Author Report for: Yang XNo contact information in database for Yang X
Chen Q, Sun S, Yang X, Yan H, Wang K, Ba X, Wang H Ref: Toxics, 11:, 2023 : PubMed ESTHER: Chen_2023_Toxics_11_ PubMedSearch: Chen 2023 Toxics 11 PubMedID: 37235217 Abstract Silkworm Bombyx mori (L.) (Lepidoptera: Bombycidae) is a critical insect for silk producers, but the inappropriate application of insecticides negatively affects the physiology and behavior of silkworms. This study found that the effects of neonicotinoid insecticides applied using two spraying methods on the growth and development of silkworms were different: the median lethal concentration (LC(50)) values of two pesticides applied using the leaf-dipping method were 0.33 and 0.83 mg L(-1) and those of two pesticides applied using the quantitative spraying method were 0.91 and 1.23 mg kg(-1). The concentration of pesticides on the mulberry leaves did not decrease after their application using the quantitative spraying method, and a uniform spraying density was observed after the mulberry leaves were air-dried (no liquid) under realistic conditions. We then treated silkworms with the quantitative spraying method and leaf-dipping method. The treatment of silkworm larvae with imidacloprid and thiamethoxam at sublethal concentrations significantly prolonged the development time and significantly decreased the weight and pupation rate, as well as economic indicators of enamel layers and sputum production. Thiamethoxam treatment significantly increased the activities of carboxylesterase (CarE) and glutathione-S-transferase (GST). The activity of CarE and GST increased, decreased, and then increased, and the highest activity was detected on the 10th and 12th days. Thiamethoxam exposure significantly elevated the transcription levels of CarE-11, GSTe3 and GSTz2 and induced DNA damage in hemocytes. This study confirmed that the quantitative spray method is more stable than the leaf-dipping method. Moreover, imidacloprid and thiamethoxam treatment affected the economy and indexes of silkworms and induced changes in detoxification enzymes and DNA damage in silkworms. These results provide a basis for understanding the mechanism of the sublethal effects of insecticides on silkworms. Title: Targeting soluble epoxide hydrolase promotes osteogenic-angiogenic coupling via activating SLIT3/HIF-1alpha signalling pathway Gao L, Chen W, Li L, Li J, Kongling W, Zhang Y, Yang X, Zhao Y, Bai J, Wang F Ref: Cell Prolif, :e13403, 2023 : PubMed ESTHER: Gao_2023_Cell.Prolif__e13403 PubMedSearch: Gao 2023 Cell.Prolif e13403 PubMedID: 36636821 Inhibitor(s) related to this paper: TPPU Abstract Type H vessels have recently been identified to modulate osteogenesis. Epoxyeicostrioleic acids (EETs) have an essential contribution to vascular homeostasis. However, whether increased EETs with soluble epoxide hydrolase (sEH) inhibitor TPPU enhance the coupling of angiogenesis and osteogenesis remains largely unknown. The effects of TPPU on cross-talk between co-cultured human umbilical vein endothelial cells (HUVECs) and human dental pulp stem cells (hDPSCs), and on long bone growth and calvarial defect repair in mice were investigated in vitro and in vivo. TPPU enhanced osteogenic differentiation of co-cultured HUVECs and hDPSCs in vitro and increased type H vessels, and long bone growth and bone repair of calvarial defect. Mechanistically, TPPU promoted cell proliferation and angiogenesis, reclined cell apoptosis, and significantly increased CD31(hi) EMCN(hi) endothelial cells (ECs) and SLIT3 and HIF-1alpha expression levels in co-cultured HUVECs and hDPSCs. Knockdown of Slit3 in hDPSCs or Hif-1alpha in HUVECs impaired the formation of CD31(hi) EMCN(hi) ECs and reversed TPPU-induced osteogenesis. We defined a previously unidentified effect of TPPU coupling angiogenesis and osteogenesis. TPPU induced type H vessels by upregulating the expression of hDPSCs-derived SLIT3, which resulted in the activation of ROBO1/YAP1/HIF-1alpha signalling pathway in ECs. Targeting metabolic pathways of EETs represents a new strategy to couple osteogenesis and angiogenesis, sEH is a promising therapeutic target for bone regeneration and repair. Title: MAGL inhibition relieves synovial inflammation and pain via regulating NOX4-Nrf2 redox balance in osteoarthritis Li X, Tao H, Zhou J, Zhang L, Shi Y, Zhang C, Sun W, Chu M, Chen K and Hao Y <3 more author(s)> Li X, Tao H, Zhou J, Zhang L, Shi Y, Zhang C, Sun W, Chu M, Chen K, Gu C, Yang X, Geng D, Hao Y (- 3) Ref: Free Radic Biol Med, 208:13, 2023 : PubMed ESTHER: Li_2023_Free.Radic.Biol.Med_208_13 PubMedSearch: Li 2023 Free.Radic.Biol.Med 208 13 PubMedID: 37516370 Gene_locus related to this paper: human-MGLL Inhibitor(s) related to this paper: MJN110 Abstract Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage injury, hyperplasia of bone and inflammatory lesions of synovium. Monoacylglycerol lipase (MAGL), a member of the alpha/beta hydrolase superfamily, is involved in regulation of injury protection and immune-inflammation response. Autoinflammatory response of the synovium and the release of inflammatory mediators play critical roles in occurrence of early-stage OA. Fibroblast-like synoviocytes (FLSs) are resident mesenchymal cells of the synovial tissue. Considering that MAGL inhibition regulates the inflammatory signaling cascade, it is crucial to ascertain the biological effects and specific mechanisms of MAGL in alleviating inflammatory infiltration of OA FLSs. The aim of this study was to investigate the effect of MAGL on biological function in OA FLSs. Results from in vitro experiments showed that MAGL blockade not only effectively inhibited proliferation, invasion and migration of FLSs, but also downregulated expression of inflammatory-associated proteins. Sequencing results indicated that MAGL inhibition significantly suppressed NOX4-mediated oxidative stress, thus promoting Nrf2 nuclear accumulation and inhibiting generation of intracellular reactive oxygen species (ROS). Attenuation of NOX4 further alleviated redox dysplasia and ultimately improved tumor-like phenotypes, such as abnormal proliferation, migration and migration of FLSs. In vivo results corroborated this finding, with MAGL inhibition found to modulate pain and disease progression in an OA rat model. Collectively, these results indicate that MAGL administration is an ideal therapy treating OA. Title: Identification of metabolizing enzyme genes associated with xenobiotics and odorants in the predatory stink bug Arma custos based on transcriptome analysis Li W, Zou J, Yang X, Yang M, Jiang P, Wang X, Huang C, He Y Ref: Heliyon, 9:e18657, 2023 : PubMed ESTHER: Li_2023_Heliyon_9_e18657 PubMedSearch: Li 2023 Heliyon 9 e18657 PubMedID: 37576196 Abstract The predatory stink bug, Arma custos, is a highly effective beneficial predator of crop pests. The lack of gene information related to xenobiotic detoxification and odorant degrading enzymes in the predator stink bugs to date has limited our ability for more in-depth studies of biological control. Hence, we conducted de novo assembly of the A. custos transcriptome from guts, antennae, and other tiussue samples of 5th instar larvae using Illumina sequencing technology. A total of 91, 50 and 23 genes of cytochrome P450 monooxygenases (CYPs), carboxyl/choline esterases (CCEs) and glutathione S-transferases (GSTs) genes were identified, respectively. Gene expansions of CYP3 and CYP4 clans and the hormone and pheromone processing CCE class were found in A. custos. Analysis of tissue-specific expression patterns showed that 37 CYPs, 14 CCEs and 8 GSTs were enriched in guts, and 6 CYPs, 5 CCEs and 2 GSTs were up-regulated in antennae, suggesting their potential roles on xenobiotics detoxification and ordorant degradation. Gene information data presented here could be useful for a deeper understanding of the ecology, physiology and behavior of this beneficial species and could be helpful to improve their bio-control efficiency. Title: Serum cholinesterase as a new nutritional indicator for predicting weaning failure in patients Liu J, Shao T, Chen H, Ma C, Lu X, Yang X, Song K, Wang L, Lei S, Wang D Ref: Front Med (Lausanne), 10:1175089, 2023 : PubMed ESTHER: Liu_2023_Front.Med.(Lausanne)_10_1175089 PubMedSearch: Liu 2023 Front.Med.(Lausanne) 10 1175089 PubMedID: 37502364 Abstract AIM: The objective of this study is to examine the correlation between patient serum cholinesterase (SCHE) concentration and weaning failure in the context of invasive mechanical ventilation (IMV), as well as to identify predictors of ventilator weaning failure. Additionally, this study investigates the potential relationship between SCHE and nutritional risk for developing more effective weaning strategies. METHOD: A retrospective observational study was conducted. The sample was collected from 227 patients with IMV over 48h who underwent SBT before weaning. Relevant experimental samples and data collection were analyzed at the time of patient admission and before the initiation of the SBT. The correlation between SCHE and weaning failure was determined by multifactorial logistic regression and propensity matching scores. RESULTS: Weaning was successful in 127 patients and failed in 100 patients. Depending on the difficulty of weaning, 55 of these patients had difficulty in weaning and 45 had long-term weaning. In the crude cohort, experimental data collected on the day of SBT showed that SCHE concentrations were higher in patients with successful weaning than in those with failed weaning (4,514 u/l vs. 3,190 u/l p<0.01). The critical value for predicting weaning failure was SCHE 3,228 u/l (p<0.01). Ventilator weaning failure was predicted by multifactorial logistic regression analysis of SCHE, heart rate, and PaO(2) before SBT, with SCHE predicting ventilator weaning failure (AUC 0.714; 95% CI 0.647-0.782) better than heart rate (AUC 0.618; 95% CI 0.545-0.690), PaO(2) (AUC 0.59; 95% CI 0.515-0.664). After propensity-matched scores, SCHE remained an independent predictor of weaning failure (p=0.05). And the SCHE concentration was strongly correlated with the patient's weaning difficulties (p<0.01). The Nutrition Risk in Critically Ill (NUTRIC) score was also significantly correlated with SCHE according to Spearman's correlation analysis (p<0.01). CONCLUSION: Our study revealed that the patients who experienced weaning failure exhibited lower SCHE values compared to those who successfully underwent weaning. Before spontaneous breathing trial (SBT), SCHE, heart rate, and PaO(2) were identified as independent predictors of weaning failure. Following propensity score matching (PSM), SCHE and heart rate remained independent predictors. Patients with SCHE levels below 3,228 u/l should undergo careful evaluation before weaning. Our findings suggest that malnutrition may be a contributing factor to weaning failure in patients. Title: Smartphone-assisted sensor array constructed by copper-based laccase-like nanozymes for specific identification and discrimination of organophosphorus pesticides Song D, Tian T, Yang X, Wang L, Sun Y, Li Y, Huang H Ref: Food Chem, 424:136477, 2023 : PubMed ESTHER: Song_2023_Food.Chem_424_136477 PubMedSearch: Song 2023 Food.Chem 424 136477 PubMedID: 37263094 Abstract Accurate pesticide identification is of great importance for regulating food safety. However, the discrimination between organophosphorus pesticides (OPs) and carbamate pesticides (CPs) is still a challenge for existing analytical methods based on cholinesterase inhibition. It mainly because of the similar inhibitory effect of OPs and CPs on cholinesterase. Herein, we found that OPs and CPs differentially affected nanozymes with laccase-like activity, which would be interfered by OPs in different degrees rather than CPs. Thus, we fabricated a nanozyme sensor array and successfully achieved the OPs identification and similar individual discrimination, ignoring the interference from CPs or other potential interferents (antibiotics, ions, other pesticides). On the basis of nanozyme sensor array, a portable method using smartphone was constructed and utilized to determine OPs in fruits and vegetables. This work would contribute to the development of portable sensors and the highly selective identification and discrimination of OPs in complex samples. Title: 4-Methylbenzylidene camphor triggers estrogenic effects via the brain-liver-gonad axis in zebrafish larvae Xian H, Li Z, Ye R, Dai M, Feng Y, Bai R, Guo J, Yan X, Yang X and Huang Z <1 more author(s)> Xian H, Li Z, Ye R, Dai M, Feng Y, Bai R, Guo J, Yan X, Yang X, Chen D, Huang Z (- 1) Ref: Environ Pollut, :122260, 2023 : PubMed ESTHER: Xian_2023_Environ.Pollut__122260 PubMedSearch: Xian 2023 Environ.Pollut 122260 PubMedID: 37506809 Abstract 4-Methylbenzylidene camphor (4-MBC), an emerging contaminant, is a widely-used ultraviolet (UV) filter incorporated into cosmetics because it protects the skin from UV rays and counters photo-oxidation. Despite the well-established estrogenic activity of 4-MBC, the link between this activity and its effects on neurobehavior and the liver remains unknown. Thus, we exposed zebrafish larvae to environmentally relevant concentrations of 4-MBC with 1.39, 4.17, 12.5 and 15.4 microg/mL from 3 to 5 days postfertilization. We found that 4-MBC produced an estrogenic effect by intensifying fluorescence in the transgenic zebrafish, which was counteracted by co-exposure with estrogen receptor antagonist. 4-MBC-upregulated estrogen receptor alpha (eralpha) mRNA, and an interaction between 4-MBC and ERalpha suggested ERalpha's involvement in the 4-MBC-induced estrogenic activity. RNA sequencing unearthed 4-MBC-triggered responses in estrogen stimulus and lipid metabolism. Additionally, 4-MBC-induced hypoactivity and behavioral phenotypes were dependent on the estrogen receptor (ER) pathway. This may have been associated with the disruption of acetylcholinesterase and acetylcholine activities. As a result, 4-MBC increased vitellogenin expression and caused lipid accumulation in the liver of zebrafish larvae. Collectively, this is the first study to report 4-MBC-caused estrogenic effects through the brain-liver-gonad axis. It provides novel insight into how 4-MBC perturbs the brain and liver development. Title: Combined exposure to titanium dioxide and tetracycline induces neurotoxicity in zebrafish Xu L, Yang X, He Y, Hu Q, Fu Z Ref: Comparative Biochemistry & Physiology C Toxicol Pharmacol, :109562, 2023 : PubMed ESTHER: Xu_2023_Comp.Biochem.Physiol.C.Toxicol.Pharmacol__109562 PubMedSearch: Xu 2023 Comp.Biochem.Physiol.C.Toxicol.Pharmacol 109562 PubMedID: 36764589 Abstract In aquatic environment, engineered materials may inevitably interact with the coexisted organic pollutants, which affect their bioavailability and toxicity. In this contribution, the combined impacts of tetracycline (TC) and titanium dioxide nanoparticles (TiO(2) NPs) on the neurodevelopment of zebrafish larvae were investigated, and the underlying mechanisms were further elucidated. Firstly, it was confirmed that the co-existence of TC would increase the size and decrease the zeta potential of TiO(2) NPs. Following, developmental indicators and motor behaviors were investigated. Our results indicated that co-exposure to TC and TiO(2) NPs exhibited enhanced embryonic malformation rates and abnormal nervous system development in zebrafish embryos. Meanwhile, the locomotor behavior was increased upon treatment of TC and TiO(2) NP. Further, pathway enrichment analyses of transcriptomic sequencing provided detailed information that either lipid metabolism or PPAR signaling pathway were significantly affected in the co-exposure group. Also, TC + TiO(2) NP exposure significantly changed the mRNA expression of neural development-related genes and up-regulated the expression levels of neurotransmitters like 5-hydroxytryptamine, dopamine, acetylcholinesterase, and gamma-aminobutyric acid. Taken together, our results demonstrated that the co-exposure of TC and TiO(2) NPs had the potential to cause neurotoxicity in zebrafish embryos. Title: Toxicity and Physiological Effects of Nine Lamiaceae Essential Oils and Their Major Compounds on Reticulitermes dabieshanensis Yang X, Jin C, Wu Z, Han H, Zhang Z, Xie Y, Zhang D Ref: Molecules, 28:, 2023 : PubMed ESTHER: Yang_2023_Molecules_28_ PubMedSearch: Yang 2023 Molecules 28 PubMedID: 36903258 Abstract The volatile metabolites of Salvia sclarea, Rosmarinus officinalis, Thymus serpyllum, Mentha spicata, Melissa officinalis, Origanum majorana, Mentha piperita, Ocimum basilicum and Lavandula angustifolia were determined by gas chromatography-mass spectrometry. The vapor insecticidal properties of the analyzed essential oils and their compounds were screened using Reticulitermes dabieshanensis workers. The most effective oils were S. sclarea (major constituent linalyl acetate, 65.93%), R. officinalis (1,8-cineole, 45.56%), T. serpyllum (thymol, 33.59%), M. spicata (carvone, 58.68%), M. officinalis (citronellal, 36.99%), O. majorana (1,8-cineole, 62.29%), M. piperita (menthol, 46.04%), O. basilicum (eugenol, 71.08%) and L. angustifolia (linalool, 39.58%), which exhibited LC(50) values ranging from 0.036 to 1.670 microL/L. The lowest LC(50) values were recorded for eugenol (0.060 microL/L), followed by thymol (0.062 microL/L), carvone (0.074 microL/L), menthol (0.242 microL/L), linalool (0.250 microL/L), citronellal (0.330 microL/L), linalyl acetate (0.712 microL/L) and 1,8-cineole (1.478 microL/L). The increased activity of esterases (ESTs) and glutathione S-transferase (GST) were observed but only alongside the decreased activity of acetylcholinesterase (AChE) in eight main components. Our results indicate that S. sclarea, R. officinalis, T. serpyllum, M. spicata, M. officinalis, O. marjorana, M. piperita, O. basilicum and L. angustifolia essential oils (EOs) and their compounds, linalyl acetate, 1,8-cineole, thymol, carvone, citronellal, menthol, eugenol and linalool could be developed as control agents against termites. Title: Frequency and polymorphism of acetylcholinesterase gene involved in the organophosphate resistance of Musca domestica in Guizhou Province, China Yang X, Mou R, Liang Q, Cheng J, Wu Y, Tan W, Wu J Ref: Archives of Insect Biochemistry & Physiology, :e22045, 2023 : PubMed ESTHER: Yang_2023_Arch.Insect.Biochem.Physiol__e22045 PubMedSearch: Yang 2023 Arch.Insect.Biochem.Physiol e22045 PubMedID: 37602787 Abstract Organophosphate (OP) resistance has been prevalent in Musca domestica populations worldwide since 1960s. Previous studies have demonstrated that point mutations of the acetylcholinesterase gene (Ace) are one of the important molecular mechanisms underlying OP resistance. However, few studies have investigated the molecular mechanisms of OP resistance in the past 10 years in China. In this study, we investigated the status of OP resistance and genetic diversity of Ace in the field populations of houseflies in Guizhou Province of China. The bioassays showed that the houseflies had 142-304-fold resistance to dichlorvos (DDVP) and 122-364-fold resistance to temephos, compared to the susceptible houseflies. Five nonsynonymous mutations (Y226F, V260L, G342A/V, F407Y) in Ace were detected among the 7 field populations, with an average frequency of 5.4%, 55%, 68%, 32%, and 94%, respectively, of which the Y226F mutation had not been reported previously. Eleven combinations of triple mutations (at positions 260, 342, and 407) were observed, of which the combination 260L/V+342A/V+407Y was predominant. The ZY and AS populations showed greatest diversity of allelic combination and the other five populations showed different distributions among different regions. These results indicate that the resistance to OPs is prevalent among the housefly populations and target-site insensitivity is the main cause of resistance in Guizhou Province. The difference in distribution and the allelic diversity of Ace in field populations may be due to the complexity and variability of insecticide application. It is necessary to monitor resistance to insecticides and conduct management of houseflies in Guizhou Province. Title: Smartphone-based colorimetric sensor array using gold nanoparticles for rapid distinguishment of multiple pesticides in real samples Zhao T, Liang X, Guo X, Yang X, Guo J, Zhou X, Huang X, Zhang W, Wang Y and Zhou H <2 more author(s)> Zhao T, Liang X, Guo X, Yang X, Guo J, Zhou X, Huang X, Zhang W, Wang Y, Liu Z, Jiang Z, Zhou H (- 2) Ref: Food Chem, 404:134768, 2023 : PubMed ESTHER: Zhao_2023_Food.Chem_404_134768 PubMedSearch: Zhao 2023 Food.Chem 404 134768 PubMedID: 36444090 Abstract A simple, sensitive method for pesticide distinguishment based on a colorimetric sensor array using diverse gold nanoparticles (AuNPs) at room temperature is presented in this study. Acetylcholinesterase (AChE) hydrolysis ability was influenced by different pesticides and produced different concentrations of thiocholine by hydrolyzing acetylthiocholine iodide (ATCh). Thiocholine could be easily linked to the AuNPs through an Aus-sS covalent bond, and AuNPs underwent aggregation, resulting in a visible color change due to alteration of surface plasmon resonance properties. Based on these results, we successfully distinguished eight pesticides (glyphosate, thiram, imidacloprid, tribenuron methyl, nicosulfuron, thifensulfuron methyl, dichlorprop, and fenoprop) utilizing five different AuNPs by colorimetric assay. The limit of detection (LOD) of this visual method for all pesticides was less than 1.5x 10(-7) M, which was more sensitive than the U.S. Environmental Protection Agency regulations specify (1.18s-s3.91x10(-6) M). This method was further improved by combining a portable smartphone device with a color picking application using (color name AR) and RGB (red, green, blue) values. The method was successfully applied to pesticide residue distinguishment in real samples by linear discriminant analysis (LDA). Title: The MAX2-KAI2 module promotes salicylic acid-mediated immune responses in Arabidopsis Zheng X, Liu F, Yang X, Li W, Chen S, Yue X, Jia Q, Sun X Ref: J Integr Plant Biol, :, 2023 : PubMed ESTHER: Zheng_2023_J.Integr.Plant.Biol__ PubMedSearch: Zheng 2023 J.Integr.Plant.Biol PubMedID: 36738234 Abstract Arabidopsis MORE AXILLARY GROWTH2 (MAX2) is a key component in the strigolactone (SL) and karrikin (KAR) signaling pathways and regulates the degradation of SUPPRESSOR OF MAX2 1/SMAX1-like (SMAX1/SMXL) proteins, which are transcriptional co-repressors that regulate plant architecture, as well as abiotic and biotic stress responses. The max2 mutation reduces resistance against Pseudomonas syringae pv. tomato (Pst). To uncover the mechanism of MAX2-mediated resistance, we evaluated the resistance of various SL and KAR signaling pathway mutants. The resistance of SL-deficient mutants and of dwarf 14 (d14) was similar to that of the wild type, whereas the resistance of the karrikin insensitive 2 (kai2) mutant was compromised, demonstrating that the KAR signaling pathway, not the SL signaling pathway, positively regulates the immune response. We measured the resistance of smax1 and smxl mutants, as well as the double, triple, and quadruple mutants with max2, which revealed that both the smax1 mutant and smxl6/7/8 triple mutant rescue the low resistance phenotype of max2 and that SMAX1 accumulation diminishes resistance. The susceptibility of smax1D, containing a degradation-insensitive form of SMAX1, further confirmed the SMAX1 function in the resistance. The relationship between the accumulation of SMAX1/SMXLs and disease resistance suggested that the inhibitory activity of SMAX1 to resistance requires SMXL6/7/8. Moreover, exogenous application of KAR2 enhanced resistance against Pst, but KAR-induced resistance depended on salicylic acid (SA) signaling. Inhibition of karrikin signaling delayed SA-mediated defense responses and inhibited pathogen-induced protein biosynthesis. Together, we propose that the MAX2-KAI2-SMAX1 complex regulates resistance with the assistance of SMXL6/7/8 and SA signaling and that SMAX1/SMXLs possibly form a multimeric complex with their target transcription factors to fine-tune immune responses. This article is protected by copyright. All rights reserved. Title: Identification and Validation of Reliable Reference Genes for Gene Expression Studies in Koelreuteria paniculata Gao K, Khan WU, Li J, Huang S, Yang X, Guo T, Guo B, Wu R, An X Ref: Genes (Basel), 13:, 2022 : PubMed ESTHER: Gao_2022_Genes.(Basel)_13_ PubMedSearch: Gao 2022 Genes.(Basel) 13 PubMedID: 35627099 Abstract RT-qPCR is considered a rapid and reliable technique for analyzing gene expression. This technique is commonly used to analyze the expression of various genes at diverse transcriptional levels in different samples. However, few studies have characterized ornamental Koelreuteria species for reliable reference genes. In this study, eight reference genes were evaluated as controls in RT-qPCR with SYBR green to quantify gene expression in different Koelreuteria paniculata samples. All selected reference genes showed a broad range of C(t) values in all samples, which was supportive of their variable expression. Our results showed significant variation in the stable expression of K. paniculata genes. Sample data, analyzed using geNorm, NormFinder, and BestKeeper, showed that phospholipase (PLA2) and beta-actin (ACT) were the most suitable and statistically reliable reference genes, whereas ribosomal protein L13 (RPL13) and elongation factor 1-alpha (EF1alpha) were less stable and unsuitable for use as internal controls. To compare gene expression levels, two or more reference genes should be used for data normalization. Thus, the stability and expression of both PLA2 and ACT were believed to provide better normalization and quantification of the transcript levels for gene expression studies in K. paniculata. Title: Enantioselective Total Synthesis of (+)-Sieboldine A and Analogues Thereof Huang BB, Zhao YL, Lei K, Zhong LR, Yang X, Yao ZJ Ref: Org Lett, :, 2022 : PubMed ESTHER: Huang_2022_Org.Lett__ PubMedSearch: Huang 2022 Org.Lett PubMedID: 36214606 Abstract An 11-step enantioselective total synthesis of (+)-sieboldine A (1) has been accomplished from (5R)-methylcyclohex-2-en-1-one (16), in which an intramolecular ketone/ester reductive coupling followed by one-pot acidic treatment to quickly construct the unique oxa-spiroacetal and a TsOH-catalyzed displacement to directly form the characteristic N-hydroxyazacyclononane ring successfully served as the key methodologies. Moreover, several full-skeleton analogues of 1 were also synthesized on the basis of the advanced intermediates, and their inhibitory effects on electric eel acetylcholinesterase were examined. Title: Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity Jia Y, Shi S, Cheng B, Cheng S, Liu L, Meng P, Yang X, Chu X, Wen Y and Guo X <1 more author(s)> Jia Y, Shi S, Cheng B, Cheng S, Liu L, Meng P, Yang X, Chu X, Wen Y, Zhang F, Guo X (- 1) Ref: Front Nutr, 9:935112, 2022 : PubMed ESTHER: Jia_2022_Front.Nutr_9_935112 PubMedSearch: Jia 2022 Front.Nutr 9 935112 PubMedID: 35990316 Abstract BACKGROUND: T-2 toxin is recognized as one of the high-risk environmental factors for etiology and pathogenesis of Kashin-Beck disease (KBD). Previous evidence indicates decreased serum fluorine level in KBD patients. However, whether fluoride could regulate carboxylesterase 1 (CES1)-mediated T-2 toxin hydrolysis and alter its chondrocyte toxicity remains largely unknown. METHODS: In this study, in vitro hydrolytic kinetics were explored using recombinant human CES1. HPLC-MS/MS was used to quantitative determination of hydrolytic metabolites of T-2 toxin. HepG2 cells were treated with different concentration of sodium fluoride (NaF). qRT-PCR and western blot analysis were used to compare the mRNA and protein expression levels of CES1. C28/I2 cells were treated with T-2 toxin, HT-2 toxin, and neosolaniol (NEO), and then cell viability was determined by MTT assay, cell apoptosis was determined by Annexin V-FITC/PI, Hoechst 33258 staining, and cleaved caspase-3, and cell cycle was monitored by flow cytometry assay, CKD4 and CDK6. RESULTS: We identified that recombinant human CES1 was involved in T-2 toxin hydrolysis to generate HT-2 toxin, but not NEO, and NaF repressed the formation of HT-2 toxin. Both mRNA and protein expression of CES1 were significantly down-regulated in a dose-dependent manner after NaF treatment in HepG2 cells. Moreover, we evaluated the chondrocyte toxicity of T-2 toxin and its hydrolytic metabolites. Results showed that T-2 toxin induced strongest cell apoptosis, followed by HT-2 toxin and NEO. The decreased the proportion of cells in G0/G1 phase was observed with the descending order of T-2 toxin, HT-2 toxin, and NEO. CONCLUSIONS: This study reveals that CES1 is responsible for the hydrolysis of T-2 toxin, and that fluoride impairs CES1-mediated T-2 toxin detoxification to increase its chondrocyte toxicity. This study provides novel insight into understanding the relationship between fluoride and T-2 toxin in the etiology of KBD. Title: Bioaccumulation and toxicity of terbuthylazine in earthworms (Eisenia fetida) Li S, Yuan Y, Wang X, Cai L, Wang J, Zhao Y, Jiang L, Yang X Ref: Environ Toxicol Pharmacol, 97:104016, 2022 : PubMed ESTHER: Li_2022_Environ.Toxicol.Pharmacol_97_104016 PubMedSearch: Li 2022 Environ.Toxicol.Pharmacol 97 104016 PubMedID: 36435387 Abstract Terbuthylazine is an effective and widely used s-triazine herbicide. However, limited data exists on its toxicity and bioaccumulation in earthworms (Eisenia fetida). In this study, we investigated the bioaccumulation, antioxidant enzyme activity, detoxification enzyme activity, and DNA damage in earthworms when exposed to terbuthylazine. The results indicated that terbuthylazine in soil had low bioaccumulation in earthworms and the biota-soil accumulation factors of terbuthylazine declined with an increasing soil terbuthylazine concentration. In the enzyme activity assays, the superoxide dismutase (SOD), catalase (CAT), and glutathione-S-transferase (GST) activities showed upward trends when compared with the control. The carboxylesterase (CarE) activity increased on day 21. The 8-hydroxy-2-deoxyguanosine (8-OHdG) content, a DNA damage bioindicator, was higher than that of the control on day 21. Combined with the integrated biological response index version 2 analysis, these results can provide a comprehensive evaluation of the toxicological effects that terbuthylazine has on earthworms and soil ecosystems. Title: Colorimetric Assay for Acetylcholinesterase Activity and Inhibitor Screening Based on Metal-Organic Framework Nanosheets Wang Y, Xue Y, Zhao Q, Wang S, Sun J, Yang X Ref: Analytical Chemistry, 94:16345, 2022 : PubMed ESTHER: Wang_2022_Anal.Chem_94_16345 PubMedSearch: Wang 2022 Anal.Chem 94 16345 PubMedID: 36444539 Abstract Alzheimer's disease (AD) is a common chronic neurodegenerative disease that manifests as cognitive impairment and behavioral deficits and severely threatens the health of the elderly. Acetylcholinesterase (AChE) plays a vital role in biological signaling and is an essential target for the early diagnosis and treatment of AD. Herein, 2D Zn-TCPP(Fe) nanosheets (NSs) employing Zn(2+) and Fe-bound tetrakis(4-carboxyphenyl)porphyrin ligands were prepared through a surfactant-assisted synthetic method. The ultrathin two-dimensional (2D) metal-organic framework structures exhibited high peroxidase-like activity, which allowed the catalysis of the H(2)O(2)-initiated oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (ox-TMB). Such catalytic performance inspired us to develop a convenient, rapid, and sensitive acetylcholinesterase activity assay, during which AChE can catalyze the substrate acetylthiocholine (ATCh) to produce thiocholine (TCh), and TCh could especially enable the degradation of 2D Zn-TCPP(Fe) NSs accompanied by the reduction of ox-TMB production. Our proposed sensing system exhibited favorable selectivity and sensitivity (LOD of 0.029 mU/mL) and has excellent potential to evaluate AChE activity in human serum samples and to screen AChE inhibitors. This colorimetric assay could provide an alternative pathway for early diagnosis and drug screening of AD, facilitating the development of AD therapy. Title: An easily available endoplasmic reticulum targeting near-infrared fluorescent probe for esterase imaging in vitro and in vivo Xiang C, Xiang J, Yang X, Zhu B, Mo Q, Zhou L, Gong P Ref: Analyst, :, 2022 : PubMed ESTHER: Xiang_2022_Analyst__ PubMedSearch: Xiang 2022 Analyst PubMedID: 35107444 Abstract Here, we report an easily available endoplasmic reticulum-targeting near-infrared fluorescent probe (ER-CE), which can detect esterase in the endoplasmic reticulum and monitor the changes in the esterase amount in tumors in mice in real time. These results indicate that ER-CE is expected to become a powerful analysis tool for the research of endoplasmic reticulum esterase-related diseases. Title: Ratiometric imaging of butyrylcholinesterase activity in mice with nonalcoholic fatty liver using an AIE-based fluorescent probe Xiang C, Xiang J, Yang X, Li C, Zhou L, Jiang D, Peng Y, Xu Z, Deng G and Gong P <3 more author(s)> Xiang C, Xiang J, Yang X, Li C, Zhou L, Jiang D, Peng Y, Xu Z, Deng G, Zhu B, Zhang P, Cai L, Gong P (- 3) Ref: J Mater Chem B, :, 2022 : PubMed ESTHER: Xiang_2022_J.Mater.Chem.B__ PubMedSearch: Xiang 2022 J.Mater.Chem.B PubMedID: 35583194 Abstract Butyrylcholinesterase (BChE) is an essential human biomarker which is related to liver and neurodegenerative diseases. It is of great significance to develop a fluorescent probe that can image BChE in vitro and in vivo. Unfortunately, most fluorescent probes that are based on a single change in fluorescence intensity are susceptible to environmental interference. Therefore, we reported an easily available ratiometric fluorescent probe, TB-BChE, with aggregation-induced emission (AIE) characteristics for ratiometric imaging of BChE. TB-BChE demonstrated excellent sensitivity (LOD = 39.24 ng mL(-1)) and specificity for BChE. Moreover, we have successfully studied the ratiometric imaging of TB-BChE to BChE in a nonalcoholic fatty liver disease model. These results indicated that TB-BChE is expected to become a powerful analysis tool for butyrylcholinesterase research in basic medicine and clinical applications. Title: Association of the Cholinergic Anti-Inflammatory Pathway Activity with Proinflammatory Factors and Prognosis of Patients with Acute Respiratory Distress Syndrome Yang Y, Zhang J, Yang X, Yang J Ref: Evid Based Complement Alternat Med, 2022:8302701, 2022 : PubMed ESTHER: Yang_2022_Evid.Based.Complement.Alternat.Med_2022_8302701 PubMedSearch: Yang 2022 Evid.Based.Complement.Alternat.Med 2022 8302701 PubMedID: 35664939 Abstract OBJECTIVE: The cholinergic anti-inflammatory pathway (CAP) has been shown to modulate cytokine release by activating alpha-7 nicotinic acetylcholine receptors (alpha7nAChR) in monocytes/macrophages. However, their association with proinflammatory factors and prognosis in patients with acute respiratory distress syndrome (ARDS) has not been clarified. Here, we explored the correlation between CAP activity, proinflammatory factors, and the prognosis of ARDS patients. METHODS: The data of patients with ARDS (n = 65; underwent treatment) and healthy individuals (the control group; n = 65; underwent routine physical examination) at the Chongqing People's Hospital were investigated. Based on the survival status, ARDS patients were divided into a death ARDS group (n = 22) and a survival ARDS group (n = 43), and based on the diagnostic criteria of ARDS, the patients were also divided into a severe ARDS group (n = 30) and a mild-to-moderate ARDS group (n = 35). The levels of acetylcholine (ACh), acetylcholinesterase (AChE), and alpha7nAChR mRNA in peripheral blood monocytes were assessed. The levels of TNF-alpha and IL-6 in peripheral serum and peripheral monocytes were detected by ELISA and Western blot tests. The association between alpha7nAChR and inflammatory factors and prognosis was analyzed. The receiver-operating characteristic (ROC) curve was used to evaluate the reliability of CAP-related factors in predicting the survival status of ARDS patients. RESULTS: Compared with the control group, the levels of ACh, AChE, and alpha7nAChR mRNA of the ARDS group were significantly decreased. And, the ACh, AChE, and alpha7nAChR mRNA levels in the death/severe ARDS group were significantly lower than in the survival/mild-to-moderate ARDS group. However, the levels of TNF-alpha and IL-6 were significantly higher in the severe/death ARDS group. Furthermore, we observed that CAP-related factors were negatively correlated with the levels of IL-6 and TNF-alpha in peripheral serum in the ARDS group. The ROC curve showed that CAP-related factors were reliable markers for predicting the survival status of ARDS patients. CONCLUSION: The related factors of the cholinergic anti-inflammatory pathway were significantly decreased in patients with ARDS, suggesting the ACh, AChE, and alpha7nAChR levels as potential indicators to evaluate the severity and prognosis status of ARDS patients. Title: Neurotoxicity and transcriptome changes in embryonic zebrafish induced by halobenzoquinone exposure Yang X, Wang C, Yang L, Zheng Q, Liu Q, Wawryk NJP, Li XF Ref: J Environ Sci (China), 117:129, 2022 : PubMed ESTHER: Yang_2022_J.Environ.Sci.