389, 2016 : PubMed ESTHER: Wang_2016_J.Enzyme.Inhib.Med.Chem_31_389 PubMedSearch: Wang 2016 J.Enzyme.Inhib.Med.Chem 31 389 PubMedID: 25798687 Abstract Because of the complexity of Alzheimer's disease (AD), the multi-target-directed ligand (MTDL) strategy is expected to provide superior effects for the treatment of AD, instead of the classic one-drug-one-target strategy. In this context, we focused on the design, synthesis and evaluation of homoisoflavonoid derivatives as dual acetyl cholinesterase (AChE) and monoamine oxidase (MAO-B) inhibitors. Among all the synthesized compounds, compound 10 provided a desired balance of AChE and hMAO-B inhibition activities, with IC50 value of 3.94 and 3.44 muM, respectively. Further studies revealed that compound 10 was a mixed-type inhibitor of AChE and an irreversible inhibitor of hMAO-B, which was also confirmed by molecular modeling studies. Taken together, the data indicated that 10 was a promising dual functional agent for the treatment of AD. Title: Display of fungal hydrophobin on the Pichia pastoris cell surface and its influence on Candida antarctica lipase B Wang P, He J, Sun Y, Reynolds M, Zhang L, Han S, Liang S, Sui H, Lin Y Ref: Applied Microbiology & Biotechnology, 100:5883, 2016 : PubMed ESTHER: Wang_2016_Appl.Microbiol.Biotechnol_100_5883 PubMedSearch: Wang 2016 Appl.Microbiol.Biotechnol 100 5883 PubMedID: 26969039 Abstract To modify the Pichia pastoris cell surface, two classes of hydrophobins, SC3 from Schizophyllum commune and HFBI from Trichoderma reesei, were separately displayed on the cell wall. There was an observable increase in the hydrophobicity of recombinant strains. Candida antarctica lipase B (CALB) was then co-displayed on the modified cells, generating strains GS115/SC3-61/CALB-51 and GS115/HFBI-61/CALB-51. Interestingly, the hydrolytic and synthetic activities of strain GS115/HFBI-61/CALB-51 increased by 37 and 109 %, respectively, but decreased by 26 and 43 %, respectively, in strain GS115/SC3-61/CALB-51 compared with the hydrophobin-minus recombinant strain GS115/CALB-GCW51. The amount of glycerol by-product from the transesterification reaction adsorbed on the cell surface was significantly decreased following hydrophobin modification, removing the glycerol barrier and allowing substrates to access the active sites of lipases. Electron micrographs indicated that the cell wall structures of both recombinant strains appeared altered, including changes to the inner glucan layer and outer mannan layer. These results suggest that the display of hydrophobins can change the surface structure and hydrophobic properties of P. pastoris and affect the catalytic activities of CALB displayed on the surface of P. pastoris cells. Title: Facilitating the Evolution of Esterase Activity from a Promiscuous Enzyme (Mhg) with Catalytic Functions of Amide Hydrolysis and Carboxylic Acid Perhydrolysis by Engineering the Substrate Entrance Tunnel Yan X, Wang J, Sun Y, Zhu J, Wu S Ref: Applied Environmental Microbiology, 82:6748, 2016 : PubMed ESTHER: Yan_2016_Appl.Environ.Microbiol_82_6748 PubMedSearch: Yan 2016 Appl.Environ.Microbiol 82 6748 PubMedID: 27613682 Gene_locus related to this paper: 9mico-e3svs0 Abstract Promiscuous enzymes are generally considered to be starting points in the evolution of offspring enzymes with more specific or even novel catalytic activities, which is the molecular basis of producing new biological functions. Mhg, a typical alpha/beta fold hydrolase, was previously reported to have both gamma-lactamase and perhydrolase activities. However, despite having high structural similarity to and sharing an identical catalytic triad with an extensively studied esterase from Pseudomonas fluorescens, this enzyme did not show any esterase activity. Molecular docking and sequence analysis suggested a possible role for the entry of the binding pocket in blocking the entrance tunnel, preventing the ester compounds from entering into the pocket. By engineering the entrance tunnel with only one or two amino acid substitutions, we successfully obtained five esterase variants of Mhg. The variants exhibited a very broad substrate acceptance, hydrolyzing not only the classical p-nitrophenol esters but also various types of chiral esters, which are widely used as drug intermediates. Site 233 at the entrance tunnel of Mhg was found to play a pivotal role in modulating the three catalytic activities by adjusting the size and shape of the tunnel, with different amino acid substitutions at this site facilitating different activities. Remarkably, the variant with the L233G mutation was a very specific esterase without any gamma-lactamase and perhydrolase activities. Considering the amino acid conservation and differentiation, this site could be a key target for future protein engineering. In addition, we demonstrate that engineering the entrance tunnel is an efficient strategy to regulate enzyme catalytic capabilities. IMPORTANCE: Promiscuous enzymes can act as starting points in the evolution of novel catalytic activities, thus providing a molecular basis for the production of new biological functions. In this study, we identified a critical amino acid residue (Leu233) at the entry of the substrate tunnel of a promiscuous enzyme, Mhg. We found that substitution of this residue with smaller amino acids such as Gly, Ala, Ser, or Pro endowed the enzyme with novel esterase activity. Different amino acids at this site can facilitate different catalytic activities. These findings exhibited universal significance in this subset of alpha/beta fold hydrolases, including Mhg. Furthermore, we demonstrate that engineering the entrance tunnel is an efficient strategy to evolve new enzyme catalytic capabilities. Our study has important implications for the regulation of enzyme catalytic promiscuity and development of protein engineering methodologies. Title: Using gastric juice lncRNA-ABHD11-AS1 as a novel type of biomarker in the screening of gastric cancer Yang Y, Shao Y, Zhu M, Li Q, Yang F, Lu X, Xu C, Xiao B, Sun Y, Guo J Ref: Tumour Biol, 37:1183, 2016 : PubMed ESTHER: Yang_2016_Tumour.Biol_37_1183 PubMedSearch: Yang 2016 Tumour.Biol 37 1183 PubMedID: 26280398 Gene_locus related to this paper: human-ABHD11 Abstract Long noncoding RNAs (lncRNAs) play vital roles in tumorigenesis. However, the diagnostic values of most lncRNAs are largely unknown. To investigate whether gastric juice lncRNA-ABHD11-AS1 can be a potential biomarker in the screening of gastric cancer, 173 tissue samples and 130 gastric juice from benign lesion, gastric dysplasia, gastric premalignant lesions, and gastric cancer were collected. ABHD11-AS1 levels were detected by reverse transcription-polymerase chain reaction. Then, the relationships between ABHD11-AS1 levels and clinicopathological factors of patients with gastric cancer were investigated. The results showed that ABHD11-AS1 levels in gastric cancer tissues were significantly higher than those in other tissues. Its levels in gastric juice from gastric cancer patients were not only significantly higher than those from cases of normal mucosa or minimal gastritis, atrophic gastritis, and gastric ulcers but also associated with gender, tumor size, tumor stage, Lauren type, and blood carcinoembryonic antigen (CEA) levels. More importantly, when using gastric juice ABHD11-AS1 as a marker, the positive detection rate of early gastric cancer patients was reached to 71.4 %. Thanks to the special origin of gastric juice, these results indicate that gastric juice ABHD11-AS1 may be a potential biomarker in the screening of gastric cancer. Title: DWARF14 is a non-canonical hormone receptor for strigolactone Yao R, Ming Z, Yan L, Li S, Wang F, Ma S, Yu C, Yang M, Chen L and Xie D <15 more author(s)> Yao R, Ming Z, Yan L, Li S, Wang F, Ma S, Yu C, Yang M, Chen L, Li Y, Yan C, Miao D, Sun Z, Yan J, Sun Y, Wang L, Chu J, Fan S, He W, Deng H, Nan F, Li J, Rao Z, Lou Z, Xie D (- 15) Ref: Nature, 536:469, 2016 : PubMed ESTHER: Yao_2016_Nature_536_469 PubMedSearch: Yao 2016 Nature 536 469 PubMedID: 27479325 Gene_locus related to this paper: arath-AtD14 Abstract Classical hormone receptors reversibly and non-covalently bind active hormone molecules, which are generated by biosynthetic enzymes, to trigger signal transduction. The alpha/beta hydrolase DWARF14 (D14), which hydrolyses the plant branching hormone strigolactone and interacts with the F-box protein D3/MAX2, is probably involved in strigolactone detection. However, the active form of strigolactone has yet to be identified and it is unclear which protein directly binds the active form of strigolactone, and in which manner, to act as the genuine strigolactone receptor. Here we report the crystal structure of the strigolactone-induced AtD14-D3-ASK1 complex, reveal that Arabidopsis thaliana (At)D14 undergoes an open-to-closed state transition to trigger strigolactone signalling, and demonstrate that strigolactone is hydrolysed into a covalently linked intermediate molecule (CLIM) to initiate a conformational change of AtD14 to facilitate interaction with D3. Notably, analyses of a highly branched Arabidopsis mutant d14-5 show that the AtD14(G158E) mutant maintains enzyme activity to hydrolyse strigolactone, but fails to efficiently interact with D3/MAX2 and loses the ability to act as a receptor that triggers strigolactone signalling in planta. These findings uncover a mechanism underlying the allosteric activation of AtD14 by strigolactone hydrolysis into CLIM, and define AtD14 as a non-canonical hormone receptor with dual functions to generate and sense the active form of strigolactone. Title: Insights into Adaptations to a Near-Obligate Nematode Endoparasitic Lifestyle from the Finished Genome of Drechmeria coniospora Zhang L, Zhou Z, Guo Q, Fokkens L, Miskei M, Pocsi I, Zhang W, Chen M, Wang L and Lin M <12 more author(s)> Zhang L, Zhou Z, Guo Q, Fokkens L, Miskei M, Pocsi I, Zhang W, Chen M, Wang L, Sun Y, Donzelli BG, Gibson DM, Nelson DR, Luo JG, Rep M, Liu H, Yang S, Wang J, Krasnoff SB, Xu Y, Molnar I, Lin M (- 12) Ref: Sci Rep, 6:23122, 2016 : PubMed ESTHER: Zhang_2016_Sci.Rep_6_23122 PubMedSearch: Zhang 2016 Sci.Rep 6 23122 PubMedID: 26975455 Gene_locus related to this paper: 9hypo-a0a151ga75, 9hypo-a0a151gbh5, 9hypo-a0a151gd50, 9hypo-a0a151ggb9, 9hypo-a0a151gjd5, 9hypo-a0a151gtv2, 9hypo-a0a151gxh2, 9hypo-a0a151gaw8, 9hypo-a0a151gia2 Abstract Nematophagous fungi employ three distinct predatory strategies: nematode trapping, parasitism of females and eggs, and endoparasitism. While endoparasites play key roles in controlling nematode populations in nature, their application for integrated pest management is hindered by the limited understanding of their biology. We present a comparative analysis of a high quality finished genome assembly of Drechmeria coniospora, a model endoparasitic nematophagous fungus, integrated with a transcriptomic study. Adaptation of D. coniospora to its almost completely obligate endoparasitic lifestyle led to the simplification of many orthologous gene families involved in the saprophytic trophic mode, while maintaining orthologs of most known fungal pathogen-host interaction proteins, stress response circuits and putative effectors of the small secreted protein type. The need to adhere to