Yao Y

References (49)

Title : Characterization and validation of fatty acid metabolism-related genes predicting prognosis, immune infiltration, and drug sensitivity in endometrial cancer - Li_2024_Biotechnol.Appl.Biochem__
Author(s) : Li H , Zhou T , Zhang Q , Yao Y , Hua T , Zhang J , Wang H
Ref : Biotechnol Appl Biochem , : , 2024
Abstract : Endometrial cancer is considered to be the second most common tumor of the female reproductive system, and patients diagnosed with advanced endometrial cancer have a poor prognosis. The influence of fatty acid metabolism in the prognosis of patients with endometrial cancer remains unclear. We constructed a prognostic risk model using transcriptome sequencing data of endometrial cancer and clinical information of patients from The Cancer Genome Atlas (TCGA) database via least absolute shrinkage and selection operator regression analysis. The tumor immune microenvironment was analyzed using the CIBERSORT algorithm, followed by functional analysis and immunotherapy efficacy prediction by gene set variation analysis. The role of model genes in regulating endometrial cancer in vitro was verified by CCK-8, colony formation, wound healing, and transabdominal invasion assays, and verified in vivo by subcutaneous tumor transplantation in nude mice. A prognostic model containing 14 genes was constructed and validated in 3 cohorts and clinical samples. The results showed differences in the infiltration of immune cells between the high-risk and low-risk groups, and that the high-risk group may respond better to immunotherapy. Experiments in vitro confirmed that knockdown of epoxide hydrolase 2 (EPHX2) and acyl-CoA oxidase like (ACOXL) had an inhibitory effect on EC cells, as did overexpression of hematopoietic prostaglandin D synthase (HPGDS). The same results were obtained in experiments in vivo. Prognostic models related to fatty acid metabolism can be used for the risk assessment of endometrial cancer patients. Experiments in vitro and in vivo confirmed that the key genes HPGDS, EPHX2, and ACOXL in the prognostic model may affect the development of endometrial cancer.
ESTHER : Li_2024_Biotechnol.Appl.Biochem__
PubMedSearch : Li_2024_Biotechnol.Appl.Biochem__
PubMedID: 38616327

Title : Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections - Xiao_2024_J.Control.Release_369_39
Author(s) : Xiao J , Yin M , Yang M , Ren J , Liu C , Lian J , Lu X , Jiang Y , Yao Y , Luo J
Ref : J Control Release , 369 :39 , 2024
Abstract : The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.
ESTHER : Xiao_2024_J.Control.Release_369_39
PubMedSearch : Xiao_2024_J.Control.Release_369_39
PubMedID: 38508523

Title : The value of cholinesterase inhibitors for improving neuropsychiatric and functional assessment scores in patients with alzheimer disease: a systematic review and meta-analysis of on placebo-controlled RCTs - Zhang_2024_Int.J.Surg__
Author(s) : Zhang Y , Sun Y , Hu X , Yao Y , Wang J
Ref : Int J Surg , : , 2024
Abstract : INTRODUCTION: At present, increasing reports from different aspects indicated that cholinesterase inhibitors (ChEIs) may be effective on improving neuropsychiatric and functional assessment scores in patients with Alzheimer disease (AD). However, no studies comprehensively and detailedly evaluated the effect of ChEIs on AD. The present analysis was designed to comprehensively evaluate the efficacy and safety of ChEIs for AD. METHODS: Two independent researchers systematically reviewed 1096 searching records in PubMed, Embase, Cochrane Library and Web of Science from inception to May 10, 2023, and finally identified 12 randomized, double-blind, placebo-controlled trials with 6908 participants according to predetermined inclusion and exclusion criteria. The effects were assessed with standardized mean difference (SMD) or odds ratio (OR). The primary outcomes were the mean change and least squares (LS) mean change from baseline to endpoint of neuropsychiatric and functional assessment scores. The secondary outcome was adverse events of ChEIs when compared to placebo for patients with AD. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2 and and Stata 12.0. RESULTS: Pooled analysis indicated that ChEIs significantly improved the assessment scores of the AD Assessment Scale (ADAS) (SMD -1.57; 95% CI -2.64 to -0.51), Clinician's Interview-Based Impression of Change-Plus caregiver input (CIBIC-Plus) (SMD -0.28; 95% CI -0.41 to -0.15), the Neuropsychiatric Inventory (NPI) (both SMD -1.67; 95% CI -2.88 to -0.47 for 10-tiem total score and SMD -1.83; 95% CI -3.25 to -0.42 for 12-tiem total score), and the AD Cooperative Study-Activities of Daily Living (ADCS-ADL) total score (SMD 2.44; 95% CI 1.29 to 3.59), evaluated with mean change from baseline to endpoint. In addition, when evaluated with the LS mean change from baseline to endpoint, ChEIs significantly improved Mini-Mental State Examination (MMSE) total score, the Clinician Interview-Based Impression of Severity, CIBIC-Plus, ADCS-ADL total score, NPI, ADAS. Regarding to adverse events (AEs) of patients with AD, it indicated that compared to placebo, ChEIs did not increase the frequency of severe and serious AEs (fatal or nonfatal) as well as the incidence of death. CONCLUSIONS: Our analysis indicated that ChEIs treatment generally improved neuropsychiatric and functional assessment scores in patients with AD though opposite result was observed in Wechsler Memory Scale. ChEIs had an acceptable safety profile in patients with AD without increasing of any crucial adverse or outcomes.
ESTHER : Zhang_2024_Int.J.Surg__
PubMedSearch : Zhang_2024_Int.J.Surg__
PubMedID: 38573101