(China)_117_129 PubMedSearch: Yang 2022 J.Environ.Sci.(China) 117 129 PubMedID: 35725065 Abstract Halobenzoquinones (HBQs) are emerging disinfection byproducts (DBPs) with a widespread presence in drinking water that exhibit much higher cytotoxicity than regulated DBPs. However, the developmental neurotoxicity of HBQs has not been studied in vivo. In this work, we studied the neurotoxicity of HBQs on zebrafish embryos, after exposure to varying concentrations (0-8 micromol/L) of three HBQs, 2,5-dichloro-1,4-benzoquinone (2,5-DCBQ), 2,6-dichloro-1,4-benzoquinone (2,6-DCBQ), and 2,5-dibromo-1,4-benzoquinone (2,5-DBBQ) for 4 to 120 hr post fertilization (hpf). HBQ exposure significantly decreased the locomotor activity of larvae, accompanied by significant reduction of neurotransmitters (dopamine and gamma-aminobutyric acid) and acetylcholinesterase activity. Furthermore, the expression of genes involved in neuronal morphogenesis (gfap, alpha1-tubulin, mbp, and syn-2alpha) were downregulated by 4.4-, 5.2-, 3.0-, and 4.5-fold in the 5 micromol/L 2,5-DCBQ group and 2.0-, 1.6-, 2.1-, and 2.3-fold in the 5 micromol/L 2,5-DBBQ group, respectively. Transcriptomic analysis revealed that HBQ exposure affected the signaling pathways of neural development. This study demonstrates the significant neurotoxicity of HBQs in embryonic zebrafish and provides molecular evidence for understanding the potential mechanisms of HBQ neurotoxicity. Title: The role of butyrylcholinesterase in the regulation of cognitive dysfunction in minimal hepatic encephalopathy: A potential blood marker of disease evolution Yang X, Dang P, Liu W, Ma W, Ge X, Zhu K, Wang M, Huang X, Ding X, Wang X Ref: Front Neurol, 13:900997, 2022 : PubMed ESTHER: Yang_2022_Front.Neurol_13_900997 PubMedSearch: Yang 2022 Front.Neurol 13 900997 PubMedID: 36341087 Abstract BACKGROUND AND AIMS: Patients with cirrhosis commonly experience minimal hepatic encephalopathy (MHE), and alterations in neurotransmitters have been thought to be related to cognitive function. However, the relationship between alterations in peripheral and central butyrylcholinesterase (BuChE) with MHE disease progression remains unknown. As such, this study was designed to investigate potential changes in peripheral and central BuChE activity and their effects on cognitive function in the context of MHE. MATERIALS AND METHODS: We enrolled 43 patients with cirrhosis secondary to hepatitis B, 20 without MHE and 23 with MHE, and 25 with healthy controls (HC). All the selected subjects underwent resting-state functional MRI, and the original images were processed to obtain the regional homogeneity (ReHo) brain maps. Thereafter, the correlation of BuChE activity with ReHo, number connection test of type A (NCT-A), and digital symbol test (DST) scores with MHE patients were analyzed using Person correlation analysis. Meanwhile, we purchased 12 Sprague-Dawley (SD) rats and divided them into an experimental group (n = 6) and a control group (n = 6). The rats in the experimental group were intraperitoneally injected with thioacetamide (TAA) to prepare MHE model rats. After modeling, we used the Morris water maze (MWM) and elevated plus maze (EPM) to assess the cognition function and exploratory behavior of all rats. The activity of serum, hippocampus, and frontal lobe tissue BuChE was detected by ELISA. RESULTS: BuChE activity gradually decreased among the HC, patients with cirrhosis, and MHE groups (all P < 0.01). We observed a linear correlation between serum BuChE and NCT-A and DST scores in MHE patients (all P < 0.01). We noted that BuChE activity can negatively correlate with ReHo values in the left middle temporal gyrus and left inferior temporal gyrus, and positively correlate with ReHo values in the right inferior frontal gyrus, and also found that the peripheral BuChE activity of MHE rats was significantly lower than their control counterparts, and the BuChE activity in frontal lobe extracts was significantly higher than the control rats (all P < 0.05). CONCLUSION: The altered activity of BuChE may contribute to cognitive impairment in MHE patients, which may be a potential biomarker of disease evolution in the context of MHE. Title: Phenolic and bisamide derivatives from Aglaia odorata and their biological activities Yang X, Yu Y, Wu P, Liu J, Li Y, Tao L, Tan R, Hao X, Yuan C, Yi P Ref: Nat Prod Res, :1, 2022 : PubMed ESTHER: Yang_2022_Nat.Prod.Res__1 PubMedSearch: Yang 2022 Nat.Prod.Res 1 PubMedID: 36580570 Abstract Three new compounds (1-3), including two bisamide derivatives (1 and 2) and a lignin (3), along with 15 known compounds were isolated from Aglaia odorata. Compound 2 was a pair of enantiomers and successfully resolved into the anticipated enantiomers. Their structures were elucidated by extensive spectroscopic analysis, electronic circular dichroism (ECD) calculations, and X-ray crystallography. Three compounds showed excellent inhibitory activities on alpha-glucosidase with IC(50) values ranging from 54.48 to 240.88 microM, better than that of the positive control (acarbose, IC(50) = 590.94 microM). Moreover, compounds 3, 13, and 15 presented moderate inhibitory activities against butyrylcholinesterase. Compound 17 exhibited potent PTP1B inhibitory activity with an IC(50) value of 179.45 microM. Representative active compounds were performed for the molecular docking study. Herein, we described the isolation, structure elucidation, the inhibitory effects on three enzymes, and molecular docking of the isolates from the title plant. Title: Substrate-Binding Mode of a Thermophilic PET Hydrolase and Engineering the Enzyme to Enhance the Hydrolytic Efficacy Zeng W, Li X, Yang Y, Min J, Huang JW, Liu W, Niu D, Yang X, Han X and Guo RT <3 more author(s)> Zeng W, Li X, Yang Y, Min J, Huang JW, Liu W, Niu D, Yang X, Han X, Zhang L, Dai L, Chen CC, Guo RT (- 3) Ref: ACS Catal, 12:3033, 2022 : PubMed ESTHER: Zeng_2022_ACS.Catal_12_3033 PubMedSearch: Zeng 2022 ACS.Catal 12 3033 Gene_locus related to this paper: 9bact-g9by57 Inhibitor(s) related to this paper: MHET Abstract Polyethylene terephthalate (PET) is among the most extensively produced plastics, but huge amounts of PET wastes that have accumulated in the environment have become a serious threat to the ecosystem. Applying PET hydrolytic enzymes to depolymerize PET is an attractive measure to manage PET pollution, and searching for more effective enzymes is a prerequisite to achieve this goal. A thermostable cutinase that originates from the leaf-branch compost termed ICCG is the most effective PET hydrolase reported so far. Here, we illustrated the crystal structure of ICCG in complex with the PET analogue, mono(2-hydroxyethyl)terephthalic acid, to reveal the enzyme-substrate interaction network. Furthermore, we applied structure-based engineering to modify ICCG and screened for variants that exhibit higher efficacy than the parental enzyme. As a result, several variants with the measured melting temperature approaching 99 C and elevated PET hydrolytic activity were obtained. Finally, crystallographic analyses were performed to reveal the structural stabilization effects mediated by the introduced mutations. These results are of importance in the context of understanding the mechanism of action of the thermostable PET hydrolytic enzyme and shall be beneficial to the development of PET biodegradation platforms. Title: Biodegradation of Free Gossypol by Helicoverpa armigera Carboxylesterase Expressed in Pichia pastoris Zhang L, Yang X, Huang R, Nie C, Niu J, Chen C, Zhang W Ref: Toxins (Basel), 14:816, 2022 : PubMed ESTHER: Zhang_2022_Toxins.(Basel)_14_816 PubMedSearch: Zhang 2022 Toxins.(Basel) 14 816 PubMedID: 36548713 Abstract Gossypol is a polyphenolic toxic secondary metabolite derived from cotton. Free gossypol in cotton meal is remarkably harmful to animals. Furthermore, microbial degradation of gossypol produces metabolites that reduce feed quality. We adopted an enzymatic method to degrade free gossypol safely and effectively. We cloned the gene cce001a encoding carboxylesterase (CarE) into pPICZalphaA and transformed it into Pichia pastoris GS115. The target protein was successfully obtained, and CarE CCE001a could effectively degrade free gossypol with a degradation rate of 89%. When esterase was added, the exposed toxic groups of gossypol reacted with different amino acids and amines to form bound gossypol, generating substances with (M + H) m/z ratios of 560.15, 600.25, and 713.46. The molecular formula was C(27)H(28)O(13), C(34)H(36)N(2)O(6), and C(47)H(59)N(3)O(3). The observed instability of the hydroxyl groups caused the substitution and shedding of the group, forming a substance with m/z of 488.26 and molecular formula C(31)H(36)O(5). These properties render the CarE CCE001a a valid candidate for the detoxification of cotton meal. Furthermore, the findings help elucidate the degradation process of gossypol in vitro. Title: Maternally inherited diabetes and deafness coexists with lipoprotein lipase gene mutation-associated severe hyperlipidemia that was resistant to fenofibrate and atorvastatin, but sensitive to bezafibrate: A case report Zhang X, Chen Y, Tong N, Shao Q, Zhou Y, Mu T, Yang X, Zhang Y Ref: J Diabetes Investig, 13:397, 2022 : PubMed ESTHER: Zhang_2022_J.Diabetes.Investig_13_397 PubMedSearch: Zhang 2022 J.Diabetes.Investig 13 397 PubMedID: 34460997 Gene_locus related to this paper: human-LPL Abstract Maternally inherited diabetes and deafness is a rare genetic disease mainly caused by a point mutation in mitochondrial deoxyribonucleic acid. Lipoprotein lipase gene mutations are associated with familial dyslipidemias, which are difficult to manage. We reported for the first time a case that had both maternally inherited diabetes and severe hyperlipidemia caused by lipoprotein lipase gene mutation (C.347(exon3)G>C) that was resistant to fenofibrate and atorvastatin. We were able to manage the patient's hyperlipidemia with bezafibrate, and her diabetes was well controlled with insulin. In conclusion, genetic testing is helpful in identifying rare and interesting cases when clinicians suspect inheritable diseases. Additionally, when one fibrate drug is ineffective in treating hyperlipidemia, it might be worthwhile trying another fibrate. Title: Ric8 acts as a regulator of G-protein signaling required for nematode-trapping lifecycle of Arthrobotrys oligospora Bai N, Zhang G, Wang W, Feng H, Yang X, Zheng Y, Yang L, Xie M, Zhang KQ, Yang J Ref: Environ Microbiol, :, 2021 : PubMed ESTHER: Bai_2021_Environ.Microbiol__ PubMedSearch: Bai 2021 Environ.Microbiol PubMedID: 34431203 Abstract Resistance to inhibitors of cholinesterase 8 (Ric8) is a conserved guanine nucleotide exchange factor that is involved in the regulation of G-protein signaling in filamentous fungi. Here, we characterized an orthologous Ric8 (AoRic8) in Arthrobotrys oligospora by multi-omics analyses. The Aoric8 deletion (deltaAoric8) mutants lost an ability to produce traps essential for nematode predation, accompanied by a marked reduction in cAMP level. Yeast two-hybrid assay revealed that AoRic8 interacted with G-protein subunit Galpha1. Moreover, the mutants were compromised in mycelia growth, conidiation, stress resistance, endocytosis, cellular components, and intrahyphal hyphae. Revealed by transcriptomic analysis differentially upregulated genes in the absence of Aoric8 were involved in cell cycle, DNA replication, and recombination during trap formation while downregulated genes were primarily involved in organelles, carbohydrate metabolism, and amino acid metabolism. Metabolomic analysis showed that many compounds were markedly downregulated in deltaAoric8 mutants versus the wild-type strain. Our results demonstrated a crucial role for AoRic8 in the fungal growth, environmental adaption, and nematode predation through control of cell cycle, organelle, and secondary metabolism by G-protein signaling. This article is protected by copyright. All rights reserved. Title: Total synthesis of (-)-brazilane via a lipase-catalyzed desymmetrisation reaction Guo X, Xue Z, Xu D, Tu Q, Chang H, Yang X, Huang S Ref: Nat Prod Res, :1, 2021 : PubMed ESTHER: Guo_2021_Nat.Prod.Res__1 PubMedSearch: Guo 2021 Nat.Prod.Res 1 PubMedID: 33970713 Abstract Herein, we described the asymmetric total synthesis of (-)-brazilane, an optically active natural product. The key steps of this synthetic approach are a lipase-catalyzed desymmetrisation reaction of a prochiral diol using vinyl acetate to prepare a chiral primary alcohol and a trifluoroacetic acid-catalyzed one pot intramolecular tandem Prins/Friedel-Crafts reaction used to construct the cis-fused chromane and indane framework. Title: Health benefits and phenolic compounds of Moringa oleifera leaves: A comprehensive review Hassan MA, Xu T, Tian Y, Zhong Y, Ali FAZ, Yang X, Lu B Ref: Phytomedicine, 93:153771, 2021 : PubMed ESTHER: Hassan_2021_Phytomedicine_93_153771 PubMedSearch: Hassan 2021 Phytomedicine 93 153771 PubMedID: 34700271 Abstract BACKGROUND: Moringa oleifera Lam (MO) is native to India and is a cash crop widely cultivated in tropical and sub-tropical areas. The health improving properties of MO has been studied from a long time ago for the numerous phenolic compounds, including vitamins, flavonoids, phenolic acids, isothiocyanates, tannins and saponins, which are present in considerable amounts in the plant. A growing spectrum of therapeutic characteristics of MO leaves has been found and used in the remission or treatment of oxidative stress, liver disease, neurological disease, hyperglycemia and cancer. HYPOTHESIS: This review focused on researches applying MO or MO leaf extract as a functional food or cure against various disease and cellular injuries. We believed it would help the discovery of therapeutic application of MO and understanding of MO phytochemistry. METHODS: The data collected in this review were extracted from researches indexed in Web of Science, google scholar, PubMed, Science Direct and Scopus to find out health benefits and biological activities of MO leaves polyphenols. The studies reporting mechanistic route of phenolic compounds of MO leaves were also considered in the present study. RESULTS: It has been reported that polyphenols of MO leaf have protective characteristics against neurodegenerative disorders through reducing DNA damage, activation of AchE activity and inhibition of caspase-3 activity. It has been reported that, they protected the kidney from damage caused by melamine through suppressed the pro-inflammatory cytokine, metallopeptidase inhibitor 1 (TIMP-1), and kidney injury molecule 1 (KIM-1). Similarly, methanol extract of MO leaves has low hypoglycemic attributes and attenuate the risk of diabetes caused by alloxan by enhancing lipid metabolism and stimulating insulin release, glucose uptake, and glycogen synthesis. In addition, MO leaves are becoming the best phytomedicine to reduce hypertension, which are naturally known as angiotensin-1converting enzyme (ACE), acetylcholinesterase, arginase and phosphodiesterase 5 (PDE5) inhibitors. CONCLUSION: MO leaves extract as a health promoting food additives for human and animals due to its great protective effect against many diseases and the widely persistent environmental toxins which disrupted cellular metabolic function. More studies are required to use the phenolic compounds of MO leaves to develop and produce drugs for controlling and treatment of various diseases. Title: A non-integrated iPSC line (SDQLCHi042-A) from a boy suffering from familial combined hyperlipidemia with compound heterozygous mutations of lipoprotein lipase gene Li Z, Zhang X, Li X, Yang Y, Xin H, Yang X, Liu N, Gai Z, Liu Y Ref: Stem Cell Res, 53:102313, 2021 : PubMed ESTHER: Li_2021_Stem.Cell.Res_53_102313 PubMedSearch: Li 2021 Stem.Cell.Res 53 102313 PubMedID: 34087978 Gene_locus related to this paper: human-LPL Abstract In this study, peripheral blood monouclear cells (PBMCs) were donated from a boy suffering from familial combined hyperlipidemia confirmed by clinical and genetic diagnosis, which carried compound heterozygous mutations of lipoprotein lipase (LPL) gene. The induced pluripotent stem cell (iPSC) was generated with non-integrated episomal vectors carrying OCT4, SOX2, KLF4, BCL-XL and C-MYC. The iPSCs presented the morphology of pluripotent cells, highly expressed mRNA and protein of pluripotent markers, excellent differentiation potency in vitro and normal karyotype, and bore LPL gene mutations. Title: Intestinal UGT1A1 and protection against Irinotecan-induced toxicity in a novel UGT1A1 tissue-specific humanized mouse model Mennillo E, Yang X, Weber AA, Maruo Y, Verreault M, Barbier O, Chen S, Tukey RH Ref: Drug Metabolism & Disposition: The Biological Fate of Chemicals, :, 2021 : PubMed ESTHER: Mennillo_2021_Drug.Metab.Dispos__ PubMedSearch: Mennillo 2021 Drug.Metab.Dispos PubMedID: 34697081 Abstract The human UDP-glucuronosyltransferases (UGTs) represent an important family of drug-metabolizing enzymes, with UGT1A1 targeting the conjugation and detoxification of many exogenous substances including pharmaceutical drugs. In this study we generated humanized UGT1A1 mice expressing the human UGT1A1 gene in either liver (hUGT1A1(HEP) ) or intestine (hUGT1A1(GI) ), enabling experiments to examine tissue-specific properties of UGT1A1 specific glucuronidation. Hepatic and intestinal tissue-specific expression and function of UGT1A1 were demonstrated. Although the liver is considered a major organ for detoxification, intestinal UGT1A1 is an important contributor for drug clearance. Mice were challenged with irinotecan (CPT-11), a prodrug hydrolyzed by carboxylesterases to form the active metabolite SN-38 and detoxified by UGT1A1. Humanized UGT1A1(HEP) mice, that have no intestinal UGT1A1, displayed a greater lethality rate when exposed to CPT-11 than hUGT1A1(GI) mice. When exposed to a low dose of CPT-11 (10 mg/kg), hUGT1A1(HEP) mice displayed greater intestinal inflammatory (IL-1beta and IL-6) insult in addition to p53-triggered apoptotic responses. In vitro studies with intestinal crypt organoids exposed to CPT-11 confirmed the results observed in vivo and indicated that CPT-11 impacts stemness, apoptosis, and ER stress in organoids deficient UGT1A1. When we examined the induction of ER stress in organoids with thapsigargin (TGN), an inhibitor of sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), apoptosis and the caspase surge that occurred in hUGT1A1(HEP) mice were blocked in hUGT1A1(GI) organoids. This study reveals the importance of intestinal UGT1A1 in preventing inflammation, apoptosis, and loss of intestinal stemness capacity upon systemic challenge with an important chemotherapeutic agent. Significance Statement Hepatic and intestinal UGT1A1 play a key role in the metabolism and detoxification of endogenous and exogenous compounds. The use of tissue-specific humanized models expressing UGT1A1 in liver or intestine has confirmed the relevance of the intestinal tract in the detoxification of irinotecan. Mechanistic studies using intestinal organoids highlighted the importance of UGT1A1 in reducing inflammation, apoptosis, and loss of stemness. These new models provide valuable tools for studying tissue-specific glucuronidation of substances that are metabolized by human UGT1A1. Title: Adsorption mechanism of two pesticides on polyethylene and polypropylene microplastics: DFT calculations and particle size effects Mo Q, Yang X, Wang J, Xu H, Li W, Fan Q, Gao S, Yang W, Gao C and Zhang Y <2 more author(s)> Mo Q, Yang X, Wang J, Xu H, Li W, Fan Q, Gao S, Yang W, Gao C, Liao D, Li Y, Zhang Y (- 2) Ref: Environ Pollut, 291:118120, 2021 : PubMed ESTHER: Mo_2021_Environ.Pollut_291_118120 PubMedSearch: Mo 2021 Environ.Pollut 291 118120 PubMedID: 34520951 Abstract Polyethylene (PE) and polypropylene (PP) microplastics (MPs), as carriers, can bind with pesticides, which propose harmful impacts to aqueous ecosystems. Meanwhile, carbofuran and carbendazim (CBD), two widely used carbamate pesticides, are toxic to humans because of the inhibition of acetylcholinesterase activity. The interaction between two MPs and two pesticides could start in farmland and be maintained during transportation to the ocean. Herein, the adsorption behavior and mechanism of carbofuran and carbendazim (CBD) by PE and PP MPs were investigated via characterization and density functional theory (DFT) simulation. The adsorption kinetic and thermodynamic data were best described by pseudo-second-order kinetics and the Freundlich models. The adsorption behaviors of individual carbofuran/CBD on both MPs were very similar. The CBD adsorption rate and capacity of PE and PP MPs were higher than those of carbofuran. This phenomenon explained the lower negative effects of DOM (oxalic acid, glycine (Gly)) on CBD adsorption relative to those of carbofuran. The presence of oxalic acid and Gly decreased the PE adsorption by 20.40-48.02% and the PP adsorption by 19.27-42.11%, respectively. It indicated the significance of DOM in carbofuran cycling. The adsorption capacities were negatively correlated with MPs size, indicating the importance of specific surficial area. Fourier transformation infrared spectroscopy before and after adsorption suggested that the adsorption process did not produce any new covalent bond. Instead, intermolecular van der Waals forces were one of the primary adsorption mechanisms of carbofuran and CBD by MPs, as evidenced by DFT calculations. Based on the zeta potential, the electrostatic interaction explained the higher adsorption CBD by MPs than carbofuran. Title: Chemical composition of essential oils from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare and their acaricidal effects on Haemaphysalis longicornis (Acari: Ixodidae) Qiao Y, Yu Z, Bai L, Li H, Zhang S, Liu J, Gao Z, Yang X Ref: Ecotoxicology & Environmental Safety, 224:112672, 2021 : PubMed ESTHER: Qiao_2021_Ecotoxicol.Environ.Saf_224_112672 PubMedSearch: Qiao 2021 Ecotoxicol.Environ.Saf 224 112672 PubMedID: 34416637 Abstract Chemical acaricides are mainly used in traditional tick control, which leads to the emergence of tick resistance and concurrently results in environmental pollution. In the present study, the chemical constituents of essential oils (EOs) from Thymus mongolicus, Cinnamomum verum, and Origanum vulgare was analyzed, and their potential application was evaluated to control the vector tick Haemaphysalis longicornis, which is widely distributed over vast areas of Eurasia, Australia, and New Zealand. Gas chromatography-mass spectrometry analysis revealed that the phenols thymol and carvacrol accounted for 34.66% and 75.72% of the EOs of T. mongolicus and O. vulgare, respectively, whereas trans-cinnamaldehyde (49.42%) was the main constituent of C. verum EO. Immersion tests showed that the EOs of C. verum and O. vulgare had significant acaricidal activity against larval H. longicornis, with the 50% lethal concentration (LC(50)) being 16.07 and 18.02 mg/mL, respectively, and the 95% lethal concentration (LC(95)) being 120.37 and 130.09 mg/mL, respectively. The EOs of O. vulgare and T. mongolicus showed significant acaricidal activity against unfed adult H. longicornis, with LC(50) being 43.50 and 44.21 mg/mL, respectively, and LC(95) being 113.66 and 137.99 mg/mL, respectively. The fumigant toxicity test showed significant acaricidal activity of the three EOs against both unfed and engorged nymphal and adult H. longicornis. Enzyme assays revealed that the EOs of both C. verum and O. vulgare significantly inhibited glutathione S-transferase activity (P < 0.05). In contrast, the activities of carboxylesterase and multifunction oxidases were significantly inhibited by EOs extracted from all three plants (P < 0.05). Taken together, these findings suggest that plant EOs may serve as an environment-friendly alternative for synthetic acaricides in future tick control. Title: Supplemental Choline Modulates Growth Performance and Gut Inflammation by Altering the Gut Microbiota and Lipid Metabolism in Weaned Piglets Qiu Y, Liu S, Hou L, Li K, Wang L, Gao K, Yang X, Jiang Z Ref: J Nutr, 151:20, 2021 : PubMed ESTHER: Qiu_2021_J.Nutr_151_20 PubMedSearch: Qiu 2021 J.Nutr 151 20 PubMedID: 33245135 Abstract BACKGROUND: Whether dietary choline and bile acids affect lipid use via gut microbiota is unclear. OBJECTIVES: This study aimed to investigate the effect of choline and bile acids on growth performance, lipid use, intestinal immunology, gut microbiota, and bacterial metabolites in weaned piglets. METHODS: A total of 128 weaned piglets [Duroc x (Landrace x Yorkshire), 21-d-old, 8.21 +/- 0.20 kg body weight (BW)] were randomly allocated to 4 treatments (8 replicate pens per treatment, each pen containing 2 males and 2 females; n = 32 per treatment) for 28 d. Piglets were fed a control diet (CON) or the CON diet supplemented with 597 mg choline/kg (C), 500 mg bile acids/kg (BA) or both (C + BA) in a 2 x 2 factorial design. Growth performance, intestinal function, gut microbiota, and metabolites were determined. RESULTS: Compared with diets without choline, choline supplementation increased BW gain (6.13%), average daily gain (9.45%), gain per feed (8.18%), jejunal lipase activity (60.2%), and duodenal IL10 gene expression (51%), and decreased the mRNA abundance of duodenal TNFA (TNFalpha) (40.7%) and jejunal toll-like receptor 4 (32.9%) (P < 0.05); additionally, choline increased colonic butyrate (29.1%) and the abundance of Lactobacillus (42.3%), while decreasing the bile acid profile (55.8% to 57.6%) and the abundance of Parabacteroides (75.8%), Bacteroides (80.7%), and unidentified-Ruminococcaceae (32.5%) (P >= 0.05). Compared with diets without BA, BA supplementation decreased the mRNA abundance of colonic TNFA (37.4%), NF-kappaB p65 (42.4%), and myeloid differentiation factor 88 (42.5%) (P >= 0.01); BA also increased colonic butyrate (20.9%) and the abundance of Lactobacillus (39.7%) and Faecalibacterium (71.6%) and decreased that of Parabacteroides (67.7%) (P < 0.05). CONCLUSIONS: Choline supplementation improved growth performance and prevented gut inflammation in weaned piglets by altering gut microbiota and lipid metabolism. BA supplementation suppressed intestinal inflammation with no effect on growth performance, which was associated with changed gut microbiota and metabolites. Title: Bacillus thuringiensis and Chlorantraniliprole Trigger the Expression of Detoxification-Related Genes in the Larval Midgut of Plutella xylostella Shabbir MZ, Yang X, Batool R, Yin F, Kendra PE, Li ZY Ref: Front Physiol, 12:780255, 2021 : PubMed ESTHER: Shabbir_2021_Front.Physiol_12_780255 PubMedSearch: Shabbir 2021 Front.Physiol 12 780255 PubMedID: 34966290 Abstract Background: Diamondback moth (DBM), Plutella xylostella (L.), has developed resistance to many insecticides. The molecular mechanism of DBM resistance to Bt-G033A combined with chlorantraniliprole (CL) remains undefined. Methods: In this study, field-resistant strains of Plutella xylostella to three pesticides, namely, Bacillus thuringiensis (Bt) toxin (Bt-G033A), CL, and a mixture of Bt + CL, were selected to evaluate the resistance level. Additionally, transcriptomic profiles of a susceptible (SS-DBM), field-resistant (FOH-DBM), Bt-resistant (Bt-DBM), CL-resistant (CL-DBM), and Bt + CL-resistant (BtC-DBM) strains were performed by comparative analysis to identify genes responsible for detoxification. Results: The Bt-G033A was the most toxic chemical to all the DBM strains among the three insecticides. The comparative analysis identified 25,518 differentially expressed genes (DEGs) between pairs/combinations of strains. DEGs were enriched in pathways related to metabolic and catalytic activity and ABC transporter in resistant strains. In total, 17 metabolic resistance-related candidate genes were identified in resistance to Bt-G033A, CL, and Bt + CL by co-expression network analysis. Within candidate genes, the majority was upregulated in key genes including cytochrome P450, glutathione S-transferase (GST), carboxylesterase, and acetylcholinesterase in CL- and BtC-resistant strains. Furthermore, aminopeptidase N (APN), alkaline phosphatase (ALP), cadherin, trypsin, and ABC transporter genes were eminent as Bt-resistance-related genes. Expression patterns of key genes by the quantitative real-time PCR (qRT-PCR) proved the credibility of transcriptome data and suggest their association in the detoxification process. Conclusion: To date, this study is the most comprehensive research presenting functional transcriptome analysis of DBM using Bt-G033A and CL combined insecticidal activity. Title: A thiamine-triggered fluormetric assay for acetylcholinesterase activity and inhibitor screening based on oxidase-like activity of MnO(2) nanosheets Xiao T, Wang S, Yan M, Huang J, Yang X Ref: Talanta, 221:121362, 2021 : PubMed ESTHER: Xiao_2021_Talanta_221_121362 PubMedSearch: Xiao 2021 Talanta 221 121362 PubMedID: 33076048 Abstract Acetylcholinesterase (AChE) plays an essential role in biological signal transmission, the aberrant expression of which could cause diverse neurodegenerative diseases. Herein, based on the oxidase-like activity of manganese dioxide nanosheets (MnO(2) NSs), we found that MnO(2) NSs could directly oxidize thiamine into intensely fluorescent thiochrome without the need of peroxides. When AChE was introduced, acetylthiocholine could be hydrolyzed to generate thiocholine, which efficiently triggered the reduction of MnO(2) NSs into Mn(2+), resulting in the decrease of fluorescence. Owing to the inhibiting effect of tacrine to the AChE activity, the decomposition of MnO(2) was hindered, thus leading to the fluorescence recovery. According to the above mechanism, we constructed a simple, low-cost, label-free, facile and rapid synthetic fluorescent biosensor for highly sensitive and selective detection of AChE activity and screening of its inhibitor. This biosensor obtained a good linear range from 0.02 to 1 mU/mL and an extremely low detection limit of 15 muU/mL for AChE assay, as well as a sensitive screening for tacrine and an excellent applicability in human serum samples. These results suggested that our proposed method would be potentially applied in monitoring the disease progression. Title: Dipeptidyl peptidase IV is required for endometrial carcinoma cell proliferation and tumorigenesis via the IL-6/STAT3 pathway Yang X, Zhu Y, Shi Q, Zhao X, Huang Y, Yao F, Zhang Y, Wang Z Ref: J Obstet Gynaecol Res, :, 2021 : PubMed ESTHER: Yang_2021_J.Obstet.Gynaecol.Res__ PubMedSearch: Yang 2021 J.Obstet.Gynaecol.Res PubMedID: 33969570 Abstract AIM: To study the functions and signaling pathways controlled by dipeptidyl peptidase IV (DPPIV) in endometrial carcinoma (EC). METHODS: DPPIV expression in EC cells was detected by flow cytometry, reverse transcription-polymerase chain reaction analysis and Western blot. Interleukin-6 (IL-6) expression in the supernatant was measured by enzyme-linked immunosorbent assay. The protein levels of signal transducers and activators of transcription-3 (STAT3), phosphorylate STAT3, cellular Myc, and vascular endothelial growth factor in EC cells were measured by Western blot. Colony formation assays were used to assess the clonogenicity of EC cells. Ki67 immunostaining and cell counting were used to test the proliferative ability of EC cells. Nude mouse tumorigenicity assay was used to confirm DPPIV promotes the tumorigenicity of EC cells. A cell counting kit-8 assay was used to determine the half-maximal inhibitory concentration of sitagliptin. RESULTS: Overexpression of DPPIV in EC cells with low DPPIV expression promoted cell proliferation in vitro (p < 0.01) and enhanced tumorigenicity in vivo (p < 0.05). Conversely, knocking down DPPIV expression in EC cells with high DPPIV expression inhibited cell proliferation (p < 0.01) and in vivo tumorigenicity (p < 0.01). DPPIV promoted EC cell proliferation via activation of IL-6/STAT3 signaling pathway, and that IL-6 could trigger a positive feedback loop that increased DPPIV expression (p < 0.01). Furthermore, the DPPIV inhibitor reduced STAT3 expression (p < 0.01) and inhibited growth of EC cells (p < 0.001). CONCLUSION: DPPIV enhances the properties that allow tumorigenesis in EC via IL-6 and STAT3 signaling. Title: A norbisabolane and an arabitol benzoate from Talaromyces marneffei, an endophytic fungus of Epilobium angustifolium Yang ZD, Zhang XD, Yang X, Yao XJ, Shu ZM Ref: Fitoterapia, 153:104948, 2021 : PubMed ESTHER: Yang_2021_Fitoterapia_153_104948 PubMedSearch: Yang 2021 Fitoterapia 153 104948 PubMedID: 34087409 Abstract A norbisabolane and an arabitol benzoate, Talaromarnine A (1), Talaromarnine B (2), together with eight known compounds were obtained from cultures of Talaromyces marneffei, an endophytic fungus of Epilobium angustifolium. Their structures were elucidated by IR, MS, 1D and 2D NMR spectra, and their absolute configuration was determined by single-crystal X-ray diffraction and molecular computation. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but no compounds exhibited significant activities. Title: Evidence-based complementary and alternative medicine bioinformatics approach through network pharmacology and molecular docking to determine the molecular mechanisms of Erjing pill in Alzheimer's disease Yang X, Guan Y, Yan B, Xie Y, Zhou M, Wu Y, Yao L, Qiu X, Yan F and Huang L <1 more author(s)> Yang X, Guan Y, Yan B, Xie Y, Zhou M, Wu Y, Yao L, Qiu X, Yan F, Chen Y, Huang L (- 1) Ref: Exp Ther Med, 22:1252, 2021 : PubMed ESTHER: Yang_2021_Exp.Ther.Med_22_1252 PubMedSearch: Yang 2021 Exp.Ther.Med 22 1252 PubMedID: 34539848 Abstract Erjing pill, a Traditional Chinese Medicine (TCM) formulation composed of Polygonatum sibiricum and Lycium chinense, has an important role in the treatment of Alzheimer's disease (AD). However, the underlying mechanisms of the action of Erjing pill in AD have remained elusive. In the present study, the key ingredients of Erjing pill were investigated and the active components and their mechanisms of action on AD were analyzed based on networks pharmacology. By using the TCM and TCM Systems Pharmacology and databases, the components of Erjing pill were screened and the data were captured using Discovery Studio. The SwissTarget webserver database was used to predict the potential protein targets of Erjing pill components for pathologies related to AD. The data were further analyzed with the disease targets of AD based on analysis of the Online Mendelian Inheritance in Man, DiGSeE and Therapeutic Target Database. Subsequent analysis of mechanistic pathways of the screened components and protein targets allowed us to construct a network by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, which revealed potential molecular mechanisms of Erjing pill against AD. Finally, the protective effect of three active components on neurons was verified using an in vitro injury model of PC12 cells induced by Abeta(25-35). The results indicated that 65 bioactive components of Erjing pill, including lauric acid and zederone, and 6 targets, including acetylcholinesterase, butylcholinesterase and amyloid protein precursor, were closely associated with the prevention and treatment of AD. The molecular components of Erjing pill were indicated to be involved in various biological signaling processes, mainly in synaptic signal transmission, transsynaptic signal transmission and chemical synaptic transmission. Furthermore, related pathways targeted by Erjing pill in AD included the regulation of neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, serotoninergic synapses, calcium signaling pathways and dopaminergic synapses. A cell viability assay indicated that the compounds (polygonatine A, polygonatine C and 4',5-dihydroxyflavone) assessed were able to significantly improve the survival rate and increase the Ca(2+) level in a PC12 cell model of AD induced by amyloid-beta(25-35). The present study revealed that the mechanisms of action of Erjing pill to prevent and treat AD included a multicompound, multitarget and multipathway regulatory network. Title: Cholinesterase level is a predictor of systemic inflammatory response syndrome and complications after cardiopulmonary bypass Yang Y, Yang X, Yang J Ref: Ann Palliat Med, 10:11714, 2021 : PubMed ESTHER: Yang_2021_Ann.Palliat.Med_10_11714 PubMedSearch: Yang 2021 Ann.Palliat.Med 10 11714 PubMedID: 34872296 Abstract BACKGROUND: To study the changes of serum cholinesterase (S-ChE) levels in patients with systemic inflammatory response syndrome (SIRS) after cardiopulmonary bypass (CPB) and its predictive value for multiple organ dysfunction syndrome (MODS). METHODS: Forty-two patients with SIRS after CPB were selected as the SIRS group. Another 42 patients who did not develop SIRS after CPB were selected as the control group. The S-ChE levels of patients were compared between the two groups at the time of intensive care unit (ICU) admission and 48 hours after admission to the ICU. The correlation between S-ChE levels and Acute Physiology and Chronic Health EvaluationII (APACHEII) score, tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) levels was compared between the two groups at the time of ICU admission and 48 hours after ICU admission, and receiver operator characteristic (ROC) curve analysis was used to analyze the accuracy of S-ChE level in diagnosing MODS in patients with SIRS after CPB. RESULTS: There was no significant difference in the S-ChE levels among the non-SIRS patients between the time of admission to the ICU and 48 hours later. However, the S-ChE levels in SIRS patients exhibited a decreasing trend from 48 hours after ICU admission compared with those at the time of ICU admission. Meanwhile, the S-ChE levels were obviously lower in SIRS patients than in non-SIRS patients at those two time points. Furthermore, we found that S-ChE levels were negatively correlated with APACHEII scores as well as the levels of TNF-alpha and IL-6 at ICU admission and 48 hours after ICU admission in SIRS patients. Meanwhile, S-ChE levels were associated with the occurrence of MODS of SIRS patients. Subsequent ROC curve analysis revealed that early S-ChE levels could predict the occurrence of SIRS complicated by MODS after CBP. CONCLUSIONS: S-ChE was significantly decreased in patients with SIRS after CPB, and the decrease of S-ChE in the early stage was closely related to the severity of SIRS after CBP and the increase of inflammatory cytokines. Meanwhile, there was a close relationship between S-ChE activity and MODS in the early stage. Title: Melatonin inhibits lipid accumulation to repress prostate cancer progression by mediating the epigenetic modification of CES1 Zhou L, Zhang C, Yang X, Liu L, Hu J, Hou Y, Tao H, Sugimura H, Chen Z and Chen K <1 more author(s)> Zhou L, Zhang C, Yang X, Liu L, Hu J, Hou Y, Tao H, Sugimura H, Chen Z, Wang L, Chen K (- 1) Ref: Clin Transl Med, 11:e449, 2021 : PubMed ESTHER: Zhou_2021_Clin.Transl.Med_11_e449 PubMedSearch: Zhou 2021 Clin.Transl.Med 11 e449 PubMedID: 34185414 Gene_locus related to this paper: human-CES1 Abstract BACKGROUND: Androgen deprivation therapy (ADT) is the main clinical treatment for patients with advanced prostate cancer (PCa). However, PCa eventually progresses to castration-resistant prostate cancer (CRPC), largely because of androgen receptor variation and increased intratumoral androgen synthesis. Several studies have reported that one abnormal lipid accumulation is significantly related to the development of PCa. Melatonin (MLT) is a functionally pleiotropic indoleamine molecule and a key regulator of energy metabolism. The aim of our study is finding the links between CRPC and MLT and providing the basis for MLT treatment for CRPC. METHODS: We used animal CRPC models with a circadian rhythm disorder, and PCa cell lines to assess the role of melatonin in PCa. RESULTS: We demonstrated that MLT treatment inhibited tumor growth and reversed enzalutamide resistance in animal CRPC models with a circadian rhythm disorder. A systematic review and meta-analysis demonstrated that MLT is positively associated with an increased risk of developing advanced PCa. Restoration of carboxylesterase 1 (CES1) expression by MLT treatment significantly reduced lipid droplet (LD) accumulation, thereby inducing apoptosis by increasing endoplasmic reticulum stress, reducing de novo intratumoral androgen synthesis, repressing CRPC progression and reversing the resistance to new endocrine therapy. Mechanistic investigations demonstrated that MLT regulates the epigenetic modification of CES1. Ces1-knockout (Ces(-/-) ) mice verified the important role of endogenous Ces1 in PCa. CONCLUSIONS: Our findings provide novel preclinical and clinical information about the role of melatonin in advanced PCa and characterize the importance of enzalutamide combined with MLT administration as a therapy for advanced PCa. Title: DECR1 directly activates HSL to promote lipolysis in cervical cancer cells Zhou H, Zhang J, Yan Z, Qu M, Zhang G, Han J, Wang F, Sun K, Wang L, Yang X Ref: Biochimica & Biophysica Acta Molecular & Cellular Biology Lipids, :159090, 2021 : PubMed ESTHER: Zhou_2021_Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids__159090 PubMedSearch: Zhou 2021 Biochim.Biophys.Acta.Mol.Cell.Biol.Lipids 159090 PubMedID: 34896618 Abstract Fatty acids have a high turnover rate in cancer cells to supply energy for tumor growth and proliferation. Lipolysis is particularly important for the regulation of fatty acid homeostasis and in the maintenance of cancer cells. In the current study, we explored how 2,4-Dienoyl-CoA reductase (DECR1), a short-chain dehydrogenase/reductase associated with mitochondrial and cytoplasmic compartments, promotes cancer cell growth. We report that DECR1 overexpression significantly reduced the triglyceride (TAG) content in HeLa cells; conversely, DECR1 silencing increased intracellular TAG content. Subsequently, our experiments demonstrate that DECR1 promotes lipolysis via effects on hormone sensitive lipase (HSL). The direct interaction of DECR1 with HSL increases HSL phosphorylation and activity, facilitating the translocation of HSL to lipid droplets. The ensuing enhancement of lipolysis thus increases the release of free fatty acids. Downstream effects include the promotion of cervical cancer cell migration and growth, associated with the enhanced levels of p62 protein. In summary, high levels of DECR1 serves to enhance lipolysis and the release of fatty acid energy stores to support cervical cancer cell growth. Title: Decreased T-cell mediated hepatic injury in concanavalin A-treated PLRP2-deficient mice Ge W, Gao Y, Zhao Y, Yang Y, Sun Q, Yang X, Xu X, Zhang J Ref: Int Immunopharmacol, 85:106604, 2020 : PubMed ESTHER: Ge_2020_Int.Immunopharmacol_85_106604 PubMedSearch: Ge 2020 Int.Immunopharmacol 85 106604 PubMedID: 32428799 Gene_locus related to this paper: mouse-LIPR2 Abstract Concanavalin A (Con A) activates innate immunity and causes liver damage mediated by cytotoxic T lymphocytes (CTL) in mice. The Pancreatic lipase-related protein 2 (PLRP2) is induced by interleukin (IL)-4 in vitro in CTLs and associated with CTL functions. We examined the role of PLRP2 in a mouse model of Con A-induced T cell-mediated hepatitis. PLRP2-knockout and wild-type (WT) mice were inoculated with 20 mg/kg Con A. Mice lacking PLRP2 reduced Con A-induced hepatitis, which was manifested by a decrease in serum aminotransferase and histopathological assessment. The expression and secretion of cytokines including tumor necrosis factor-alpha (TNF-alpha), interferon (IFN)-gamma, IL-6, and IL-1beta were suppressed in Con A-treated PLRP2-knockout mice. In PLRP2 knockout mice, Con A-induced liver chemokines and adhesion molecules (such as MIP-1alpha, MIP-1beta, ICAM-1 and MCP-1) were also down regulated. In the WT liver treated with Con A, the number of T cells (CD4(+) and CD8(+)) and macrophages (CD11b(+) F4/80(+)) increased significantly, while the lack of PLRP2 reduced the number of T cells in the liver, but had no effect on macrophages. The shift of the metabolic profiles was impaired in Con A-treated PLRP2-knockout mice compared to WT mice. In conclusion, these results indicate that PLRP2 deficiency reduces T-cell mediated Con A-induced hepatitis, and suggest PLRP2 is a potential target of anti-inflammatory and immunomodulatory drugs to treat immune-mediated hepatitis. Title: GDSL lipase occluded stomatal pore 1 is required for wax biosynthesis and stomatal cuticular ledge formation Tang J, Yang X, Xiao C, Li J, Chen Y, Li R, Li S, Lu S, Hu H Ref: New Phytol, 228:1880, 2020 : PubMed ESTHER: Tang_2020_New.Phytol_228_1880 PubMedSearch: Tang 2020 New.Phytol 228 1880 PubMedID: 32542680 Abstract The plant leaf surface is coated with a waterproof cuticle layer. Cuticle facing the stomatal pore surface needs to be sculpted to form outer cuticular ledge (OCL) after stomatal maturation for efficient gas exchange. Here, we characterized the roles of Arabidopsis GDSL lipase, Occlusion of Stomatal Pore 1 (OSP1), in wax biosynthesis and stomatal OCL formation. OSP1 mutation results in significant reduction in leaf wax synthesis and occlusion of stomata, leading to increased epidermal permeability, decreased transpiration rate, and enhanced drought tolerance. We demonstrated that OSP1 activity is critical for its role in wax biosynthesis and stomatal function. In vitro enzymatic assays demonstrated that OSP1 possesses thioesterase activity, particularly on C22:0 and C26:0 acyl-CoAs. Genetic interaction analyses with CER1 (ECERIFERUM 1), CER3 (ECERIFERUM 3) and MAH1 (Mid-chain Alkane Hydroxylase 1) in wax biosynthesis and stomatal OCL formation showed that OSP1 may act upstream of CER3 in wax biosynthesis, and implicate that wax composition percentage changes and keeping ketones in a lower level play roles, at least partially, in forming stomatal ledges. Our findings provided insights into the molecular mechanism mediating wax biosynthesis and highlighted the link between wax biosynthesis and the process of stomatal OCL formation. Title: Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G Ref: Cell Res, 30:269, 2020 : PubMed Title: Sanger's Reagent Sensitized Photocleavage of Amide Bond for Constructing Photocages and Regulation of Biological Functions Wei T, Lu S, Sun J, Xu Z, Yang X, Wang F, Ma Y, Shi Y, Chen X Ref: Journal of the American Chemical Society, :, 2020 : PubMed ESTHER: Wei_2020_J.Am.Chem.Soc__ PubMedSearch: Wei 2020 J.Am.Chem.Soc PubMedID: 32023409 Abstract Photolabile groups offer promising tools to study biological processes with highly spatial and temporal control. In the investigation, we designed and prepared several new glycine amide derivatives of Sanger's reagent and demonstrated that they serve as a new class of photocages for Zn2+ and an acetylcholinesterase (AChE) inhibitor. We showed that the mechanism for photocleavage of these substances involves initial light-driven cyclization between the 2,4-dinitrophenyl and glycine methylene groups to form acyl benzimidazole N-oxides, which undergo secondary photoinduced decarboxylation in association with rupture of an amide bond. The cleavage reactions proceed with modest to high quantum yields. We demonstrated that these derivatives can be used in targeted intracellular delivery of Zn2+, fluorescent imaging by light-triggered Zn2+ release, and regulation of biological processes including the enzymatic activity of carbonic anhydrase (CA), negative regulation of N-methyl-D-aspartate receptors (NMDARs) and pulse rate of cardiomyocytes. The successful proof-of-concept examples described above open a new avenue for using Sanger's reagent-based glycine amides as photocages for the exploration of complex cellular functions and signaling pathways. Title: Combining antioxidant astaxantin and cholinesterase inhibitor huperzine A boosts neuroprotection Yang X, Wei HM, Hu GY, Zhao J, Long LN, Li CJ, Zhao ZJ, Zeng HK, Nie H Ref: Mol Med Rep, :, 2020 : PubMed ESTHER: Yang_2020_Mol.Med.Rep__ PubMedSearch: Yang 2020 Mol.Med.Rep PubMedID: 31922239 Abstract Oxidative stress is a pathophysiological condition resulting in neurotoxicity, which is possibly associated with neurodegenerative disorders. In this study, the antioxidative effects of the antioxidant astaxanthin (AXT) in combination with huperzine A (HupA), which is used as a cholinesterase inhibitor for the treatment of Alzheimer's disease, were investigated. PC12 cells were treated with either tertbutyl hydroperoxide (TBHP), or with the toxic version of betaamyloid, Abeta2535, to induce oxidative stress and neurotoxicity. Cell viability, morphology, lactate dehydrogenase (LDH) release, intracellular accumulation of reactive oxygen species (ROS), superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were determined, while neuroprotection was also monitored using an MTT assay. It was found that combining AXT with HupA significantly increased the viability of PC12 cells, prevented membrane damage (as measured by LDH release), attenuated intracellular ROS formation, increased SOD activity and decreased the level of MDA after TBHP exposure when compared to these drugs administered alone. Pretreatment with HupA and AXT decreased toxic damage produced by Abeta2535. These data indicated that combining an antioxidant with a cholinesterase inhibitor increases the degree of neuroprotection; with future investigation this could be a potential therapy used to decrease neurotoxicity in the brain. Title: Neuroprotective Effects of Higenamine Against the Alzheimer's Disease Via Amelioration of Cognitive Impairment, Abeta Burden, Apoptosis and Regulation of Akt/GSK3beta Signaling Pathway Yang X, Du W, Zhang Y, Wang H, He M Ref: Dose Response, 18:1559325820972205, 2020 : PubMed ESTHER: Yang_2020_Dose.Response_18_1559325820972205 PubMedSearch: Yang 2020 Dose.Response 18 1559325820972205 PubMedID: 33354171 Abstract The present investigation was envisaged to elucidate the neuroprotective effect of Higenamine (HGN) against aluminum chloride (AlCl(3)) triggered experimental Alzheimer's disease (AD) rat model. Thirty-six male albino Wister rats were randomized and divided in 6 groups and subjected to experimentation for 6 weeks. Control group, AlCl(3) (100 mg/kg orally), HGN (50 mg/kg orally), HGN25, HGN50, HGN75 (HGN 25, 50 and 75 mg/kg respectively and AlCl(3) 100 mg/kg orally). After completion of 42 days protocol, the animals were subjected to passive avoidance test. The animals were then anesthetized by intramuscularly injecting ketamine hydrochloride (24 mg/kg body weight) and euthanized by cervical amputation. Cortical and hippocampal tissues were carefully removed and were employed for quantification of aluminum and acetylcholinesterase. The tissues were quantified using Western blotting and detection kits for APP, Abeta(1-42), beta and gamma secretases, Bax, Bad, caspases-9, cyto-c, pAkt and pGSK-3beta, and oxidative markers. HGN significantly protected AlCl(3) induced memory and learning impairments, Al overload, AChE hyperactivity, amyloid beta (Abeta) burden and apoptosis in brain tissues via activating Akt/GSK3beta pathway. HGN attenuated oxidative damage induced by Al by modulation of oxidative markers. Our findings advocate the neuroprotective effect of HGN in AlCl(3) induced AD rat model. Title: Diosgenin alleviates hypercholesterolemia via SRB1/CES-1/CYP7A1/FXR pathway in high-fat diet-fed rats Yu L, Lu H, Yang X, Li R, Shi J, Yu Y, Ma C, Sun F, Zhang S, Zhang F Ref: Toxicol Appl Pharmacol, :115388, 2020 : PubMed ESTHER: Yu_2020_Toxicol.Appl.Pharmacol__115388 PubMedSearch: Yu 2020 Toxicol.Appl.Pharmacol 115388 PubMedID: 33383043 Abstract Phytosterol diosgenin (DG) exhibits cholesterol-lowering properties. Few studies focused on the underlying mechanism of DG attenuation of hypercholesterolemia by promoting cholesterol metabolism. To investigate the roles of SRB1/CES-1/CYP7A1/FXR pathways in accelerating cholesterol elimination and alleviating hypercholesterolemia, a rat model of hypercholesterolemia was induced by providing a high-fat diet (HFD). Experimental rat models were randomly divided into a normal control (Con) group, HFD group, low-dose DG (LDG) group (150mg/kg/d), high-dose DG (HDG) group (300mg/kg) and Simvastatin (Sim) group (4mg/kg/d). Body weights, serum and hepatic lipid parameters of rats were tested. The expression levels of scavenger receptor class B type I (SRB1), carboxylesterase-1 (CES-1), cholesterol7alpha- hydroxylase (CYP7A1), and farnesoid X receptor (FXR) were determined. The results showed that DG reduced weight and lowered lipid levels in HFD-fed rats. Pathological morphology analyses revealed that DG notably improved hepatic steatosis and intestinal structure. Further studies showed the increased hepatic SRB1, CES-1, CYP7A1 and inhibited FXR-mediated signaling in DG-fed rats, which contributing to the decrease of hepatic cholesterol. DG also increased intestinal SRB1 and CES-1, inhibiting cholesterol absorption and promoting RCT. The expression levels of these receptors in the HDG group were higher than LDG and Sim groups. These data suggested that DG accelerated reverse cholesterol transport (RCT) and enhanced cholesterol elimination via SRB1/CES-1/CYP7A1/FXR pathway, and DG might be a new candidate for the alleviation of hypercholesterolemia. Title: Downregulation of microRNA-124 prevents the development of acute liver failure through the upregulation of PIM-3 Zan T, Piao L, Yang X, Gu Y, Liu B Ref: Exp Physiol, 105:108, 2020 : PubMed ESTHER: Zan_2020_Exp.Physiol_105_108 PubMedSearch: Zan 2020 Exp.Physiol 105 108 PubMedID: 31628693 Abstract NEW FINDINGS: * What is the central question of this study? Does miR-124 affect cell proliferation and apoptosis in acute liver failure (ALF) mice? * What is the main finding and its importance? Inhibiting miR-124 targets PIM-3 and thus upregulates its expression, consequently inhibiting liver cell apoptosis and promoting cell proliferation, ultimately preventing the progression of ALF. This highlights a promising competitive new target for ALF treatment. ABSTRACT: Acute liver failure (ALF) is a complicated syndrome frequently leading to dysfunction and failure of various organs. MicroRNAs (miRNAs) have played crucial roles in the development and progression of human diseases, including ALF. However, the potential role of miR-124 in ALF still remains elusive. Thus, we investigated the underlying mechanism by which miR-124 influences ALF in a mouse model of ALF. Initially, ALF mouse models were established using d-galactosamine and lipopolysaccharide. Then we detected the serum biochemical parameters of liver, and pathological characteristics and ultrastructure of liver tissues. Next, we determined miR-124 and PIM-3 expression in liver tissues and cells using RT-qPCR and western blot analysis. The interaction between miR-124 and PIM-3 was identified using the dual luciferase reporter gene assay. Subsequently, expression of miR-124 and PIM-3 in liver cells was altered to explore their effects on primary liver cell proliferation, the cell cycle and apoptosis. The results obtained showed that ALF mice exhibited a decreased cholinesterase level with increased levels of alanine aminotransferase, aspartate transaminase and total bilirubin as well as abundant liver cell apoptosis and necrosis. miR-124 was upregulated while PIM-3 was downregulated in ALF tissues and cells. Besides, the PIM-3 gene was a target of miR-124 and was inhibited by miR-124. Overexpression of miR-124 or silencing of PIM-3 reduced Bcl-2 expression but elevated tumour necrosis factor alpha expression, and resulted in a reduction in liver cell proliferation but an increase in cell apoptosis in ALF mice. Altogether, miR-124 functions as a disease-promoting miRNA with potential in stimulating ALF by targeting PIM-3. Title: Two new compounds, Talaromycin A and B, isolated from an endophytic fungus, Talaromyces aurantiacus Zhang YF, Yang ZD, Yang X, Yang LJ, Yao XJ, Shu ZM Ref: Nat Prod Res, 34:2802, 2020 : PubMed ESTHER: Zhang_2020_Nat.Prod.Res_34_2802 PubMedSearch: Zhang 2020 Nat.Prod.Res 34 2802 PubMedID: 30929454 Abstract Two new compounds Talaromycin A (1) and Talaromycin B (2) were isolated from a liquid culture of Talaromyces aurantiacus. The structures of 1 and 2 were elucidated by IR, MS, 1D and 2D NMR spectra and comparison of the experimental and calculated electronic circular dichroism spectra. Additional known compounds (3-6) were also isolated. These compounds were tested for monoamine oxidase, acetylcholinesterase and PI3K inhibitory activity, but showed only weak activity. Title: Plasma cholinesterase is associated with Chinese adolescent overweight or obesity and metabolic syndrome prediction Han Y, Ma Y, Liu Y, Zhao Z, Zhen S, Yang X, Xu Z, Wen D Ref: Diabetes Metab Syndr Obes, 12:685, 2019 : PubMed ESTHER: Han_2019_Diabetes.Metab.Syndr.Obes_12_685 PubMedSearch: Han 2019 Diabetes.Metab.Syndr.Obes 12 685 PubMedID: 31190929 Abstract Purpose: To determine the plasma concentrations of butyrylcholinesterase (BChE), also known as pseudocholinesterase, in different weight categories of adolescents, and to explore the possible association between plasma BChE and overweight (OW), obesity, and metabolic syndrome (MetS) in Chinese adolescents. Patients and methods: This cross-sectional study included 1,236 Chinese adolescents (194 obese [OB], 188 OW, 732 normal weight [NW], and 122 underweight [UW]). The biochemical variables and anthropometric variables of the study participants were evaluated. Plasma BChE level was measured by DGKC method. Results: OB was associated with a higher prevalence of upper strata plasma BChE levels when compared with the BChE levels in UW, NW, and OW group. A logistic regression analysis showed that plasma BChE was positively associated with the OB group when compared with the NW group. Boys in the OW group, but not the OB group, had a significantly higher prevalence of upper stratum of BChE levels. Plasma triglyceride, total cholesterol, low-density lipoprotein-cholesterol, and ApoB levels were positively associated with the upper stratum of BChE levels when compared with lower stratum. MetS and most of its components were more prevalent among subjects with upper stratum rather than lower stratum BChE levels. Receiver operating characteristic curves for plasma BChE in subjects with MetS indicated that the AUC was 0.80 (95%CI:0.70-0.90,P<0.001) and 0.89 (95%CI:0.82-0.95,P<0.001) in girls and boys, respectively. After adjusting for age, the multivariate-adjusted odds ratio for MetS in the upper stratum of BChE levels was 8.73 (95%CI: 3.49-21.84) in the boys cohorts and also in the girls cohorts (OR=1.71, 95%CI: 1.35-21.70). Conclusion: This study confirmed an association between BChE levels and weight status in Chinese adolescents, and demonstrated that the upper strata of plasma BChE levels were associated with being OW, and even more highly associated with obesity. Plasma BChE levels were positively associated with MetS and its components and could be useful for identifying adolescents with MetS. Title: Effects of cadmium on fecundity and defence ability of Drosophila melanogaster Hu X, Fu W, Yang X, Mu Y, Gu W, Zhang M Ref: Ecotoxicology & Environmental Safety, 171:871, 2019 : PubMed ESTHER: Hu_2019_Ecotoxicol.Environ.Saf_171_871 PubMedSearch: Hu 2019 Ecotoxicol.Environ.Saf 171 871 PubMedID: 30665104 Abstract Cadmium (chemical symbol, Cd) is an extremely common pollutant that poses a toxicity threat to organisms. Therefore, we tested Drosophila melanogaster fecundity, Cd accumulation, and activity of two enzymes following Cd stress and used quantitative real-time polymerase chain reaction (qPCR) to quantify the mRNA expression levels of several genes involved in fecundity and defence. D. melanogaster was placed in a medium containing different concentrations of Cd (13, 26, and 52mgL(-1)), following which, inductively coupled plasma atomic emission spectroscopy showed that Cd accumulation in Drosophila increased with the increase in its dietary intake. We also observed that Cd at these concentrations significantly prolonged the mating latency in females and reduced the number of eggs laid. However, the same Cd concentrations did not affect male fecundity. Acetylcholinesterase activity was only detected at 52mgL(-1) Cd in both sexes, whereas glutathione S-transferase activity was inhibited at 26 and 52mgL(-1) Cd in females. The results of qPCR indicated that exposure to 13-52mgL(-1) Cd affected the expression of reproduction-related genes, including downregulation of enok and upregulation of dally and dpp. The same level of exposure also induced transcriptional responses from three defence-related genes (hsp70, gstd2, and gstd6). Taken together, the results revealed that Cd exposure might negatively affect the expression of genes associated with D. melanogaster reproduction and trigger the transcription of defence-related genes. We suggest that further analyses of fecundity and defence responses may help develop indicators of Cd toxicity and improve our understanding of antitoxin defences. Title: Wortmannine H, a phenylpentenol isolated from an endophytic fungus, Talaromyces wortmannii LGT-4 Li XF, Yang ZD, Yang X, Yang LJ, Yao XJ, Shu ZM Ref: Nat Prod Res, :1, 2019 : PubMed ESTHER: Li_2019_Nat.Prod.Res__1 PubMedSearch: Li 2019 Nat.Prod.Res 1 PubMedID: 31711315 Abstract A new phenylpentenol, wortmannine H (1) was isolated from Talaromyces wortmannii LGT-4, an endophytic fungus of Tripterygium wilfordii. The structure of 1 was elucidated by IR, MS, 1D and 2D NMR spectra and comparison of the experimental and calculated optical rotatory dispersion (ORD). Monoamine oxidase (MAO), acetylcholinesterase (AChE) and phosphoinositide 3-kinase (PI3Kalpha) inhibitory activities of 1 was also tested. The compound did not show good biological activity. 