and penetrate the host cuticle led to a selective radiation of surface proteins and hydrolytic enzymes. Although the endoparasite has a simplified secondary metabolome, it produces a novel peptaibiotic family that shows antibacterial, antifungal and nematicidal activities. Our analyses emphasize the basic malleability of the D. coniospora genome: loss of genes advantageous for the saprophytic lifestyle; modulation of elements that its cohort species utilize for entomopathogenesis; and expansion of protein families necessary for the nematode endoparasitic lifestyle. Title: Lp-PLA2 Antagonizes Left Ventricular Healing After Myocardial Infarction by Impairing the Appearance of Reparative Macrophages He S, Chousterman BG, Fenn A, Anzai A, Nairz M, Brandt M, Hilgendorf I, Sun Y, Ye YX and Swirski FK <6 more author(s)> He S, Chousterman BG, Fenn A, Anzai A, Nairz M, Brandt M, Hilgendorf I, Sun Y, Ye YX, Iwamoto Y, Tricot B, Weissleder R, Macphee C, Libby P, Nahrendorf M, Swirski FK (- 6) Ref: Circ Heart Fail, 8:980, 2015 : PubMed ESTHER: He_2015_Circ.Heart.Fail_8_980 PubMedSearch: He 2015 Circ.Heart.Fail 8 980 PubMedID: 26232205 Abstract BACKGROUND: Healing after myocardial infarction (MI) involves the biphasic accumulation of inflammatory Ly-6C(high) and reparative Ly-6C(low) monocytes/macrophages. Excessive inflammation disrupts the balance between the 2 phases, impairs infarct healing, and contributes to left ventricle remodeling and heart failure. Lipoprotein-associated phospholipase A2 (Lp-PLA2), a member of the phospholipase A2 family of enzymes, produced predominantly by leukocytes, participates in host defenses and disease. Elevated Lp-PLA2 levels associate with increased risk of cardiovascular events across diverse patient populations, but the mechanisms by which the enzyme elicits its effects remain unclear. This study tested the role of Lp-PLA2 in healing after MI. METHODS AND Title: Critical thresholds of liver function parameters for ketosis prediction in dairy cows using receiver operating characteristic (ROC) analysis Sun Y, Wang B, Shu S, Zhang H, Xu C, Wu L, Xia C Ref: Vet Q, 35:159, 2015 : PubMed ESTHER: Sun_2015_Vet.Q_35_159 PubMedSearch: Sun 2015 Vet.Q 35 159 PubMedID: 25831953 Abstract BACKGROUND: Fatty liver syndrome and ketosis are important metabolic disorders in high-producing cows during early lactation with fatty liver usually preceding ketosis. To date, parameters for early prediction of the risk of ketosis have not been investigated in China. OBJECTIVE: To determine the predictive value of some parameters on the risk of ketosis in China. ANIMALS AND Title: Association of endothelial lipase gene-384A/C with coronary artery disease in Han Chinese people Xie L, Sun Y, Tong Y, Liu Y, Deng Y Ref: BMJ Open, 5:e007621, 2015 : PubMed ESTHER: Xie_2015_BMJ.Open_5_e007621 PubMedSearch: Xie 2015 BMJ.Open 5 e007621 PubMedID: 26124511 Gene_locus related to this paper: human-LIPG Abstract OBJECTIVES: The endothelial lipase gene (LIPG) is one of the important genes in the metabolism of high-density lipoprotein cholesterol (HDL-C) and may be involved in the pathogenesis of coronary artery disease (CAD). MATERIALS AND Title: Genome sequencing of adzuki bean (Vigna angularis) provides insight into high starch and low fat accumulation and domestication Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y and Wan P <17 more author(s)> Yang K, Tian Z, Chen C, Luo L, Zhao B, Wang Z, Yu L, Li Y, Sun Y, Li W, Chen Y, Zhang Y, Ai D, Zhao J, Shang C, Ma Y, Wu B, Wang M, Gao L, Sun D, Zhang P, Guo F, Wang W, Wang J, Varshney RK, Ling HQ, Wan P (- 17) Ref: Proc Natl Acad Sci U S A, 112:13213, 2015 : PubMed ESTHER: Yang_2015_Proc.Natl.Acad.Sci.U.S.A_112_13213 PubMedSearch: Yang 2015 Proc.Natl.Acad.Sci.U.S.A 112 13213 PubMedID: 26460024 Gene_locus related to this paper: phaan-a0a0l9ttq5, phaan-a0a0l9vh69, phaan-a0a0l9vh89, phaan-a0a0s3tc53, vigrr-a0a1s3v914, phaan-a0a0s3s998, phaan-a0a0s3siv8, phaan-a0a0l9uys5, phaan-a0a0s3rp07, phaan-a0a0s3rbq0, vigrr-a0a1s3tul4, phaan-a0a0s3smk7, phaan-a0a0s3slm9, phaan-a0a0l9ujf5, phaan-a0a0l9til9, phaan-a0a0l9uqr2, phaan-a0a0l9v1m8, phaan-a0a0l9uc60, phaan-a0a0l9ucr8 Abstract Adzuki bean (Vigna angularis), an important legume crop, is grown in more than 30 countries of the world. The seed of adzuki bean, as an important source of starch, digestible protein, mineral elements, and vitamins, is widely used foods for at least a billion people. Here, we generated a high-quality draft genome sequence of adzuki bean by whole-genome shotgun sequencing. The assembled contig sequences reached to 450 Mb (83% of the genome) with an N50 of 38 kb, and the total scaffold sequences were 466.7 Mb with an N50 of 1.29 Mb. Of them, 372.9 Mb of scaffold sequences were assigned to the 11 chromosomes of adzuki bean by using a single nucleotide polymorphism genetic map. A total of 34,183 protein-coding genes were predicted. Functional analysis revealed that significant differences in starch and fat content between adzuki bean and soybean were likely due to transcriptional abundance, rather than copy number variations, of the genes related to starch and oil synthesis. We detected strong selection signals in domestication by the population analysis of 50 accessions including 11 wild, 11 semiwild, 17 landraces, and 11 improved varieties. In addition, the semiwild accessions were illuminated to have a closer relationship to the cultigen accessions than the wild type, suggesting that the semiwild adzuki bean might be a preliminary landrace and play some roles in the adzuki bean domestication. The genome sequence of adzuki bean will facilitate the identification of agronomically important genes and accelerate the improvement of adzuki bean. Title: Genome Sequence of the epsilon-Poly-l-Lysine-Producing Strain Streptomyces albulus NK660, Isolated from Soil in Gutian, Fujian Province, China Gu Y, Yang C, Wang X, Geng W, Sun Y, Feng J, Wang Y, Quan Y, Che Y and Wang S <6 more author(s)> Gu Y, Yang C, Wang X, Geng W, Sun Y, Feng J, Wang Y, Quan Y, Che Y, Zhang C, Gong T, Zhang W, Gao W, Zuo Z, Song C, Wang S (- 6) Ref: Genome Announc, 2:e00532, 2014 : PubMed ESTHER: Gu_2014_Genome.Announc_2_e00532 PubMedSearch: Gu 2014 Genome.Announc 2 e00532 PubMedID: 24926050 Gene_locus related to this paper: stra9-a0a059w351 Abstract We determined the complete genome sequence of a soil bacterium, Streptomyces albulus NK660. It can produce epsilon-poly-l-lysine, which has antimicrobial activity against a spectrum of microorganisms. The genome of S. albulus NK660 contains a 9,360,281-bp linear chromosome and a 12,120-bp linear plasmid. Title: Discovery of indanone derivatives as multi-target-directed ligands against Alzheimer's disease Huang L, Miao H, Sun Y, Meng F, Li X Ref: Eur Journal of Medicinal Chemistry, 87C:429, 2014 : PubMed ESTHER: Huang_2014_Eur.J.Med.Chem_87C_429 PubMedSearch: Huang 2014 Eur.J.Med.Chem 87C 429 PubMedID: 25282266 Abstract A series of indanone derivatives were designed, synthesized, and tested using a variety of assays to assess their potential as anti-Alzheimer's disease (AD) agents. The investigations assessed the activities of the agents for the inhibition of cholinesterases (AChE and BCHE), the inhibition of amyloid beta (Abeta) self-assembly, and the catalysis of the disassembly of preformed Abeta oligomers and measured their antioxidant activities. Our results demonstrate that most of the synthesized compounds demonstrated good inhibitory activity against AChE with IC50 values in the nanomolar range. In particular, compounds 9 (IC50 = 14.8 nM) and 14 (IC50 = 18.6 nM) exhibited markedly higher inhibitory activities than tacrine and similar activities to donepezil. In addition, 9 and 14 significantly inhibited Abeta aggregation (inhibition rates of 85.5% and 83.8%, respectively), catalysed the disaggregation of Abeta fibrils generated by self-induced Abeta aggregation, and exhibited antioxidant activity. Furthermore, these two compounds can cross the blood-brain barrier (BBB) in vitro. These properties highlight the potential of these new compounds to be developed as multi-functional drugs for the treatment of Alzheimer's disease. Title: New multi-target-directed small molecules against Alzheimer's disease: a combination of resveratrol and clioquinol Mao F, Yan J, Li J, Jia X, Miao H, Sun Y, Huang L, Li X Ref: Org Biomol Chem, 12:5936, 2014 : PubMed ESTHER: Mao_2014_Org.Biomol.Chem_12_5936 PubMedSearch: Mao 2014 Org.Biomol.Chem 12 5936 PubMedID: 24986600 Abstract Alzheimer's disease (AD) is currently one of the most difficult and challenging diseases to treat. Based on the 'multi-target-directed ligands' (MTDLs) strategy, we designed and synthesised a series of new compounds against AD by combining the pharmacophores of resveratrol and clioquinol. The results of biological activity tests showed that the hybrids exhibited excellent MTDL properties: a significant ability to inhibit self-induced beta-amyloid (Abeta) aggregation and copper(II)-induced Abeta aggregation, potential antioxidant behaviour (ORAC-FL value of 0.9-3.2 Trolox equivalents) and biometal chelation. Among these compounds, (E)-5-(4-hydroxystyryl)quinoline-8-ol (10c) showed the most potent ability to inhibit self-induced Abeta aggregation (IC50 = 8.50 microM) and copper(II)-induced Abeta aggregation and to disassemble the well-structured Abeta fibrils generated by self- and copper(II)-induced Abeta aggregation. Note that 10c could also control Cu(I/II)-triggered hydroxyl radical (OH) production by halting copper redox cycling via metal complexation, as confirmed by a Cu-ascorbate redox system assay. Importantly, 10c did not show acute toxicity in mice at doses of up to 2000 mg kg1 and was able to cross the blood-brain barrier (BBB), according to a parallel artificial membrane permeation assay. These results indicate that compound 10c is a promising multifunctional compound for the development of novel drugs for AD. Title: Pegylation improves the pharmacokinetics and bioavailability of small-molecule drugs hydrolyzable by esterases: a study of phospho-Ibuprofen Mattheolabakis G, Wong CC, Sun Y, Amella CA, Richards R, Constantinides PP, Rigas B Ref: Journal of Pharmacology & Experimental Therapeutics, 351:61, 2014 : PubMed ESTHER: Mattheolabakis_2014_J.Pharmacol.Exp.Ther_351_61 PubMedSearch: Mattheolabakis 2014 J.Pharmacol.Exp.Ther 351 61 PubMedID: 25047517 Abstract Esterase hydrolysis of drugs can accelerate their elimination, thereby limiting their efficacy. Polyethylene glycol (PEG) covalently attached to drugs (pegylation) is known to improve the efficiency of many drugs. Using as a test agent the novel phospho-ibuprofen (PI), we examined whether pegylation of PI could abrogate its hydrolytic degradation by esterases; PI, known to inhibit colon cancer growth, has a carboxylic ester hydrolyzable by carboxylesterases (CES). We covalently attached mPEG-2000 to PI (PI-PEG) and studied its stability by exposing it to cells overexpressing CES and by administering it to mice. We also evaluated PI-PEG's anticancer efficacy in human colon cancer xenografts and in Apc(min/+) mice. PI-PEG was stable in the presence of cells overexpressing CES1 or CES2, whereas PI was extensively hydrolyzed (90.2 +/- 0.7%, 14.3 +/- 1.1%, mean +/- S.E.M.). In mice, PI was nearly completely