Title : Curcumin hybrid molecules for the treatment of Alzheimer's disease: Structure and pharmacological activities - Zang_2023_Eur.J.Med.Chem_265_116070
Author(s) : Zang WB , Wei HL , Zhang WW , Ma W , Li J , Yao Y
Ref : Eur Journal of Medicinal Chemistry , 265 :116070 , 2023
Abstract : Alzheimer's disease (AD) is the most common neurodegenerative disease among the elderly. Contemporary treatments can only relieve symptoms but fail to delay disease progression. Curcumin is a naturally derived compound that has demonstrated significant therapeutic effects in AD treatment. Recently, molecular hybridization has been utilized to combine the pharmacophoric groups present in curcumin with those of other AD drugs, resulting in a series of novel compounds that enhance the therapeutic efficacy through multiple mechanisms. In this review, we firstly provide a concise summary of various pathogenetic hypotheses of AD and the mechanism of action of curcumin in AD, as well as the concept of molecular hybridization. Subsequently, we focus on the recent development of hybrid molecules derived from curcumin, summarizing their structures and pharmacological activities, including cholinesterase inhibitory activity, Abeta aggregation inhibitory activity, antioxidant activity, and other activities. The structure-activity relationships were further discussed.
ESTHER : Zang_2023_Eur.J.Med.Chem_265_116070
PubMedSearch : Zang_2023_Eur.J.Med.Chem_265_116070
PubMedID: 38134747

Title : Prediction of treatment response to antipsychotic drugs for precision medicine approach to schizophrenia: randomized trials and multiomics analysis - Guo_2023_Mil.Med.Res_10_24
Author(s) : Guo LK , Su Y , Zhang YY , Yu H , Lu Z , Li WQ , Yang YF , Xiao X , Yan H , Lu TL , Li J , Liao YD , Kang ZW , Wang LF , Li Y , Li M , Liu B , Huang HL , Lv LX , Yao Y , Tan YL , Breen G , Everall I , Wang HX , Huang Z , Zhang D , Yue WH
Ref : Mil Med Res , 10 :24 , 2023
Abstract : BACKGROUND: Choosing the appropriate antipsychotic drug (APD) treatment for patients with schizophrenia (SCZ) can be challenging, as the treatment response to APD is highly variable and difficult to predict due to the lack of effective biomarkers. Previous studies have indicated the association between treatment response and genetic and epigenetic factors, but no effective biomarkers have been identified. Hence, further research is imperative to enhance precision medicine in SCZ treatment. METHODS: Participants with SCZ were recruited from two randomized trials. The discovery cohort was recruited from the CAPOC trial (n = 2307) involved 6 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, Quetiapine, Aripiprazole, Ziprasidone, and Haloperidol/Perphenazine (subsequently equally assigned to one or the other) groups. The external validation cohort was recruited from the CAPEC trial (n = 1379), which involved 8 weeks of treatment and equally randomized the participants to the Olanzapine, Risperidone, and Aripiprazole groups. Additionally, healthy controls (n = 275) from the local community were utilized as a genetic/epigenetic reference. The genetic and epigenetic (DNA methylation) risks of SCZ were assessed using the polygenic risk score (PRS) and polymethylation score, respectively. The study also examined the genetic-epigenetic interactions with treatment response through differential methylation analysis, methylation quantitative trait loci, colocalization, and promoter-anchored chromatin interaction. Machine learning was used to develop a prediction model for treatment response, which was evaluated for accuracy and clinical benefit using the area under curve (AUC) for classification, R(2) for regression, and decision curve analysis. RESULTS: Six risk genes for SCZ (LINC01795, DDHD2, SBNO1, KCNG2, SEMA7A, and RUFY1) involved in cortical morphology were identified as having a genetic-epigenetic interaction associated with treatment response. The developed and externally validated prediction model, which incorporated clinical information, PRS, genetic risk score (GRS), and proxy methylation level (proxyDNAm), demonstrated positive benefits for a wide range of patients receiving different APDs, regardless of sex [discovery cohort: AUC = 0.874 (95% CI 0.867-0.881), R(2) = 0.478; external validation cohort: AUC = 0.851 (95% CI 0.841-0.861), R(2) = 0.507]. CONCLUSIONS: This study presents a promising precision medicine approach to evaluate treatment response, which has the potential to aid clinicians in making informed decisions about APD treatment for patients with SCZ. Trial registration Chinese Clinical Trial Registry ( https://www.chictr.org.cn/ ), 18. Aug 2009 retrospectively registered: CAPOC-ChiCTR-RNC-09000521 ( https://www.chictr.org.cn/showproj.aspx?proj=9014 ), CAPEC-ChiCTR-RNC-09000522 ( https://www.chictr.org.cn/showproj.aspx?proj=9013 ).
ESTHER : Guo_2023_Mil.Med.Res_10_24
PubMedSearch : Guo_2023_Mil.Med.Res_10_24
PubMedID: 37269009