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: Fluevirines E and F, two new alkaloids from Flueggea virosa Yang X, Liu J, Huo Z, Yuwen H, Li Y, Zhang Y Ref: Nat Prod Res, :1, 2019 : PubMed ESTHER: Yang_2019_Nat.Prod.Res__1 PubMedSearch: Yang 2019 Nat.Prod.Res 1 PubMedID: 30721084 Abstract Two new alkaloids, fluevirines E (1) and F (2), along with six known Securinega alkaloids, were isolated from the methanol extract of the twigs and leaves of Flueggea virosa. The structures and absolute configurations of the new compounds were elucidated by means of MS, NMR, and ECD analyses. Compound 1 is a new dimeric indole alkaloid while 2 is a new securinega-type alkaloid. The in vitro cytotoxic activities of the isolated alkaloids against several human cancer cell lines and their acetylcholinesterase inhibitory activity were also evaluated. Title: Biomarker Effects in Carassius auratus Exposure to Ofloxacin, Sulfamethoxazole and Ibuprofen Yang X, Xu X, Wei X, Wan J, Zhang Y Ref: Int J Environ Research Public Health, 16:, 2019 : PubMed ESTHER: Yang_2019_Int.J.Environ.Res.Public.Health_16_ PubMedSearch: Yang 2019 Int.J.Environ.Res.Public.Health 16 PubMedID: 31075982 Abstract Ofloxacin, sulfamethoxazole and ibuprofen are three commonly used drugs which can be detected in aquatic environments. To assess their ecotoxicity, the effects of these three pharmaceuticals and their mixture on AChE (acetylcholinesterase) activity in the brain, and EROD (7-ethoxyresorufin-O-deethylase) and SOD (superoxide dismutase) activities in the liver of the freshwater crucian carp Carassius auratus were tested after exposure for 1, 2, 4 and 7 days. The results showed that treatments with 0.002(-)0.01 mg/L ofloxacin and 0.0008(-)0.004 mg/L sulfamethoxazole did not significantly change AChE, EROD and SOD activities. AChE activity was significantly inhibited in response to treatment with 0.05mg/L ofloxacin and 0.02mg/L sulfamethoxazole. All three biomarkers were induced significantly in treatments with ibuprofen and the mixture of the three pharmaceuticals at all the tested concentrations. The combined effects of ofloxacin, sulfamethoxazole and ibuprofen were compared with their isolated effects on the three biomarkers, and the results indicated that exposure to ibuprofen and the mixture at environmentally relevant concentrations could trigger adverse impacts on Carassius auratus. The hazard quotient (HQ) index also demonstrated a high risk for ibuprofen. Moreover, the present study showed that the effects of ofloxacin, sulfamethoxazole and ibuprofen might be additive on the physiological indices of Carassius auratus. Title: Hippocampal Proteomic Alteration in Triple Transgenic Mouse Model of Alzheimer's Disease and Implication of PINK 1 Regulation in Donepezil Treatment Zhou X, Xiao W, Su Z, Cheng J, Zheng C, Zhang Z, Wang Y, Wang L, Xu B and Pui Man Hoi M <2 more author(s)> Zhou X, Xiao W, Su Z, Cheng J, Zheng C, Zhang Z, Wang Y, Wang L, Xu B, Li S, Yang X, Pui Man Hoi M (- 2) Ref: J Proteome Res, 18:1542, 2019 : PubMed ESTHER: Zhou_2019_J.Proteome.Res_18_1542 PubMedSearch: Zhou 2019 J.Proteome.Res 18 1542 PubMedID: 30484658 Abstract Donepezil is a clinically approved acetylcholinesterase inhibitor (AChEI) for cognitive improvement in Alzheimer's disease (AD). Donepezil has been used as a first-line agent for the symptomatic treatment of AD, but its ability to modify disease pathology and underlying mechanisms is not clear. We investigated the protective effects and underlying mechanisms of donepezil in AD-related triple transgenic (APPSwe/PSEN1M146V/MAPTP301L) mouse model (3xTg-AD). Mice (8-month old) were treated with donepezil (1.3 mg/kg) for 4 months and evaluated by behavioral tests for assessment of cognitive functions, and the hippocampal tissues were examined by protein analysis and quantitative proteomics. Behavioral tests showed that donepezil significantly improved the cognitive capabilities of 3xTg-AD mice. The levels of soluble and insoluble amyloid beta proteins (Abeta1-40 and Abeta1-42) and senile plaques were reduced in the hippocampus. Golgi staining of the hippocampus showed that donepezil prevented dendritic spine loss in hippocampal neurons of 3xTg-AD mice. Proteomic studies of the hippocampal tissues identified 3131 proteins with altered expression related to AD pathology, of which 262 could be significantly reversed with donepezil treatment. Bioinformatics with functional analysis and protein-protein interaction (PPI) network mapping showed that donepezil significantly elevated the protein levels of PINK 1, NFASC, MYLK2, and NRAS in the hippocampus, and modulated the biological pathways of axon guidance, mitophagy, mTOR, and MAPK signaling. The substantial upregulation of PINK 1 with donepezil was further verified by Western blotting. Donepezil exhibited neuroprotective effects via multiple mechanisms. In particular, PINK 1 is related to mitophagy and cellular protection from mitochondrial dysfunction, which might play important roles in AD pathogenesis and represent a potential therapeutic target. 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: Evidence that microplastics aggravate the toxicity of organophosphorus flame retardants in mice (Mus musculus) Deng Y, Zhang Y, Qiao R, Bonilla MM, Yang X, Ren H, Lemos B Ref: J Hazard Mater, 357:348, 2018 : PubMed ESTHER: Deng_2018_J.Hazard.Mater_357_348 PubMedSearch: Deng 2018 J.Hazard.Mater 357 348 PubMedID: 29908513 Inhibitor(s) related to this paper: Tris(2-chloroethyl)-phosphate Abstract This study was performed to reveal the health risks of co-exposure to organophosphorus flame retardants (OPFRs) and microplastics (MPs). We exposed mice to polyethylene (PE) and polystyrene (PS) MPs and OPFRs [tris (2-chloroethy) phosphate (TCEP) and tris (1,3-dichloro-2-propyl) phosphate (TDCPP)] for 90 days. Biochemical markers and metabolomics were used to determine whether MPs could enhance the toxicity of OPFRs. Superoxide dismutase (SOD) and catalase (CAT) increased (p<0.05) by 21% and 26% respectively in 10mug/L TDCPP+PE group compared to TDCPP group. Lactate dehydrogenase (LDH) in TDCPP+MPs groups were higher (18%-30%) than that in TDCPP groups (p<0.05). Acetylcholinesterase (AChE) in TCEP+PE groups were lower (10%-19%) than those in TCEP groups (p<0.05). These results suggested that OPFR co-exposure with MPs induced more toxicity than OPFR exposure alone. Finally, in comparison to controls we observed that 29, 41, 41, 26, 40 and 37 metabolites changed significantly (p<0.05; fold-change>1.2) in TCEP, TCEP+PS, TCEP+PE, TDCPP, TDCPP+PS and TDCPP+PE groups, respectively. Most of these metabolites are related to pathways of amino acid and energy metabolism. Our results indicate that MPs aggravate the toxicity of OPFRs and highlight the health risks of MP co-exposure with other pollutants. Title: The opium poppy genome and morphinan production Guo L, Winzer T, Yang X, Li Y, Ning Z, He Z, Teodor R, Lu Y, Bowser TA and Ye K <1 more author(s)> Guo L, Winzer T, Yang X, Li Y, Ning Z, He Z, Teodor R, Lu Y, Bowser TA, Graham IA, Ye K (- 1) Ref: Science, 362:343, 2018 : PubMed ESTHER: Guo_2018_Science_362_343 PubMedSearch: Guo 2018 Science 362 343 PubMedID: 30166436 Gene_locus related to this paper: papso-a0a4y7jba3 Abstract Morphinan-based painkillers are derived from opium poppy (Papaver somniferum L.). We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively. Synteny analysis suggests a whole-genome duplication at ~7.8 million years ago and ancient segmental or whole-genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 million years ago. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provide insight into how this cluster evolved. Paralog analysis identified P450 and oxidoreductase genes that combined to form the STORR gene fusion essential for morphinan biosynthesis in opium poppy. Thus, gene duplication, rearrangement, and fusion events have led to evolution of specialized metabolic products in opium poppy. Title: Assessment of the oxidative and genotoxic effects of the glyphosate-based herbicide roundup on the freshwater shrimp, Macrobrachium nipponensis Hong Y, Yang X, Huang Y, Yan G, Cheng Y Ref: Chemosphere, 210:896, 2018 : PubMed ESTHER: Hong_2018_Chemosphere_210_896 PubMedSearch: Hong 2018 Chemosphere 210 896 PubMedID: 30208549 Abstract In the present study, an acute toxic test was performed to assess the oxidative stress and genotoxic effects of the herbicide on the freshwater shrimp Macrobrachium nipponensis. The results showed that the 48-h and 96-h LC50 values of Roundup to M. nipponensis were 57.684mg/L and 11.237mg/L, respectively. For further investigation, the shrimps were exposed to sublethal concentrations of 0.35, 0.70, 1.40, 2.80 and 5.60mg/L for 96h. A significant decrease in total haemocytes count (THC) was observed at concentration of 5.60mg/L throughout the experiment. The level of superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) in all the treatments decreased in a dose- and time-dependent manner except for the concentration group of 0.35mg/L. The malondialdehyde (MDA), hydrogen peroxide (H2O2) and protein carbonyl in serum increased significantly at concentrations of 2.80mg/L and 5.60mg/L. A significant decrease in acetylcholinesterase (AChE) activity was observed at each concentration (P0.05). In addition, the micronucleus (MN) frequency of haemocytes significantly increased (P0.05) at concentrations of 1.40, 2.80 and 5.60mg/L, whereas the comet ratio and %DNA in the tails exhibited a clear time- and dose-dependent response during the exposure. The analysis of the integrated biomarker response (IBR) showed the induction of oxidative stress biomarkers and the inhibition of antioxidants, and this dose-dependent relation suggests the sensitivity and availability of all the biomarkers. These results revealed that Roundup had a prominent toxic effect on M. nipponensis based on the antioxidative response inhibition and genotoxicity. Title: Csn5 Is Required for the Conidiogenesis and Pathogenesis of the Alternaria alternata Tangerine Pathotype Wang M, Yang X, Ruan R, Fu H, Li H Ref: Front Microbiol, 9:508, 2018 : PubMed ESTHER: Wang_2018_Front.Microbiol_9_508 PubMedSearch: Wang 2018 Front.Microbiol 9 508 PubMedID: 29616013 Gene_locus related to this paper: altal-actt2 Abstract The COP9 signalosome (CSN) is a highly conserved protein complex involved in the ubiquitin-proteasome system. Its metalloisopeptidase activity resides in subunit 5 (CSN5). Functions of csn5 in phytopathogenic fungi are poorly understood. Here, we knocked out the csn5 ortholog (Aacsn5) in the tangerine pathotype of Alternaria alternata. The deltaAacsn5 mutant showed a moderately reduced growth rate compared to the wildtype strain and was unable to produce conidia. The growth of deltaAacsn5 mutant was not affected in response to oxidative and osmotic stresses. Virulence assays revealed that deltaAacsn5 induced no or significantly reduced necrotic lesions on detached citrus leaves. The defects in hyphal growth, conidial sporulation, and pathogenicity of deltaAacsn5 were restored by genetic complementation of the mutant with wildtype Aacsn5. To explore the molecular mechanisms of conidiation and pathogenesis underlying Aacsn5 regulation, we systematically examined the transcriptomes of both deltaAacsn5 and the wildtype. Generally, 881 genes were overexpressed and 777 were underexpressed in the deltaAacsn5 mutant during conidiation while 694 overexpressed and 993 underexpressed during infection. During asexual development, genes related to the transport processes and nitrogen metabolism were significantly downregulated; the expression of csn1-4 and csn7 in deltaAacsn5 was significantly elevated; secondary metabolism gene clusters were broadly affected; especially, the transcript level of the whole of cluster 28 and 30 was strongly induced. During infection, the expression of the host-specific ACT toxin gene cluster which controls the biosynthesis of the citrus specific toxin was significantly repressed; many other SM clusters with unknown products were also regulated; 86 out of 373 carbohydrate-active enzymes responsible for breaking down the plant dead tissues showed uniquely decreased expression. Taken together, our results expand our understanding of the roles of csn5 on conidiation and pathogenicity in plant pathogenic fungi and provide a foundation for future investigations. Title: Oxidation pretreatment by calcium hypochlorite to improve the sensitivity of enzyme inhibition-based detection of organophosphorus pesticides Yang X, Dai J, Yang L, Ma M, Zhao SJ, Chen XG, Xiao H Ref: J Sci Food Agric, 98:2624, 2018 : PubMed ESTHER: Yang_2018_J.Sci.Food.Agric_98_2624 PubMedSearch: Yang 2018 J.Sci.Food.Agric 98 2624 PubMedID: 29072792 Abstract BACKGROUND: Enzyme inhibition-based detection is the most widely used method for rapid detection of organophosphorus pesticides (OPs) in food and agricultural products. However, the accuracy of the method is negatively affected by low inhibitory activities of OPs with PS moiety on acetylcholinesterase. RESULTS: We demonstrated that oxidation pretreatments with bromine, hydrogen peroxide, or calcium hypochlorite significantly enhanced the enzyme inhibitory activities of these OPs. Especially, calcium hypochlorite (0.05%) pretreatment converted the PS moiety in OPs to PO and produced the most potent and steady inhibitory effect on the enzyme. This, in turn, resulted in a dramatic increase in the sensitivity of enzyme inhibition-based detection of these OPs by as much as 2 to 7 orders of magnitude. Importantly, this enhanced detection of OPs was validated in various vegetable samples. CONCLUSION: Our findings provide a solid basis to use calcium hypochlorite pretreatment for the improved detection of OPs by the enzyme inhibition-based method. (c) 2017 Society of Chemical Industry. Title: Identification and characterization of a novel alkalistable and salt-tolerant esterase from the deep-sea hydrothermal vent of the East Pacific Rise Yang X, Wu L, Xu Y, Ke C, Hu F, Xiao X, Huang J Ref: Microbiologyopen, 7:e00601, 2018 : PubMed ESTHER: Yang_2018_Microbiolopen_7_e00601 PubMedSearch: Yang 2018 Microbiolopen 7 e00601 PubMedID: 29504251 Gene_locus related to this paper: 9bact-a0a2s1gux0 Abstract A novel esterase gene selected from metagenomic sequences of deep-sea hydrothermal vents was successfully expressed in Escherichia coli. The recombinant protein (est-OKK), which belongs to the lipolytic enzyme family V, exhibited high activity toward pNP-esters with short acyl chains and especially p-nitrophenyl butyrate. Site-mutagenesis results confirmed that est-OKK contains the nonclassical catalytic tetrad predicted by alignment and computational modeling. The est-OKK protein is a moderately thermophilic enzyme that is relatively thermostable, and highly salt-tolerant, which remained stable in 3 mol/L NaCl for 6 hr. The est-OKK protein showed the considerable alkalistability, displayed optimal activity at pH 9.0 and maintained approximately 70% of its residual activity after incubation at pH 10 for 4 hr. Furthermore, the est-OKK activity was strongly resistant to a variety of metal ions such as Co(2+) , Zn(2+) , Fe(2+) , Na(+) , and K(+) ; nonionic detergents such as Tween-20, Tween-80; and organic solvents such as acetone and isopropanol. Taken together, the novel esterase with unique characteristics may give us a new insight into the family V of lipolytic enzymes, and could be a highly valuable candidate for biotechnological applications such as organic synthesis reactions or food and pharmaceutical industries. Title: Identification and characterization of a novel carboxylesterase from Phaseolus vulgaris for detection of organophosphate and carbamates pesticides Yang X, Dai J, Zhao S, Li R, Goulette T, Chen X, Xiao H Ref: J Sci Food Agric, 98:5095, 2018 : PubMed ESTHER: Yang_2018_J.Sci.Food.Agric_98_5095 PubMedSearch: Yang 2018 J.Sci.Food.Agric 98 5095 PubMedID: 29604085 Abstract BACKGROUND: Organophosphate and carbamate pesticide residues in food and the environment pose a great threat to human health and have made the easy and rapid detection of these pesticide residues an important task. Discovering new enzyme sources from plants can help reduce the cost of large-scale applications of rapid pesticide detection via enzyme inhibition. RESULTS: Plant esterase from kidney beans was purified. Kidney bean esterase is identified as a carboxylesterase by substrate and inhibitor specificity tests and mass spectrometry identification. The kidney bean esterase demonstrates optimal catalytic activity at 40 degrees C, pH 6.5 and an enzyme concentration of 0.30 microg mL(-1) . The kidney bean esterase can be inhibited by organophosphate and carbamate pesticides, which can be substituted for acetylcholinesterase. The limit of detection of the purified kidney bean esterase was two- to 20-fold higher than that of the crude one. The method detection limit meets the detection requirement for the maximum residue limits (MRL) in actual samples. CONCLUSION: The findings of the present study provide a new source of enzymes for pesticides detection by enzyme inhibition. (c) 2018 Society of Chemical Industry. Title: Novel 8-hydroxyquinoline derivatives targeting beta-amyloid aggregation, metal chelation and oxidative stress against Alzheimer's disease Yang X, Cai P, Liu Q, Wu J, Yin Y, Wang X, Kong L Ref: Bioorganic & Medicinal Chemistry, 26:3191, 2018 : PubMed ESTHER: Yang_2018_Bioorg.Med.Chem_26_3191 PubMedSearch: Yang 2018 Bioorg.Med.Chem 26 3191 PubMedID: 29729985 Abstract A series of multitargeted 8-hydroxyquinoline derivatives were designed and synthesized for the treatment of Alzheimer's disease (AD). In vitro studies indicated that most of the prepared compounds exhibited significant inhibitory effects against self-induced Abeta(1-42) aggregation and potential antioxidant properties especially compound 5b (IC(50) = 5.64 microM for self-induced Abeta aggregation; the oxygen radical absorbance capacity using fluorescein (ORAC-FL) value is 2.63 Trolox equivalents). Notably, 5b can chelate biometals and inhibit Cu(2+)/Zn(2+)-induced Abeta(1-42) aggregation. The cell assays showed that 5b had excellent protective effects against oxidative toxin H(2)O(2) and presented low neurotoxicity in PC12 cells. Furthermore, 5b could penetrate the blood-brain barrier (BBB) in vitro and did not show any acute toxicity in mice at doses up to 2000 mg/kg in vivo. Our findings provide a rationale for the potential application of compound 5b as a lead compound in AD therapy. Title: Neurotrophins and cholinergic enzyme regulated by calpain-2: New insights into neuronal apoptosis induced by polybrominated diphenyl ether-153 Zhang H, Yang X, Li X, Zhang Z, Hou L, Wang Z, Niu Q, Wang T Ref: Toxicol Lett, 291:29, 2018 : PubMed ESTHER: Zhang_2018_Toxicol.Lett_291_29 PubMedSearch: Zhang 2018 Toxicol.Lett 291 29 PubMedID: 29621559 Abstract Polybrominated diphenyl ether-153 (BDE-153) has been demonstrated to induce neuronal apoptosis in rat cerebral cortex and primary neurons. Neurotrophins and cholinergic enzymes play critical roles in the neuronal survival, maintenance, synaptic plasticity and learning memory, however, their roles in neuronal apoptosis following the BDE-153 treatment remain unclear. In this study, we firstly explored the possible predominant pathway underlying the neuronal apoptotic induced by the BDE-153 treatment in rat cerebral cortex, by measuring expression levels (mRNA and protein) of p53, caspase-3, 8, 9, calpain-1, and calpain-2, detected the levels (protein contents and mRNA) of neurotrophins including brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), nerve growth factor (NGF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4), and measured acetylcholinesterase (AchE) and choline acetyltransferase (ChaT) activities in rat cerebral cortex and primary neurons following BDE-153 treatment with or without pretreatment with inhibitors. Results showed that the neuronal apoptosis induced by BDE-153 was dependent on p53, and dependent on more calpain-2 than caspase-3 in the cerebral cortex of rats. Following the BDE-153 treatment, the protein contents and mRNA levels of BDNF, GDNF, NGF, NT-3, and NT-4, as well as the AchE and ChaT activities were significantly decreased in the cerebral cortex and primary neurons when compared to the untreated group. When pretreated primary neurons with calpain inhibitor PD150606 or cyclin-dependent kinase (cdk5, the downstream complex of calpain) inhibitor Roscovitine, the neurotrophins contents and activities of ChaT and AchE were reverted, along with the improvement of neuron survival compared with BDE-153 treatment alone. We conclude that neurotrophins and cholinergic enzymes were regulated by the calpain-2 activation and its downstream cdk5 pathway, and which was involved in the neuronal apoptosis induced by the BDE-153 treatment. Title: Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease Chen Z, Digiacomo M, Tu Y, Gu Q, Wang S, Yang X, Chu J, Chen Q, Han Y and Pi R <5 more author(s)> Chen Z, Digiacomo M, Tu Y, Gu Q, Wang S, Yang X, Chu J, Chen Q, Han Y, Chen J, Nesi G, Sestito S, Macchia M, Rapposelli S, Pi R (- 5) Ref: Eur Journal of Medicinal Chemistry, 125:784, 2017 : PubMed ESTHER: Chen_2017_Eur.J.Med.Chem_125_784 PubMedSearch: Chen 2017 Eur.J.Med.Chem 125 784 PubMedID: 27736684 Abstract A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Abeta) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Abeta self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD. Title: Chlorpyrifos and chlorpyrifos oxon impair the transport of membrane bound organelles in rat cortical axons Gao J, Naughton SX, Beck WD, Hernandez CM, Wu G, Wei Z, Yang X, Bartlett MG, Terry AV, Jr. Ref: Neurotoxicology, 62:111, 2017 : PubMed ESTHER: Gao_2017_Neurotoxicol_62_111 PubMedSearch: Gao 2017 Neurotoxicol 62 111 PubMedID: 28600141 Abstract Chlorpyrifos (CPF) is an extensively used organophosphorus pesticide that has recently come under increasing scrutiny due to environmental health concerns particularly its association with neurodevelopmental defects. While the insecticidal actions and acute toxicity of CPF are attributed to its oxon metabolite (CPO) which potently inhibits the cholinergic enzyme acetylcholinesterase (AChE), there is significant evidence that CPF, CPO, and other organophosphates may affect a variety of neuronal targets and processes that are not directly related to AChE. Previously, in adult rat sciatic nerves ex vivo and postnatal neurons from rats in vitro we observed that CPF and CPO impaired the movements of vesicles and mitochondria in axons. Here, in embryonic neurons from rats in culture, we evaluated 24h exposures to CPF and CPO across picomolar to micromolar concentrations for effects on fast axonal transport of membrane bound organelles (MBOs) that contained the amyloid precursor protein (APP) tagged with the fluorescent marker, Dendra2 (APPDendra2). The most notable observations of this study were concentration-dependent decreases in the velocity and percentage of MBOs moving in the anterograde direction, an increase in the number of stationary MBOs, and an increased frequency of pauses associated with both CPF and CPO. These effects occurred at concentrations that did not significantly inhibit AChE activity, they were not blocked by cholinergic receptor antagonists, and they were not associated with compromised cell viability. These effects of CPF and CPO may be significant given the importance of axonal transport to neuronal development as well the function of fully developed neurons. Title: Multitarget drug design strategy against Alzheimer's disease: Homoisoflavonoid Mannich base derivatives serve as acetylcholinesterase and monoamine oxidase B dual inhibitors with multifunctional properties Li Y, Qiang X, Luo L, Yang X, Xiao G, Zheng Y, Cao Z, Sang Z, Su F, Deng Y Ref: Bioorganic & Medicinal Chemistry, 25:714, 2017 : PubMed ESTHER: Li_2017_Bioorg.Med.Chem_25_714 PubMedSearch: Li 2017 Bioorg.Med.Chem 25 714 PubMedID: 27923535 Abstract A series of homoisoflavonoid Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease. It demonstrated that most of the derivatives were selective AChE and MAO-B dual inhibitors with good multifunctional properties. Among them, compound 10d displayed the comprehensive advantages, with excellent AChE and MAO-B inhibitory activities (IC50=2.49+/-0.08nM and 1.74+/-0.0581muM, respectively), good self- and Cu2+-induced Abeta1-42 aggregation inhibitory potency, antioxidant activity, biometal chelating ability and high BBB permeability. These multifunctional properties make 10d as an excellent candidate for the development of efficient drugs against AD. Title: Imaging and Detection of Carboxylesterase in Living Cells and Zebrafish Pretreated with Pesticides by a New Near-Infrared Fluorescence Off-On Probe Li D, Li Z, Chen W, Yang X Ref: Journal of Agricultural and Food Chemistry, 65:4209, 2017 : PubMed ESTHER: Li_2017_J.Agric.Food.Chem_65_4209 PubMedSearch: Li 2017 J.Agric.Food.Chem 65 4209 PubMedID: 28475833 Abstract A new near-infrared fluorescence off-on probe was developed and applied to fluorescence imaging of carboxylesterase in living HepG-2 cells and zebrafish pretreated with pesticides (carbamate, organophosphorus, and pyrethroid). The probe was readily prepared by connecting (4-acetoxybenzyl)oxy as a quenching and recognizing moiety to a stable hemicyanine skeleton that can be formed via the decomposition of IR-780. The fluorescence off-on response of the probe to carboxylesterase is based on the enzyme-catalyzed spontaneous hydrolysis of the carboxylic ester bond, followed by a further fragmentation of the phenylmethyl unit and thereby the fluorophore release. Compared with the only existing near-infrared carboxylesterase probe, the proposed probe exhibits superior analytical performance, such as near-infrared fluorescence emission over 700 nm as well as high selectivity and sensitivity, with a detection limit of 4.5 x 10-3 U/mL. More importantly, the probe is cell membrane permeable, and its applicability has been successfully demonstrated for monitoring carboxylesterase activity in living HepG-2 cells and zebrafish pretreated with pesticides, revealing that pesticides can effectively inhibit the activity of carboxylesterase. The superior properties of the probe make it of great potential use in indicating pesticide exposure. Title: Multifunctional thioxanthone derivatives with acetylcholinesterase, monoamine oxidases and beta-amyloid aggregation inhibitory activities as potential agents against Alzheimer's disease Luo L, Li Y, Qiang X, Cao Z, Xu R, Yang X, Xiao G, Song Q, Tan Z, Deng Y Ref: Bioorganic & Medicinal Chemistry, 25:1997, 2017 : PubMed ESTHER: Luo_2017_Bioorg.Med.Chem_25_1997 PubMedSearch: Luo 2017 Bioorg.Med.Chem 25 1997 PubMedID: 28237559 Abstract A series of 1-hydroxyl-3-aminoalkoxy-thioxanthone derivatives were designed, synthesized and evaluated as potential multifunctional agents against Alzheimer's disease (AD). The results indicated that most of these compounds exhibited good AChE and MAOs inhibitory activities, significant inhibition of self- and Cu2+-induced Abeta1-42 aggregation, and moderate to good antioxidant activities. Specifically, compound 9e displayed high inhibitory potency toward AChE (IC50=0.59+/-0.02muM), MAO-A and MAO-B (IC50=1.01+/-0.02muM and 0.90+/-0.01muM respectively), excellent efficiency to block both self- and Cu2+-induced Abeta1-42 aggregation (74.8+/-1.2% and 87.7+/-1.9% at 25muM, respectively), good metal-chelating property and a low toxicity in SH-SY5Y cells. Furthermore, kinetic and molecular modeling studies revealed that compound 9e binds simultaneously to the catalytic active site and peripheral anionic site of AChE, and could penetrate the BBB. Collectively, these results suggested that 9e might be a potential multifunctional agent for further development in the treatment of AD. Title: The metastatic suppressor NDRG1 inhibits EMT, migration and invasion through interaction and promotion of caveolin-1 ubiquitylation in human colorectal cancer cells Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M and Sun J <2 more author(s)> Mi L, Zhu F, Yang X, Lu J, Zheng Y, Zhao Q, Wen X, Lu A, Wang M, Zheng M, Ji J, Sun J (- 2) Ref: Oncogene, 36:4323, 2017 : PubMed ESTHER: Mi_2017_Oncogene_36_4323 PubMedSearch: Mi 2017 Oncogene 36 4323 PubMedID: 28346422 Gene_locus related to this paper: human-NDRG1 Abstract N-myc downstream-regulated gene 1 (NDRG1) has been reported to act as a key regulatory molecule in tumor progression-related signaling pathways, especially in tumor metastasis. However, the related mechanism has not been fully discovered yet. Herein we demonstrated that the novel molecule of cell migration and invasion, caveolin-1, has direct interaction with NDRG1 in human colorectal cancer (CRC) cells. Moreover, we discovered that NDRG1 reduces caveolin-1 protein expression through promoting its ubiquitylation and subsequent degradation via the proteasome in CRC cells. In addition, caveolin-1 mediates the suppressive function of NDRG1 in epithelial-mesenchymal transition, migration and invasion in vitro and metastasis in vivo. These results help to fulfill the potential mechanisms of NDRG1 in anti-metastatic treatment for human colorectal cancer. Title: Nature-based molecules combined with rivastigmine: A symbiotic approach for the synthesis of new agents against Alzheimer's disease Nesi G, Chen Q, Sestito S, Digiacomo M, Yang X, Wang S, Pi R, Rapposelli S Ref: Eur Journal of Medicinal Chemistry, 141:232, 2017 : PubMed ESTHER: Nesi_2017_Eur.J.Med.Chem_141_232 PubMedSearch: Nesi 2017 Eur.J.Med.Chem 141 232 PubMedID: 29031070 Abstract Starting from nature as original source, new potential agents with pleiotropic activities have been synthesized and evaluated as neuroprotective agents. In this work, novel nature-based hybrids, combining antioxidant motifs with rivastigmine, have been designed and synthesized. The biological results revealed that the new compounds inhibit both AChE and BuChE. In particular, lipoic acid hybrids LA1, LA2, LA3 resulted to be the most potent inhibitors of BuChE showing IC(50) values ranging from 340 to 378 nM. Analogously, all the compounds were able to inhibit the self beta-amyloid(1-42) aggregation. The gallic acid hybrid GA2 as well as the 2-chromonecarboxylic acid hybrids CA1 and CA2 prevented the self-mediated Abeta aggregation with percentages of inhibition ranging from 53% to 59%. Finally, some of them also show potent neuroprotective effects against glutamate-induced cell death and low toxicity in HT22 cells. Title: Genome assembly with in vitro proximity ligation data and whole-genome triplication in lettuce Reyes-Chin-Wo S, Wang Z, Yang X, Kozik A, Arikit S, Song C, Xia L, Froenicke L, Lavelle DO and Michelmore RW <9 more author(s)> Reyes-Chin-Wo S, Wang Z, Yang X, Kozik A, Arikit S, Song C, Xia L, Froenicke L, Lavelle DO, Truco MJ, Xia R, Zhu S, Xu C, Xu H, Xu X, Cox K, Korf I, Meyers BC, Michelmore RW (- 9) Ref: Nat Commun, 8:14953, 2017 : PubMed ESTHER: Reyes-Chin-Wo_2017_Nat.Commun_8_14953 PubMedSearch: Reyes-Chin-Wo 2017 Nat.Commun 8 14953 PubMedID: 28401891 Gene_locus related to this paper: lacsa-a0a2j6jnd3, lacsa-a0a2j6l6y4, lacsa-a0a2j6mjs5, lacsa-a0a2j6mk82, lacsa-a0a2j6k5z4, lacsa-a0a2j6mk08, lacsa-a0a2j6mhc5, lacsa-a0a2j6m8d0, lacsa-a0a2j6mdb6, lacsa-a0a2j6mdh6, lacsa-a0a2j6jnf0, lacsa-a0a2j6mji4, lacsa-a0a2j6ke81, lacsa-a0a2j6jip3, lacsa-a0a2j6jir5, lacsa-a0a2j6ksa7, lacsa-a0a2j6l4a3 Abstract Lettuce (Lactuca sativa) is a major crop and a member of the large, highly successful Compositae family of flowering plants. Here we present a reference assembly for the species and family. This was generated using whole-genome shotgun Illumina reads plus in vitro proximity ligation data to create large superscaffolds; it was validated genetically and superscaffolds were oriented in genetic bins ordered along nine chromosomal pseudomolecules. We identify several genomic features that may have contributed to the success of the family, including genes encoding Cycloidea-like transcription factors, kinases, enzymes involved in rubber biosynthesis and disease resistance proteins that are expanded in the genome. We characterize 21 novel microRNAs, one of which may trigger phasiRNAs from numerous kinase transcripts. We provide evidence for a whole-genome triplication event specific but basal to the Compositae. We detect 26% of the genome in triplicated regions containing 30% of all genes that are enriched for regulatory sequences and depleted for genes involved in defence. Title: Design, synthesis and biological evaluation of 4'-aminochalcone-rivastigmine hybrids as multifunctional agents for the treatment of Alzheimer's disease Xiao G, Li Y, Qiang X, Xu R, Zheng Y, Cao Z, Luo L, Yang X, Sang Z and Deng Y <1 more author(s)> Xiao G, Li Y, Qiang X, Xu R, Zheng Y, Cao Z, Luo L, Yang X, Sang Z, Su F, Deng Y (- 1) Ref: Bioorganic & Medicinal Chemistry, 25:1030, 2017 : PubMed ESTHER: Xiao_2017_Bioorg.Med.Chem_25_1030 PubMedSearch: Xiao 2017 Bioorg.Med.Chem 25 1030 PubMedID: 28011206 Abstract A series of 4'-aminochalcone-revastigmine hybrids were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. The results showed that most of these compounds exhibited good multifunctional activities. In particular, compound 6c displayed the best inhibitory potency on acetylcholinesterase (IC50=4.91muM), and significant antioxidative activity with a value 2.83-fold of Trolox. The kinetic analysis of AChE inhibition revealed that 6c showed mixed-type inhibition, binding simultaneously to the catalytic active site and peripheral anionic site of AChE. In addition, 6c inhibited self-induced Abeta1-42 aggregation and Cu2+-induced Abeta1-42 aggregation by 89.5% and 79.7% at 25muM respectively, as well as acted as a selective monoamine oxidase B inhibitor (IC50=0.29muM) and a selective biometal chelator. Furthermore, 6c could cross the blood-brain barrier in vitro. Based on these results, Compound 6c could be considered as a very promising lead compound for Alzheimer's disease. Title: Pyridoxine-resveratrol hybrids Mannich base derivatives as novel dual inhibitors of AChE and MAO-B with antioxidant and metal-chelating properties for the treatment of Alzheimer's disease Yang X, Qiang X, Li Y, Luo L, Xu R, Zheng Y, Cao Z, Tan Z, Deng Y Ref: Bioorg Chem, 71:305, 2017 : PubMed ESTHER: Yang_2017_Bioorg.Chem_71_305 PubMedSearch: Yang 2017 Bioorg.Chem 71 305 PubMedID: 28267984 Abstract A series of pyridoxine-resveratrol hybrids Mannich base derivatives as multifunctional agents have been designed, synthesized and evaluated for cholinesterase (ChE) and monoamine oxidase (MAO) inhibitory activity. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and metal-chelating properties were also tested. The results showed that most of these compounds could selectively inhibit acetylcholinesterase (AChE) and MAO-B. Among them, compounds 7d and 8b exhibited the highest potency for AChE inhibition with IC50 values of 2.11muM and 1.56muM, respectively, and compound 7e exhibited the highest MAO-B inhibition with an IC50 value of 2.68muM. The inhibition kinetic analysis revealed that compound 7d showed a mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. Molecular modeling study was also performed to investigate the binding mode of these hybrids with MAO-B. In addition, all target compounds displayed good antioxidant and metal-chelating properties. Taken together, these preliminary findings can be a new starting point for further development of multifunctional agents for Alzheimer's disease. Title: N-myc downstream-regulated gene 1 promotes oxaliplatin-triggered apoptosis in colorectal cancer cells via enhancing the ubiquitination of Bcl-2 Yang X, Zhu F, Yu C, Lu J, Zhang L, Lv Y, Sun J, Zheng M Ref: Oncotarget, 8:47709, 2017 : PubMed ESTHER: Yang_2017_Oncotarget_8_47709 PubMedSearch: Yang 2017 Oncotarget 8 47709 PubMedID: 28537875 Gene_locus related to this paper: human-NDRG1 Abstract N-myc downstream-regulated gene1 (NDRG1) has been identified as a potent tumor suppressor gene. The molecular mechanisms of anti-tumor activity of NDRG1 involve its suppressive effects on a variety of tumorigenic signaling pathways. The purpose of this study was to investigate the role of NDRG1 in the apoptosis of colorectal cancer (CRC) cells. We first collected the clinical data of locally advanced rectal cancer (LARC) patients receiving oxaliplatin-based neoadjuvant chemotherapy in our medical center. Correlation analysis revealed that NDRG1 positively associated with the downstaging rates and prognosis of patients. Then, the effects of over-expression and depletion of NDRG1 gene on apoptosis of colorectal cancer were tested in vitro and in vivo. NDRG1 over-expression promoted apoptosis in colorectal cancer cells whereas depletion of NDRG1 resulted in resistance to oxaliplatin treatment. Furthermore, we observed that Bcl-2, a major anti-apoptotic protein, was regulated by NDRG1 at post-transcriptional level. By binding Protein kinase Calpha (PKCalpha), a classical regulating factor of Bcl-2, NDRG1 enhanced the ubiquitination and degradation of Bcl-2, thus promoting apoptosis in CRC cells. In addition, NDRG1 inhibited tumor growth and promoted apoptosis in mouse xenograft model. In conclusion,NDRG1 promotes oxaliplatin-triggered apoptosis in colorectal cancer. Therefore, colorectal cancer patients can be stratified by the expression level of NDRG1. NDRG1-positive patients may benefit from oxaliplatin-containing chemotherapy regimens whereas those with negative NDRG1 expression should avoid the usage of this cytotoxic drug. Title: Transcriptional responses in the hepatopancreas of Eriocheir sinensis exposed to deltamethrin Yang Z, Zhang Y, Jiang Y, Zhu F, Zeng L, Wang Y, Lei X, Yao Y, Hou Y and Hu K <3 more author(s)> Yang Z, Zhang Y, Jiang Y, Zhu F, Zeng L, Wang Y, Lei X, Yao Y, Hou Y, Xu L, Xiong C, Yang X, Hu K (- 3) Ref: PLoS ONE, 12:e0184581, 2017 : PubMed ESTHER: Yang_2017_PLoS.One_12_e0184581 PubMedSearch: Yang 2017 PLoS.One 12 e0184581 PubMedID: 28910412 Abstract Deltamethrin is an important pesticide widely used against ectoparasites. Deltamethrin contamination has resulted in a threat to the healthy breeding of the Chinese mitten crab, Eriocheir sinensis. In this study, we investigated transcriptional responses in the hepatopancreas of E. sinensis exposed to deltamethrin. We obtained 99,087,448, 89,086,478, and 100,117,958 raw sequence reads from control 1, control 2, and control 3 groups, and 92,094,972, 92,883,894, and 92,500,828 raw sequence reads from test 1, test 2, and test 3 groups, respectively. After filtering and quality checking of the raw sequence reads, our analysis yielded 79,228,354, 72,336,470, 81,859,826, 77,649,400, 77,194,276, and 75,697,016 clean reads with a mean length of 150 bp from the control and test groups. After deltamethrin treatment, a total of 160 and 167 genes were significantly upregulated and downregulated, respectively. Gene ontology terms "biological process," "cellular component," and "molecular function" were enriched with respect to cell killing, cellular process, other organism part, cell part, binding, and catalytic. Pathway analysis using the Kyoto Encyclopedia of Genes and Genomes showed that the metabolic pathways were significantly enriched. We found that the CYP450 enzyme system, carboxylesterase, glutathione-S-transferase, and material (including carbohydrate, lipid, protein, and other substances) metabolism played important roles in the metabolism of deltamethrin in the hepatopancreas of E. sinensis. This study revealed differentially expressed genes related to insecticide metabolism and detoxification in E. sinensis for the first time and will help in understanding the toxicity and molecular metabolic mechanisms of deltamethrin in E. sinensis. Title: Altered methylations of H19, Snrpn, Mest and Peg3 are reversible by developmental reprogramming in kidney tissue of ICSI-derived mice Zhan Q, Qi X, Wang N, Le F, Mao L, Yang X, Yuan M, Lou H, Xu X and Jin F <1 more author(s)> Zhan Q, Qi X, Wang N, Le F, Mao L, Yang X, Yuan M, Lou H, Xu X, Chen X, Jin F (- 1) Ref: Sci Rep, 7:11936, 2017 : PubMed ESTHER: Zhan_2017_Sci.Rep_7_11936 PubMedSearch: Zhan 2017 Sci.Rep 7 11936 PubMedID: 28931827 Abstract Although the prevalence of Intracytoplasmic sperm injection (ICSI) has increased year by year, there remains concern about the safety of these procedures because of reports of the increased risk for imprinting disorders. Previous research has demonstrated that gonadotropin stimulation contributes to an increased incidence of epimutations in ICSI-derived mice. However, the epimutations in ICSI offspring after removing the effect of gonadotropin stimulation and the possibility that epimutations are reversible by developmental reprogramming has not been investigated. Our study is the first to investigate the effect of ICSI itself on methylation and exclude the effect of superovulation using the kidney tissues from the adult and old mice. We found reduced methylation and up-regulated expression of the imprinted genes, H19, Mest and Peg3, in adult ICSI mice, but the above alterations observed in adult mice were not detected in old ICSI mice. At the Snrpn DMR, methylation status was not altered in adult ICSI-derived mice, but hypermethylation and correlated down-regulated expression of Snrpn were observed in old mice. In conclusion, ICSI manipulation and early embryo culture resulted in alterations of methylation in differentially methylated region of H19, Mest, Peg3 and Snrpn, and the alterations were reprogrammed by developmental reprogramming. Title: Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice Zhang SJ, Xu TT, Li L, Xu YM, Qu ZL, Wang XC, Huang SQ, Luo Y, Luo NC and Wang Q <3 more author(s)> Zhang SJ, Xu TT, Li L, Xu YM, Qu ZL, Wang XC, Huang SQ, Luo Y, Luo NC, Lu P, Shi YF, Yang X, Wang Q (- 3) Ref: Oncotarget, 8:49338, 2017 : PubMed ESTHER: Zhang_2017_Oncotarget_8_49338 PubMedSearch: Zhang 2017 Oncotarget 8 49338 PubMedID: 28521305 Abstract The Chinese formula Bushen-Yizhi (BSYZ) has been reported to ameliorate cognitive dysfunction. However the mechanism is still unclear. In this study, we employ an aging model, SAMP8 mice, to explore whether BSYZ could protect dementia through SIRT1/endoplasmic reticulum (ER) stress pathway. Morris water maze and the fearing condition test results show that oral administration of BSYZ (1.46 g/kg/d, 2.92 g/kg/d and 5.84 g/kg/d) and donepezil (3 mg/kg/d) shorten the escape latency, increase the crossing times of the original position of the platform and the time spent in the target quadrant, and increase the freezing time. BSYZ decreases the activity of acetylcholinesterase (AChE), and increases the activity of choline acetyltransferase (ChAT) and the concentration of acetylcholine (Ach) in both hippocampus and cortex. In addition, western blot results (Bcl-2, Bax and Caspase-3) and TUNEL staining show that BSYZ prevents neuron from apoptosis, and elevates the expression of neurotrophic factors, including nerve growth factor (NGF), postsynapticdensity 95 (PSD95) and synaptophysin (SYN), in both hippocampus and cortex. BSYZ also increases the protein expression of SIRT1 and alleviates ER stress-associated proteins (PERK, IRE-1alpha, eIF-2alpha, BIP, PDI and CHOP). These results indicate that the neuroprotective mechanism of BSYZ might be related with SIRT1/ER stress pathway. Title: Neuroprotective effects of polygalacic acid on scopolamine-induced memory deficits in mice Guo C, Shen J, Meng Z, Yang X, Li F Ref: Phytomedicine, 23:149, 2016 : PubMed ESTHER: Guo_2016_Phytomedicine_23_149 PubMedSearch: Guo 2016 Phytomedicine 23 149 PubMedID: 26926176 Abstract BACKGROUND: Polygala tenuifolia Willd is a Traditional Chinese Medicine used for the treatment of learning and memory deficits. Triterpenoid saponins, the main bioactive compounds of Polygala tenuifolia Willd, are easily hydrolyzed to polygalacic acid (PA). PURPOSE: The present study was undertaken to investigate the neuroprotective effects of PA on scopolamine-induced cognitive dysfunction and to elucidate its underlying mechanisms of action. Title: Hydrogen sulfide may attenuate methylmercury-induced neurotoxicity via mitochondrial preservation Han J, Yang X, Chen X, Li Z, Fang M, Bai B, Tan D Ref: Chemico-Biological Interactions, 263:66, 2016 : PubMed ESTHER: Han_2016_Chem.Biol.Interact_263_66 PubMedSearch: Han 2016 Chem.Biol.Interact 263 66 PubMedID: 28027877 Abstract Hydrogen sulfide (H2S) is a protective molecule and a novel gaseous mediator. Here we explored whether H2S donor (NaHS) could attenuate methylmercury (MeHg)-induced neurotoxicity in rats. The adult rats were randomly divided into four groups, i.e., control, NaHS, MeHg, and NaHS + MeHg groups. Rats of the NaHS + MeHg group were intraperitoneally (i.p) injected with 5.6 mg/kg/d of NaHS together with 5 mug/kg/d of MeHg. Rats of the MeHg group and NaHS group were injected with 5 mug/kg/d of MeHg and 5.6 mg/kg/d of NaHS, respectively. All treatments were continued for 20 d, and the cerebral cortex of the rats was evaluated. The results showed that NaHS significantly reduced MeHg-induced oxidative stress, as indicated by reduced lipid peroxide content, and increased glutathione levels and glutathione peroxidase and thioredoxin reductase activities. NaHS attenuated MeHg-induced mitochondrial damage, as indicated by increased mitochondrial activity, reduced mitochondrial swelling, and the release of cytochrome C and apoptosis-inducing factors. NaHS also decreased the number of apoptotic cells compared to that observed in MeHg only-treated rats, as indicated in a TUNEL assay. Finally, NaHS increased DNA and RNA content, and the activities of acetylcholinesterase and Na+/K+-ATPase. These indices were all lower in the MeHg group than in the control group, and NaHS alone did not observably influence any of these indices compared to the control. Our results demonstrate that H2S may protect against MeHg-induced neurotoxicity, and the mechanisms appear to involve the inhibition of oxidative stress and the protection of mitochondria. Title: Anti-phytopathogen, multi-target acetylcholinesterase inhibitory and antioxidant activities of metabolites from endophytic Chaetomium globosum Li W, Yang X, Yang Y, Duang R, Chen G, Li X, Li Q, Qin S, Li S and Ding Z <1 more author(s)> Li W, Yang X, Yang Y, Duang R, Chen G, Li X, Li Q, Qin S, Li S, Zhao L, Ding Z (- 1) Ref: Nat Prod Res, :1, 2016 : PubMed ESTHER: Li_2016_Nat.Prod.Res__1 PubMedSearch: Li 2016 Nat.Prod.Res 1 PubMedID: 26744178 Abstract Fourteen metabolites with various structure types were isolated from endophytic Chaetomium globosum. Five compounds were separated from genus Chaetomium for the first time. Some compounds exhibited remarkable inhibition against phytopathogenic fungi causing root rot of Panax notoginseng. Compounds 1-5 had significant DPPH-free radical-scavenging activity. Compounds 3 and 5 indicated significant inhibitions against the acetylcholinesterase (AChE). From preliminary structure-activity relationship, it was found that the oxygenic five-membered ring of 3 and 5 was crucial in the anti-AChE activity. These structures provide new templates for the potential treatment and management of plant diseases and Alzheimer disease. Title: Pterostilbene-O-acetamidoalkylbenzylamines derivatives as novel dual inhibitors of cholinesterase with anti-beta-amyloid aggregation and antioxidant properties for the treatment of Alzheimer's disease Li Y, Qiang X, Yang X, Luo L, Xiao G, Cao Z, Tan Z, Deng Y Ref: Bioorganic & Medicinal Chemistry Lett, 26:2035, 2016 : PubMed ESTHER: Li_2016_Bioorg.Med.Chem.Lett_26_2035 PubMedSearch: Li 2016 Bioorg.Med.Chem.Lett 26 2035 PubMedID: 26947607 Abstract A series of pterostilbene-O-acetamidoalkylbenzylamines were designed, synthesized and evaluated as dual inhibitors of AChE and BuChE. To further explore the multifunctional properties of the new derivatives, their antioxidant activities and inhibitory effects on self-induced Abeta1-42 aggregation and HuAChE-induced Abeta1-40 aggregation were also tested. The results showed that most of these compounds could effectively inhibit AChE and BuChE. Particularly, compound 21d exhibited the best AChE inhibitory activity (IC50=0.06muM) and good inhibition of BuChE (IC50=28.04muM). Both the inhibition kinetic analysis and molecular modeling study revealed that these compounds showed mixed-type inhibition, binding simultaneously to the CAS and PAS of AChE. In addition to cholinesterase inhibitory activities, these compounds showed different levels of antioxidant activity. However, the inhibitory activities against self-induced and HuAChE-induced Abeta aggregation of these new derivatives were unsatisfied. Taking into account the results of the biological evaluation, further modifications will be designed in order to increase the potency on the different targets. The results displayed in this Letter can be a new starting point for further development of multifunctional agents for Alzheimer's disease. Title: Aurone Mannich base derivatives as promising multifunctional agents with acetylcholinesterase inhibition, anti-beta-amyloid aggragation and neuroprotective properties for the treatment of Alzheimer's disease Li Y, Qiang X, Luo L, Yang X, Xiao G, Liu Q, Ai J, Tan Z, Deng Y Ref: Eur Journal of Medicinal Chemistry, 126:762, 2016 : PubMed ESTHER: Li_2016_Eur.J.Med.Chem_126_762 PubMedSearch: Li 2016 Eur.J.Med.Chem 126 762 PubMedID: 27951485 Abstract A series of aurone Mannich base derivatives were designed, synthesized and evaluated as multifunctional agents for the treatment of Alzheimer's disease. In vitro assays demonstrated that most of the derivatives were selective AChE inhibitors with good multifunctional properties. Among them, compound 7d exhibited outstanding inhibitory activity for RatAChE, EeAChE and HuAChE (IC50 = 0.00878 +/- 0.0002 muM, 0.0212 +/- 0.006 muM and 0.0371 +/- 0.004 muM, respectively). Moreover, 7d displayed high antioxidant activity and could confer significant neuroprotective effect against H2O2-induced PC-12 cell injury. In addition, 7d also showed biometal chelating abilities, good self- and Cu2+-induced Abeta1-42 aggregation inhibitory potency and high BBB permeability. These multifunctional properties highlight 7d as promising candidate for further studies directed to the development of novel drugs against AD. Title: Structure, cytotoxic activity and mechanism of protoilludane sesquiterpene aryl esters from the mycelium of Armillaria mellea Li Z, Wang Y, Jiang B, Li W, Zheng L, Yang X, Bao Y, Sun L, Huang Y, Li Y Ref: J Ethnopharmacol, 184:119, 2016 : PubMed ESTHER: Li_2016_J.Ethnopharmacol_184_119 PubMedSearch: Li 2016 J.Ethnopharmacol 184 119 PubMedID: 26952552 Gene_locus related to this paper: armos-armb Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Armillaria mellea (Vahl. ex. Fr.) Karst is an important traditional Chinese medicine used in dispelling wind and removing obstruction in the meridians, and strengthening tendons and bones. Armillaria mellea has been recorded in the book Caobenshiyi which was written by ancestor for the function of suppressing hyderactive liver for calming endogenous wind medicine. The aim of this study is to investigate the cytotoxic activity for liver cell lines (normal and cancerous) of protoilludane sesquiterpene aryl esters from the mycelium of A. mellea. MATERIALS AND METHODS: A systemic fractionation of the mycelium extracts of A. mellea and relative activity mechanisms were studied. RESULTS: Two new protoilludane sesquiterpene aryl esters named 5'-methoxy-armillasin (1) and 5-hydroxyl-armillarivin (2) were isolated. In addition, eight known protoilludane sesquiterpene aryl esters armillaridin (3), armillartin (4), armillarin (5), melleolide B (6), armillarilin (7), armillasin (8), armillarigin (9) and melleolide (10) were also isolated from the mycelium of A. mellea. The relative configurations of the two new compounds were confirmed by NOESY spectra. Among ten protoilludane sesquiterpene aryl esters, compounds 2, 3, 4, 7, 8, 9 and 10 were active constituents with highly cytotoxic activity against HepG2 cells (4.95-37.65microg/mL). We reported here for the time, that compound 10 (melleolide) showed anti-tumor ability on hepatoma cell. The relative mechanism was assessed on HepG2 cells. CONCLUSIONS: Among all the ten protoilludane sesquiterpene aryl esters, melleolide (10) showed the best cytotoxic activity for HepG2 cells (4.95microg/mL) and lower activity for L02 cells (16.05microg/mL). Mechanism study showed that melleolide decreased the viability of the cancer cells with varying levels of cleaved-caspase 3, caspase 8, caspase 9, Bax and Ki67 expression. On the other hand, melleolide induced HepG2 cell cycle arrest at the G2/M phase. Title: Effects of caffeic acid on learning deficits in a model of Alzheimer's disease Wang Y, Li J, Hua L, Han B, Zhang Y, Yang X, Zeng Z, Bai H, Yin H, Lou J Ref: Int J Mol Med, 38:869, 2016 : PubMed ESTHER: Wang_2016_Int.J.Mol.Med_38_869 PubMedSearch: Wang 2016 Int.J.Mol.Med 38 869 PubMedID: 27430591 Abstract Caffeic acid is a type of phenolic acid and organic acid. It is found in food (such as tomatoes, carrots, strawberries, blueberries and wheat), beverages (such as wine, tea, coffee and apple juice) as well as Chinese herbal medicines. In the present study, we examined the effects of caffeic acid on learning deficits in a rat model of Alzheimer's disease (AD). The rats were randomly divided into three groups: i) control group, ii) AD model group and iii) caffeic acid group. Caffeic acid significantly rescued learning deficits and increased cognitive function in the rats with AD as demonstrated by the Morris water maze task. Furthermore, caffeic acid administration resulted in a significant decrease in acetylcholinesterase activity and nitrite generation in the rats with AD compared with the AD model group. Furthermore, caffeic acid suppressed oxidative stress, inflammation, nuclear factorkappaBp65 protein expression and caspase3 activity as well as regulating the protein expression of p53 and phosphorylated (p-)p38 MAPK expression in the rats with AD. These experimental results indicate that the beneficial effects of caffeic acid on learning deficits in a model of AD were due to the suppression of oxidative stress and inflammation through the p38 MAPK signaling pathway. Title: An integrated molecular docking and rescoring method for predicting the sensitivity spectrum of various serine hydrolases to organophosphorus pesticides Yang LL, Yang X, Li GB, Fan KG, Yin PF, Chen XG Ref: J Sci Food Agric, 96:2184, 2016 : PubMed ESTHER: Yang_2016_J.Sci.Food.Agric_96_2184 PubMedSearch: Yang 2016 J.Sci.Food.Agric 96 2184 PubMedID: 26172068 Abstract BACKGROUND: The enzymatic chemistry method is currently the most widely used method for the rapid detection of organophosphorus (OP) pesticides, but the enzymes used, such as cholinesterases, lack sufficient sensitivity to detect low concentrations of OP pesticides present in given samples. Serine hydrolase is considered an ideal enzyme source in seeking high-sensitivity enzymes used for OP pesticide detection. However, it is difficult to systematically evaluate sensitivities of various serine hydrolases to OP pesticides by in vitro experiments. This study aimed to establish an in silico method to predict the sensitivity spectrum of various serine hydrolases to OP pesticides. Title: Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing Yang X, Coulombe-Huntington J, Kang S, Sheynkman GM, Hao T, Richardson A, Sun S, Yang F, Shen YA and Vidal M <28 more author(s)> Yang X, Coulombe-Huntington J, Kang S, Sheynkman GM, Hao T, Richardson A, Sun S, Yang F, Shen YA, Murray RR, Spirohn K, Begg BE, Duran-Frigola M, MacWilliams A, Pevzner SJ, Zhong Q, Trigg SA, Tam S, Ghamsari L, Sahni N, Yi S, Rodriguez MD, Balcha D, Tan G, Costanzo M, Andrews B, Boone C, Zhou XJ, Salehi-Ashtiani K, Charloteaux B, Chen AA, Calderwood MA, Aloy P, Roth FP, Hill DE, Iakoucheva LM, Xia Y, Vidal M (- 28) Ref: Cell, 164:805, 2016 : PubMed ESTHER: Yang_2016_Cell_164_805 PubMedSearch: Yang 2016 Cell 164 805 PubMedID: 26871637 Gene_locus related to this paper: human-NDRG4 Abstract While alternative splicing is known to diversify the functional characteristics of some genes, the extent to which protein isoforms globally contribute to functional complexity on a proteomic scale remains unknown. To address this systematically, we cloned full-length open reading frames of alternatively spliced transcripts for a large number of human genes and used protein-protein interaction profiling to functionally compare hundreds of protein isoform pairs. The majority of isoform pairs share less than 50% of their interactions. In the global context of interactome network maps, alternative isoforms tend to behave like distinct proteins rather than minor variants of each other. Interaction partners specific to alternative isoforms tend to be expressed in a highly tissue-specific manner and belong to distinct functional modules. Our strategy, applicable to other functional characteristics, reveals a widespread expansion of protein interaction capabilities through alternative splicing and suggests that many alternative "isoforms" are functionally divergent (i.e., "functional alloforms"). Title: Polysaccharides from Pleurotus ostreatus alleviate cognitive impairment in a rat model of Alzheimer's disease Zhang Y, Yang X, Jin G Ref: Int J Biol Macromol, 92:935, 2016 : PubMed ESTHER: Zhang_2016_Int.J.Biol.Macromol_92_935 PubMedSearch: Zhang 2016 Int.J.Biol.Macromol 92 935 PubMedID: 27498414 Abstract This study was conducted to evaluate the effects of polysaccharides extracted from Pleurotus ostreatus (POP) on d-galactose and AlCl3-induced cognitive impairments. A behavioral test suggested that POP significantly decreased escape latency and increased crossing parameters of platform quadrant in a Morris water maze test. Furthermore, POP decreased error numbers and increased passive avoidance latency in a step-down test. Biochemical examinations revealed that POP significantly elevated superoxide dismutase, glutathione peroxidase, and catalase activities; and reduced malondialdehyde levels and acetylcholinesterase activity. Moreover, POP could decrease amyloid beta peptide formation and tau phosphorylation by elevating the expression of protein phosphatase 2A as well as by reducing the expression of amyloid precursor protein (APP), beta-site APP clearing enzyme1, and glycogen synthase kinase 3beta. These findings provide scientific evidence to support the exploitation of POP as a safe and effective drug to prevent and treat Alzheimer's disease. Title: Production of Diacylglycerol-enriched Oil by Glycerolysis of Soybean Oil using a Bubble Column Reactor in a Solvent-free System Zhang N, Yang X, Fu J, Chen Q, Song Z, Wang Y Ref: J Oleo Sci, 65:207, 2016 : PubMed ESTHER: Zhang_2016_J.Oleo.Sci_65_207 PubMedSearch: Zhang 2016 J.Oleo.Sci 65 207 PubMedID: 26876674 Abstract In this study, diacylglycerol-enriched soybean oil (DESO) was synthesized through Lipozyme 435-catalyzed glycerolysis of soybean oil (SO) in a solvent-free system using a modified bubble column reactor. The effects of enzyme load, mole ratio of glycerol to soybean oil, reaction temperature, gas flow and reaction time on DAG production were investigated. The selected conditions were established as being enzyme load of 4 wt% (mass of substrates), glycerol/soybean oil mole ratio of 20:1, reaction temperature of 80 degC, gas flow of 10.6 cm/min, and a reaction time of 2.5 h, obtaining the DAG content of 49.4+/-0.5 wt%. The reusability of Lipozyme 435 was evaluated by monitoring the contents of DAG, monoacylglycerol (MAG) and triacylglycerol (TAG) in 10 consecutive runs. After purified by one-step molecular distillation, the DAG content of 63.5+/-0.3 wt% was achieved in DESO. The mole ratio of 1, 3-DAG to 1, 2-DAG was 2:1 and the fatty acid composition had no significant difference from that of soybean oil. However, the thermal properties of DESO and SO had considerable differences. Polymorphic form of DESO were mainly the beta form and minor amounts of the beta' form. Granular aggregation and round-shaped crystals were detected in DESO. Title: Carbon dots-assisted colorimetric and fluorometric dual-mode protocol for acetylcholinesterase activity and inhibitors screening based on the inner filter effect of silver nanoparticles Zhao D, Chen C, Sun J, Yang X Ref: Analyst, 141:3280, 2016 : PubMed ESTHER: Zhao_2016_Analyst_141_3280 PubMedSearch: Zhao 2016 Analyst 141 3280 PubMedID: 27099097 Abstract In this work, we proposed an original and versatile dual-readout (colorimetric and fluorometric) protocol by means of silver nanoparticles (AgNPs) and fluorescent carbon dots (CDs), which was amenable to rapid, ultrasensitive assay of acetylcholinesterase (AChE) activity and its inhibitors. The sensing mechanism was based on the non-fluorescence state of CDs resulting from the inner filter effect (IFE) of AgNPs and the specific AChE-catalyzed hydrolysis of acetylthiocholine (ATCh) into thiocholine (TCh). Herein, the generated positively-charged and thiol-bearing TCh at trace concentration levels could trigger the aggregation of AgNPs through the well-known electrostatic and Ag-SH interactions, thereby turning the sensing solutions grey and recovering the IFE-quenched fluorescence simultaneously. Furthermore, the existence of IFE mechanism was conceivably confirmed by combining the zeta potentials, fluorescence spectra, UV-vis spectra, fluorescence lifetime and TEM measurements. As far as we know, the present study has reported the first dual-mode proposal for assessing AChE activity by using a CDs-based IFE sensing strategy, where the detection limit was as low as 0.021 mU mL(-1) and 0.016 mU mL(-1) by colorimetric and fluorometric measurements, respectively. On the other hand, the proposed assay was feasible to screen AChE inhibitors such as tacrine and carbaryl. Meanwhile, this rationally designed dual-mode sensing platform featured simplicity, rapidity, flexibility and diversity, which was demonstrated by the quantitative detection of spiked carbaryl in apple juice samples with satisfactory results. Title: Synthesis and pharmacological evaluation of multifunctional tacrine derivatives against several disease pathways of AD Digiacomo M, Chen Z, Wang S, Lapucci A, Macchia M, Yang X, Chu J, Han Y, Pi R, Rapposelli S Ref: Bioorganic & Medicinal Chemistry Lett, 25:807, 2015 : PubMed ESTHER: Digiacomo_2015_Bioorg.Med.Chem.Lett_25_807 PubMedSearch: Digiacomo 2015 Bioorg.Med.Chem.Lett 25 807 PubMedID: 25597007 Abstract A novel series of tacrine derivatives were designed and synthesized by combining caffeic acid (CA), ferulic acid (FA) and lipoic acid (LA) with tacrine. The antioxidant study revealed that all the hybrids have much more antioxidant capacities compared to CA. Among these compounds, 1b possessed a good ability to inhibit the beta-amyloid protein (Abeta) self-aggregation, sub-micromole acetylcholinesterase (AChE)/butyrylcholinesterase (BCHE) inhibitory, modest BACE1 inhibitory. Moreover, compound 1b also was a DPPH radical scavenger and copper chelatory as well as had potent neuroprotective effects against glutamate-induced cell death with low toxicity in HT22 cells. Our findings suggest that the compound 1b might be a promising lead multi-targeted ligand and worthy of further developing for the therapy of Alzheimer's disease. Title: Optimization of Fermentation Medium for Extracellular Lipase Production from Aspergillus niger Using Response Surface Methodology Jia J, Yang X, Wu Z, Zhang Q, Lin Z, Guo H, Lin CS, Wang J, Wang Y Ref: Biomed Res Int, 2015:497462, 2015 : PubMed ESTHER: Jia_2015_Biomed.Res.Int_2015_497462 PubMedSearch: Jia 2015 Biomed.Res.Int 2015 497462 PubMedID: 26366414 Abstract Lipase produced by Aspergillus niger is widely used in various industries. In this study, extracellular lipase production from an industrial producing strain of A. niger was improved by medium optimization. The secondary carbon source, nitrogen source, and lipid were found to be the three most influential factors for lipase production by single-factor experiments. According to the statistical approach, the optimum values of three most influential parameters were determined: 10.5 g/L corn starch, 35.4 g/L soybean meal, and 10.9 g/L soybean oil. Using this optimum medium, the best lipase activity was obtained at 2,171 U/mL, which was 16.4% higher than using the initial medium. All these results confirmed the validity of the model. Furthermore, results of the Box-Behnken Design and quadratic models analysis indicated that the carbon to nitrogen (C/N) ratio significantly influenced the enzyme production, which also suggested that more attention should be paid to the C/N ratio for the optimization of enzyme production. Title: Efficacy and safety of galantamine treatment for patients with Alzheimer's disease: a meta-analysis of randomized controlled trials Jiang D, Yang X, Li M, Wang Y Ref: J Neural Transm, 122:1157, 2015 : PubMed ESTHER: Jiang_2015_J.Neural.Transm_122_1157 PubMedSearch: Jiang 2015 J.Neural.Transm 122 1157 PubMedID: 25547862 Abstract Cholinesterase inhibitors treatment is considered as a common therapeutic approach for Alzheimer's disease (AD) by numerous reported studies, but the role of currently available drugs for AD is still controversial. Our study aimed to evaluate the efficacy and safety of galantamine for the treatment of AD, and provide the basis and reference for clinical rational drug use. Randomized controlled trials (RCTs) of galantamine for AD published up to April 30, 2014 were searched. A random or fixed-effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean difference (MD) with a 95 % confidence interval (CI). Heterogeneity was assessed by Q test and I (2) statistic. The outcome measurements were as follows: the changes of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Neuropsychiatric Inventory (NPI), Clinicians' Interview-Based Impression of Change with Caregiver's Input (CIBIC+), adverse effects and dropouts. Eleven articles with 4,074 participants were included. Administration of galantamine for 8-28 weeks (16-40 mg daily) led to significant improvements in ADAS-cog score [P < 0.00001, MD = -2.95, 95 % CI (-3.32, -2.57)], MMSE score [P = 0.003, MD = 2.50, 95 % CI (0.86, 4.15)], NPI score [P = 0.001, MD = -1.58, 95 % CI (-2.54, -0.62)], and CIBIC+ scale [P < 0.00001, RR = 1.26, 95 % CI (1.15, 1.39)], but not in ADL score [P = 0.43, MD = 0.71, 95 % CI (-1.07, 2.48)]. More adverse events and dropouts occurred in the galantamine group than that in the placebo group, the differences were statistically significant (all P < 0.05). Galantamine could significantly improve cognitive, behavioral, and global performances in patients with AD. In addition, we need to use it with caution in the clinical treatment. Title: Comparison of Candidate Pairs of Hydrolytic Enzymes for Spectrophotometric-dual-enzyme-simultaneous-assay Liu H, Yuan M, Yang X, Hu X, Liao J, Dang J, Xie Y, Pu J, Li Y and Liao F <1 more author(s)> Liu H, Yuan M, Yang X, Hu X, Liao J, Dang J, Xie Y, Pu J, Li Y, Zhan CG, Liao F (- 1) Ref: Anal Sci, 31:421, 2015 : PubMed ESTHER: Liu_2015_Anal.Sci_31_421 PubMedSearch: Liu 2015 Anal.Sci 31 421 PubMedID: 25958872 Abstract Spectrophotometric-dual-enzyme-simultaneous-assay (SDESA) for enzyme-linked-immunosorbent-assay (ELISA) of two components in one well is a patented platform when a special pair of labels is accessible. With microplate readers, alkaline phosphatase on 4-nitro-1-naphthylphosphate (4NNPP) served as label A; Pseudomonas aeruginosa arylsulfatase (PAAS) and acetylcholinesterase (AChE) on their substrates derived from 4-nitrophenol/analogue served as candidate label B, and were compared for SDESA with an engineered alkaline phosphatase of Eschrichia coli (ECAP). For SDESA, the interference from overlapped absorbance was corrected based on linear additivity of absorbance to derive initial rates reflected by absorbance change at 450 nm for ECAP and at 405 nm for PAAS or AChE, after the correction of spontaneous hydrolysis. For SDESA with ECAP, AChE already had sufficient activity in an optimized buffer; PAAS was more favorable for substrate stability and product absorbance except for lower activity. Therefore, PAAS engineered for sufficient activity plus alkaline phosphatase is absorbing for ELISA via SDESA. Title: Gold nanoclusters-Cu ensemble-based fluorescence turn-on and real-time assay for acetylcholinesterase activity and inhibitor screening Sun J, Yang X Ref: Biosensors & Bioelectronics, 74:177, 2015 : PubMed ESTHER: Sun_2015_Biosens.Bioelectron_74_177 PubMedSearch: Sun 2015 Biosens.Bioelectron 74 177 PubMedID: 26141104 Abstract Based on the specific binding of Cu2+ ions to the 11-mercaptoundecanoic acid (11-MUA)-protected AuNCs with intense orange-red emission, we have proposed and constructed a novel fluorescent nanomaterials-metal ions ensemble at a nonfluorescence off-state. Subsequently, an AuNCs@11-MUA-Cu2+ ensemble-based fluorescent chemosensor, which is amenable to convenient, sensitive, selective, turn-on and real-time