hydrolyzed. Intravenous administration of PI-PEG resulted in significant levels in blood and in colon cancer xenografts (xenograft values in parentheses): area under the curve for 0-24 hours = 2351 (2621) (nmol/g) x h; Cmax = 1965 (886) nmol/g; Tmax = 0.08 (2) hour. The blood levels of ibuprofen, its main hydrolytic product, were minimal. Compared with controls, PI-PEG inhibited the growth of the xenografts by 74.8% (P < 0.01) and reduced intestinal tumor multiplicity in Apc(min/+) mice by 73.1% (P < 0.01), prolonging their survival (100% versus 55.1% of controls; P = 0.013). Pegylation protects PI from esterase hydrolysis and improves its pharmacokinetics. In preclinical models of colon cancer, PI-PEG is a safe and efficacious agent that merits further evaluation. Title: The treatment of Alzheimer's disease using Chinese Medicinal Plants: From disease models to potential clinical applications Su Y, Wang Q, Wang C, Chan K, Sun Y, Kuang H Ref: J Ethnopharmacol, 152:403, 2014 : PubMed ESTHER: Su_2014_J.Ethnopharmacol_152_403 PubMedSearch: Su 2014 J.Ethnopharmacol 152 403 PubMedID: 24412377 Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease (AD) is characterized by the sustained higher nervous disorders of the activities and functions of the brain. Due to its heavy burden on society and the patients' families, it is urgent to review the treatments for AD to provide basic data for further research and new drug development. Among these treatments, Chinese Material Medica (CMM) has been traditionally clinical used in China to treat AD for a long time with obvious efficacy. With the further research reports of CMM, new therapeutic materials may be recovered from troves of CMM. However, So far, little or no review work has been reported to conclude anti-AD drugs from CMM in literature. Therefore, a systematic introduction of CMM anti-AD research progress is of great importance and necessity. This paper strives to systematically describe the progress of CMM in the treatment of AD, and lays a basis data for anti-AD drug development from CMM, and provides the essential theoretical support for the further development and utilization of CMM resources through a more comprehensive research of the variety of databases regarding CMM anti-AD effects reports. MATERIAL AND Title: A Platform for Screening Potential Anticholinesterase Fractions and Components Obtained from Anemarrhena asphodeloides Bge for Treating Alzheimer's Disease Sun Y, Peng Y, Li LG, Zheng LW, Lin DJ, Li LZ, Song SJ Ref: Evid Based Complement Alternat Med, 2014:524650, 2014 : PubMed ESTHER: Sun_2014_Evid.Based.Complement.Alternat.Med_2014_524650 PubMedSearch: Sun 2014 Evid.Based.Complement.Alternat.Med 2014 524650 PubMedID: 24864153 Abstract Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. Cholinesterase inhibitors are widely used for the symptomatic treatment of Alzheimer's disease to enhance central cholinergic transmission. In this study, a bioactivity-oriented screening platform based on a modified Ellman's method and HPLC-QTOF MS technique was developed to rapidly screen active agents of Anemarrhena asphodeloides Bge. The 60% ethanol fraction from an ethyl acetate extract exhibited the most potential anticholinesterase activity. Fifteen steroid saponins were identified by the mass spectrum, standards and literature reports. Twenty-five compounds were isolated from the active fraction. The results showed that compounds with the C6-C3-C6 skeleton probably had both AChE and BCHE inhibitory activities. Xanthone and benzene derivatives exhibited no or little activity. Lignans showed weak BCHE inhibitory activity. The steroidal saponins demonstrated moderate or weak AChE inhibitory activity. Title: Molecular Basis of the General Base Catalysis of an alpha/beta-Hydrolase Catalytic Triad Sun Y, Yin S, Feng Y, Li J, Zhou J, Liu C, Zhu G, Guo Z Ref: Journal of Biological Chemistry, 289:15867, 2014 : PubMed ESTHER: Sun_2014_J.Biol.Chem_289_15867 PubMedSearch: Sun 2014 J.Biol.Chem 289 15867 PubMedID: 24737327 Gene_locus related to this paper: ecoli-YFBB Inhibitor(s) related to this paper: SHCHC Abstract The serine-histidine-aspartate triad is well known for its covalent, nucleophilic catalysis in a diverse array of enzymatic transformations. Here we show that its nucleophilicity is shielded and its catalytic role is limited to being a specific general base by an open-closed conformational change in the catalysis of (1R,6R)-2-succinyl-6-hydroxy-2,4-cyclohexadiene-1-carboxylate synthase (or MenH), a typical alpha/beta-hydrolase fold enzyme in the vitamin K biosynthetic pathway. This enzyme is found to adopt an open conformation without a functional triad in its ligand-free form and a closed conformation with a fully functional catalytic triad in the presence of its reaction product. The open-to-closed conformational transition involves movement of half of the alpha-helical cap domain, which causes extensive structural changes in the alpha/beta-domain and forces the side chain of the triad histidine to adopt an energetically disfavored gauche conformation to form the functional triad. NMR analysis shows that the inactive open conformation without a triad prevails in ligand-free solution and is converted to the closed conformation with a properly formed triad by the reaction product. Mutation of the residues crucial to this open-closed transition either greatly decreases or completely eliminates the enzyme activity, supporting an important catalytic role for the structural change. These findings suggest that the open-closed conformational change tightly couples formation of the catalytic triad to substrate binding to enhance the substrate specificities and simultaneously shield the nucleophilicity of the triad, thus allowing it to expand its catalytic power beyond the nucleophilic catalysis. Title: Reversal of advanced disease in lysosomal acid lipase deficient mice: a model for lysosomal acid lipase deficiency disease Sun Y, Xu YH, Du H, Quinn B, Liou B, Stanton L, Inskeep V, Ran H, Jakubowitz P and Grabowski GA <1 more author(s)> Sun Y, Xu YH, Du H, Quinn B, Liou B, Stanton L, Inskeep V, Ran H, Jakubowitz P, Grilliot N, Grabowski GA (- 1) Ref: Mol Genet Metab, 112:229, 2014 : PubMed ESTHER: Sun_2014_Mol.Genet.Metab_112_229 PubMedSearch: Sun 2014 Mol.Genet.Metab 112 229 PubMedID: 24837159 Gene_locus related to this paper: mouse-1llip Abstract Lysosomal acid lipase (LAL) is an essential enzyme that hydrolyzes triglycerides (TG) and cholesteryl esters (CE) in lysosomes. Mutations of the LIPA gene lead to Wolman disease (WD) and cholesterol ester storage disease (CESD). The disease hallmarks include hepatosplenomegaly and extensive storage of CE and/or TG. The effects of intravenous investigational enzyme therapy (ET) on survival and efficacy were evaluated in Lipa knock out, lal-/- mice with advanced disease using recombinant human LAL (rhLAL). Comparative ET was conducted with lower doses (weekly, 0.8 and 3.2mg/kg) beginning at 16 weeks (study 1), and with higher dose (10mg/kg) in early (8-weeks), middle (16-weeks) and late (24-weeks) disease stages (study 2). In study 1, rhLAL extended the life span of lal-/- mice in a dose dependent manner by 52 (0.8 mg/kg) or 94 (3.2mg/kg) days. This was accompanied by partial correction of cholesterol and TG levels in spleen and liver. In study 2, the high dose resulted in a significant improvement in organ size (liver, spleen and small intestine) and tissue histology as well as significant decreases in cholesterol and TG in all three groups. In the treated livers and spleens the cholesterol and TG levels were reduced to below treatment initiation levels indicating a reversal of disease manifestations, even in advanced disease. ET diminished liver fibrosis and macrophage proliferation. These results show that LAL deficiency can be improved biochemically and histopathologically by various dosages of ET, even in advanced disease. Title: Mudskipper genomes provide insights into the terrestrial adaptation of amphibious fishes You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W and Shi Q <31 more author(s)> You X, Bian C, Zan Q, Xu X, Liu X, Chen J, Wang J, Qiu Y, Li W, Zhang X, Sun Y, Chen S, Hong W, Li Y, Cheng S, Fan G, Shi C, Liang J, Tom Tang Y, Yang C, Ruan Z, Bai J, Peng C, Mu Q, Lu J, Fan M, Yang S, Huang Z, Jiang X, Fang X, Zhang G, Zhang Y, Polgar G, Yu H, Li J, Liu Z, Ravi V, Coon SL, Yang H, Venkatesh B, Shi Q (- 31) Ref: Nat Commun, 5:5594, 2014 : PubMed ESTHER: You_2014_Nat.Commun_5_5594 PubMedSearch: You 2014 Nat.Commun 5 5594 PubMedID: 25463417 Gene_locus related to this paper: 9gobi-a0a3b4bh68, 9gobi-a0a3b4bmj6, 9gobi-a0a3b4alj9, 9gobi-a0a3b4biy6, 9gobi-a0a3b4ah01, 9gobi-a0a3b3z8m7, 9gobi-a0a3b4aaj5, 9gobi-a0a3b4b6y7 Abstract Mudskippers are amphibious fishes that have developed morphological and physiological adaptations to match their unique lifestyles. Here we perform whole-genome sequencing of four representative mudskippers to elucidate the molecular mechanisms underlying these adaptations. We discover an expansion of innate immune system genes in the mudskippers that may provide defence against terrestrial pathogens. Several genes of the ammonia excretion pathway in the gills have experienced positive selection, suggesting their important roles in mudskippers' tolerance to environmental ammonia. Some vision-related genes are differentially lost or mutated, illustrating genomic changes associated with aerial vision. Transcriptomic analyses of mudskippers exposed to air highlight regulatory pathways that are up- or down-regulated in response to hypoxia. The present study provides a valuable resource for understanding the molecular mechanisms underlying water-to-land transition of vertebrates. Title: Genome sequence of Anopheles sinensis provides insight into genetics basis of mosquito competence for malaria parasites Zhou D, Zhang D, Ding G, Shi L, Hou Q, Ye Y, Xu Y, Zhou H, Xiong C and Zhu C <12 more author(s)> Zhou D, Zhang D, Ding G, Shi L, Hou Q, Ye Y, Xu Y, Zhou H, Xiong C, Li S, Yu J, Hong S, Yu X, Zou P, Chen C, Chang X, Wang W, Lv Y, Sun Y, Ma L, Shen B, Zhu C (- 12) Ref: BMC Genomics, 15:42, 2014 : PubMed ESTHER: Zhou_2014_BMC.Genomics_15_42 PubMedSearch: Zhou 2014 BMC.Genomics 15 42 PubMedID: 24438588 Gene_locus related to this paper: anoga-Q7PVF9, 9dipt-a0a084vlt1, 9dipt-a0a084vdq2, 9dipt-sime3xf.a, 9dipt-sime3xf.b, 9dipt-a0a084vbj8, 9dipt-a0a084wan7, 9dipt-a0a084wik4, 9dipt-a0a084wk64, 9dipt-a0a084wez8, 9dipt-a0a084vji7, 9dipt-a0a084vlc2, 9dipt-a0a084vsa5, 9dipt-a0a084wlk0, 9dipt-a0a084wah8, 9dipt-a0a084wln4, 9dipt-a0a084we78, 9dipt-a0a084wjm6, 9dipt-a0a084wjm7, 9dipt-a0a084we77, 9dipt-a0a084wlk1, 9dipt-a0a084we80, 9dipt-a0a084wjm4, 9dipt-a0a084w1n7, 9dipt-a0a084we79, 9dipt-a0a084wev9, 9dipt-a0a084vlc3, 9dipt-a0a084vdq4, 9dipt-a0a084vdq5, 9dipt-a0a084vdq1, 9dipt-a0a084wah9, 9dipt-a0a084wan6, 9dipt-a0a084wlj8, 9dipt-a0a084wk45, 9dipt-a0a084wk46, 9dipt-a0a084wlj9, 9dipt-a0a084vsa4, 9dipt-a0a084vs93, 9dipt-a0a084wl93, anosi-a0a0f7kyf5, anosi-a0a0f7l1f2, anosi-a0a084wum0, anost-a0a182xxz0, anosi-a0a084vn28, anosi-a0a084vpt0, anoga-q7q887 Abstract BACKGROUND: Anopheles sinensis is an important mosquito vector of Plasmodium vivax, which is the most frequent and widely distributed cause of recurring malaria throughout