Title : Prognostic and Immunological Roles of CES2 in Breast Cancer and Potential Application of CES2-Targeted Fluorescent Probe DDAB in Breast Surgery - Qu_2023_Int.J.Gen.Med_16_1567
Author(s) : Qu W , Yao Y , Liu Y , Jo H , Zhang Q , Zhao H
Ref : Int J Gen Med , 16 :1567 , 2023
Abstract : PURPOSE: The expression and function of CES2 in breast cancer (BRCA) has not been fully elucidated. The purpose of this study was to investigate its clinical significance in BRCA. PATIENTS AND METHODS: Bioinformatics analysis tools and databases, including The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) databases, SURVIVAL packages, STRING database, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene set variation analysis (GSVA), and Tumor Immunity Estimation Resource (TIMER), were utilized to measure the expression level and clarify the clinical significance of CES2 in BRCA. In addition, we verified the expression level of CES2 in BRCA at the cellular and tissue levels by Western blot, immunohistochemistry (IHC) and real-time fluorescence quantitative PCR assays. Furthermore, DDAB is the first reported near-infrared fluorescent probe that can be used to monitor CES2 in vivo. We applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time and verified its physicochemical properties and labeling sorting ability by CCK-8, cytofluorimetric imaging, flow cytometry fluorescence detection, and isolated human tumor tissue imaging assays. RESULTS: The expression of CES2 was higher in normal tissues than that in BRCA tissues. Patients with lower CES2 expression in the BRCA T4 stage had a poorer prognosis. Finally, we applied the CES2-targeted fluorescent probe DDAB in BRCA for the first time, which was demonstrated to have good cellular imaging performance with low biological toxicity in BRCA cells and ex vivo human breast tumor tissue models. CONCLUSION: CES2 can be considered a potential biomarker to predict the prognosis of breast cancer at stage T4 and might contribute to the development of immunological treatment strategies. Meanwhile, CES2 is able to distinguish between breast normal and tumor tissues, the CES2-targeting NIR fluorescent probe DDAB may have potential for surgical applications in BRCA.
ESTHER : Qu_2023_Int.J.Gen.Med_16_1567
PubMedSearch : Qu_2023_Int.J.Gen.Med_16_1567
PubMedID: 37139258
Gene_locus related to this paper: human-CES2