assay of acetylcholinesterase (AChE), could be developed by using acetylthiocholine (ATCh) as the substrate. Herein, the sensing ensemble solution exhibits a marvelous fluorescent enhancement in the presence of AChE and ATCh, where AChE hydrolyzes its active substrate ATCh into thiocholine (TCh), and then TCh captures Cu2+ from the ensemble, accompanied by the conversion from fluorescence off-state to on-state of the AuNCs. The AChE activity could be detected less than 0.05mU/mL within a good linear range from 0.05 to 2.5mU/mL. Our proposed fluorescence assay can be utilized to evaluate the AChE activity quantitatively in real biological sample, and furthermore to screen the inhibitor of AChE. As far as we know, the present study has reported the first analytical proposal for sensing AChE activity in real time by using a fluorescent nanomaterials-Cu2+ ensemble or focusing on the Cu2+-triggered fluorescence quenching/recovery. This strategy paves a new avenue for exploring the biosensing applications of fluorescent AuNCs, and presents the prospect of AuNCs@11-MUA-Cu2+ ensemble as versatile enzyme activity assay platforms by means of other appropriate substrates/analytes. Title: Expanding the biotechnology potential of lactobacilli through comparative genomics of 213 strains and associated genera Sun Z, Harris HM, McCann A, Guo C, Argimon S, Zhang W, Yang X, Jeffery IB, Cooney JC and O'Toole PW <21 more author(s)> Sun Z, Harris HM, McCann A, Guo C, Argimon S, Zhang W, Yang X, Jeffery IB, Cooney JC, Kagawa TF, Liu W, Song Y, Salvetti E, Wrobel A, Rasinkangas P, Parkhill J, Rea MC, O'Sullivan O, Ritari J, Douillard FP, Paul Ross R, Yang R, Briner AE, Felis GE, de Vos WM, Barrangou R, Klaenhammer TR, Caufield PW, Cui Y, Zhang H, O'Toole PW (- 21) Ref: Nat Commun, 6:8322, 2015 : PubMed ESTHER: Sun_2015_Nat.Commun_6_8322 PubMedSearch: Sun 2015 Nat.Commun 6 8322 PubMedID: 26415554 Gene_locus related to this paper: 9laco-a0a0r1hz65, 9laco-a0a0r1j1t4, 9laco-a0a0r1j3p0, 9laco-a0a0r1k3i0, 9laco-a0a0r1k563, 9laco-a0a0r1kgb3, 9laco-a0a0r1kji2, 9laco-a0a0r1kwq5, 9laco-a0a0r1l700, 9laco-a0a0r1p6l8, 9laco-a0a0r1q939, 9laco-a0a0r1qv39, 9laco-a0a0r1wj75, laccl-a0a0r2bne3, 9laco-a0a0r2dnk9, 9laco-a0a0r2ds70, 9laco-a0a0r2k127, 9laco-a0a0r2lee7, 9laco-a0a0r2lqt2, 9laco-a0a0r2m354, 9laco-a0a0r2n9f2, 9laco-a0a0r2nrk2, lacze-a0a0r1ekw6, 9laco-a0a0r1ju11, 9laco-a0a0r1k516, 9laco-a0a0r1leq9, 9laco-a0a0r1lul8, 9laco-a0a0r1lzg4, 9laco-a0a0r1mhp8, 9laco-a0a0r1mjt1, 9laco-a0a0r1nv21, 9laco-a0a0r1q1p6, 9laco-a0a0r1qm41, 9laco-a0a0r1qs58, 9laco-a0a0r1rgu0, 9laco-a0a0r1tg12, 9laco-a0a0r1u777, 9laco-a0a0r1ufv3, 9laco-a0a0r1ul77, 9laco-a0a0r1vad0, 9laco-a0a0r1w3f4, 9laco-a0a0r1w9r8, 9laco-a0a0r1wpq2, 9laco-a0a0r1x2g3, 9laco-a0a0r2abe6, 9laco-a0a0r2b6w1, 9laco-a0a0r2b8g1, 9laco-a0a0r2ch10, 9laco-a0a0r2cld6, 9laco-a0a0r2cv38, 9laco-a0a0r2d3x3, 9laco-a0a0r2dct2, 9laco-a0a0r2flt3, 9laco-a0a0r2frk5, 9laco-a0a0r2guq4, 9firm-a0a0r2h5m0, weivi-a0a0r2h8r4, 9lact-a0a0r2hnx4, 9lact-a0a0r2jkt6, 9lact-a0a0r2jmz1, 9laco-a0a0r2jwg5, 9laco-a0a0r2jxu0, 9laco-a0a0r2jxw0, lacam-a0a0r2kgt3, 9laco-a0a0r2kx86, 9laco-a0a0r2mxi6, 9laco-a0a0r1vln2, 9laco-a0a0r2ca25, 9laco-a0a0r1zjs2, weipa-c5rbw8 Abstract Lactobacilli are a diverse group of species that occupy diverse nutrient-rich niches associated with humans, animals, plants and food. They are used widely in biotechnology and food preservation, and are being explored as therapeutics. Exploiting lactobacilli has been complicated by metabolic diversity, unclear species identity and uncertain relationships between them and other commercially important lactic acid bacteria. The capacity for biotransformations catalysed by lactobacilli is an untapped biotechnology resource. Here we report the genome sequences of 213 Lactobacillus strains and associated genera, and their encoded genetic catalogue for modifying carbohydrates and proteins. In addition, we describe broad and diverse presence of novel CRISPR-Cas immune systems in lactobacilli that may be exploited for genome editing. We rationalize the phylogenomic distribution of host interaction factors and bacteriocins that affect their natural and industrial environments, and mechanisms to withstand stress during technological processes. We present a robust phylogenomic framework of existing species and for classifying new species. Title: Intraperitoneal Administration of a Novel TAT-BDNF Peptide Ameliorates Cognitive Impairments via Modulating Multiple Pathways in Two Alzheimer's Rodent Models Wu Y, Luo X, Liu X, Liu D, Wang X, Guo Z, Zhu L, Tian Q, Yang X, Wang JZ Ref: Sci Rep, 5:15032, 2015 : PubMed ESTHER: Wu_2015_Sci.Rep_5_15032 PubMedSearch: Wu 2015 Sci.Rep 5 15032 PubMedID: 26463268 Abstract Although Alzheimer's disease (AD) has been reported for more than 100 years, there is still a lack of effective cures for this devastating disorder. Among the various obstacles that hold back drug development, the blood-brain barrier (BBB) is one of them. Here, we constructed a novel fusion peptide by linking the active domain of brain-derived neurotrophic factor (BDNF) with an HIV-encoded transactivator of transcription (TAT) that has a strong membrane-penetrating property. After intraperitoneal injection, the eGFP-TAT could be robustly detected in different brain regions. By using scopolamine-induced rats and APPswe mice representing AD-like cholinergic deficits and amyloidosis, respectively, we found that intraperitoneal administration of the peptide significantly improved spatial memory with activation of the TrkB/ERK1/2/Akt pathway and restoration of several memory-associated proteins in both models. Administration of the peptide also modulated beta-amyloid and tau pathologies in APPswe mice, and it increased the amount of M receptor with modulation of acetylcholinesterase in scopolamine-induced rats. We conclude that intraperitoneal administration of our TAT-BDNF peptide could efficiently target multiple molecular pathways in the brain and improve the cognitive functions in AD-like rodent models. Title: The resurrection genome of Boea hygrometrica: A blueprint for survival of dehydration Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y and He Y <14 more author(s)> Xiao L, Yang G, Zhang L, Yang X, Zhao S, Ji Z, Zhou Q, Hu M, Wang Y, Chen M, Xu Y, Jin H, Xiao X, Hu G, Bao F, Hu Y, Wan P, Li L, Deng X, Kuang T, Xiang C, Zhu JK, Oliver MJ, He Y (- 14) Ref: Proc Natl Acad Sci U S A, 112:5833, 2015 : PubMed ESTHER: Xiao_2015_Proc.Natl.Acad.Sci.U.S.A_112_5833 PubMedSearch: Xiao 2015 Proc.Natl.Acad.Sci.U.S.A 112 5833 PubMedID: 25902549 Gene_locus related to this paper: 9lami-a0a2z7c6k4, 9lami-a0a2z7bgj4 Abstract "Drying without dying" is an essential trait in land plant evolution. Unraveling how a unique group of angiosperms, the Resurrection Plants, survive desiccation of their leaves and roots has been hampered by the lack of a foundational genome perspective. Here we report the approximately 1,691-Mb sequenced genome of Boea hygrometrica, an important resurrection plant model. The sequence revealed evidence for two historical genome-wide duplication events, a compliment of 49,374 protein-coding genes, 29.15% of which are unique (orphan) to Boea and 20% of which (9,888) significantly respond to desiccation at the transcript level. Expansion of early light-inducible protein (ELIP) and 5S rRNA genes highlights the importance of the protection of the photosynthetic apparatus during drying and the rapid resumption of protein synthesis in the resurrection capability of Boea. Transcriptome analysis reveals extensive alternative splicing of transcripts and a focus on cellular protection strategies. The lack of desiccation tolerance-specific genome organizational features suggests the resurrection phenotype evolved mainly by an alteration in the control of dehydration response genes. Title: Substrate-Assisted Catalysis in the Reaction Catalyzed by Salicylic Acid Binding Protein 2 (SABP2), a Potential Mechanism of Substrate Discrimination for Some Promiscuous Enzymes Yao J, Guo H, Chaiprasongsuk M, Zhao N, Chen F, Yang X Ref: Biochemistry, 54:5366, 2015 : PubMed ESTHER: Yao_2015_Biochemistry_54_5366 PubMedSearch: Yao 2015 Biochemistry 54 5366 PubMedID: 26244568 Abstract Although one of an enzyme's hallmarks is the high specificity for their natural substrates, substrate promiscuity has been reported more frequently. It is known that promiscuous enzymes generally show different catalytic efficiencies to different substrates, but our understanding of the origin of such differences is still lacking. Here we report the results of quantum mechanical/molecular mechanical simulations and an experimental study of salicylic acid binding protein 2 (SABP2). SABP2 has promiscuous esterase activity toward a series of substrates but shows a high activity toward its natural substrate, methyl salicylate (MeSA). Our results demonstrate that this enzyme may use substrate-assisted catalysis involving the hydroxyl group from MeSA to enhance the activity and achieve substrate discrimination. Title: Layer-by-layer assembled carbon nanotube-acetylcholinesterase/biopolymer renewable interfaces: SPR and electrochemical characterization Zhang Y, Arugula MA, Kirsch JS, Yang X, Olsen E, Simonian AL Ref: Langmuir, 31:1462, 2015 : PubMed ESTHER: Zhang_2015_Langmuir_31_1462 PubMedSearch: Zhang 2015 Langmuir 31 1462 PubMedID: 25562675 Abstract Developing simple, reliable, and cost-effective methods of renewing an inhibited biocatalyst (e.g., enzymatic interfaces) on biosensors is needed to advance multiuse, reusable sensor applications. We report a method for the renewal of layer-by-layer (LbL) self-assembled inhibition-based enzymatic interfaces in multiwalled carbon nanotube (MWCNT) armored acetylcholinesterase (AChE) biosensors. The self-assembly process of MWCNT dispersed enzymes/biopolymers was investigated using surface plasmon resonance (SPR). The LbL fabrication consisted of alternating cushion layers of positively charged CNT-polyethylenimine (CNT-PEI) and negatively charged CNT-deoxyribonucleic acid (CNT-DNA) and a functional interface consisting of alternating layers of CNT-PEI and negatively charged CNT-acetylcholine esterase (CNT-AChE, pH 7.4). The observed SPR response signal increased while assembling the different layers, indicating the buildup of multiple layers on the Au surface. A partial desorption of the top enzymatic layer in the LbL structure was observed with a desorption strategy employing alkaline treatment. This indicates that the strong interaction of CNT-biopolymer conjugates with the Au surface was a result of both electrostatic interactions between biopolymers and the surface binding energy from CNTs: the closer the layers are to the Au surface, the stronger the interactions. In contrast, a similar LbL assembly of soluble enzyme/polyelectrolytes resulted in stronger desorption on the surface after the alkaline treatment; this led to the investigation of AChE layer removal, permanently inhibited after pesticide exposure on glassy carbon (GC) electrodes, while keeping the cushion layers intact. The desorption strategy permitted the SPR and electrochemical electrode surfaces to be regenerated multiple times by the subsequent self-assembly of fresh PEI/AChE layers. Flow-mode electrochemical amperometric analysis demonstrated good stability toward the determination of acetylcholine with 97.1 +/- 2.7% renewability. Our simple, inexpensive approach shows the potential of renewable LbL self-assembled functional interfaces for multiple uses in a wide field of applications such as biosensing, various biotechnological processes, and the food and health industries. Title: Protein interaction network of alternatively spliced isoforms from brain links genetic risk factors for autism Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S and Iakoucheva LM <20 more author(s)> Corominas R, Yang X, Lin GN, Kang S, Shen Y, Ghamsari L, Broly M, Rodriguez M, Tam S, Trigg SA, Fan C, Yi S, Tasan M, Lemmens I, Kuang X, Zhao N, Malhotra D, Michaelson JJ, Vacic V, Calderwood MA, Roth FP, Tavernier J, Horvath S, Salehi-Ashtiani K, Korkin D, Sebat J, Hill DE, Hao T, Vidal M, Iakoucheva LM (- 20) Ref: Nat Commun, 5:3650, 2014 : PubMed ESTHER: Corominas_2014_Nat.Commun_5_3650 PubMedSearch: Corominas 2014 Nat.Commun 5 3650 PubMedID: 24722188 Gene_locus related to this paper: human-NLGN3 Abstract Increased risk for autism spectrum disorders (ASD) is attributed to hundreds of genetic loci. The convergence of ASD variants have been investigated using various approaches, including protein interactions extracted from the published literature. However, these datasets are frequently incomplete, carry biases and are limited to interactions of a single splicing isoform, which may not be expressed in the disease-relevant tissue. Here we introduce a new interactome mapping approach by experimentally identifying interactions between brain-expressed alternatively spliced variants of ASD risk factors. The Autism Spliceform Interaction Network reveals that almost half of the detected interactions and about 30% of the newly identified interacting partners represent contribution from splicing variants, emphasizing the importance of isoform networks. Isoform interactions greatly contribute to establishing direct physical connections between proteins from the de novo autism CNVs. Our findings demonstrate the critical role of spliceform networks for translating genetic knowledge into a better understanding of human diseases. Title: Detoxification enzymes of Bemisia tabaci B and Q: biochemical characteristics and gene expression profiles Guo L, Xie W, Wang S, Wu Q, Li R, Yang N, Yang X, Pan H, Zhang Y Ref: Pest Manag Sci, 70:1588, 2014 : PubMed ESTHER: Guo_2014_Pest.Manag.Sci_70_1588 PubMedSearch: Guo 2014 Pest.Manag.Sci 70 1588 PubMedID: 24488614 Abstract BACKGROUND: The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae), is one of the most invasive and destructive pests of field crops worldwide. The sibling species B and Q are the two most damaging members of the B. tabaci species complex. That Q is more resistant than B to many insecticides has been well documented. Over the last decade, Q has gradually displaced B and has become the dominant form of B. tabaci in field agricultural systems in most parts of China. To help understand the differences in insecticide resistance, the activities and gene expression profiles of detoxification enzymes in B. tabaci B and Q were investigated. Title: Bioconcentration, metabolism, and biomarker responses in freshwater fish Carassius auratus exposed to roxithromycin Liu J, Lu G, Wang Y, Yan Z, Yang X, Ding J, Jiang Z Ref: Chemosphere, 99:102, 2014 : PubMed ESTHER: Liu_2014_Chemosphere_99_102 PubMedSearch: Liu 2014 Chemosphere 99 102 PubMedID: 24210552 Abstract To investigate the distribution, bioconcentration, metabolism, and biomarker responses of macrolide antibiotic roxithromycin (ROX) in fish, crucian carp (Carassius auratus) were exposed to various concentrations of ROX (4, 20, and 100mugL(-1)) for 20d. The ROX content in different tissues was quantified using UPLC/MS/MS. The liver exhibited the highest ROX concentration followed by the bile, gills, and muscle tissues. After 15d of exposure to different concentrations of ROX, the bioconcentration factors were 2.15-38.0 in the liver, 0.950-20.7 in the bile, 0.0506-19.7 in the gill, and 0.0439-13.8 in the muscle; these results were comparable to the estimated BCF values. The metabolites formed in the bile were identified based on metabolic identification in human bile. Additionally, the biomarkers, including acetylcholinesterase in the brain, as well as 7-ethoxyresorufin O-deethylase and superoxide dismutase in the liver changed significantly after 5, 10, 15, and 20d of exposure (P<0.05). Our results suggest that ROX can accumulate and be metabolized in fish; therefore, interactions between ROX or its metabolites and the biological systems may induce biochemical disturbances in fish. Title: The genome of Eucalyptus grandis Myburg AA, Grattapaglia D, Tuskan GA, Hellsten U, Hayes RD, Grimwood J, Jenkins J, Lindquist E, Tice H and Schmutz J <70 more author(s)> Myburg AA, Grattapaglia D, Tuskan GA, Hellsten U, Hayes RD, Grimwood J, Jenkins J, Lindquist E, Tice H, Bauer D, Goodstein DM, Dubchak I, Poliakov A, Mizrachi E, Kullan AR, Hussey SG, Pinard D, van der Merwe K, Singh P, van Jaarsveld I, Silva-Junior OB, Togawa RC, Pappas MR, Faria DA, Sansaloni CP, Petroli CD, Yang X, Ranjan P, Tschaplinski TJ, Ye CY, Li T, Sterck L, Vanneste K, Murat F, Soler M, Clemente HS, Saidi N, Cassan-Wang H, Dunand C, Hefer CA, Bornberg-Bauer E, Kersting AR, Vining K, Amarasinghe V, Ranik M, Naithani S, Elser J, Boyd AE, Liston A, Spatafora JW, Dharmwardhana P, Raja R, Sullivan C, Romanel E, Alves-Ferreira M, Kulheim C, Foley W, Carocha V, Paiva J, Kudrna D, Brommonschenkel SH, Pasquali G, Byrne M, Rigault P, Tibbits J, Spokevicius A, Jones RC, Steane DA, Vaillancourt RE, Potts BM, Joubert F, Barry K, Pappas GJ, Strauss SH, Jaiswal P, Grima-Pettenati J, Salse J, Van de Peer Y, Rokhsar DS, Schmutz J (- 70) Ref: Nature, 510:356, 2014 : PubMed ESTHER: Myburg_2014_Nature_510_356 PubMedSearch: Myburg 2014 Nature 510 356 PubMedID: 24919147 Gene_locus related to this paper: eucgr-a0a059d0n8, eucgr-a0a059cm68, eucgr-a0a059d783, eucgr-a0a059af93, eucgr-a0a059awi0, eucgr-a0a059awt4, eucgr-a0a059ar83, eucgr-a0a059ayw5, eucgr-a0a059az75, eucgr-a0a059azj1, eucgr-a0a059azq5, eucgr-a0a059bkm2, eucgr-a0a059bl38, eucgr-a0a059a7m2, eucgr-a0a059a6p6, eucgr-a0a059a6p1, eucgr-a0a059a5e9 Abstract Eucalypts are the world's most widely planted hardwood trees. Their outstanding diversity, adaptability and growth have made them a global renewable resource of fibre and energy. We sequenced and assembled >94% of the 640-megabase genome of Eucalyptus grandis. Of 36,376 predicted protein-coding genes, 34% occur in tandem duplications, the largest proportion thus far in plant genomes. Eucalyptus also shows the highest diversity of genes for specialized metabolites such as terpenes that act as chemical defence and provide unique pharmaceutical oils. Genome sequencing of the E. grandis sister species E. globulus and a set of inbred E. grandis tree genomes reveals dynamic genome evolution and hotspots of inbreeding depression. The E. grandis genome is the first reference for the eudicot order Myrtales and is placed here sister to the eurosids. This resource expands our understanding of the unique biology of large woody perennials and provides a powerful tool to accelerate comparative biology, breeding and biotechnology. Title: Whole-genome sequencing of cultivated and wild peppers provides insights into Capsicum domestication and specialization Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M and Zhang Z <58 more author(s)> Qin C, Yu C, Shen Y, Fang X, Chen L, Min J, Cheng J, Zhao S, Xu M, Luo Y, Yang Y, Wu Z, Mao L, Wu H, Ling-Hu C, Zhou H, Lin H, Gonzalez-Morales S, Trejo-Saavedra DL, Tian H, Tang X, Zhao M, Huang Z, Zhou A, Yao X, Cui J, Li W, Chen Z, Feng Y, Niu Y, Bi S, Yang X, Cai H, Luo X, Montes-Hernandez S, Leyva-Gonzalez MA, Xiong Z, He X, Bai L, Tan S, Liu D, Liu J, Zhang S, Chen M, Zhang L, Zhang Y, Liao W, Wang M, Lv X, Wen B, Liu H, Luan H, Yang S, Wang X, Xu J, Li X, Li S, Wang J, Palloix A, Bosland PW, Li Y, Krogh A, Rivera-Bustamante RF, Herrera-Estrella L, Yin Y, Yu J, Hu K, Zhang Z (- 58) Ref: Proc Natl Acad Sci U S A, 111:5135, 2014 : PubMed ESTHER: Qin_2014_Proc.Natl.Acad.Sci.U.S.A_111_5135 PubMedSearch: Qin 2014 Proc.Natl.Acad.Sci.U.S.A 111 5135 PubMedID: 24591624 Gene_locus related to this paper: capch-q75qh4, capan-a0a1u8fuf5, capan-a0a1u8gmz3, capan-a0a1u8f879, capan-a0a1u8ftr2, capan-a0a1u8g8s6 Abstract As an economic crop, pepper satisfies people's spicy taste and has medicinal uses worldwide. To gain a better understanding of Capsicum evolution, domestication, and specialization, we present here the genome sequence of the cultivated pepper Zunla-1 (C. annuum L.) and its wild progenitor Chiltepin (C. annuum var. glabriusculum). We estimate that the pepper genome expanded approximately 0.3 Mya (with respect to the genome of other Solanaceae) by a rapid amplification of retrotransposons elements, resulting in a genome comprised of approximately 81% repetitive sequences. Approximately 79% of 3.48-Gb scaffolds containing 34,476 protein-coding genes were anchored to chromosomes by a high-density genetic map. Comparison of cultivated and wild pepper genomes with 20 resequencing accessions revealed molecular footprints of artificial selection, providing us with a list of candidate domestication genes. We also found that dosage compensation effect of tandem duplication genes probably contributed to the pungent diversification in pepper. The Capsicum reference genome provides crucial information for the study of not only the evolution of the pepper genome but also, the Solanaceae family, and it will facilitate the establishment of more effective pepper breeding programs. Title: Intronic DNA elements regulate Nrf2 chemical responsiveness of the human microsomal epoxide hydrolase gene (EPHX1) through a far upstream alternative promoter Su S, Yang X, Omiecinski CJ Ref: Biochimica & Biophysica Acta, 1839:493, 2014 : PubMed ESTHER: Su_2014_Biochim.Biophys.Acta_1839_493 PubMedSearch: Su 2014 Biochim.Biophys.Acta 1839 493 PubMedID: 24704207 Abstract In humans, microsomal epoxide hydrolase (mEH) contributes important biological functions that underlie both detoxification and bioactivation fates arising from exposures to foreign chemicals. Previously, we discovered that human mEH gene transcription is initiated from alternative promoters. The respective transcripts are programmed with tissue specificity and the upstream E1b promoter contributes predominantly to mEH expression. The results presented demonstrate that exposures to the Nrf2 activators, sulforaphane (SFN) and tert-butylhydroquinone (tBHQ), markedly activate E1b transcription in human lung and liver cells. Genomic analyses identified two major DNase I hypersensitive regions (HS-1 and HS-2) within the ~15kb intervening sequence separating E1b from the downstream E1 promoter. In BEAS-2B cells, the Nrf2 effectors, SFN and tBHQ, selectively activated the more distal HS-2 through an antioxidant response element (ARE). An activator protein 1/12-O-tetradecanoylphorbol-13-acetate interaction was further identified within the HS-2 enhancer that functioned to additionally contribute to ARE-mediated induction responsiveness of the E1b promoter. The results demonstrate that ARE modulation, integrated with additional transcriptional complexes, regulates the tissue-specific expression of mEH and that these processes likely coordinate both the protective and bioactivation functions contributed by mEH activities in human tissues. Title: Influence of butyl benzyl phthalate (BBP) exposure on nervous system and antioxidant system in zebrafish Zhang C, Yang X, He Z, Zhong Q, Guo J, Hu XJ, Xiong L, Liu D Ref: Ecotoxicology, 23:1854, 2014 : PubMed ESTHER: Zhang_2014_Ecotoxicology_23_1854 PubMedSearch: Zhang 2014 Ecotoxicology 23 1854 PubMedID: 25239577 Abstract In order to observe the toxic effects of butyl benzyl phthalate (BBP) on zebrafish, the AChE and SOD activity of zebrafish exposed to different concentrations of BBP (0, 0.332, 0.665, 1.33 mg L(-1)) in a short-term (7d) test were determined. Semi-quantitative PCR was used to determine the mRNA transcript levels of the AChE and SOD gene in zebrafish brain and muscle. The results showed: AChE activity decreased with increased exposure concentration, and was significantly inhibited (p < 0.01) compared with the control group at 0.665 mg L(-1) concentration. Low BBP concentrations stimulated and high concentrations inhibited SOD activity with a concentration of 0.332 mg L(-1) resulting in a significant induction (p < 0.05) compared with the control, and 0.665 and 1.33 mg L(-1) concentrations resulting in significant inhibition (p < 0.05, p < 0.01) relative to the control group. The RT-PCR data showed a decrease in brain and muscle mRNA transcription of AChE gene with an increase in exposure concentration. The mRNA transcription of SOD in the brain was not different between the exposed groups and control group; in muscle, the mRNA transcription inhibition decreased and then increased: all differences from the control were statistically significant. Title: Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H and Cai W <5 more author(s)> Dai Z, Qi W, Li C, Lu J, Mao Y, Yao Y, Li L, Zhang T, Hong H, Li S, Zhou T, Yang Z, Yang X, Gao G, Cai W (- 5) Ref: Mol Cell Endocrinol, 377:123, 2013 : PubMed ESTHER: Dai_2013_Mol.Cell.Endocrinol_377_123 PubMedSearch: Dai 2013 Mol.Cell.Endocrinol 377 123 PubMedID: 23850519 Abstract Both elevated plasma free fatty acids (FFA) and accumulating triglyceride in adipose tissue are observed in the process of obesity and insulin resistance. This contradictory phenomenon and its underlying mechanisms have not been thoroughly elucidated. Recent studies have demonstrated that pigment epithelium-derived factor (PEDF) contributes to elevated plasma FFA and insulin resistance in obese mice via the activation of adipose triglyceride lipase (ATGL). However, we found that PEDF downregulated adipose ATGL protein expression despite of enhancing lipolysis. Plasma PEDF and FFA were increased in associated with a progressive high-fat-diet, and those outcomes were also accompanied by fat accumulation and a reduction in adipose ATGL. Exogenous PEDF injection downregulated adipose ATGL protein expression and elevated plasma FFA, while endogenous PEDF neutralization significantly rescued the adipose ATGL reduction and also reduced plasma FFA in obese mice. PEDF reduced ATGL protein expression in a time- and dose-dependent manner in differentiated 3T3-L1 cells. Small interfering RNA-mediated PEDF knockdown and antibody-mediated PEDF blockage increased endogenous ATGL expression, and PEDF overexpression downregulated ATGL. PEDF resulted in a decreased half-life of ATGL and regulated ATGL degradation via ubiquitin-dependent proteasomal degradation pathway. PEDF stimulated lipolysis via ATGL using ATGL inhibitor bromoenol lactone, and PEDF also downregulated G0/G1 switch gene 2 (G0S2) expression, which is an endogenous inhibitor of ATGL activation. Overall, PEDF attenuated ATGL protein accumulation via proteasome-mediated degradation in adipocytes, and PEDF also promoted lipolysis by activating ATGL. Elevated PEDF may contribute to progressive obesity and insulin resistance via its dual regulation of ATGL. Title: Loss-of-function variation in the DPP6 gene is associated with autosomal dominant microcephaly and mental retardation Liao C, Fu F, Li R, Yang WQ, Liao HY, Yan JR, Li J, Li SY, Yang X, Li DZ Ref: Eur Journal of Medical Genetics, 56:484, 2013 : PubMed ESTHER: Liao_2013_Eur.J.Med.Genet_56_484 PubMedSearch: Liao 2013 Eur.J.Med.Genet 56 484 PubMedID: 23832105 Gene_locus related to this paper: human-DPP6 Abstract The molecular basis of autosomal dominant microcephaly, a disorder associated with small head circumferences that results in variable mental retardation, is largely unknown. In the present study, we conducted a variation analysis of the DPP6 gene in patients with autosomal dominant microcephaly and variable mental retardation. The copy number variation analysis of DPP6 was performed on DNA samples from 22 patients with microcephaly using high-resolution, array-based genomic hybridization, and sequence analysis was performed to screen mutations in another 50 microcephalic patients. Two de novo deletions and one missense mutation in familial microcephalic patients were identified. The transfection of plasmids encoding green fluorescent protein-pLLU2G-shDPP6 fusion proteins in mouse brains revealed that the decreased expression of the DPP6 gene slightly reduced the weight of the mouse brains and resulted in mouse learning disabilities compared with their wild-type littermates. Our data indicate that the loss-of-function variations in DPP6 are associated with autosomal dominant microcephaly and mental retardation. DPP6 appears to play a major role in the regulation of proliferation and migration of neurons in neurogenesis, most likely by participating in neuronal electrical excitability, synaptic integration, and plasticity. Title: Contamination by metals and pharmaceuticals in northern Taihu Lake (China) and its relation to integrated biomarker response in fish Lu G, Yang X, Li Z, Zhao H, Wang C Ref: Ecotoxicology, 22:50, 2013 : PubMed ESTHER: Lu_2013_Ecotoxicology_22_50 PubMedSearch: Lu 2013 Ecotoxicology 22 50 PubMedID: 23053787 Abstract Taihu Lake is the largest shallow freshwater lake in eastern China and is suffering not only from an increasingly serious threat of eutrophication but also potential ecological risk due to the input of emerging contaminants. Active biomonitoring was conducted in Taihu Lake using transplanted goldfish (Carassius auratus) to determine the contamination by pharmaceuticals and metals and to assess the potential ecological risk. A suite of biomarkers including acetylcholinesterase, ethoxyresorufin O-deethylase, glutathione S-transferase, glutathione peroxidase and superoxide dismutase activities in fish after 7, 14, 21 and 28 days of exposure in situ, as well as pharmaceuticals and metals in water, were determined during the field exposure period. The results indicate that pharmaceuticals exist mainly in Zhushan Bay and Meiliang Bay, while metals are present mainly in Gong Bay. An integrated biomarker response (IBR) was calculated and used to evaluate the ecological risk of the polluted area of Taihu Lake. It was found that Zhushan Bay might present higher risk to fish, followed by Meiliang Bay. IBR values were in good agreement with copper and caffeine concentrations. Title: Expression of a novel mRNA transcript for human microsomal epoxide hydrolase (EPHX1) is regulated by short open reading frames within its 5'-untranslated region Nguyen HL, Yang X, Omiecinski CJ Ref: Rna, 19:752, 2013 : PubMed ESTHER: Nguyen_2013_RNA_19_752 PubMedSearch: Nguyen 2013 RNA 19 752 PubMedID: 23564882 Abstract Microsomal epoxide hydrolase (mEH, EPHX1) is a critical xenobiotic-metabolizing enzyme, catalyzing both detoxification and bioactivation reactions that direct the disposition of chemical epoxides, including the carcinogenic metabolites of several polycyclic aromatic hydrocarbons. Recently, we discovered that a previously unrecognized and primate-specific EPHX1 transcript, termed E1-b, was actually the predominant driver of EPHX1 expression in all human tissues. In this study, we identify another human EPHX1 transcript, designated as E1-b'. Unusually, both the E1-b and E1-b' mRNA transcripts are generated from the use of a far upstream gene promoter, localized approximately 18.5 kb 5'-upstream of the EPHX1 protein-coding region. Although expressed at comparatively lower levels than E1-b, the novel E1-b' transcript is readily detected in all tissues examined, with highest levels maintained in human ovary. The E1-b' mRNA possesses unusual functional features in its 5'-untranslated region, including a GC-rich leader sequence and two upstream AUGs that encode for short peptides of 26 and 17 amino acids in length, respectively. Results from in vitro transcription/translation assays and direct transfection in mammalian cells of either the E1-b' transcript or the encoded peptides demonstrated that the E1-b' upstream open reading frames (uORFs) are functional, with their presence markedly inhibiting the translation of EPHX1 protein, both in cis and in trans configurations. These unique uORF peptides exhibit no homology to any other known uORF sequences but likely function to mediate post-transcription regulation of EPHX1 and perhaps more broadly as translational regulators in human cells. Title: Draft Genome Sequence of Ralstonia solanacearum Race 4 Biovar 4 Strain SD54 Shan W, Yang X, Ma W, Yang Y, Guo X, Guo J, Zheng H, Li G, Xie B Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Shan_2013_Genome.Announc_1_e00890 PubMedSearch: Shan 2013 Genome.Announc 1 e00890 PubMedID: 24356823 Gene_locus related to this paper: ralso-PCAD Abstract Ralstonia solanacearum is an important etiological agent that can cause serious bacterial wilt in a very wide range of potential host plants, including ginger. Here, we report the complete genome sequence of R. solanacearum SD54, a race 4 biovar 4 (R4B4) strain from a diseased ginger plant in China. Title: An Inhibitory Antibody against Dipeptidyl Peptidase IV Improves Glucose Tolerance in Vivo Tang J, Majeti J, Sudom A, Xiong Y, Lu M, Liu Q, Higbee J, Zhang Y, Wang Y and Wang Z <12 more author(s)> Tang J, Majeti J, Sudom A, Xiong Y, Lu M, Liu Q, Higbee J, Zhang Y, Wang Y, Wang W, Cao P, Xia Z, Johnstone S, Min X, Yang X, Shao H, Yu T, Sharkov N, Walker N, Tu H, Shen W, Wang Z (- 12) Ref: Journal of Biological Chemistry, 288:1307, 2013 : PubMed ESTHER: Tang_2013_J.Biol.Chem_288_1307 PubMedSearch: Tang 2013 J.Biol.Chem 288 1307 PubMedID: 23184939 Gene_locus related to this paper: ratno-dpp4 Abstract Dipeptidyl peptidase IV (DPP-IV) degrades the incretin hormone glucagon-like peptide 1 (GLP-1). Small molecule DPP-IV inhibitors have been used as treatments for type 2 diabetes to improve glucose tolerance. However, each of the marketed small molecule drugs has its own limitation in terms of efficacy and side effects. To search for an alternative strategy of inhibiting DPP-IV activity, we generated a panel of tight binding inhibitory mouse monoclonal antibodies (mAbs) against rat DPP-IV. When tested in vitro, these mAbs partially inhibited the GLP-1 cleavage activity of purified enzyme and rat plasma. To understand the partial