Asia, and particularly in China, Korea, and Japan. Title: Pharmacokinetic evaluation of the anticancer prodrug simmitecan in different experimental animals Hu ZY, Li XX, Du FF, Yang JL, Niu W, Xu F, Wang FQ, Li C, Sun Y Ref: Acta Pharmacol Sin, 34:1437, 2013 : PubMed ESTHER: Hu_2013_Acta.Pharmacol.Sin_34_1437 PubMedSearch: Hu 2013 Acta.Pharmacol.Sin 34 1437 PubMedID: 24056706 Abstract Aim:To investigate the pharmacokinetics and disposition of simmitecan (L-P) that was a water-soluble ester prodrug of chimmitecan (L-2-Z) with potent anti-tumor activities in different experimental animals, and to assess its drug-drug interaction potential.Methods:SD rats were injected with a single iv bolus doses of L-P (3.75, 7.5 and 15 mg/kg). The pharmacokinetics, tissue distribution, excretion and metabolism of L-P and its active metabolite L-2-Z were studied through quantitative measurements and metabolite profiling with LC/MS. The binding of L-P and L-2-Z to rat plasma proteins was examined using an ultrafiltration method. Systemic exposures of beagle dogs to L-P as well as drug distribution in tumors of the nude mice xenograft model of human hepatic cancer SMMC-7721 cells were also examined. The metabolism of L-P by liver mcirosomal carboxylesterase in vitro was investigated in different species. The effects of L-P and L-2-Z on cytochrome P450 enzymes were examined using commercial screening kits.Results:The in vivo biotransformation of L-P to L-2-Z showed a significant species difference, with a mean elimination half-life t1/2 of approximately 1.4 h in rats and 1.9 h in dogs. The systemic exposure levels of L-P and L-2-Z were increased in a dose-dependent manner. In rats, approximately 66% of L-P and 79% of L-2-Z were bound to plasma proteins. In rats and the nude mice bearing human hepatic cancers, most organ tissues had significantly higher concentrations of L-P than the corresponding plasma levels. In the tumor tissues, the L-P levels were comparable to those of plasma, whereas the L-2-Z levels were lower than the L-P levels. In rats, L-P was eliminated mainly via biliary excretion, but metabolism played an important role in elimination of the intact L-P. Finally, L-P and L-2-Z exerted moderate inhibition on the activity of CYP3A4 in vitro.Conclusion:L-P and L-2-Z have relatively short elimination half-lives and L-P is mainly eliminated via biliary excretion. The species difference in the conversion of L-P to L-2-Z and potential drug-drug interactions due to inhibition of CYP3A4 should be considered in further studies. Title: Synthesis and Evaluation of Multi-Target-Directed Ligands against Alzheimer's Disease Based on the Fusion of Donepezil and Ebselen Luo Z, Sheng J, Sun Y, Lu C, Yan J, Liu A, Luo HB, Huang L, Li X Ref: Journal of Medicinal Chemistry, 56:9089, 2013 : PubMed ESTHER: Luo_2013_J.Med.Chem_56_9089 PubMedSearch: Luo 2013 J.Med.Chem 56 9089 PubMedID: 24160297 Inhibitor(s) related to this paper: Selenepezil, Ebselen Abstract A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 muM for Electrophorus electricus acetylcholinesterase and 0.097 muM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 muM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (nu0 = 123.5 muM min(-1)), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system. Title: Genome analysis reveals insights into physiology and longevity of the Brandt's bat Myotis brandtii Seim I, Fang X, Xiong Z, Lobanov AV, Huang Z, Ma S, Feng Y, Turanov AA, Zhu Y and Gladyshev VN <19 more author(s)> Seim I, Fang X, Xiong Z, Lobanov AV, Huang Z, Ma S, Feng Y, Turanov AA, Zhu Y, Lenz TL, Gerashchenko MV, Fan D, Hee Yim S, Yao X, Jordan D, Xiong Y, Ma Y, Lyapunov AN, Chen G, Kulakova OI, Sun Y, Lee SG, Bronson RT, Moskalev AA, Sunyaev SR, Zhang G, Krogh A, Wang J, Gladyshev VN (- 19) Ref: Nat Commun, 4:2212, 2013 : PubMed ESTHER: Seim_2013_Nat.Commun_4_2212 PubMedSearch: Seim 2013 Nat.Commun 4 2212 PubMedID: 23962925 Gene_locus related to this paper: myobr-s7mf99, myobr-s7n4r2, myobr-s7neb7, myobr-s7ney7, myobr-s7n9l2, myobr-s7nk13, myobr-s7mh20, myobr-s7pbt8, myobr-s7mux2, myobr-s7mjb5, myobr-s7n6x5, myobr-s7nnt6, myobr-s7n728.2, myobr-s7n728.3, myobr-s7n8d2, myobr-s7nqw0, myobr-s7mju4, myolu-g1nth4, myobr-s7mij5, myobr-s7pr94, myolu-g1q4e3, myolu-g1p353 Abstract Bats account for one-fifth of mammalian species, are the only mammals with powered flight, and are among the few animals that echolocate. The insect-eating Brandt's bat (Myotis brandtii) is the longest-lived bat species known to date (lifespan exceeds 40 years) and, at 4-8 g adult body weight, is the most extreme mammal with regard to disparity between body mass and longevity. Here we report sequencing and analysis of the Brandt's bat genome and transcriptome, which suggest adaptations consistent with echolocation and hibernation, as well as altered metabolism, reproduction and visual function. Unique sequence changes in growth hormone and insulin-like growth factor 1 receptors are also observed. The data suggest that an altered growth hormone/insulin-like growth factor 1 axis, which may be common to other long-lived bat species, together with adaptations such as hibernation and low reproductive rate, contribute to the exceptional lifespan of the Brandt's bat. Title: Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine-Homoisoflavonoid hybrids Sun Y, Chen J, Chen X, Huang L, Li X Ref: Bioorganic & Medicinal Chemistry, 21:7406, 2013 : PubMed ESTHER: Sun_2013_Bioorg.Med.Chem_21_7406 PubMedSearch: Sun 2013 Bioorg.Med.Chem 21 7406 PubMedID: 24128814 Abstract A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases (MAOs). Most of the compounds were found to be potent against both ChEs and MAO-B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent against AChE and MAO-B with IC50 values of 67.9nM and 0.401muM, respectively. This compound was observed to cross the blood-brain barrier (BBB) in a parallel artificial membrane permeation assay for the BBB (PAMPA-BBB). The results indicated that compound 8b is an excellent multifunctional promising compound for development of novel drugs for Alzheimer's disease (AD). Title: Cell debris self-immobilized thermophilic lipase: a biocatalyst for synthesizing aliphatic polyesters Sun Y, Yang Y, Wang C, Liu J, Shi W, Zhu X, Lu L, Li Q Ref: Appl Biochem Biotechnol, 170:399, 2013 : PubMed ESTHER: Sun_2013_Appl.Biochem.Biotechnol_170_399 PubMedSearch: Sun 2013 Appl.Biochem.Biotechnol 170 399 PubMedID: 23536248 Abstract The paper explored the catalytic activity of a cell debris self-immobilized thermophilic lipase for polyester synthesis, using the ring-opening polymerization of sigma-caprolactone as model. Effects of biocatalyst concentration, temperature, and reaction medium on monomer conversion and product molecular weight were systematically evaluated. The biocatalyst displayed high catalytic activity at high temperatures (70-90 degreesC), with 100 % monomer conversion. High monomer conversion values (>90 %) were achieved in both hydrophobic and hydrophilic solvents, and also in solvent-free system, with the exception of dichloromethane. Poly(sigma-caprolactone) was obtained in 100 % monomer conversion, with a number-average molecular weight of 1,680 g/mol and a polydispersity index of 1.35 in cyclohexane at 70 degreesC for 72 h. Furthermore, the biocatalyst exhibited excellent operational stability, with monomer conversion values exceeding 90 % over the course of 15 batch reactions. Title: CHRNA7 Polymorphisms and Response to Cholinesterase Inhibitors in Alzheimer's Disease Weng PH, Chen JH, Chen TF, Sun Y, Wen LL, Yip PK, Chu YM, Chen YC Ref: PLoS ONE, 8:e84059, 2013 : PubMed ESTHER: Weng_2013_PLoS.One_8_e84059 PubMedSearch: Weng 2013 PLoS.One 8 e84059 PubMedID: 24391883 Abstract BACKGROUND: CHRNA7 encodes the alpha7 nicotinic acetylcholine receptor subunit, which is important to Alzheimer's disease (AD) pathogenesis and cholinergic neurotransmission. Previously, CHRNA7 polymorphisms have not been related to cholinesterase inhibitors (ChEI) response. Title: Choline acetate enhanced the catalytic performance of Candida rogusa lipase in AOT reverse micelles Xue L, Zhao Y, Yu L, Sun Y, Yan K, Li Y, Huang X, Qu Y Ref: Colloids Surf B Biointerfaces, 105C:81, 2013 : PubMed ESTHER: Xue_2013_Colloids.Surf.B.Biointerfaces_105C_81 PubMedSearch: Xue 2013 Colloids.Surf.B.Biointerfaces 105C 81 PubMedID: 23352950 Abstract Choline acetate is an ionic liquid composed of a kosmotropic anion and a chaotropic cation. According to Hofmeister series, a kosmotropic anion and/or a chaotropic cation could stabilize an enzyme, thereby facilitating the retention of the catalytic activity of the enzyme. In this work, we first report the influence of choline acetate on the activity and stability of lipase in AOT/water/isooctane reverse micelles. The indicator reaction is the lipase-catalyzed hydrolysis of 4-nitrophenyl butyrate. The results show that a low level of choline acetate does not affect the microstructure of the AOT reverse micelles, but the ionic liquid can improve the catalytic efficiency of lipase. Fluorescence spectra show that a high level of choline acetate has an impact on the conformation of lipase, so the activation is mainly due to the influence of choline acetate on the nucleophilicity of water. Infrared spectra demonstrate that choline acetate can form stronger hydrogen bonds with water surrounding lipase, and therefore enhance the nucleophilicity of the water, which makes it easier to attack the acyl enzyme intermediate, thereby increasing the activity of the lipase-catalyzed hydrolysis of the ester. A study on the stability of lipase in AOT reverse micelles indicates that the ionic liquid is able to maintain the activity of lipase to a certain extent. The effect of choline acetate is consistent with that predicted based on Hofmeister series. Title: [Expression and molecular evolution of recombinant acetylcholinesterase for detection of pesticide residues: a review] Dong J, Li Z, Lei H, He Y, Wang H, Sun Y Ref: Sheng Wu Gong Cheng Xue Bao, 28:557, 2012 : PubMed ESTHER: Dong_2012_Sheng.Wu.Gong.Cheng.Xue.Bao_28_557 PubMedSearch: Dong 2012 Sheng.Wu.Gong.Cheng.Xue.Bao 28 557 PubMedID: 22916494 Abstract Acetylcholinesterase (AChE) plays a key role in the pesticide determination. However, the extraction of AChE from natural materials has the disadvantages of low yield, complex purification and poor stability. Therefore, the preparation of recombinant AChE with high performance becomes the hot topic of researchers in recent years. In this article we summarize the progress in the expression of recombinant AChE and the improvement of its analytical characteristic. Finally, we point out that the directed evolution strategy combined with surface display technology is the future trend on improving recombinant AChE activity. Title: Examining the interactome of huperzine A by magnetic biopanning Guo W, Liu S, Peng J, Wei X, Sun Y, Qiu Y, Gao G, Wang P, Xu Y Ref: PLoS ONE, 7:e37098, 2012 : PubMed ESTHER: Guo_2012_PLoS.One_7_e37098 PubMedSearch: Guo 2012 PLoS.One 7 e37098 PubMedID: 22615909 Abstract Huperzine A is a bioactive compound derived from traditional Chinese medicine plant Qian Ceng Ta (Huperzia serrata), and was found to have multiple neuroprotective effects. In addition to being a potent