Title : Investigating the Regulatory Mechanism of the Sesquiterpenol Nerolidol from a Plant on Juvenile Hormone-Related Genes in the Insect Spodoptera exigua - Dai_2023_Int.J.Mol.Sci_24_
Author(s) : Dai H , Liu B , Yang L , Yao Y , Liu M , Xiao W , Li S , Ji R , Sun Y
Ref : Int J Mol Sci , 24 : , 2023
Abstract : Various plant species contain terpene secondary metabolites, which disrupt insect growth and development by affecting the activity of juvenile hormone-degrading enzymes, and the juvenile hormone (JH) titers maintained in insects. Nerolidol, a natural sesquiterpenol belonging to the terpenoid group, exhibits structural similarities to insect JHs. However, the impact of nerolidol on insect growth and development, as well as its underlying molecular mechanism, remains unclear. Here, the effects of nerolidol on Spodoptera exigua were investigated under treatment at various sub-lethal doses (4.0 mg/mL, 1.0 mg/mL, 0.25 mg/mL). We found that a higher dose (4.0 mg/mL) of nerolidol significantly impaired the normal growth, development, and population reproduction of S. exigua, although a relatively lower dose (0.25 mg/mL) of nerolidol had no significant effect on this growth and development. Combined transcriptome sequencing and gene family analysis further revealed that four juvenile hormone esterase (JHE)-family genes that are involved in juvenile hormone degradation were significantly altered in S. exigua larvae after nerolidol treatment (4.0 mg/mL). Interestingly, the juvenile hormone esterase-like (JHEL) gene Sexi006721, a critical element responsive to nerolidol stress, was closely linked with the significant augmentation of JHE activity and JH titer in S. exigua (R(2) = 0.94, p < 0.01). Taken together, we speculate that nerolidol can function as an analog of JH by modulating the expression of the enzyme genes responsible for degrading JH, resulting in JH disorders and ultimately disrupting the development of insect larvae. This study ultimately provides a theoretical basis for the sustainable control of S. exigua in the field whilst proposing a new perspective for the development of novel biological pesticides.
ESTHER : Dai_2023_Int.J.Mol.Sci_24_
PubMedSearch : Dai_2023_Int.J.Mol.Sci_24_
PubMedID: 37686136

Title : Therapeutic effects of total saikosaponins from Radix bupleuri against Alzheimer's disease - Li_2022_Front.Pharmacol_13_940999
Author(s) : Li J , Zou B , Cheng XY , Yang XH , Zhao CH , Ma RX , Tian JX , Yao Y
Ref : Front Pharmacol , 13 :940999 , 2022
Abstract : Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory loss and cognitive dysfunction in the elderly, with amyloid-beta (Abeta) deposition and hyperphosphorylation of tau protein as the main pathological feature. Nuclear factor 2 (Nrf2) is a transcription factor that primarily exists in the cytosol of hippocampal neurons, and it is considered as an important regulator of autophagy, oxidative stress, and inflammation. Total saikosaponins (TS) is the main bioactive component of Radix bupleuri (Chaihu). In this study, it was found that TS could ameliorate cognitive dysfunction in APP/PS1 transgenic mice and reduce Abeta generation and senile plaque deposition via activating Nrf2 and downregulating the expression of beta-secretase 1 (BACE1). In addition, TS can enhance autophagy by promoting the expression of Beclin-1 and LC3-II, increasing the degradation of p62 and NDP52 and the clearance of phosphorylated tau (p-tau), and reducing the expression of p-tau. It can also downregulate the expression of nuclear factor-kappaB (NF-kappaB) to inhibit the activation of glial cells and reduce the release of inflammatory factors. In vitro experiments using PC12 cells induced by Abeta, TS could significantly inhibit the aggregation of Abeta and reduce cytotoxicity. It was found that Nrf2 knock-out weakened the inhibitory effect of TS on BACE1 and NF-kappaB transcription in PC12 cells. Moreover, the inhibitory effect of TS on BACE1 transcription was achieved by promoting the binding of Nrf2 and the promoter of BACE1 ARE1. Results showed that TS downregulated the expression of BACE1 and NF-kappaB through Nrf2, thereby reducing the generation of Abeta and inhibiting neuroinflammation. Furthermore, TS can ameliorate synaptic loss and alleviate oxidative stress. In gut microbiota analysis, dysbiosis was demonstrated in APP/PS1 transgenic mice, indicating a potential link between gut microbiota and AD. Furthermore, TS treatment reverses the gut microbiota disorder in APP/PS1 mice, suggesting a therapeutic strategy by remodeling the gut microbe. Collectively, these data shows that TS may serve as a potential approach for AD treatment. Further investigation is needed to clarify the detailed mechanisms underlying TS regulating gut microbiota and oxidative stress.
ESTHER : Li_2022_Front.Pharmacol_13_940999
PubMedSearch : Li_2022_Front.Pharmacol_13_940999
PubMedID: 35935875