inhibition, we solved the co-crystal structure of one of the mAb Fabs (Ab1) in complex with rat DPP-IV. Although Ab1 does not bind at the active site, it partially blocks the side opening, which prevents the large substrates such as GLP-1 from accessing the active site, but not small molecules such as sitagliptin. When Ab1 was tested in vivo, it reduced plasma glucose and increased plasma GLP-1 concentration during an oral glucose tolerance test in rats. Together, we demonstrated the feasibility of using mAbs to inhibit DPP-IV activity and to improve glucose tolerance in a diabetic rat model. Title: Transcriptome profiling of the whitefly Bemisia tabaci reveals stage-specific gene expression signatures for thiamethoxam resistance Yang N, Xie W, Jones CM, Bass C, Jiao X, Yang X, Liu B, Li R, Zhang Y Ref: Insect Molecular Biology, 22:485, 2013 : PubMed ESTHER: Yang_2013_Insect.Mol.Biol_22_485 PubMedSearch: Yang 2013 Insect.Mol.Biol 22 485 PubMedID: 23889345 Abstract Bemisia tabaci has developed high levels of resistance to many insecticides including the neonicotinoids and there is strong evidence that for some compounds resistance is stage-specific. To investigate the molecular basis of B. tabaci resistance to the neonicotinoid thiamethoxam we used a custom whitefly microarray to compare gene expression in the egg, nymph and adult stages of a thiamethoxam-resistant strain (TH-R) with a susceptible strain (TH-S). Gene ontology and bioinformatic analyses revealed that in all life stages many of the differentially expressed transcripts encoded enzymes involved in metabolic processes and/or metabolism of xenobiotics. Several of these are candidate resistance genes and include the cytochrome P450 CYP6CM1, which has been shown to confer resistance to several neonicotinoids previously, a P450 belonging to the Cytochrome P450s 4 family and a glutathione S-transferase (GST) belonging to the sigma class. Finally several ATP-binding cassette transporters of the ABCG subfamily were highly over-expressed in the adult stage of the TH-R strain and may play a role in resistance by active efflux. Here, we evaluated both common and stage-specific gene expression signatures and identified several candidate resistance genes that may underlie B. tabaci resistance to thiamethoxam. Title: NDRG3 and NDRG4, two novel tumor-related genes Yang X, An L, Li X Ref: Biomed Pharmacother, 67:681, 2013 : PubMed ESTHER: Yang_2013_Biomed.Pharmacother_67_681 PubMedSearch: Yang 2013 Biomed.Pharmacother 67 681 PubMedID: 23725756 Abstract The N-myc downstream-regulated genes, NDRG3 and NDRG4, are suggested to play important roles in biological processes and pathogenesis. Expression of NDRG3 and NDRG4 has been shown to be reduced or absent in numerous cancer cell lines and tumor types, suggesting that they may exert function as a tumor suppressor gene. In this review, we will summarize the current research on NDRG3 and NDRG4, including the molecular structure, cellular and tissue distribution, biological function, and function in cancer. We tried to show their significance in studying disease and their therapeutic potential. Title: Draft Genome Sequences of Three Salmonella enterica Serotype Agona Strains from China Zhang J, Cao G, Xu X, Jin H, Yang X, Allard M, Brown E, Meng J Ref: Genome Announc, 1:, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00203 PubMedSearch: Zhang 2013 Genome.Announc 1 E00203 PubMedID: 23469342 Gene_locus related to this paper: salty-STY1441 Abstract Salmonellosis has been one of the major contributors to the global public health burden. Salmonella enterica serotype Agona has ranked among the top 10 and top 20 most frequent Salmonella serotypes isolated from human sources in China and the United States, respectively. We report draft genomes of three S. Agona strains from China. Title: Whole-Genome Sequences of Four Salmonella enterica Serotype Newport Strains from Humans Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X and Meng J <2 more author(s)> Zhang J, Cao G, Xu X, Jin H, Zhang Q, Chen J, Yang X, Pan H, Zhang X, Allard M, Brown E, Meng J (- 2) Ref: Genome Announc, 1:E00213, 2013 : PubMed ESTHER: Zhang_2013_Genome.Announc_1_E00213 PubMedSearch: Zhang 2013 Genome.Announc 1 E00213 PubMedID: 23661485 Gene_locus related to this paper: salty-STY1441 Abstract Salmonellosis contributes significantly to the public health burden globally. Salmonella enterica serotype Newport is among Salmonella serotypes most associated with food-borne illness in the United States and China. It was thought to be polyphyletic and to contain different lineages. We report draft genomes of four S. Newport strains isolated from humans in China. Title: Reference genome sequence of the model plant Setaria Bennetzen JL, Schmutz J, Wang H, Percifield R, Hawkins J, Pontaroli AC, Estep M, Feng L, Vaughn JN and Devos KM <24 more author(s)> Bennetzen JL, Schmutz J, Wang H, Percifield R, Hawkins J, Pontaroli AC, Estep M, Feng L, Vaughn JN, Grimwood J, Jenkins J, Barry K, Lindquist E, Hellsten U, Deshpande S, Wang X, Wu X, Mitros T, Triplett J, Yang X, Ye CY, Mauro-Herrera M, Wang L, Li P, Sharma M, Sharma R, Ronald PC, Panaud O, Kellogg EA, Brutnell TP, Doust AN, Tuskan GA, Rokhsar D, Devos KM (- 24) Ref: Nat Biotechnol, 30:555, 2012 : PubMed ESTHER: Bennetzen_2012_Nat.Biotechnol_30_555 PubMedSearch: Bennetzen 2012 Nat.Biotechnol 30 555 PubMedID: 22580951 Gene_locus related to this paper: setit-k3xwe0, setit-k3xfs7, setit-k3yh36, setit-k3zes3, setit-k3zlj8, setvi-a0a4u6wd58, setit-a0a368qif6, setit-a0a368sru6, setit-a0a368q9x4, setit-k3zri0, setit-k3ysv0, setit-k3xj49 Abstract We generated a high-quality reference genome sequence for foxtail millet (Setaria italica). The approximately 400-Mb assembly covers approximately 80% of the genome and >95% of the gene space. The assembly was anchored to a 992-locus genetic map and was annotated by comparison with >1.3 million expressed sequence tag reads. We produced more than 580 million RNA-Seq reads to facilitate expression analyses. We also sequenced Setaria viridis, the ancestral wild relative of S. italica, and identified regions of differential single-nucleotide polymorphism density, distribution of transposable elements, small RNA content, chromosomal rearrangement and segregation distortion. The genus Setaria includes natural and cultivated species that demonstrate a wide capacity for adaptation. The genetic basis of this adaptation was investigated by comparing five sequenced grass genomes. We also used the diploid Setaria genome to evaluate the ongoing genome assembly of a related polyploid, switchgrass (Panicum virgatum). Title: Single and combined effects of selected pharmaceuticals at sublethal concentrations on multiple biomarkers in Carassius auratus Li Z, Lu G, Yang X, Wang C Ref: Ecotoxicology, 21:353, 2012 : PubMed ESTHER: Li_2012_Ecotoxicology_21_353 PubMedSearch: Li 2012 Ecotoxicology 21 353 PubMedID: 21947668 Abstract In this study, the sublethal effects of caffeine, sulfamethoxazole and their mixture on goldfish (Carassius auratus) were investigated, the biomarkers including acetylcholinesterase (AChE) in brain, 7-ethoxyresorufin O-deethylase (EROD), glutathione S-transferase (GST) and superoxide dismutase (SOD) in liver and vitellogenin (VTG) in serum were determined after 1, 2, 4, and 7 days of exposure. AChE activity was significantly inhibited by caffeine (>/=0.4 mg/l), sulfamethoxazole (>/=0.4 mg/l) and their mixtures (>/=0.048 mg/l) during all exposure periods, and obvious concentration-response and time-response relationships were obtained. EROD, GST and SOD activities were significantly increased by individual compounds and mixtures in most cases. GST induction exhibited bell-shaped concentration-response curves. Serum VTG was significantly induced by 2 mg/l of caffeine, 10 mg/l of sulfamethoxazole and the mixtures at concentrations >/=1.2 mg/l. In general, the two pharmaceuticals induced similar biological responses. The joint effect of caffeine/sulfamethoxazole was additive with regard to AChE and GST activity variation and was antagonistic with regard to EROD and SOD induction. The results indicated that multiple biomarker response method might be a useful tool for describing an integrated toxicological effect of chemicals. VTG induction suggested that caffeine and sulfamethoxazole may cause a slightly feminization effect. Title: Characterization of a thermostable beta-glucosidase from Aspergillus fumigatus Z5, and its functional expression in Pichia pastoris X33 Liu D, Zhang R, Yang X, Zhang Z, Song S, Miao Y, Shen Q Ref: Microb Cell Fact, 11:25, 2012 : PubMed ESTHER: Liu_2012_Microb.Cell.Fact_11_25 PubMedSearch: Liu 2012 Microb.Cell.Fact 11 25 PubMedID: 22340848 Abstract BACKGROUND: Recently, the increased demand of energy has strongly stimulated the research on the conversion of lignocellulosic biomass into reducing sugars for the subsequent production, and beta-glucosidases have been the focus because of their important roles in a variety fundamental biological processes and the synthesis of useful beta-glucosides. Although the beta-glucosidases of different sources have been investigated, the amount of beta-glucosidases are insufficient for effective conversion of cellulose. The goal of this work was to search for new resources of beta-glucosidases, which was thermostable and with high catalytic efficiency. Title: Highly efficient biosynthesis of sucrose-6-acetate with cross-linked aggregates of Lipozyme TL 100 L Yang X, Zheng P, Ni Y, Sun Z Ref: J Biotechnol, 161:27, 2012 : PubMed ESTHER: Yang_2012_J.Biotechnol_161_27 PubMedSearch: Yang 2012 J.Biotechnol 161 27 PubMedID: 22728393 Abstract As a short chain monoester, sucrose-6-acetate (S-6-a) is a key intermediate in the preparation of an eminent sweetener (sucralose). To replace the traditional multi-step chemical route for sucralose biosynthesis, enzymatic synthesis of S-6-a was investigated, using cross-linked enzyme aggregates (CLEAs) of Lipozyme TL 100 L. The optimal CLEA preparation conditions was obtained as follows: using 33.3% (v/v) PEG600 co-precipitated with additive of D-sorbierite, then cross-linking with 1.5% (v/v) glutaraldehyde at 0 degreeC for 4 h. As a result, the immobilized Lipozyme had high specific bioactivity (34.64 U/g) of transesterification in non-aqueous media. With these immobilized enzymes, the optimum transesterification conditions were investigated systematically, including CLEA loading, the mole ratio of vinyl acetate versus sucrose, temperature and reaction time, etc. The results showed that the highest concentration and yield of S-6-a was 49.8 g/L and 87.46%, respectively. Further experiments showed that the resulting CLEAs also had much higher operational stability than the commercial Lipozyme TLIM. The present work has paved a new path for the large-scale bioproduction of S-6-a with immobilized lipase in the future. Title: Complete genome of Pseudomonas mendocina NK-01, which synthesizes medium-chain-length polyhydroxyalkanoates and alginate oligosaccharides Guo W, Wang Y, Song C, Yang C, Li Q, Li B, Su W, Sun X, Song D and Wang S <1 more author(s)> Guo W, Wang Y, Song C, Yang C, Li Q, Li B, Su W, Sun X, Song D, Yang X, Wang S (- 1) Ref: Journal of Bacteriology, 193:3413, 2011 : PubMed ESTHER: Guo_2011_J.Bacteriol_193_3413 PubMedSearch: Guo 2011 J.Bacteriol 193 3413 PubMedID: 21551299 Gene_locus related to this paper: pseme-PHAZ, psemn-f4dpi6, psemn-f4dyl0, psemn-f4dqg5, pseme-a0a081x852, psemn-f4dv64 Abstract Pseudomonas mendocina NK-01 can synthesize medium-chain-length polyhydroxyalkanoate (PHA(MCL)) and alginate oligosaccharides (AO) simultaneously from glucose under conditions of limited nitrogen. Here, we report the complete sequence of the 5.4-Mbp genome of Pseudomonas mendocina NK-01, which was isolated from farmland soil in Tianjin, China. Title: Complete genome sequence of Paenibacillus polymyxa SC2, a strain of plant growth-promoting Rhizobacterium with broad-spectrum antimicrobial activity Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H and Du B <7 more author(s)> Ma M, Wang C, Ding Y, Li L, Shen D, Jiang X, Guan D, Cao F, Chen H, Feng R, Wang X, Ge Y, Yao L, Bing X, Yang X, Li J, Du B (- 7) Ref: Journal of Bacteriology, 193:311, 2011 : PubMed ESTHER: Ma_2011_J.Bacteriol_193_311 PubMedSearch: Ma 2011 J.Bacteriol 193 311 PubMedID: 21037012 Gene_locus related to this paper: paep6-e0rmc7, paeps-e3e5s8, paeps-e3ebx3, paeps-e3e602 Abstract Paenibacillus polymyxa SC2 is an important plant growth-promoting rhizobacterium (PGPR). Here, we report the complete genome sequence of P. polymyxa SC2. Multiple sets of functional genes have been found in the genome. As far as we know, this is the first complete genome sequence of Paenibacillus polymyxa. Title: Whole-genome sequences of four Mycobacterium bovis BCG vaccine strains Pan Y, Yang X, Duan J, Lu N, Leung AS, Tran V, Hu Y, Wu N, Liu D and Zhu B <6 more author(s)> Pan Y, Yang X, Duan J, Lu N, Leung AS, Tran V, Hu Y, Wu N, Liu D, Wang Z, Yu X, Chen C, Zhang Y, Wan K, Liu J, Zhu B (- 6) Ref: Journal of Bacteriology, 193:3152, 2011 : PubMed ESTHER: Pan_2011_J.Bacteriol_193_3152 PubMedSearch: Pan 2011 J.Bacteriol 193 3152 PubMedID: 21478353 Gene_locus related to this paper: myctu-RV1215C Abstract Mycobacterium bovis Bacille Calmette-Guerin (BCG) is the only vaccine available against tuberculosis (TB). A number of BCG strains are in use, and they exhibit biochemical and genetic differences. We report the genome sequences of four BCG strains representing different lineages, which will help to design more effective TB vaccines. Title: Production of extremely pure diacylglycerol from soybean oil by lipase-catalyzed glycerolysis Wang W, Li T, Ning Z, Wang Y, Yang B, Yang X Ref: Enzyme Microb Technol, 49:192, 2011 : PubMed ESTHER: Wang_2011_Enzyme.Microb.Technol_49_192 PubMedSearch: Wang 2011 Enzyme.Microb.Technol 49 192 PubMedID: 22112408 Abstract Research work was objectively targeted to synthesize highly pure diacylglycerol (DAG) with glycerolysis of soybean oil in a solvent medium of t-butanol. Three commercial immobilized lipases (Lipozyme RM IM, Lipozyme TL IM and Novozym 435) were screened, and Novozym 435 was the best out of three candidates. Batch reaction conditions of the enzymatic glycerolysis, the substrate mass ratio, the reaction temperature and the substrate concentration, were studied. The optimal reaction conditions were achieved as 6.23:1 mass ratio of soybean oil to glycerol, 40% (w/v) of substrate concentration in t-butanol and reaction temperature of 50 degreeC. A two-stage molecular distillation was employed for purification of DAG from reaction products. Scale-up was attempted based on the optimized reaction conditions, 98.7% (24 h) for the conversion rate of soybean oil, 48.5% of DAG in the glycerolysis products and 96.1% for the content of DAG in the final products were taken in account as the results. Title: Development and validation of a sample stabilization strategy and a UPLC-MS/MS method for the simultaneous quantitation of acetylcholine (ACh), histamine (HA), and its metabolites in rat cerebrospinal fluid (CSF) Zhang Y, Tingley FD, 3rd, Tseng E, Tella M, Yang X, Groeber E, Liu J, Li W, Schmidt CJ, Steenwyk R Ref: Journal of Chromatography B Analyt Technol Biomed Life Sciences, 879:2023, 2011 : PubMed ESTHER: Zhang_2011_J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci_879_2023 PubMedSearch: Zhang 2011 J.Chromatogr.B.Analyt.Technol.Biomed.Life.Sci 879 2023 PubMedID: 21684223 Abstract A UPLC-MS/MS assay was developed and validated for simultaneous quantification of acetylcholine (ACh), histamine (HA), tele-methylhistamine (t-mHA), and tele-methylimidazolacetic acid (t-MIAA) in rat cerebrospinal fluid (CSF). The biological stability of ACh in rat CSF was investigated. Following fit-for-purpose validation, the method was applied to monitor the drug-induced changes in ACh, HA, t-mHA, and t-MIAA in rat CSF following administration of donepezil or prucalopride. The quantitative method utilizes hydrophilic interaction chromatography (HILIC) Core-Shell HPLC column technology and a UPLC system to achieve separation with detection by positive ESI LC-MS/MS. This UPLC-MS/MS method does not require extraction or derivatization, utilizes a stable isotopically labeled internal standard (IS) for each analyte, and allows for rapid throughput with a 4 min run time. Without an acetylcholinesterase (AChE) inhibitor present, ACh was found to have 1.9+/-0.4 min in vitro half life in rat CSF. Stability studies and processing modification, including the use of AChE inhibitor eserine, extended this half life to more than 60 min. The UPLC-MS/MS method, including stabilization procedure, was validated over a linear concentration range of 0.025-5 ng/mL for ACh and 0.05-10 ng/mL for HA, t-mHA, and t-MIAA. The intra-run precision and accuracy for all analytes were 1.9-12.3% CV and -10.2 to 9.4% RE, respectively, while inter-run precision and accuracy were 4.0-16.0% CV and -5.3 to 13.4% RE, respectively. By using this developed and validated method, donepezil caused increases in ACh levels at 0.5, 1, 2, and 4h post dose as compared to the corresponding vehicle group, while prucalopride produced approximately 1.6- and 3.1-fold increases in the concentrations of ACh and t-mHA at 1h post dose, respectively, compared to the vehicle control. Overall, this methodology enables investigations into the use of CSF ACh and HA as biomarkers in the study of these neurotransmitter systems and related drug discovery efforts. Title: Brominated aliphatic hydrocarbons and sterols from the sponge Xestospongia testudinaria with their bioactivities Zhou X, Lu Y, Lin X, Yang B, Yang X, Liu Y Ref: Chemistry & Physic of Lipids, 164:703, 2011 : PubMed ESTHER: Zhou_2011_Chem.Phys.Lipids_164_703 PubMedSearch: Zhou 2011 Chem.Phys.Lipids 164 703 PubMedID: 21864515 Abstract Four brominated aliphatic hydrocarbons (1-4), including a novel brominated ene-tetrahydrofuran named as mutafuran H (1), and five sterols (5-9) were isolated from the South China Sea sponge Xestospongia testudinaria. The structure of 1 was determined on the basis of NMR ((1)H, (13)C NMR, HSQC, HMBC, (1)H-(1)H COSY, and NOESY), MS, and optical rotation analysis. Known compounds were identified by comparison of their NMR data with those reported in the literature. Compounds 1-4, and 6-9 were evaluated for their toxicity against Artemia salina larvae, and anti-acetylcholinesterase activity. Title: A novel molecular marker for early detection and evaluating prognosis of gastric cancer: N-myc downstream regulated gene-1 (NDRG1) Jiang K, Shen Z, Ye Y, Yang X, Wang S Ref: Scand J Gastroenterol, 45:898, 2010 : PubMed ESTHER: Jiang_2010_Scand.J.Gastroenterol_45_898 PubMedSearch: Jiang 2010 Scand.J.Gastroenterol 45 898 PubMedID: 20388062 Abstract OBJECTIVE N-myc downstream regulated gene-1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 was recently found to significantly down regulate in a variety of different neoplasms. Its significance in gastric cancer has not been studied. MATERIALS AND METHODS: NDRG1 was detected at its protein level by immunohistochemistry in formalin-fixed and paraffin-embedded sections with a total of 110 pair gastric cancer specimens including tumor and corresponding paraneoplastic tissues; NDRG1 mRNA was detected by real time-polymerase chain reaction. Meanwhile, the correlations between NDRG1 and clinicopathological factors were observed. Overexpression of NDRG1 has influence on the biological behavior of gastric cancer cell, which was detected by cell growth assay, apoptosis assay, and in vitro motility and invasion assay. RESULTS: NDRG1 protein was down regulated in gastric cancer tissues, and the NDRG1 low expression rate was 73.6% (79/110). Moreover, NDRG1 expression has a significant inverse correlation with tumor stromal invasion, lymph node metastasis, pathological stage, but not with distant metastasis. The patients with low NDRG1 expression had a significantly shorter survival opportunity than those with high NDRG1 expression. In addition, overexpression of NDRG1 induced early apoptosis and inhibited SGC7901 cell proliferation and its motility and invasion capability. Title: Differential control of ATGL-mediated lipid droplet degradation by CGI-58 and G0S2 Lu X, Yang X, Liu J Ref: Cell Cycle, 9:2719, 2010 : PubMed ESTHER: Lu_2010_Cell.Cycle_9_2719 PubMedSearch: Lu 2010 Cell.Cycle 9 2719 PubMedID: 20676045 Abstract Lipid droplets (LDs) are intracellular storage sites for triacylglyerols (TAGs)and steryl esters, and play essential roles in energy metabolism and membrane biosynthesis. Adipose triglyceride lipase (ATGL) is the key enzyme for TAG hydrolysis (lipolysis) in adipocytes and LD degradation in nonadipocyte cells. Lipase activity of ATGL in vivo largely depends on its C-terminal sequence as well as coactivation by CGI-58. Here we demonstrate that the C-terminal hydrophobic domain in ATGL is required for LD targeting and CGI-58-independent LD degradation. Overexpression of wild type ATGL causes a dramatic decrease in LD size and number, whereas a mutant lacking the hydrophobic domain fails to localize to LDs and to affect their morphology. Interestingly, coexpression of CGI-58 is able to promote LD turnover mediated by this ATGL mutant. Recently we have discovered that G0S2 acts as an inhibitor of ATGL activity and ATGL-mediated lipolysis. Here we show that G0S2 binds to ATGL irrelevantly of its activity state or the presence of CGI-58. In G0S2-expressing cells, the combined expression of CGI-58 and ATGL is incapable of stimulating LD turnover. We propose that CGI-58 and G0S2 regulate ATGL via non-competing mechanisms. Title: Genome sequencing and analysis of the model grass Brachypodium distachyon. Vogel JP, Garvin DF, Mockler TC, Schmutz J, Rokhsar D, Bevan MW, Barry K, Lucas S, Harmon-Smith M and Baxter I <127 more author(s)> Vogel JP, Garvin DF, Mockler TC, Schmutz J, Rokhsar D, Bevan MW, Barry K, Lucas S, Harmon-Smith M, Lail K, Tice H, Grimwood J, McKenzie N, Huo N, Gu YQ, Lazo GR, Anderson OD, You FM, Luo MC, Dvorak J, Wright J, Febrer M, Idziak D, Hasterok R, Lindquist E, Wang M, Fox SE, Priest HD, Filichkin SA, Givan SA, Bryant DW, Chang JH, Wu H, Wu W, Hsia AP, Schnable PS, Kalyanaraman A, Barbazuk B, Michael TP, Hazen SP, Bragg JN, Laudencia-Chingcuanco D, Weng Y, Haberer G, Spannagl M, Mayer K, Rattei T, Mitros T, Lee SJ, Rose JK, Mueller LA, York TL, Wicker T, Buchmann JP, Tanskanen J, Schulman AH, Gundlach H, Bevan M, de Oliveira AC, Maia Lda C, Belknap W, Jiang N, Lai J, Zhu L, Ma J, Sun C, Pritham E, Salse J, Murat F, Abrouk M, Bruggmann R, Messing J, Fahlgren N, Sullivan CM, Carrington JC, Chapman EJ, May GD, Zhai J, Ganssmann M, Gurazada SG, German M, Meyers BC, Green PJ, Tyler L, Wu J, Thomson J, Chen S, Scheller HV, Harholt J, Ulvskov P, Kimbrel JA, Bartley LE, Cao P, Jung KH, Sharma MK, Vega-Sanchez M, Ronald P, Dardick CD, De Bodt S, Verelst W, Inz D, Heese M, Schnittger A, Yang X, Kalluri UC, Tuskan GA, Hua Z, Vierstra RD, Cui Y, Ouyang S, Sun Q, Liu Z, Yilmaz A, Grotewold E, Sibout R, Hematy K, Mouille G, Hofte H, Michael T, Pelloux J, O'Connor D, Schnable J, Rowe S, Harmon F, Cass CL, Sedbrook JC, Byrne ME, Walsh S, Higgins J, Li P, Brutnell T, Unver T, Budak H, Belcram H, Charles M, Chalhoub B, Baxter I (- 127) Ref: Nature, 463:763, 2010 : PubMed ESTHER: Vogel_2010_Nature_463_763 PubMedSearch: Vogel 2010 Nature 463 763 PubMedID: 20148030 Gene_locus related to this paper: bradi-i1grm0, bradi-i1gx82, bradi-i1hb80, bradi-i1hkv6, bradi-i1hpu6, bradi-i1i3e4, bradi-i1i9i0, bradi-i1i435, bradi-i1ix93, bradi-i1gsk6, bradi-i1hk44, bradi-i1hk45, bradi-i1hnk7, bradi-i1hsd5, bradi-i1huy4, bradi-i1huy9, bradi-i1huz0, bradi-i1gxx9, bradi-i1hl25, bradi-i1hcw7, bradi-i1hyv6, bradi-i1hyb5, bradi-i1hvr8, bradi-i1hmu2, bradi-i1hf05, bradi-i1gry7, bradi-i1hf06, bradi-i1i5z8, bradi-i1icy3, bradi-i1j1h3, bradi-i1h1e3, bradi-i1hvr9, bradi-a0a0q3r7i7, bradi-i1i377, bradi-i1hjg5, bradi-i1h3i9, bradi-i1gsg5, bradi-a0a0q3mph9, bradi-i1h682, bradi-a0a0q3lc91, bradi-i1gx49, bradi-i1i839 Title: [The diagnostic value of butyrylcholinesterase in acute organophosphorus pesticide poisoning] Xu C, Zhang XG, Yang X, He YZ Ref: Zhongguo Wei Zhong Bing Ji Jiu Yi Xue, 22:193, 2010 : PubMed ESTHER: Xu_2010_Zhongguo.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue_22_193 PubMedSearch: Xu 2010 Zhongguo.Wei.Zhong.Bing.Ji.Jiu.Yi.Xue 22 193 PubMedID: 20398460 Abstract OBJECTIVE: To assess the value of butyrylcholinesterase (BuChE) in the diagnosis of acute organophosphorus pesticide poisoning (AOPP), and to investigate the relationship between the activity of whole blood acetylcholinesterase (AChE) and plasma BuChE in patients of AOPP in order to re-evaluate the diagnostic value of BuChE. METHODS: An improved Ellman method was employed to determine the activity of AChE and BuChE in 21 AOPP inpatients due to different kinds of pesticides (from April to September in 2009) during the course of the illness, with 26 healthy volunteers as normal control. The relationship between BuChE activity and other clinical indicators of 113 inpatients (from January 2008 to April 2009) was also retrospectively analyzed. RESULTS: The normal value of AChE and BuChE were (105 + or - 33) U/Hb and (15 807 + or - 3 495) U/L . The inhibition levels of these two enzymes were different. When the AChE activity was lower than 50%, 30% or 20%, the activity of BuChE was lower than 20%, 10% or 5% correspondingly. The tendency of changes in the two enzymes was similar and coincided well with the clinical symptoms after poisoning. The results of sequential detection showed that a significant decrease or persistent inhibition of BuChE activity by less than 5% indicated a high level of organophosphorus pesticide in the body. However, an elevation of BuChE indicated a favorable outcome. CONCLUSION: BuChE is one of the ideal diagnostic and classification criteria for AOPP. When the inhibition level of BuChE reaches 20%, AOPP is of moderate degree, when it reaches 10%, severe AOPP can be diagnosed, with different kinds of organophosphorus pesticides taken into consideration. Title: Identification of a novel splicing isoform of murine CGI-58 Yang X, Lu X, Liu J Ref: FEBS Letters, 584:903, 2010 : PubMed ESTHER: Yang_2010_FEBS.Lett_584_903 PubMedSearch: Yang 2010 FEBS.Lett 584 903 PubMedID: 20083112 Gene_locus related to this paper: mouse-abhd5 Abstract The comparative gene identification-58 (CGI-58) gene, mutations of which are linked to Chanarin-Dorfman syndrome, encodes a protein of the alpha/beta hydrolase domain subfamily. We report here a new alternative splicing isoform of the murine CGI-58 gene, termed mCGI-58S. Sequence comparison indicates the lack of second and third exons in this cDNA variant. While the full-length protein displayed perilipin-dependent localization to lipid droplets, mCGI-58S showed a predominant cytoplasmic staining when expressed in cells. mCGI-58S was incapable of activating adipose triglyceride lipase but retained the capacity to acylate lysophosphatidic acid. Overexpression of mCGI-58S failed to promote lipid droplet turnover and loss of intracellular triacylglycerols. These results suggest that this splicing event may be involved in the regulation of lipid homeostasis. Title: The G(0)/G(1) switch gene 2 regulates adipose lipolysis through association with adipose triglyceride lipase Yang X, Lu X, Lombes M, Rha GB, Chi YI, Guerin TM, Smart EJ, Liu J Ref: Cell Metab, 11:194, 2010 : PubMed ESTHER: Yang_2010_Cell.Metab_11_194 PubMedSearch: Yang 2010 Cell.Metab 11 194 PubMedID: 20197052 Abstract Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for triacylglycerol (TAG) hydrolysis in adipocytes. The precise mechanisms whereby ATGL is regulated remain uncertain. Here, we demonstrate that a protein encoded by G(0)/G(1) switch gene 2 (G0S2) is a selective regulator of ATGL. G0S2 is highly expressed in adipose tissue and differentiated adipocytes. When overexpressed in HeLa cells, G0S2 localizes to lipid droplets and prevents their degradation mediated by ATGL. Moreover, G0S2 specifically interacts with ATGL through the hydrophobic domain of G0S2 and the patatin-like domain of ATGL. More importantly, interaction with G0S2 inhibits ATGL TAG hydrolase activity. Knockdown of endogenous G0S2 accelerates basal and stimulated lipolysis in adipocytes, whereas overexpression of G0S2 diminishes the rate of lipolysis in both adipocytes and adipose tissue explants. Thus, G0S2 functions to attenuate ATGL action both in vitro and in vivo and by this mechanism regulates TAG hydrolysis. Title: Effect of early feed restriction on hepatic lipid metabolism and expression of lipogenic genes in broiler chickens Yang X, Zhuang J, Rao K, Li X, Zhao R Ref: Res Vet Sci, 89:438, 2010 : PubMed ESTHER: Yang_2010_Res.Vet.Sci_89_438 PubMedSearch: Yang 2010 Res.Vet.Sci 89 438 PubMedID: 20434185 Abstract The study was conducted to investigate the effect of early feed restriction (ER) on lipid metabolism and mitochondrial function in the liver of broiler chickens. Newly hatched broiler chickens were randomly allocated into control and ER group which was subjected to feed restriction with feed provided on alternate days from hatch to 14 days of age (14 d), followed by ad libitum feeding until the end of the experiment on 63 d. ER group exhibited significantly lower body weight throughout the experiment. Serum concentrations of total cholesterol (TC) and high density lipoprotein cholesterol (HDLC) were significantly higher in ER group at 14 d (P<0.05), and the higher serum TC level in ER group was also observed at 63 d. In contrast, the contents of triglyceride (TG), TC and lipoprotein lipase (LPL) activity in liver were significantly lower in ER group at 14 d (P<0.05). At 14 d no significant difference was detected for the mRNA expression of the acetyl-CoA carboxylase-alpha (ACC-alpha), carnitine palmitoyltransferase I (CPT-I), sterol regulatory element binding protein-1c (SREBP-1c) or peroxisome proliferator-activated receptors alpha (PPAR-alpha) between control and ER group. At 63 d ACC-alpha mRNA expression was significantly down-regulated accompanied with a significantly up-regulated CPT-ImRNA and a decreased tendency of SREBP-1c mRNA expression in ER group (P=0.09). Swollen mitochondria with fragmented and reduced cristae were observed in liver of ER group at 14 d. Meanwhile the inner mitochondria membrane viscidity increased and hepatic mitochondrial superoxide dismutase (SOD) activity decreased at 14 d. The results suggest that feed restriction at early postnatal stage may produce long-term effect on lipid metabolism of broiler chicken, probably through, at least in part, alterations in mitochondria morphology and function. Title: Neurexins physically and functionally interact with GABA(A) receptors Zhang C, Atasoy D, Arac D, Yang X, Fucillo MV, Robison AJ, Ko J, Brunger AT, Sudhof TC Ref: Neuron, 66:403, 2010 : PubMed ESTHER: Zhang_2010_Neuron_66_403 PubMedSearch: Zhang 2010 Neuron 66 403 PubMedID: 20471353 Abstract Neurexins are presynaptic cell-adhesion molecules that form trans-synaptic complexes with postsynaptic neuroligins. When overexpressed in nonneuronal cells, neurexins induce formation of postsynaptic specializations in cocultured neurons, suggesting that neurexins are synaptogenic. However, we find that when overexpressed in neurons, neurexins do not increase synapse density, but instead selectively suppressed GABAergic synaptic transmission without decreasing GABAergic synapse numbers. This suppression was mediated by all subtypes of neurexins tested, in a cell-autonomous and neuroligin-independent manner. Strikingly, addition of recombinant neurexin to cultured neurons at submicromolar concentrations induced the same suppression of GABAergic synaptic transmission as neurexin overexpression. Moreover, experiments with native brain proteins and purified recombinant proteins revealed that neurexins directly and stoichiometrically bind to GABA(A) receptors, suggesting that they decrease GABAergic synaptic responses by interacting with GABA(A) receptors. Our findings suggest that besides their other well-documented interactions, presynaptic neurexins directly act on postsynaptic GABA(A) receptors, which may contribute to regulate the excitatory/inhibitory balance in brain. Title: The measurement of serum cholinesterase activities by an integration strategy with expanded linear ranges and negligible substrate-activation Liao F, Yang D, Tang J, Yang X, Liu B, Zhao Y, Zhao L, Liao H, Yu M Ref: Clinical Biochemistry, 42:926, 2009 : PubMed ESTHER: Liao_2009_Clin.Biochem_42_926 PubMedSearch: Liao 2009 Clin.Biochem 42 926 PubMedID: 19101530 Abstract OBJECTIVES: To measure serum cholinesterase (SCHE) with an integration strategy. DESIGN AND METHODS: At 54.0 micromol/L butyrylthiolcholine, SCHE initial rates were calculated with 50.0 micromol/L butyrylthiolcholine and maximal rates via an improved integrated method if substrate consumptions within 5.0 min were over 60%, or were determined by the classical initial rate method. RESULTS: The linear range was from 16 to 1560 nkat/L, and SCHE in clinic sera showed negligible substrate-activation. CONCLUSION: This strategy was effective. Title: A common mutation in paraoxonase-2 results in impaired lactonase activity Stoltz DA, Ozer EA, Recker TJ, Estin M, Yang X, Shih DM, Lusis AJ, Zabner J Ref: Journal of Biological Chemistry, 284:35564, 2009 : PubMed ESTHER: Stoltz_2009_J.Biol.Chem_284_35564 PubMedSearch: Stoltz 2009 J.Biol.Chem 284 35564 PubMedID: 19840942 Abstract Paraoxonases (PONs) are a family of lactonases with promiscuous enzyme activity that has been implicated in multiple diseases. PON2 is intracellularly located, is the most ubiquitously