acetylcholinesterase inhibitor, it was thought to act through other mechanisms such as antioxidation, antiapoptosis, etc. However, the molecular targets involved with these mechanisms were not identified. In this study, we attempted to exam the interactome of Huperzine A using a cDNA phage display library and also mammalian brain tissue extracts. The drugs were chemically linked on the surface of magnetic particles and the interactive phages or proteins were collected and analyzed. Among the various cDNA expressing phages selected, one was identified to encode the mitochondria NADH dehydrogenase subunit 1. Specific bindings between the drug and the target phages and target proteins were confirmed. Another enriched phage clone was identified as mitochondria ATP synthase, which was also panned out from the proteome of mouse brain tissue lysate. These data indicated the possible involvement of mitochondrial respiratory chain matrix enzymes in Huperzine A's pharmacological effects. Such involvement had been suggested by previous studies based on enzyme activity changes. Our data supported the new mechanism. Overall we demonstrated the feasibility of using magnetic biopanning as a simple and viable method for investigating the complex molecular mechanisms of bioactive molecules. Title: RNA interference of two acetylcholinesterase genes in Plutella xylostella reveals their different functions He G, Sun Y, Li F Ref: Archives of Insect Biochemistry & Physiology, 79:75, 2012 : PubMed ESTHER: He_2012_Arch.Insect.Biochem.Physiol_79_75 PubMedSearch: He 2012 Arch.Insect.Biochem.Physiol 79 75 PubMedID: 22392769 Abstract Acetylcholinesterase (AChE, EC 3.1.1.7) is an important enzyme with a typical function of degrading the neurotransmitter acetylcholine. Although two ace genes were reported in Plutella xylostella, their function differences remain largely unknown. The chemically synthesized siRNAs (si-Pxace1 and si-Pxace2) were injected into the second instar larvae to knock down Pxace1 and Pxace2, either respectively or simultaneously. The mRNA abundance of Pxace1 and Pxace2 was significantly reduced to 7-33.5% of the control levels at 72 h after siRNA injection. The AChE activities were significantly decreased at 96 h after treatment. Silencing of Pxace1 or Pxace2 resulted in mortality of 33.9 and 22.9%, respectively. The survivors in siRNA-treated groups had apparent growth inhibition such as reduction in larvae weights and lengths, malformation and motor retardation. Knockdown of Pxace1 apparently affected more on larvae growth than that of Pxace2, suggesting that Pxace1 had more important roles than Pxace2. Both Pxace1 and Pxace2 genes might have atypical functions in regulating larvae growth and motor ability. Title: Inhibition of cholinesterase activity and amyloid aggregation by berberine-phenyl-benzoheterocyclic and tacrine-phenyl-benzoheterocyclic hybrids Huang L, Su T, Shan W, Luo Z, Sun Y, He F, Li X Ref: Bioorganic & Medicinal Chemistry, 20:3038, 2012 : PubMed ESTHER: Huang_2012_Bioorg.Med.Chem_20_3038 PubMedSearch: Huang 2012 Bioorg.Med.Chem 20 3038 PubMedID: 22472046 Inhibitor(s) related to this paper: Berberine Abstract A series of berberine-phenyl-benzoheterocyclic (26-29) and tacrine-phenyl-benzoheterocyclic hybrids (44-46) were synthesised and evaluated as multifunctional anti-Alzheimer's disease agents. Compound 44b, tacrine linked with phenyl-benzothiazole by 3-carbon spacers, was the most potent AChE inhibitor with an IC(50) value of 0.017 muM. This compound demonstrated similar Abeta aggregation inhibitory activity with cucurmin (51.8% vs 52.1% at 20 muM, respectively), indicating that this hybrid is an excellent multifunctional drug candidate for AD. Title: Genome sequences of wild and domestic bactrian camels Jirimutu, Wang Z, Ding G, Chen G, Sun Y, Sun Z, Zhang H, Wang L, Hasi S and Meng H <57 more author(s)> Jirimutu, Wang Z, Ding G, Chen G, Sun Y, Sun Z, Zhang H, Wang L, Hasi S, Zhang Y, Li J, Shi Y, Xu Z, He C, Yu S, Li S, Zhang W, Batmunkh M, Ts B, Narenbatu, Unierhu, Bat-Ireedui S, Gao H, Baysgalan B, Li Q, Jia Z, Turigenbayila, Subudenggerile, Narenmanduhu, Wang J, Pan L, Chen Y, Ganerdene Y, Dabxilt, Erdemt, Altansha, Altansukh, Liu T, Cao M, Aruuntsever, Bayart, Hosblig, He F, Zha-ti A, Zheng G, Qiu F, Zhao L, Zhao W, Liu B, Li C, Tang X, Guo C, Liu W, Ming L, Temuulen, Cui A, Li Y, Gao J, Wurentaodi, Niu S, Sun T, Zhai Z, Zhang M, Chen C, Baldan T, Bayaer T, Meng H (- 57) Ref: Nat Commun, 3:1202, 2012 : PubMed ESTHER: Jirimutu_2012_Nat.Commun_3_1202 PubMedSearch: Jirimutu 2012 Nat.Commun 3 1202 PubMedID: 23149746 Gene_locus related to this paper: 9ceta-s9yik4, 9ceta-s9yb99, 9ceta-s9x0n3, 9ceta-s9xqa3, 9ceta-s9xi02, camfr-s9wiw9, camfr-s9x3r3, camfr-s9xce1, camfr-s9xcr2, camfr-s9yuz0, camfr-s9xlc8, camfr-s9w5f6, camfr-s9xmm4 Abstract Bactrian camels serve as an important means of transportation in the cold desert regions of China and Mongolia. Here we present a 2.01 Gb draft genome sequence from both a wild and a domestic bactrian camel. We estimate the camel genome to be 2.38 Gb, containing 20,821 protein-coding genes. Our phylogenomics analysis reveals that camels shared common ancestors with other even-toed ungulates about 55-60 million years ago. Rapidly evolving genes in the camel lineage are significantly enriched in metabolic pathways, and these changes may underlie the insulin resistance typically observed in these animals. We estimate the genome-wide heterozygosity rates in both wild and domestic camels to be 1.0 x 10(-3). However, genomic regions with significantly lower heterozygosity are found in the domestic camel, and olfactory receptors are enriched in these regions. Our comparative genomics analyses may also shed light on the genetic basis of the camel's remarkable salt tolerance and unusual immune system. Title: Constitutive expression of Yarrowia lipolytica lipase LIP2 in Pichia pastoris using GAP as promoter Wang X, Sun Y, Ke F, Zhao H, Liu T, Xu L, Liu Y, Yan Y Ref: Appl Biochem Biotechnol, 166:1355, 2012 : PubMed ESTHER: Wang_2012_Appl.Biochem.Biotechnol_166_1355 PubMedSearch: Wang 2012 Appl.Biochem.Biotechnol 166 1355 PubMedID: 22246727 Abstract A gene encoding Yarrowia lipolytica lipase LIP2 (YlLIP2) was cloned into a constitutive expression vector pGAPZalphaA and electrotransformed into the Pichia pastoris X-33 strain. The high-yield clones obtained by high copy and enzyme activity screening were chosen as the host strains for shaking flask and fermentor culture. The results showed that glucose was the optimum carbon source for YlLIP2 production, and the maximum hydrolytic activity of recombinant YlLIP2 reached 1,315 U/ml under the flask culture at 28 degrees C, pH 7.0, for 48 h. The fed-batch fermentation was carried out in 3- and 10-l bioreactors by continuously feeding glucose into the growing medium for achieving high cell density and YlLIP2 yields. The maximum hydrolytic activity of YlLIP2 and cell density obtained in the 3-l bioreactor were 10,300 U/ml and 116 g dry cell weight (DCW)/l, respectively. The peak hydrolytic activity of YlLIP2 and cell density were further improved in the 10-l fermentor where the values respectively attained were 13,500 U/ml and 120 g DCW/l. The total protein concentration in the supernatant reached 3.3 g/l and the cell viability remained approximately 99% after 80 h of culture. Furthermore, the recombinant YlLIP2 produced in P. pastoris pGAP and pAOX1 systems have similar content of sugar (about 12%) and biochemical characteristics. The above results suggest that the GAP promoter-derived expression system of P. pastoris is effective for the expression of YlLIP2 by high cell density culture and is probably an alternative to the conventional AOX1 promoter expression system in large-scale production of industrial lipases. Title: Accurate determination of the anticancer prodrug simmitecan and its active metabolite chimmitecan in various plasma samples based on immediate deactivation of blood carboxylesterases Hu Z, Sun Y, Du F, Niu W, Xu F, Huang Y, Li C Ref: Journal of Chromatography A, 1218:6646, 2011 : PubMed ESTHER: Hu_2011_J.Chromatogr.A_1218_6646 PubMedSearch: Hu 2011 J.Chromatogr.A 1218 6646 PubMedID: 21839460 Abstract Simmitecan (L-P) is an anticancer ester prodrug, which involves activation to chimmitecan (L-2-Z). In the current study, a liquid chromatography/tandem mass spectrometry-based method was developed for simultaneous determination of L-P and L-2-Z in various plasma samples. Because L-P is rapidly converted to L-2-Z by blood carboxylesterase during and after sampling, which hampers accurate determination of L-P and L-2-Z in the biological samples, different carboxylesterase inhibitors were tested. As a result, bis(4-nitrophenyl)phosphate gave the best results with respect to inhibitory capability, hemolysis, and matrix effects and was used to deactivate blood carboxylesterases when sampling. The plasma samples were precipitated with acetonitrile and the resulting supernatants were separated using a pulse gradient method on a C18 column. Irinotecan and camptothecin were used as internal standards for quantification of L-P and L-2-Z, respectively. Protonated L-P, L-2-Z and their internal standards were generated by electrospray ionization and their precursor-product ion pairs (m/z 599-->124, 405-->361, 587-->195, and 349-->305, respectively) were used for measurement. The newly developed bioanalytical assay processed favorable accuracy and precision with lower limits of quantification of 2.1 nM for L-P and 3.4 nM for L-2-Z, and was successfully applied to pharmacokinetic studies in tumor-bearing nude mice, rats, and dogs. There are substantial species differences in the ester activity. The experimental strategies illustrated in our report may be adopted for measurement of other prodrugs (including irinotecan) or drugs subject to ester hydrolysis, as well as their metabolites, in biological matrices. Title: Decrease in the production of beta-amyloid by berberine inhibition of the expression of beta-secretase in HEK293 cells Zhu F, Wu F, Ma Y, Liu G, Li Z, Sun Y, Pei Z Ref: BMC Neurosci, 12:125, 2011 : PubMed ESTHER: Zhu_2011_BMC.Neurosci_12_125 PubMedSearch: Zhu 2011 BMC.Neurosci 12 125 PubMedID: 22152059 Inhibitor(s) related to this paper: Berberine Abstract BACKGROUND: Berberine (BER), the major alkaloidal component of Rhizoma coptidis, has multiple pharmacological effects including inhibition of acetylcholinesterase, reduction of cholesterol and glucose levels, anti-inflammatory, neuroprotective and neurotrophic effects. It has also been demonstrated that BER can reduce the production of beta-amyloid40/42, which plays a critical and primary role in the pathogenesis of Alzheimer's disease. However, the mechanism by which it accomplishes this remains unclear. RESULTS: Here, we report that BER could not only significantly decrease the production of beta-amyloid40/42 and the expression of beta-secretase (BACE), but was also able to activate the extracellular signal-regulated kinase1/2 (ERK1/2) pathway in a dose- and time-dependent manner in HEK293 cells stably transfected with APP695 containing the Swedish mutation. We also find that U0126, an antagonist of the ERK1/2 pathway, could abolish (1) the activation activity of BER on the ERK1/2 pathway and (2) the inhibition activity of BER on the production of beta-amyloid40/42 and the expression of BACE. CONCLUSION: Our data indicate that BER decreases the production of beta-amyloid40/42 by inhibiting the expression of BACE via activation of the ERK1/2 pathway. Title: GRK5 deficiency accelerates {beta}-amyloid accumulation in Tg2576 mice via impaired cholinergic activity Cheng S, Li L, He S, Liu J, Sun Y, He M, Grasing K, Premont RT, Suo WZ Ref: Journal of Biological Chemistry, 285:41541, 2010 : PubMed ESTHER: Cheng_2010_J.Biol.Chem_285_41541 PubMedSearch: Cheng 2010 J.Biol.Chem 285 41541 PubMedID: 21041302 Inhibitor(s) related to this paper: Methoctramine Abstract Membrane G protein-coupled receptor kinase 5 (GRK5) deficiency is linked to Alzheimer disease, yet its precise roles in the disease pathogenesis remain to be delineated. We have previously demonstrated that GRK5 deficiency selectively impairs desensitization of presynaptic M2 autoreceptors, which causes presynaptic M2 hyperactivity and inhibits acetylcholine release. Here we report that inactivation of one copy of Grk5 gene in transgenic mice overexpressing beta-amyloid precursor protein (APP) carrying Swedish mutations (Tg2576 or APPsw) resulted in significantly increased beta-amyloid (Abeta) accumulation, including increased Abeta(+) plaque burdens and soluble Abeta in brain lysates and interstitial fluid (ISF). In addition, secreted beta-APP fragment (sAPPbeta) also increased, whereas full-length APP level did not change, suggesting an alteration in favor of beta-amyloidogenic APP processing in these animals. Reversely, perfusion of methoctramine, a selective M2 antagonist, fully corrected the difference between the control and GRK5-deficient APPsw mice for ISF Abeta. In contrast, a cholinesterase inhibitor, eserine, although significantly decreasing the ISF Abeta in both control and GRK5-deficient APPsw mice, failed to correct the difference between them. However, combining eserine with methoctramine additively reduced the ISF Abeta further in both animals. Altogether, these findings indicate that GRK5 deficiency accelerates beta-amyloidogenic APP processing and Abeta accumulation in APPsw mice via impaired cholinergic activity and that presynaptic M2 hyperactivity is the specific target for eliminating the pathologic impact of GRK5 deficiency. Moreover, a combination of an M2 antagonist and a cholinesterase inhibitor may reach the maximal disease-modifying effect for both amyloid pathology and cholinergic dysfunction. Title: Crystal structure of a secreted lipase from Gibberella zeae reveals a novel double-lock mechanism Lou Z, Li M, Sun Y, Liu Y, Liu Z, Wu W, Rao Z Ref: Protein Cell, 1:760, 2010 : PubMed ESTHER: Lou_2010_Protein.Cell_1_760 PubMedSearch: Lou 2010 Protein.Cell 1 760 PubMedID: 21203917 Gene_locus related to this paper: gibze-q6wer3 Inhibitor(s) related to this paper: Ebelactone-B Abstract Fusarium graminearum (sexual stage: Gibberella zeae) is the causative agent of Fusarium Head Blight (FHB), which is one of the most destructive plant disease of cereals, accounting for high grain yield losses, especially for wheat and maize. Like other fungal pathogens, several extracellular enzymes secreted by G. zeae are known to be involved in host infection. Among these secreted lipases, G. zeae lipase (GZEL), which is encoded by the FGL1 gene, was demonstrated to be crucial to G. zeae pathogenicity. However, the precise mechanism of GZEL remains unclear due to a lack of detailed structural information. In this study, we report the crystal structure of GZEL at the atomic level. The structure of GZEL displays distinct structural differences compared to reported homologues and indicates a unique "double lock" enzymatic mechanism. To gain insight into substrate/inhibitor recognition, we proposed a model of GZEL in complex with substrate and the lipase inhibitor ebelactone B (based on the reported structures of GZEL homologues), which defines possible substrate binding sites within the catalytic cleft and suggests an "anti sn-l" binding mode. These results pave the way to elucidating the mechanism of GZEL and thus provide clues for the design of anti-FHB inhibitors. Title: Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial Doody RS, Ferris SH, Salloway S, Sun Y, Goldman R, Watkins WE, Xu Y, Murthy AK Ref: Neurology, 72:1555, 2009 : PubMed ESTHER: Doody_2009_Neurology_72_1555 PubMedSearch: Doody 2009 Neurology 72 1555 PubMedID: 19176895 Abstract BACKGROUND: Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms. METHODS: In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function. RESULTS: The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%). CONCLUSIONS: Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment. Title: Complete genome sequence of citrus huanglongbing bacterium, 'Candidatus Liberibacter asiaticus' obtained through metagenomics Duan Y, Zhou L, Hall DG, Li W, Doddapaneni H, Lin H, Liu L, Vahling CM, Gabriel DW and Gottwald T <3 more author(s)> Duan Y, Zhou L, Hall DG, Li W, Doddapaneni H, Lin H, Liu L, Vahling CM, Gabriel DW, Williams KP, Dickerman A, Sun Y, Gottwald T (- 3) Ref: Mol Plant Microbe Interact, 22:1011, 2009 : PubMed ESTHER: Duan_2009_Mol.Plant.Microbe.Interact_22_1011 PubMedSearch: Duan 2009 Mol.Plant.Microbe.Interact 22 1011 PubMedID: 19589076 Gene_locus related to this paper: libap-c6xhk4, libap-c6xgr3 Abstract Citrus huanglongbing is the most destructive disease of citrus worldwide. It is spread by citrus psyllids and is associated with a low-titer, phloem-limited infection by any of three uncultured species of alpha-Proteobacteria, 'Candidatus Liberibacter asiaticus', 'Ca. L. americanus', and 'Ca. L. africanus'. A complete circular 'Ca. L. asiaticus' genome has been obtained by metagenomics, using the DNA extracted from a single 'Ca. L. asiaticus'-infected psyllid. The 1.23-Mb genome has an average 36.5% GC content. Annotation revealed a high percentage of genes involved in both cell motility (4.5%) and active transport in general (8.0%), which may contribute to its virulence. 'Ca. L. asiaticus' appears to have a limited ability for aerobic respiration and is likely auxotrophic for at least five amino acids. Consistent with its intracellular nature, 'Ca. L. asiaticus' lacks type III and type IV secretion systems as well as typical free-living or plant-colonizing extracellular degradative enzymes. 'Ca. L. asiaticus' appears to have all type I secretion system genes needed for both multidrug efflux and toxin effector secretion. Multi-protein phylogenetic analysis confirmed 'Ca. L. asiaticus' as an early-branching and highly divergent member of the family Rhizobiaceae. This is the first genome sequence of an uncultured alpha-proteobacteria that is both an intracellular plant pathogen and insect symbiont. Title: Clinicopathologic features between multicentric occurence and intrahepatic metastasis of multiple hepatocellular carcinomas related to HBV Wang J, Li Q, Sun Y, Zheng H, Cui Y, Li H, Zhou H, Hao X Ref: Surg Oncol, 18:25, 2009 : PubMed ESTHER: Wang_2009_Surg.Oncol_18_25 PubMedSearch: Wang 2009 Surg.Oncol 18 25 PubMedID: 18640032 Abstract AIMS: To clarify the incidence of multicentric occurrence (MO) and intrahepatic metastasis (IM) for hepatocellular carcinoma (HCC) related to hepatitis B virus (HBV) in China and to identify the differences between them. PATIENTS AND METHODS: Histopathologic features of multiple tumors in 82 cases with HCC were analyzed. The two groups, the origin was determinable as of multicentric occurrence or as of intrahepatic metastasis, were analyzed for their survival rate, disease-free survival and clinicopathologic differences. RESULTS: According to histological findings, 19.5% and 69.5% patients were considered to be MO and IM, respectively. In total 73 cases from the histopathological method were selected and divided into group MO (16 cases) and the group IM (57 cases). Analysis of stepwise regression identified that: Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) were the most important discriminating factors between MO and IM (p<0.05). As for their prognosis, Kaplan-Meier and Log rank test showed the survival rate in group MO was significantly better than that in the group IM (p=0.003). No statistical significance was found between the disease-free survival in group MO and that in group IM (p=0.141). The analysis of Cox's proportional hazards model showed that tumor type (MO or IM) and Child's stage were the important prognostic factors (p=0.002 and 0.014, respectively). CONCLUSIONS: The incidence of MO in patients with multiple HCCs related to HBV is only about 20%, which is lower than that of Japan. Child's stage, cholinesterase (host factors), tumor size, histological grade and positive portal vein invasion (tumor factors) are the most important discriminating factors between MO and IM. The prognosis of patients with MO compared to IM is significantly better and tumor type (MO or IM) and Child's stage are important prognostic factors. Title: Integrated production for biodiesel and 1,3-propanediol with lipase-catalyzed transesterification and fermentation Xu Y, Liu H, Du W, Sun Y, Ou X, Liu D Ref: Biotechnol Lett, 31:1335, 2009 : PubMed ESTHER: Xu_2009_Biotechnol.Lett_31_1335 PubMedSearch: Xu 2009 Biotechnol.Lett 31 1335 PubMedID: 19466559 Abstract Biodiesel, a renewable alternative to fossil energy, has shown great prospects for global proliferation in the past decade. Lipase catalyzed transesterification for biodiesel production, as a biological process with many advantages has drawn increasing attention. As a by-product, glycerol accounts for about 10% w/w of biodiesel during the process of biodiesel production. As a result, the conversion of glycerol has become a common problem which has to be resolved if considering large amount of biodiesel production. Glycerol can be fermented into 1,3-propanediol, a high value added chemical with a promising future in the polymers, for example, polytrimethylene terephthalate, and also fermentation approaches for 1,3-propanediol production which have drawn more and more attention due to advantages such as relatively low investment, mild reaction conditions and using renewable sources as the starting materials. Based on the latest technology advancements in lipase-mediated transformation for biodiesel production, the aerobic fermentation technology and genetic engineering for 1,3-propanediol production, and the integrated production of 1,3-propanediol from crude glycerol could be a promising way to improve the profit of the whole process during biodiesel production. Title: pH memory of immobilized lipase for (+/-)-menthol resolution in ionic liquid Ren MY, Bai S, Zhang DH, Sun Y Ref: Journal of Agricultural and Food Chemistry, 56:2388, 2008 : PubMed ESTHER: Ren_2008_J.Agric.Food.Chem_56_2388 PubMedSearch: Ren 2008 J.Agric.Food.Chem 56 2388 PubMedID: 18338863 Abstract Magnetic DEAE-GMA-EDMA microspheres were prepared via suspension polymerization and used for the immobilization of Candida rugosa lipase by ion exchange. The effect of pH values on the immobilization of lipase was investigated. Resolution of (+/-)-menthol in the hydrophobic ionic liquid 1-butyl-3-methylimidazolium hexafluorophosphate was performed by immobilized lipase-catalyzed