expressed PON, and has the highest lactonase activity of the PON family members. Whereas some single-nucleotide polymorphisms (SNPs) in PON1 have resulted in altered enzymatic activity in serum, to date the functional consequences of SNPs on PON2 function remain unknown. We hypothesized that a common PON2 SNP would result in impaired lactonase activity. Substitution of cysteine for serine at codon 311 in recombinant PON2 resulted in normal protein production and localization but altered glycosylation and decreased lactonase activity. Moreover, we screened 200 human lung samples for the PON2 Cys(311) variant and found that in vivo this mutation impaired lactonase activity. These data suggest that impaired lactonase activity may play a role in innate immunity, atherosclerosis, and other diseases associated with the PON2 311 SNP. Title: Rational design and synthesis of highly potent anti-acetylcholinesterase activity huperzine A derivatives Yan J, Sun L, Wu G, Yi P, Yang F, Zhou L, Zhang X, Li Z, Yang X and Qiu M <1 more author(s)> Yan J, Sun L, Wu G, Yi P, Yang F, Zhou L, Zhang X, Li Z, Yang X, Luo H, Qiu M (- 1) Ref: Bioorganic & Medicinal Chemistry, 17:6937, 2009 : PubMed ESTHER: Yan_2009_Bioorg.Med.Chem_17_6937 PubMedSearch: Yan 2009 Bioorg.Med.Chem 17 6937 PubMedID: 19726199 Abstract By targeting multi-active sites of acetylcholinesterase (AChE), a series of huperzine A (Hup A) derivatives with various aromatic ring groups were designed and synthesized by Schiff reaction. They were evaluated as AChE and butyrylcholinesterase (BChE) inhibitors. Results showed very significant specificity that the group of imine derivatives could inhibit TcAChE and hAChE, but no inhibitory effect on hBChE was detected. The experiment was explained by a docking study. In the docking model, we confirmed that aromatic ring of Hup A derivatives played the pi-pi stacking against aminophenol residues of AChE, and the structure-activity relationship (SAR) was discussed. Title: Variations in DNA elucidate molecular networks that cause disease Chen Y, Zhu J, Lum PY, Yang X, Pinto S, MacNeil DJ, Zhang C, Lamb J, Edwards S and Schadt EE <12 more author(s)> Chen Y, Zhu J, Lum PY, Yang X, Pinto S, MacNeil DJ, Zhang C, Lamb J, Edwards S, Sieberts SK, Leonardson A, Castellini LW, Wang S, Champy MF, Zhang B, Emilsson V, Doss S, Ghazalpour A, Horvath S, Drake TA, Lusis AJ, Schadt EE (- 12) Ref: Nature, 452:429, 2008 : PubMed ESTHER: Chen_2008_Nature_452_429 PubMedSearch: Chen 2008 Nature 452 429 PubMedID: 18344982 Abstract Identifying variations in DNA that increase susceptibility to disease is one of the primary aims of genetic studies using a forward genetics approach. However, identification of disease-susceptibility genes by means of such studies provides limited functional information on how genes lead to disease. In fact, in most cases there is an absence of functional information altogether, preventing a definitive identification of the susceptibility gene or genes. Here we develop an alternative to the classic forward genetics approach for dissecting complex disease traits where, instead of identifying susceptibility genes directly affected by variations in DNA, we identify gene networks that are perturbed by susceptibility loci and that in turn lead to disease. Application of this method to liver and adipose gene expression data generated from a segregating mouse population results in the identification of a macrophage-enriched network supported as having a causal relationship with disease traits associated with metabolic syndrome. Three genes in this network, lipoprotein lipase (Lpl), lactamase beta (Lactb) and protein phosphatase 1-like (Ppm1l), are validated as previously unknown obesity genes, strengthening the association between this network and metabolic disease traits. Our analysis provides direct experimental support that complex traits such as obesity are emergent properties of molecular networks that are modulated by complex genetic loci and environmental factors. Title: The genome of the model beetle and pest Tribolium castaneum Richards S, Gibbs RA, Weinstock GM, Brown SJ, Denell R, Beeman RW, Gibbs R, Bucher G, Friedrich M and Grossmann D <181 more author(s)> Richards S, Gibbs RA, Weinstock GM, Brown SJ, Denell R, Beeman RW, Gibbs R, Bucher G, Friedrich M, Grimmelikhuijzen CJ, Klingler M, Lorenzen M, Roth S, Schroder R, Tautz D, Zdobnov EM, Muzny D, Attaway T, Bell S, Buhay CJ, Chandrabose MN, Chavez D, Clerk-Blankenburg KP, Cree A, Dao M, Davis C, Chacko J, Dinh H, Dugan-Rocha S, Fowler G, Garner TT, Garnes J, Gnirke A, Hawes A, Hernandez J, Hines S, Holder M, Hume J, Jhangiani SN, Joshi V, Khan ZM, Jackson L, Kovar C, Kowis A, Lee S, Lewis LR, Margolis J, Morgan M, Nazareth LV, Nguyen N, Okwuonu G, Parker D, Ruiz SJ, Santibanez J, Savard J, Scherer SE, Schneider B, Sodergren E, Vattahil S, Villasana D, White CS, Wright R, Park Y, Lord J, Oppert B, Brown S, Wang L, Weinstock G, Liu Y, Worley K, Elsik CG, Reese JT, Elhaik E, Landan G, Graur D, Arensburger P, Atkinson P, Beidler J, Demuth JP, Drury DW, Du YZ, Fujiwara H, Maselli V, Osanai M, Robertson HM, Tu Z, Wang JJ, Wang S, Song H, Zhang L, Werner D, Stanke M, Morgenstern B, Solovyev V, Kosarev P, Brown G, Chen HC, Ermolaeva O, Hlavina W, Kapustin Y, Kiryutin B, Kitts P, Maglott D, Pruitt K, Sapojnikov V, Souvorov A, Mackey AJ, Waterhouse RM, Wyder S, Kriventseva EV, Kadowaki T, Bork P, Aranda M, Bao R, Beermann A, Berns N, Bolognesi R, Bonneton F, Bopp D, Butts T, Chaumot A, Denell RE, Ferrier DE, Gordon CM, Jindra M, Lan Q, Lattorff HM, Laudet V, von Levetsow C, Liu Z, Lutz R, Lynch JA, da Fonseca RN, Posnien N, Reuter R, Schinko JB, Schmitt C, Schoppmeier M, Shippy TD, Simonnet F, Marques-Souza H, Tomoyasu Y, Trauner J, Van der Zee M, Vervoort M, Wittkopp N, Wimmer EA, Yang X, Jones AK, Sattelle DB, Ebert PR, Nelson D, Scott JG, Muthukrishnan S, Kramer KJ, Arakane Y, Zhu Q, Hogenkamp D, Dixit R, Jiang H, Zou Z, Marshall J, Elpidina E, Vinokurov K, Oppert C, Evans J, Lu Z, Zhao P, Sumathipala N, Altincicek B, Vilcinskas A, Williams M, Hultmark D, Hetru C, Hauser F, Cazzamali G, Williamson M, Li B, Tanaka Y, Predel R, Neupert S, Schachtner J, Verleyen P, Raible F, Walden KK, Angeli S, Foret S, Schuetz S, Maleszka R, Miller SC, Grossmann D (- 181) Ref: Nature, 452:949, 2008 : PubMed ESTHER: Richards_2008_Nature_452_949 PubMedSearch: Richards 2008 Nature 452 949 PubMedID: 18362917 Gene_locus related to this paper: trica-ACHE1, trica-ACHE2, trica-d2a0g9, trica-d2a0h0, trica-d2a0w9, trica-d2a0x0, trica-d2a0x1, trica-d2a0x3, trica-d2a0x4.1, trica-d2a0x4.2, trica-d2a0x6, trica-d2a2b8, trica-d2a2h1, trica-d2a3c3, trica-d2a3g9, trica-d2a5y5, trica-d2a309, trica-d2a514, trica-d2a515, trica-d2a516, trica-d2a577, trica-d2a578, trica-d6w6x8, trica-d6w7f9, trica-d6w7h2, trica-d6w8e7, trica-d6w9c0, trica-d6w855, trica-d6wac8, trica-d6wan4, trica-d6wd50, trica-d6wd73, trica-d6wd74, trica-A0A139WM97, trica-d6wfu3, trica-d6wgl2, trica-d6wj57, trica-d6wj59, trica-d6wjs3, trica-d6wl31, trica-d6wnv1, trica-d6wpl0, trica-d6wqd6, trica-d6wqr4, trica-d6ws52, trica-d6wsm0, trica-d6wu38, trica-d6wu39, trica-d6wu40, trica-d6wu41, trica-d6wu44, trica-d6wvk5, trica-d6wvz7, trica-d6wwu9, trica-d6wwv0, trica-d6wxz0, trica-d6wyy1, trica-d6wyy2, trica-d6x0z2, trica-d6x0z5, trica-d6x0z6, trica-d6x4b2, trica-d6x4e8, trica-d6x4e9, trica-d6x197, trica-d7eip7, trica-d7eld3, trica-d7us45, trica-q5wm43, trica-q5zex9, trica-d6wie5, trica-d6w7t0, trica-d6x4h0, trica-d6x4h1, trica-a0a139wae8, trica-a0a139wc96, trica-d6x325, trica-d2a4s2, trica-d6wvw8 Abstract Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control. Title: Cloning and expression of lipP, a gene encoding a cold-adapted lipase from Moritella sp.2-5-10-1 Yang X, Lin X, Fan T, Bian J, Huang X Ref: Curr Microbiol, 56:194, 2008 : PubMed ESTHER: Yang_2008_Curr.Microbiol_56_194 PubMedSearch: Yang 2008 Curr.Microbiol 56 194 PubMedID: 17973159 Abstract A gene (lipP, 837 bp in length) coding for a cold-adapted lipase of psychrophilic bacterium Moritella sp. 2-5-10-1 isolated from Antarctic region was cloned and sequenced in this study. The deduced amino acid sequence revealed a protein of 278 amino acid residues with a molecular mass of 30,521. The primary structure of the lipase deduced from the nucleotide sequence showed consensus pentapeptide containing the active serine [Gly-Trp-Ser-Leu-Gly] and a conserved His-Gly dipeptide in the N-terminal part of the enzyme. These sequences were involved in the lipase active site conformation. Structure factors that would allow proper enzyme flexibility at low temperatures were discussed. It was suggested that the changes in the primary structure of the psychrophilic lipases compared to the thermophilic ones could account for their ability to catalyze lipolysis at temperatures close to 0 degrees C. For expression, the sequence corresponding to the cold-adapted lipase of strain 2-5-10-1 was subcloned into the pET-28a expression vector to construct a recombinant lipase protein. Expression of the lipase by Escherichia coli BL21 (DE3) cells was observed as clear halos on 1% (vol/vol) tributyrin upon induction with IPTG at 25 degrees C. Title: DNA sequence and analysis of human chromosome 8 Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A and Lander ES <66 more author(s)> Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, Fitzgerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, Decaprio D, Dooley KT, Dorris L, 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES (- 66) Ref: Nature, 439:331, 2006 : PubMed ESTHER: Nusbaum_2006_Nature_439_331 PubMedSearch: Nusbaum 2006 Nature 439 331 PubMedID: 16421571 Gene_locus related to this paper: human-TG Abstract The International Human Genome Sequencing Consortium (IHGSC) recently completed a sequence of the human genome. As part of this project, we have focused on chromosome 8. Although some chromosomes exhibit extreme characteristics in terms of length, gene content, repeat content and fraction segmentally duplicated, chromosome 8 is distinctly typical in character, being very close to the genome median in each of these aspects. This work describes a finished sequence and gene catalogue for the chromosome, which represents just over 5% of the euchromatic human genome. A unique feature of the chromosome is a vast region of approximately 15 megabases on distal 8p that appears to have a strikingly high mutation rate, which has accelerated in the hominids relative to other sequenced mammals. This fast-evolving region contains a number of genes related to innate immunity and the nervous system, including loci that appear to be under positive selection--these include the major defensin (DEF) gene cluster and MCPH1, a gene that may have contributed to the evolution of expanded brain size in the great apes. The data from chromosome 8 should allow a better understanding of both normal and disease biology and genome evolution. Title: Human chromosome 11 DNA sequence and analysis including novel gene identification Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T and Sakaki Y <24 more author(s)> Taylor TD, Noguchi H, Totoki Y, Toyoda A, Kuroki Y, Dewar K, Lloyd C, Itoh T, Takeda T, Kim DW, She X, Barlow KF, Bloom T, Bruford E, Chang JL, Cuomo CA, Eichler E, Fitzgerald MG, Jaffe DB, LaButti K, Nicol R, Park HS, Seaman C, Sougnez C, Yang X, Zimmer AR, Zody MC, Birren BW, Nusbaum C, Fujiyama A, Hattori M, Rogers J, Lander ES, Sakaki Y (- 24) Ref: Nature, 440:497, 2006 : PubMed ESTHER: Taylor_2006_Nature_440_497 PubMedSearch: Taylor 2006 Nature 440 497 PubMedID: 16554811 Gene_locus related to this paper: human-PRCP Abstract Chromosome 11, although average in size, is one of the most gene- and disease-rich chromosomes in the human genome. Initial gene annotation indicates an average gene density of 11.6 genes per megabase, including 1,524 protein-coding genes, some of which were identified using novel methods, and 765 pseudogenes. One-quarter of the protein-coding genes shows overlap with other genes. Of the 856 olfactory receptor genes in the human genome, more than 40% are located in 28 single- and multi-gene clusters along this chromosome. Out of the 171 disorders currently attributed to the chromosome, 86 remain for which the underlying molecular basis is not yet known, including several mendelian traits, cancer and susceptibility loci. The high-quality data presented here--nearly 134.5 million base pairs representing 99.8% coverage of the euchromatic sequence--provide scientists with a solid foundation for understanding the genetic basis of these disorders and other biological phenomena. Title: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L and Nusbaum C <64 more author(s)> Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, Decaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C (- 64) Ref: Nature, 440:1045, 2006 : PubMed ESTHER: Zody_2006_Nature_440_1045 PubMedSearch: Zody 2006 Nature 440 1045 PubMedID: 16625196 Gene_locus related to this paper: human-NLGN2, human-NOTUM Abstract Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome. It is also enriched in segmental duplications, ranking third in density among the autosomes. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome. Title: Analysis of the DNA sequence and duplication history of human chromosome 15 Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL and Nusbaum C <58 more author(s)> Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, Fitzgerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, Decaprio D, Dorris L, 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C (- 58) Ref: Nature, 440:671, 2006 : PubMed ESTHER: Zody_2006_Nature_440_671 PubMedSearch: Zody 2006 Nature 440 671 PubMedID: 16572171 Gene_locus related to this paper: human-DPP8, human-LIPC, human-SPG21 Abstract Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome. Title: Genome sequence, comparative analysis and haplotype structure of the domestic dog Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ, 3rd and Lander ES <224 more author(s)> Lindblad-Toh K, Wade CM, Mikkelsen TS, Karlsson EK, Jaffe DB, Kamal M, Clamp M, Chang JL, Kulbokas EJ, 3rd, Zody MC, Mauceli E, Xie X, Breen M, Wayne RK, Ostrander EA, Ponting CP, Galibert F, Smith DR, deJong PJ, Kirkness E, Alvarez P, Biagi T, Brockman W, Butler J, Chin CW, Cook A, Cuff J, Daly MJ, Decaprio D, Gnerre S, Grabherr M, Kellis M, Kleber M, Bardeleben C, Goodstadt L, Heger A, Hitte C, Kim L, Koepfli KP, Parker HG, Pollinger JP, Searle SM, Sutter NB, Thomas R, Webber C, Baldwin J, Abebe A, Abouelleil A, Aftuck L, Ait-Zahra M, Aldredge T, Allen N, An P, Anderson S, Antoine C, Arachchi H, Aslam A, Ayotte L, Bachantsang P, Barry A, Bayul T, Benamara M, Berlin A, Bessette D, Blitshteyn B, Bloom T, Blye J, Boguslavskiy L, Bonnet C, Boukhgalter B, Brown A, Cahill P, Calixte N, Camarata J, Cheshatsang Y, Chu J, Citroen M, Collymore A, Cooke P, Dawoe T, Daza R, Decktor K, DeGray S, Dhargay N, Dooley K, Dorje P, Dorjee K, Dorris L, Duffey N, Dupes A, Egbiremolen O, Elong R, Falk J, Farina A, Faro S, Ferguson D, Ferreira P, Fisher S, FitzGerald M, Foley K, Foley C, Franke A, Friedrich D, Gage D, Garber M, Gearin G, Giannoukos G, Goode T, Goyette A, Graham J, Grandbois E, Gyaltsen K, Hafez N, Hagopian D, Hagos B, Hall J, Healy C, Hegarty R, Honan T, Horn A, Houde N, Hughes L, Hunnicutt L, Husby M, Jester B, Jones C, Kamat A, Kanga B, Kells C, Khazanovich D, Kieu AC, Kisner P, Kumar M, Lance K, Landers T, Lara M, Lee W, Leger JP, Lennon N, Leuper L, LeVine S, Liu J, Liu X, Lokyitsang Y, Lokyitsang T, Lui A, MacDonald J, Major J, Marabella R, Maru K, Matthews C, McDonough S, Mehta T, Meldrim J, Melnikov A, Meneus L, Mihalev A, Mihova T, Miller K, Mittelman R, Mlenga V, Mulrain L, Munson G, Navidi A, Naylor J, Nguyen T, Nguyen N, Nguyen C, Nicol R, Norbu N, Norbu C, Novod N, Nyima T, Olandt P, O'Neill B, O'Neill K, Osman S, Oyono L, Patti C, Perrin D, Phunkhang P, Pierre F, Priest M, Rachupka A, Raghuraman S, Rameau R, Ray V, Raymond C, Rege F, Rise C, Rogers J, Rogov P, Sahalie J, Settipalli S, Sharpe T, Shea T, Sheehan M, Sherpa N, Shi J, Shih D, Sloan J, Smith C, Sparrow T, Stalker J, Stange-Thomann N, Stavropoulos S, Stone C, Stone S, Sykes S, Tchuinga P, Tenzing P, Tesfaye S, Thoulutsang D, Thoulutsang Y, Topham K, Topping I, Tsamla T, Vassiliev H, Venkataraman V, Vo A, Wangchuk T, Wangdi T, Weiand M, Wilkinson J, Wilson A, Yadav S, Yang S, Yang X, Young G, Yu Q, Zainoun J, Zembek L, Zimmer A, Lander ES (- 224) Ref: Nature, 438:803, 2005 : PubMed ESTHER: Lindblad-Toh_2005_Nature_438_803 PubMedSearch: Lindblad-Toh 2005 Nature 438 803 PubMedID: 16341006 Gene_locus related to this paper: canfa-1lipg, canfa-2neur, canfa-3neur, canfa-ACHE, canfa-BCHE, canfa-cauxin, canfa-CESDD1, canfa-e2qsb1, canfa-e2qsl3, canfa-e2qsz2, canfa-e2qvk3, canfa-e2qw15, canfa-e2qxs8, canfa-e2qzs6, canfa-e2r5t3, canfa-e2r6f6, canfa-e2r7e8, canfa-e2r8v9, canfa-e2r8z1, canfa-e2r9h4, canfa-e2r455, canfa-e2rb70, canfa-e2rcq9, canfa-e2rd94, canfa-e2rgi0, canfa-e2rkq0, canfa-e2rlz9, canfa-e2rm00, canfa-e2rqf1, canfa-e2rss9, canfa-f1p6w8, canfa-f1p8b6, canfa-f1p9d8, canfa-f1p683, canfa-f1pb79, canfa-f1pgw0, canfa-f1phd0, canfa-f1phx2, canfa-f1pke8, canfa-f1pp08, canfa-f1ppp9, canfa-f1ps07, canfa-f1ptf1, canfa-f1pvp4, canfa-f1pw93, canfa-f1pwk3, canfa-pafa, canfa-q1ert3, canfa-q5jzr0, canfa-e2rmb9, canlf-f6v865, canlf-e2rjg6, canlf-e2r2h2, canlf-f1p648, canlf-f1pw90, canlf-j9p8v6, canlf-f1pcc4, canlf-e2qxh0, canlf-e2r774, canlf-f1pf96, canlf-e2rq56, canlf-j9nwb1, canlf-f1ptw2, canlf-j9p8h1, canlf-e2ree2, canlf-f1prs1, canlf-j9nus1, canlf-e2rf91, canlf-f1pg57, canlf-f1q111 Abstract Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health. Title: DNA sequence and analysis of human chromosome 18 Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA and Lander ES <45 more author(s)> Nusbaum C, Zody MC, Borowsky ML, Kamal M, Kodira CD, Taylor TD, Whittaker CA, Chang JL, Cuomo CA, Dewar K, Fitzgerald MG, Yang X, Abouelleil A, Allen NR, Anderson S, Bloom T, Bugalter B, Butler J, Cook A, Decaprio D, Engels R, Garber M, Gnirke A, Hafez N, Hall JL, Norman CH, Itoh T, Jaffe DB, Kuroki Y, Lehoczky J, Lui A, Macdonald P, Mauceli E, Mikkelsen TS, Naylor JW, Nicol R, Nguyen C, Noguchi H, O'Leary SB, O'Neill K, Piqani B, Smith CL, Talamas JA, Topham K, Totoki Y, Toyoda A, Wain HM, Young SK, Zeng Q, Zimmer AR, Fujiyama A, Hattori M, Birren BW, Sakaki Y, Lander ES (- 45) Ref: Nature, 437:551, 2005 : PubMed ESTHER: Nusbaum_2005_Nature_437_551 PubMedSearch: Nusbaum 2005 Nature 437 551 PubMedID: 16177791 Gene_locus related to this paper: human-LIPG Abstract Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements. Title: Novel agents that potentially inhibit irinotecan-induced diarrhea Yang X, Hu Z, Chan SY, Chan E, Goh BC, Duan W, Zhou S Ref: Curr Med Chem, 12:1343, 2005 : PubMed ESTHER: Yang_2005_Curr.Med.Chem_12_1343 PubMedSearch: Yang 2005 Curr.Med.Chem 12 1343 PubMedID: 15975002 Abstract Irinotecan (CPT-11, 7-ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxycamptothecin) has exhibited clinical activities against a broad spectrum of carcinomas by inhibiting DNA topoisomerase I (Topo I). However, severe and unpredictable dosing-limiting toxicities (mainly myelosuppression and severe diarrhea) hinder its clinical use. The latter consists of early and late-onset diarrhea, occurring within 24 hr or > or = 24 hr after CPT-11 administration, respectively. This review highlights novel agents potentially inhibiting CPT-11-induced diarrhea, which are designed and tested under guidance of disposition pathways and potential toxicity mechanisms. Early-onset diarrhea is observed immediately after CPT-11 infusion and probably due to the inhibition of acetylcholinesterase activity, which can be eliminated by administration of atropine. Late-onset diarrhea appears to be associated with intestinal exposure to SN-38 (7-ethyl-10-hydroxycamptothecin), the major active metabolite of CPT-11, which may bind to Topo I and induce apoptosis of intestinal epithelia, leading to the disturbance in the absorptive and secretory functions of mucosa. CPT-11 and SN-38 may also stimulate the production of pro-inflammatory cytokines and prostaglandins (PGs), thus inducing the secretion of Na(+) and Cl(-). Early treatment of severe late-onset diarrhea with oral high-dose loperamide has decreased patient morbidity. Extensive studies have been conducted to identify other potential agents to ameliorate diarrhea in preclinical and clinical models. These include intestinal alkalizing agents, oral antibiotics, enzyme inducers, P-glycoprotein (PgP) inhibitors, cyclooxygenase-2 (COX-2) inhibitors, tumor necrosis factor-alpha (TNF-alpha) inhibitors, or blockers of biliary excretion of SN-38. Further studies are needed to identify the molecular targets associated with CPT-11 toxicity and safe and effective agents for alleviating CPT-11-induced diarrhea. Title: Identification and characterization of a diverse family of neurotoxin-like peptides from the South American coral snake. Kubo T, Baptista G, Yang X, Kobayashi S, Takeda M, Prieto-Da-Silva A, Yamane T Ref: Cholinergic Mechanisms, CRC Press, :617, 2004 : PubMed ESTHER: Kubo_2004_Cholinergic.Mechanisms.CRC.Press__617 PubMedSearch: Kubo 2004 Cholinergic.Mechanisms.CRC.Press 617 Title: Host plant-induced changes in detoxification enzymes and susceptibility to pesticides in the twospotted spider mite (Acari: Tetranychidae) Yang X, Margolies DC, Zhu KY, Buschman LL Ref: J Econ Entomol, 94:381, 2001 : PubMed ESTHER: Yang_2001_J.Econ.Entomol_94_381 PubMedSearch: Yang 2001 J.Econ.Entomol 94 381 PubMedID: 11332829 Abstract Adult female twospotted spider mites, Tetranychus urticae Koch, reared on lima bean plants were moved to cucumber, maize, or new lima bean plants (the latter being a control) and evaluated after 24 h or 7 d for changes in susceptibility to three pesticides and in levels of related detoxification enzymes. The largest and most consistent changes were observed in mites feeding on cucumber. Susceptibility of mites on cucumber to the synthetic pyrethroids bifenthrin and lambda-cyhalothrin was greater than that of mites reared on lima bean and maize after only 24 h on the plants, and remained higher after 7 d. Mites on cucumber also were more susceptible to the organophosphate dimethoate than were mites on lima bean, but only after 7 d on the host. Susceptibility was inversely related to activities of both general esterase and glutathione S-transferase (GST) in mites on cucumber; general esterase and GST activities were 60 and 25% lower, respectively, than activities of twospotted spider mite on lima bean after 7 d of feeding. Mites on maize were slightly but significantly more susceptible than those on lima bean to bifenthrin, but not to lambda-cyhalothrin, after 7 d and to dimethoate after 24 h but not after 7 d. General esterase and GST activities in twospotted spider mite fed on maize for 24 h were 20 and 16% higher, respectively, than activities in twospotted spider mite on lima bean, but general esterase activity was 30% lower than lima bean-fed mites and GST was not different after 7 d. Thus, plant-induced changes in general esterase activity, perhaps in combination with GST activity, in twospotted spider mite appear to be inversely related to, and possibly responsible for, changes in susceptibility of twospotted spider mite to several pesticides, particularly the synthetic pyrethroids. General esterases appear to play less of a role in the detoxification of the organophosphate insecticide dimethoate. Title: APP processing and synaptic plasticity in presenilin-1 conditional knockout mice Yu H, Saura CA, Choi SY, Sun LD, Yang X, Handler M, Kawarabayashi T, Younkin L, Fedeles B and Shen J <4 more author(s)> Yu H, Saura CA, Choi SY, Sun LD, Yang X, Handler M, Kawarabayashi T, Younkin L, Fedeles B, Wilson MA, Younkin S, Kandel ER, Kirkwood A, Shen J (- 4) Ref: Neuron, 31:713, 2001 : PubMed ESTHER: Yu_2001_Neuron_31_713 PubMedSearch: Yu 2001 Neuron 31 713 PubMedID: 11567612 Abstract We have developed a presenilin-1 (PS1) conditional knockout mouse (cKO), in which PS1 inactivation is restricted to the postnatal forebrain. The PS1 cKO mouse is viable and exhibits no gross abnormalities. The carboxy-terminal fragments of the amyloid precursor protein differentially accumulate in the cerebral cortex of cKO mice, while generation of beta-amyloid peptides is reduced. Expression of Notch downstream effector genes, Hes1, Hes5, and Dll1, is unaffected in the cKO cortex. Although basal synaptic transmission, long-term potentiation, and long-term depression at hippocampal area CA1 synapses are normal, the PS1 cKO mice exhibit subtle but significant deficits in long-term spatial memory. These results demonstrate that inactivation of PS1 function in the adult cerebral cortex leads to reduced Abeta generation and subtle cognitive deficits without affecting expression of Notch downstream genes. Title: Transcriptional control of the neuronal nicotinic acetylcholine receptor gene cluster by the beta43' enhancer, Sp1, SCIP and ETS transcription factors Deneris ES, Francis N, McDonough J, Fyodorov D, Miller T, Yang X Ref: European Journal of Pharmacology, 393:69, 2000 : PubMed ESTHER: Deneris_2000_Eur.J.Pharmacol_393_69 PubMedSearch: Deneris 2000 Eur.J.Pharmacol 393 69 PubMedID: 10770999 Abstract Receptors assembled from the products of a neuronal beta4alpha3alpha5 NAChR gene cluster depend on these genes being coordinately regulated in particular populations of neurons. Little is known, however, about the transcriptional mechanisms that are likely to underlie their co-expression in correct neuronal cell types. We have identified several regulatory elements and transcription factors that influence transcription of the alpha3 and beta4 genes. The promoters of these genes appear to contain a common cis element that binds Sp1 transcription factors. They can be activated by the POU-domain factor SCIP and activation does not require SCIP binding sites. Between these two promoters is a cell type specific enhancer called beta43'. This enhancer has little activity in non-neuronal cells and is preferentially active in particular populations of central neurons. The clustered genes are potential targets of ETS factors as the ETS domain factor, Pet-1 can activate beta43'-dependent transcription. The neuron-selective properties of beta43' and its location suggest that it is a component of the cis regulatory information required to control expression of the beta4 and alpha3 genes in specific populations of neurons. Title: Poster: Modulation of K+ currents by muscarinic acetylcholine receptor agonists in canine atrial myocytes Yang X, Shi H, Wang H, Wang Z Ref: Life Sciences, 64:576, 1999 : PubMed Title: Characteristics of I(K) and its response to quinidine in experimental healed myocardial infarction Yuan F, Pinto JM, Li Q, Wasserlauf BJ, Yang X, Bassett AL, Myerburg RJ Ref: J Cardiovasc Electrophysiol, 10:844, 1999 : PubMed ESTHER: Yuan_1999_J.Cardiovasc.Electrophysiol_10_844 PubMedSearch: Yuan 1999 J.Cardiovasc.Electrophysiol 10 844 PubMedID: 10376922 Abstract INTRODUCTION: Mechanisms and drug treatment of serious ventricular arrhythmias in patients with healed myocardial infarction (HMI) are incompletely understood, in part because the electrophysiology and pharmacology of myocytes from noninfarcted regions of HMI hearts are not well characterized. METHODS AND Title: A cysteine-rich isoform of neuregulin controls the level of expression of neuronal nicotinic receptor channels during synaptogenesis Yang X, Kuo Y, Devay P, Yu C, Role LW Ref: Neuron, 20:255, 1998 : PubMed ESTHER: Yang_1998_Neuron_20_255 PubMedSearch: Yang 1998 Neuron 20 255 PubMedID: 9491987 Abstract We report here that neuregulin (NRG) isoforms with a conserved cysteine-rich domain (CRD) in their N terminus regulate expression of nicotinic acetylcholine receptors (nAChRs) at developing interneuronal synapses and report the isolation of transmembrane NRG isoforms with this CRD within the N-terminal portion. CRD-NRG mRNA and immunoreactive protein are detected early in developing presynaptic (visceral motor) neurons. The levels of expression of CRD-NRG peak prior to the formation of synapses with their postsynaptic partners, the ganglionic sympathetic neurons. Recombinant CRD-NRG mimics the effects of presynaptic input on target neurons. Functional deletion of CRD-NRG from presynaptic neurons abolishes the upregulation of nAChR expression induced by input-derived soluble material. Thus, CRD-NRG appears to be both a necessary and a sufficient signal for the control of neuronal nAChR expression during synaptogenesis. Title: [Observations on damage and regeneration of corneal nerves of rabbit eyes with herpes simplex keratitis]. [Chinese] Wang D, Wang C, Yang X Ref: Chinese Journal of Ophthalmology, 31:52, 1995 : PubMed ESTHER: Wang_1995_Chung.Hua.Yen.Ko.Tsa.Chih_31_52 PubMedSearch: Wang 1995 Chung.Hua.Yen.Ko.Tsa.Chih 31 52 PubMedID: 7781429 Abstract An experimental study on the damage and regeneration of the corneal sensory nerves in rabbit eyes with herpes simplex keratitis (HSK) was carried out by means of acetylcholine esterase staining and transmission electron microscopy. The results indicate that the diminution of the corneal sensitivity detected clinically in HSK is caused by the damage of the terminals of the sensory nerve plexus in the epithelial and subepithelial layers of the cornea and in the later stage of HSK, the corneal sensory nerves begin to regenerate, that is the basis of the restoration of corneal sensitivity. Title: Developmental regulation of multiple nicotinic AChR channel subtypes in embryonic chick habenula neurons: contributions of both the alpha 2 and alpha 4 subunit genes Brussaard AB, Yang X, Doyle JP, Huck S, Role LW Ref: Pflugers Arch, 429:27, 1994 : PubMed ESTHER: Brussaard_1994_Pflugers.Arch_429_27 PubMedSearch: Brussaard 1994 Pflugers.Arch 429 27 PubMedID: 7708479 Abstract Habenula neurons from both early and late stage embryonic chickens express multiple subtypes of nicotinic acetylcholine receptor channels (nAChRs). The channel subtypes expressed by habenula neurons are similar in functional properties, but apparently distinct in subunit composition, from their peripheral counterparts in autonomic ganglia. Early in development, nicotine activates four classes of neuronal bungarotoxin (nBGT)-sensitive channels (approx. conductance = 15, 30, 50, 60pS) that are intermingled on the surface of habenula neuronal somata. In neurons removed from older animals, nAChR channel activity has increased 4- to 40-fold and channel subtypes have become spatially segregated from one another. Analysis of the profile of nAChR subunit gene expression by polymerase chain reaction indicates that several of the alpha-type subunit genes, including alpha 2,3,4,5,7, and alpha 8, as well as both beta 2 and beta 4, are expressed. Treatment of the neurons with subunit specific antisense oligonucleotides reveals that the alpha 2 and alpha 4 (but not alpha 3) subunits contribute to the functional profile of native nAChRs expressed by habenula neurons. Consideration of the functional properties and apparent subunit composition of autonomic ganglion nAChRs in the chick suggests that habenula neurons may utilize a very distinct set of subunit combinations to produce an array of nAChR channel subtypes similar in both conductance and pharmacological profile to those expressed by sympathetic neurons. Title: Effects of dietary fatty acids on growth, feed efficiency and liver RNA and DNA content of Arctic charr, Salvelinus alpinus (L.) Yang X, Dick TA Ref: Aquaculture, 116:57, 1993 : PubMed Title: Uptake of antisense oligonucleotides and functional block of acetylcholine receptor subunit gene expression in primary embryonic neurons Yu C, Brussaard AB, Yang X, Listerud M, Role LW Ref: Dev Genet, 14:296, 1993 : PubMed ESTHER: Yu_1993_Dev.Genet_14_296 PubMedSearch: Yu 1993 Dev.Genet 14 296 PubMedID: 7693387 Abstract Several recent studies have used antisense oligonucleotides in the nervous system to probe the functional role of particular gene products. Since antisense oligonucleotide-mediated block of gene expression typically involves uptake of the oligonucleotides, we have characterized the mechanism of this uptake into developing neurons from embryonic chickens. Antisense oligonucleotides (15 mers) added to the bathing media are taken up into the embryonic chicken sympathetic neurons maintained in vitro. A portion of the oligonucleotide uptake is temperature dependent and saturates at extracellular oligonucleotide concentrations > or = 20 microM. This temperature sensitive, saturable component is effectively completed by single nucleotides of ATP and AMP and is reminiscent of receptor-mediated endocytosis of oligonucleotides described in non-neuronal cells. The efficiency of the oligonucleotide uptake system is dependent on the developmental stage of the animal but independent of the number of days that the neurons are maintained in vitro. Following the uptake of antisense oligonucleotides directed against ion channel subunit genes expressed by these neurons (nicotinic acetylcholine receptor subunit alpha 3; nAChR alpha 3), biophysical assays reveal that the functional expression of the target gene is largely blocked. Thus the number of wild type nAChR channels expressed is decreased by approximately 80%-90%. Furthermore, following antisense deletion of alpha 3, "mutant" nAChRs with distinct functional characteristics are expressed. In sum, these studies characterize the uptake of antisense oligonucleotide and demonstrate the functional block of specific gene expression in primary developing neurons. | |||||||
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