enantioselective esterification with propionic anhydride as acyl donor. The effects of pH condition at lipase immobilization on the conversion and enantioselectivity were investigated. As a result, pH memory of the immobilized lipase for catalyzing (+/-)-menthol resolution in the ionic liquid was observed. Better conversion and the best enantioselectivity were obtained with the immobilized lipase prepared at pH 5.0. Under the condition, (-)-menthyl propionate with enantiomeric excess of >90% was obtained. Moreover, the enantioselectivity of the immobilized lipase decreased gradually with increasing pH value. Title: How long can patients with mild or moderate Alzheimer's dementia maintain both the cognition and the therapy of cholinesterase inhibitors: a national population-based study Sun Y, Lai MS, Lu CJ, Chen RC Ref: Eur Journal of Neurology, 15:278, 2008 : PubMed ESTHER: Sun_2008_Eur.J.Neurol_15_278 PubMedSearch: Sun 2008 Eur.J.Neurol 15 278 PubMedID: 18290848 Abstract The aims of this study were to evaluate the duration of acetylcholinesterase inhibitors (AChEI) utilization as well as the patients' cognition maintenance. This study was using panel data from the Bureau of National Health Insurance (BNHI) of Taiwan from 2001 to 2004. Patients with mild or moderate AD were prescribed AChEI (donepezil, rivastigmine, or galantamine). By the regulation of BNHI, if the score of Mini-Mental Status Examination worsened by more than two points or clinical dementia rating (CDR) worsened by one or more grades in the follow-up every half year, the AChEI treatment would be terminated. Kaplan-Meier product-limit method was used to estimate duration of drug utilization. Regression model was performed to analyse the factors affecting the discontinuation of AChEI treatment. Our results showed female are more and younger than male in mild to moderate Alzheimer's dementia. The mean duration of use of AChEI was 432 days. Only 9.6% of patients maintained stable cognition tests results with continued drug refill for more than 3 years. Discontinuation rate in older patients (age > or =76 years) was higher than those in younger age (P = 0.0009). The average duration for AChEI therapy is around 14 months. The elderly are at high risk for treatment discontinuation. Title: Crystallization and preliminary crystallographic analysis of Gibberella zeae extracellular lipase Sun Y, Li M, Zhang Y, Liu L, Liu Y, Liu Z, Li X, Lou Z Ref: Acta Crystallographica Sect F Struct Biol Cryst Commun, 64:813, 2008 : PubMed ESTHER: Sun_2008_Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun_64_813 PubMedSearch: Sun 2008 Acta.Crystallogr.Sect.F.Struct.Biol.Cryst.Commun 64 813 PubMedID: 18765911 Gene_locus related to this paper: gibze-q6wer3 Abstract Fusarium head blight, one of the most destructive crop diseases, is mainly caused by Fusarium graminearum (known in its sexual stage as Gibberella zeae). F. graminearum secretes various extracellular enzymes that have been hypothesized to be involved in host infection. One of the extracellular enzymes secreted by this organism is the G. zeae extracellular lipase (GZEL), which is encoded by the FGL1 gene. In order to solve the crystal structure of GZEL and to gain a better understanding of the biological functions of the protein and of possible inhibitory mechanisms of lipase inhibitors, recombinant GZEL was crystallized at 291 K using PEG 3350 as a precipitant. A data set was collected to 2.8 A resolution from a single flash-cooled crystal (100 K). The crystal belonged to space group P2(1)2(1)2(1), with unit-cell parameters a = 78.4, b = 91.0, c = 195.8 A, alpha = beta = gamma = 90 degrees . The presence of four molecules was assumed per asymmetric unit, which gave a Matthews coefficient of 2.6 A(3) Da(-1). Title: Isolation and expression of a Malassezia globosa lipase gene, LIP1 Deangelis YM, Saunders CW, Johnstone KR, Reeder NL, Coleman CG, Kaczvinsky JR, Jr., Gale C, Walter R, Mekel M and Dawson TL, Jr. <9 more author(s)> Deangelis YM, Saunders CW, Johnstone KR, Reeder NL, Coleman CG, Kaczvinsky JR, Jr., Gale C, Walter R, Mekel M, Lacey MP, Keough TW, Fieno A, Grant RA, Begley B, Sun Y, Fuentes G, Youngquist RS, Xu J, Dawson TL, Jr. (- 9) Ref: Journal of Investigative Dermatology, 127:2138, 2007 : PubMed ESTHER: DeAngelis_2007_J.Invest.Dermatol_127_2138 PubMedSearch: DeAngelis 2007 J.Invest.Dermatol 127 2138 PubMedID: 17460728 Gene_locus related to this paper: malgo-a8puy1 Abstract Dandruff and seborrheic dermatitis (D/SD) are common hyperproliferative scalp disorders with a similar etiology. Both result, in part, from metabolic activity of Malassezia globosa and Malassezia restricta, commensal basidiomycete yeasts commonly found on human scalps. Current hypotheses about the mechanism of D/SD include Malassezia-induced fatty acid metabolism, particularly lipase-mediated breakdown of sebaceous lipids and release of irritating free fatty acids. We report that lipase activity was detected in four species of Malassezia, including M. globosa. We isolated lipase activity by washing M. globosa cells. The isolated lipase was active against diolein, but not triolein. In contrast, intact cells showed lipase activity against both substrates, suggesting the presence of at least another lipase. The diglyceride-hydrolyzing lipase was purified from the extract, and much of its sequence was determined by peptide sequencing. The corresponding lipase gene (LIP1) was cloned and sequenced. Confirmation that LIP1 encoded a functional lipase was obtained using a covalent lipase inhibitor. LIP1 was differentially expressed in vitro. Expression was detected on three out of five human scalps, as indicated by reverse transcription-PCR. This is the first step in a molecular description of lipid metabolism on the scalp, ultimately leading toward a test of its role in D/SD etiology. Title: Efficacy of multivitamin supplementation containing vitamins B6 and B12 and folic acid as adjunctive treatment with a cholinesterase inhibitor in Alzheimer's disease: a 26-week, randomized, double-blind, placebo-controlled study in Taiwanese patients Sun Y, Lu CJ, Chien KL, Chen ST, Chen RC Ref: Clin Ther, 29:2204, 2007 : PubMed ESTHER: Sun_2007_Clin.Ther_29_2204 PubMedSearch: Sun 2007 Clin.Ther 29 2204 PubMedID: 18042476 Abstract BACKGROUND: Elevated serum homocysteine levels have been associated with the development of Alzheimer's dementia (AD). The combined use of a mecobalamin capsule preparation, which contains vitamin B12 0.5 mg with an active methyl base, and an over-the-counter nutritional supplement that contains folic acid 1 mg and pyridoxine hyperchloride 5 mg may be effective as a homocysteine-lowering vitamin regimen. OBJECTIVE: The aim of this study was to determine whether oral multivitamin supplementation containing vitamins B6 and B12 and folic acid would improve cognitive function and reduce serum homocysteine levels in patients with mild to moderate AD. Title: Analysis of the role of LinA and LinB in biodegradation of delta-hexachlorocyclohexane Wu J, Hong Q, Sun Y, Hong Y, Yan Q, Li S Ref: Environ Microbiol, 9:2331, 2007 : PubMed ESTHER: Wu_2007_Environ.Microbiol_9_2331 PubMedSearch: Wu 2007 Environ.Microbiol 9 2331 PubMedID: 17686029 Abstract Commercial formulations of hexachlorocyclohexane (HCH) consist of a mixture of four isomers, alpha, beta, gamma and delta. All these four isomers are toxic and recalcitrant pollutants. Sphingobium (formerly Sphingomonas) sp. strain BHC-A is able to degrade all four HCH isomers. Eight lin genes responsible for the degradation of gamma-HCH in BHC-A were cloned and analysed for their role in the degradation of delta-HCH, and the initial conversion steps in delta-HCH catabolism by LinA and LinB in BHC-A were found. LinA dehydrochlorinated delta-HCH to produce 1,3,4,6-tetrachloro-1,4-cyclohexadiene (1,4-TCDN) via delta-pentachlorocyclohexene (delta-PCCH). Subsequently, both 1,4-TCDN and delta-PCCH are catalysed by LinB via two successive rounds of hydrolytic dechlorinations to form 2,5-dichloro-2,5-cyclohexadiene-1,4-diol (2,5-DDOL) and 2,3,5-trichloro-5-cyclohexene-1,4-diol (2,3,5-TCDL) respectively. LinB could also catalyse the hydrolytic dechlorination of delta-HCH to 2,3,5,6-tetrachloro-1,4-cyclohexanediol (TDOL) via 2,3,4,5,6-pentachlorocyclohexanol (PCHL). Title: Dandruff-associated Malassezia genomes reveal convergent and divergent virulence traits shared with plant and human fungal pathogens Xu J, Saunders CW, Hu P, Grant RA, Boekhout T, Kuramae EE, Kronstad JW, Deangelis YM, Reeder NL and Dawson TL, Jr. <11 more author(s)> Xu J, Saunders CW, Hu P, Grant RA, Boekhout T, Kuramae EE, Kronstad JW, Deangelis YM, Reeder NL, Johnstone KR, Leland M, Fieno AM, Begley WM, Sun Y, Lacey MP, Chaudhary T, Keough T, Chu L, Sears R, Yuan B, Dawson TL, Jr. (- 11) Ref: Proc Natl Acad Sci U S A, 104:18730, 2007 : PubMed ESTHER: Xu_2007_Proc.Natl.Acad.Sci.U.S.A_104_18730 PubMedSearch: Xu 2007 Proc.Natl.Acad.Sci.U.S.A 104 18730 PubMedID: 18000048 Gene_locus related to this paper: malgo-a8puy5, malgo-a8puy1, malgo-a8pvh8, malgo-a8pwh6, malgo-a8pwm2, malgo-a8pwr6, malgo-a8px35, malgo-a8pzh3, malgo-a8q1i5, malgo-a8q4e6, malgo-a8q7d0, malgo-a8q8v5, malgo-a8q9m3, malgo-a8q9n0, malgo-a8q902, malgo-a8qcr1, malgo-a8qcv4, malgo-a8qcv7, malgo-a8qcw4, malgo-a8qdf0 Abstract Fungi in the genus Malassezia are ubiquitous skin residents of humans and other warm-blooded animals. Malassezia are involved in disorders including dandruff and seborrheic dermatitis, which together affect >50% of humans. Despite the importance of Malassezia in common skin diseases, remarkably little is known at the molecular level. We describe the genome, secretory proteome, and expression of selected genes of Malassezia globosa. Further, we report a comparative survey of the genome and secretory proteome of Malassezia restricta, a close relative implicated in similar skin disorders. Adaptation to the skin environment and associated pathogenicity may be due to unique metabolic limitations and capabilities. For example, the lipid dependence of M. globosa can be explained by the apparent absence of a fatty acid synthase gene. The inability to synthesize fatty acids may be complemented by the presence of multiple secreted lipases to aid in harvesting host lipids. In addition, an abundance of genes encoding secreted hydrolases (e.g., lipases, phospholipases, aspartyl proteases, and acid sphingomyelinases) was found in the M. globosa genome. In contrast, the phylogenetically closely related plant pathogen Ustilago maydis encodes a different arsenal of extracellular hydrolases with more copies of glycosyl hydrolase genes. M. globosa shares a similar arsenal of extracellular hydrolases with the phylogenetically distant human pathogen, Candida albicans, which occupies a similar niche, indicating the importance of host-specific adaptation. The M. globosa genome sequence also revealed the presence of mating-type genes, providing an indication that Malassezia may be capable of sex. Title: Characterization of lipase in reversed micelles formulated with cibacron blue F-3GA modified span 85 Zhang DH, Guo Z, Dong XY, Sun Y Ref: Biotechnol Prog, 23:108, 2007 : PubMed ESTHER: Zhang_2007_Biotechnol.Prog_23_108 PubMedSearch: Zhang 2007 Biotechnol.Prog 23 108 PubMedID: 17269677 Abstract Sorbitan trioleate (Span 85) modified by Cibacron Blue F-3GA (CB) was prepared and used as an affinity surfactant to formulate a reversed micellar system for Candida rugosa lipase (CRL) solubilization. The system was characterized and evaluated by employing CRL-catalyzed hydrolysis of olive oil as a model reaction. The micellar hydrodynamic radius results reflected, to some extent, the redistribution of surfactant and water after enzyme addition, and the correlation between surfactant formulation, water content (W0), micellar size, and enzyme activity. An adequate modification density of CB was found to be important for the reversed micelles to retain enough hydration capacity and achieve high enzyme activity. Compared with the results in AOT-based reversed micelles, CRL in this micellar system exhibited a different activity behavior versus W0. The optimal pH and temperature of the encapsulated lipase remained unchanged, but the apparent activity was significantly higher than that of the native enzyme in bulk solution. Kinetic studies indicated that the encapsulated lipase in the reversed micelles of CB-formulated Span 85 followed the Michaelis-Menten equation. The Michaelis constant was found to decrease with increasing surfactant concentration, suggesting an increase of the enzyme affinity for the substrate. Stability of the lipase in the reversed micelles was negatively correlated to W0. 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. Title: [The mechanism of carbofuran interacts with calf thymus DNA] Zhang LJ, Min SG, Li GX, Xiong YM, Sun Y Ref: Guang Pu Xue Yu Guang Pu Fen Xi, 25:739, 2005 : PubMed ESTHER: Zhang_2005_Guang.Pu.Xue.Yu.Guang.Pu.Fen.Xi_25_739 PubMedSearch: Zhang 2005 Guang.Pu.Xue.Yu.Guang.Pu.Fen.Xi 25 739 PubMedID: 16128077 Abstract Carbofuran is an insecticide used on a variety of corps. Acute and chronic occupational exposure of humans to carbofuran has been observed to cause cholinesterase inhibition, but little is known about the interaction of carbofuran with DNA. Using the technique of UV spectrum and fluorescence quenching respectively, the interaction between carbofuran and ct DNA was studied. The UV spectrum showed that ct DNA can lead to the hypochromic effect and red shift of the UV spectrum of carbofuran. The quenching process was proved to be the single static quenching and quenching constant decreases with temperature increasing. The basis of this specificity is intercalation of insecticide between base pairs to produce ct DNA-carbofuran adducts. Furthermore, ethanol can produce Franck-condon effect on the ct DNA-carbofuran adducts. At different sodium chloride concentrations, quenching constant had no significant change, which appeared that there was little electrostatic interaction between ct DNA and carbofuran and it was intercalation. Title: Memantine alleviates toxicity induced by dichlorvos in rats Zhou Z, Dai X, Gu X, Sun Y, Zheng G, Zheng J Ref: J Occup Health, 47:96, 2005 : PubMed ESTHER: Zhou_2005_J.Occup.Health_47_96 PubMedSearch: Zhou 2005 J.Occup.Health 47 96 PubMedID: 15824473 Abstract The changes of N-methyl-D-aspartate (NMDA) receptor and protective efficacy of memantine (MEM) in rats poisoned with dichlorvos were studied. Dichlorvos evoked down-regulation of the affinity and density of [(3)H]MK-801 binding to NMDA receptor in the brain of rats receiving dichlorvos (15 and 25 mg/kg bw, i.p.). The binding capacity of NMDA receptor and acetylcholinesterase activity were determined at 4 h, 8 h, 16 h, 24 h and 48 h after treatment. When rats were given a different doses of MEM (5, 15 and 45 mg/kg bw) after poisoning (dichlorvos 25 mg/kg bw), the latency of onset of signs was postponed and the magnitude of muscular fasciculation was alleviated as the dose of MEM increased. The lower doses of MEM (5 and 15 mg/kg bw) could antagonize the dichlorvos-evoked down-regulation of NMDA receptor, while the highest dose (45 mg/kg bw) decreased the Bmax and Kd values of NMDA receptors. These results show the dichlorvos-evoked down-regulation of NMDA receptor might be self-regulation by the body to protect the central nervous system. MEM could antagonize the down-regulation of NMDA receptors, and alleviated signs of poisoning, especially reducing the magnitude of muscular fasciculation. We suggest that the role of NMDA receptor in organophosphates (OP) poisoning should receive more attention, and, that MEM treatment in acute OP poisoning, as a supplement to atropine and oxime, should be considered. Title: Characteristics of immobilized lipase on hydrophobic superparamagnetic microspheres to catalyze esterification Guo Z, Sun Y Ref: Biotechnol Prog, 20:500, 2004 : PubMed ESTHER: Guo_2004_Biotechnol.Prog_20_500 PubMedSearch: Guo 2004 Biotechnol.Prog 20 500 PubMedID: 15058995 Abstract A novel immobilized lipase (from Candida rugosa) on hydrophobic and superparamagnetic microspheres was prepared and used as a biocatalyst to catalyze esterification reactions in diverse solvents and reaction systems. The results showed that the immobilized lipase had over 2-fold higher activities in higher log P value solvents. An exponential increase of lipase activity against log P of two miscible solvent mixtures was observed for the first time. Both free and immobilized lipase achieved its maximum activity at the range of water activity (a(w)) 0.5-0.8 or higher. At a(w) 0.6, the immobilized lipase exhibited markedly higher activities in heptane and a solvent-free system than did the native lipase. In multicompetitive reactions, the alcohol specificity of the lipase showed a strong chain-length dependency, and the immobilized enzyme exhibited more preference for a longer-chain alcohol, which is different from previous reports. The immobilized lipase showed higher specificities for butyric acid and the medium-chain-length fatty acids (C(8)-C(12)). Then, the immobilized lipase was extended to solvent-free synthesis of glycerides from glycerol and fatty acids. Recovered by magnetic separation, the immobilized lipase exhibited good reusability in repeated batch reaction, indicating its promising feature for biotechnology application. Title: A complete gene cluster from Streptomyces nanchangensis NS3226 encoding biosynthesis of the polyether ionophore nanchangmycin Sun Y, Zhou X, Dong H, Tu G, Wang M, Wang B, Deng Z Ref: Chemical Biology, 10:431, 2003 : PubMed ESTHER: Sun_2003_Chem.Biol_10_431 PubMedSearch: Sun 2003 Chem.Biol 10 431 PubMedID: 12770825 Gene_locus related to this paper: strna-NANE Abstract The PKS genes for biosynthesis of the polyether nanchangmycin are organized to encode two sets of proteins (six and seven ORFs, respectively), but are separated by independent ORFs that encode an epimerase, epoxidase, and epoxide hydrolase, and, notably, an independent ACP. One of the PKS modules lacks a corresponding ACP. We propose that the process of oxidative cyclization to form the polyether structure occurs when the polyketide chain is still anchored on the independent ACP before release. 4-O-methyl-L-rhodinose biosynthesis and its transglycosylation involve four putative genes, and regulation of nanchangmycin biosynthesis seems to involve activation as well as repression. In-frame deletion of a KR6 domain generated the nanchangmycin aglycone with loss of 4-O-methyl-L-rhodinose and antibacterial activity, in agreement with the assignments of the PKS domains catalyzing specific biosynthetic steps. Title: Sequence and analysis of rice chromosome 4 Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y and Han B <61 more author(s)> Feng Q, Zhang Y, Hao P, Wang S, Fu G, Huang Y, Li Y, Zhu J, Liu Y, Hu X, Jia P, Zhao Q, Ying K, Yu S, Tang Y, Weng Q, Zhang L, Lu Y, Mu J, Zhang LS, Yu Z, Fan D, Liu X, Lu T, Li C, Wu Y, Sun T, Lei H, Li T, Hu H, Guan J, Wu M, Zhang R, Zhou B, Chen Z, Chen L, Jin Z, Wang R, Yin H, Cai Z, Ren S, Lv G, Gu W, Zhu G, Tu Y, Jia J, Chen J, Kang H, Chen X, Shao C, Sun Y, Hu Q, Zhang X, Zhang W, Wang L, Ding C, Sheng H, Gu J, Chen S, Ni L, Zhu F, Chen W, Lan L, Lai Y, Cheng Z, Gu M, Jiang J, Li J, Hong G, Xue Y, Han B (- 61) Ref: Nature, 420:316, 2002 : PubMed ESTHER: Feng_2002_Nature_420_316 PubMedSearch: Feng 2002 Nature 420 316 PubMedID: 12447439 Gene_locus related to this paper: orysa-Q7XTC5, orysa-Q7F959, orysa-q7f9i3, orysa-q7x7y5, orysa-q7xkj9, orysa-q7xr62, orysa-q7xr63, orysa-q7xr64, orysa-q7xsg1, orysa-q7xsq2, orysa-Q7XTM8, orysa-q7xts6, orysa-q7xue7, orysa-q7xv53, orysa-Q7XVB5, orysa-Q7XVG5, orysj-q0jaf0, orysj-q7f8x1 Abstract Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis. Title: [The profiles of free organophosphorus poisons in the bile of rabbits poisoned with different organophosphates] Hou Y, Fu F, Liu S, Liu C, Sun Y, Qiu S Ref: Zhonghua Nei Ke Za Zhi, 41:795, 2002 : PubMed ESTHER: Hou_2002_Zhonghua.Nei.Ke.Za.Zhi_41_795 PubMedSearch: Hou 2002 Zhonghua.Nei.Ke.Za.Zhi 41 795 PubMedID: 12654229 Abstract OBJECTIVE: To study the process and significance of the distribution of free organophosphorus poisons (FOPs) in the blood and bile of rabbits poisoned with organophosphates. METHODS: Seventy two livid blue rabbits, male, 2 - 2.5 kg in weight, were divided into 3 groups: trichlorfon (556.0 mg/kg), monocrotophos (11.12 mg/kg) and methyl parathion (37.05 mg/kg). Each group consisted of 24 rabbits. All organophosphates were administered by subcutaneous route. Blood and bile were collected at time intervals of 1, 6, 24, 96 hours after administration. Blood cells and plasma were separated. Acetylcholinesterase (AChE) activity was measured with dithiobisnitrobenzoic acid (DTNB) enzyme kinetic method. The levels of FOPs in plasma and bile were determined with enzyme inhibited method. RESULTS: From 1 h to 96 h after administration negative correlation was found between time and FOP concentration in plasma (trichlorfon, r = -0.74, P < 0.01; monocrotophos, r = -0.55, P < 0.01; methyl parathion, r = -0.69, P < 0.01), and it was also found in bile between time and FOP concentration of trichlorfon (r = -0.97, P < 0.01) and monocrotophos (r = -0.71, P < 0.01). There is no linear correlation between time and concentration of methyl parathion in bile (r = -0.14, P > 0.05). When FOPs in plasma were not detectable at 96 h after administration, high levels of FOPs could still be detected in bile [trichlorfon (300.3 +/- 174.44) IU/L; monocrotophos (362.8 +/- 136.62) IU/L; methyl parathion (101.0 +/- 75.85) IU/L]. CONCLUSION: The bile is the most important store for FOPs in animal. FOPs can exist in bile over 96 h. The process of poisoning is a changing process of absorption, distribution and redistribution and it is different owing to various physical and chemical properties of organophosphates. Title: [The acute effects of dimethoate on the muscarinic-receptors of rat brains and the relationship between muscarinic-receptors and cholinesterase] Sun Y, Zhou Z, Hu Y, Chen J, Jin T Ref: Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi, 20:293, 2002 : PubMed ESTHER: Sun_2002_Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi_20_293 PubMedSearch: Sun 2002 Zhonghua.Lao.Dong.Wei.Sheng.Zhi.Ye.Bing.Za.Zhi 20 293 PubMedID: 14694657 Abstract OBJECTIVE: To study the acute effects of dimethoate on the muscarinic-receptors(M1, M2) in the brain of rats. | |||||||
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