Title : Biodegradation of highly crystallized poly(ethylene terephthalate) through cell surface codisplay of bacterial PETase and hydrophobin - Chen_2022_Nat.Commun_13_7138
Author(s) : Chen Z , Duan R , Xiao Y , Wei Y , Zhang H , Sun X , Wang S , Cheng Y , Wang X , Tong S , Yao Y , Zhu C , Yang H , Wang Y , Wang Z
Ref : Nat Commun , 13 :7138 , 2022
Abstract : The process of recycling poly(ethylene terephthalate) (PET) remains a major challenge due to the enzymatic degradation of high-crystallinity PET (hcPET). Recently, a bacterial PET-degrading enzyme, PETase, was found to have the ability to degrade the hcPET, but with low enzymatic activity. Here we present an engineered whole-cell biocatalyst to simulate both the adsorption and degradation steps in the enzymatic degradation process of PETase to achieve the efficient degradation of hcPET. Our data shows that the adhesive unit hydrophobin and degradation unit PETase are functionally displayed on the surface of yeast cells. The turnover rate of the whole-cell biocatalyst toward hcPET (crystallinity of 45%) dramatically increases approximately 328.8-fold compared with that of purified PETase at 30 degreesC. In addition, molecular dynamics simulations explain how the enhanced adhesion can promote the enzymatic degradation of PET. This study demonstrates engineering the whole-cell catalyst is an efficient strategy for biodegradation of PET.
ESTHER : Chen_2022_Nat.Commun_13_7138
PubMedSearch : Chen_2022_Nat.Commun_13_7138
PubMedID: 36414665
Gene_locus related to this paper: idesa-peth

Title : An RDH-Plin2 axis modulates lipid droplet size by antagonizing Bmm lipase - Zhao_2022_EMBO.Rep__e52669
Author(s) : Zhao X , Wang W , Yao Y , Li X , Huang X , Wang Y , Ding M
Ref : EMBO Rep , :e52669 , 2022
Abstract : The size of lipid droplets varies greatly in vivo and is determined by both intrinsic and extrinsic factors. From an RNAi screen in Drosophila, we found that knocking down subunits of COP9 signalosome (CSN) results in enlarged lipid droplets under high-fat, but not normal, conditions. We identified CG2064, a retinol dehydrogenase (RDH) homolog, as the proteasomal degradation target of CSN in regulating lipid droplet size. RDH/CG2064 interacts with the lipid droplet-resident protein Plin2 and the RDH/CG2064-Plin2 axis acts to reduce the overall level and lipid droplet localization of Bmm/ATGL lipase. This axis is important for larval survival under prolonged starvation. Thus, we discovered an RDH-Plin2 axis modulates lipid droplet size.
ESTHER : Zhao_2022_EMBO.Rep__e52669
PubMedSearch : Zhao_2022_EMBO.Rep__e52669
PubMedID: 35132760

Title : A Proof-of-Concept Inhibitor of Endothelial Lipase Suppresses Triple-Negative Breast Cancer Cells by Hijacking the Mitochondrial Function - Yang_2022_Cancers.(Basel)_14_3763
Author(s) : Yang R , Han S , Clayton J , Haghighatian M , Tsai CC , Yao Y , Li P , Shen J , Zhou Q
Ref : Cancers (Basel) , 14 :3763 , 2022
Abstract : Triple-negative breast cancer (TNBC) cells reprogram their metabolism to provide metabolic flexibility for tumor cell growth and survival in the tumor microenvironment. While our previous findings indicated that endothelial lipase (EL/LIPG) is a hallmark of TNBC, the precise mechanism through which LIPG instigates TNBC metabolism remains undefined. Here, we report that the expression of LIPG is associated with long non-coding RNA DANCR and positively correlates with gene signatures of mitochondrial metabolism-oxidative phosphorylation (OXPHOS). DANCR binds to LIPG, enabling tumor cells to maintain LIPG protein stability and OXPHOS. As one mechanism of LIPG in the regulation of tumor cell oxidative metabolism, LIPG mediates histone deacetylase 6 (HDAC6) and histone acetylation, which contribute to changes in IL-6 and fatty acid synthesis gene expression. Finally, aided by a relaxed docking approach, we discovered a new LIPG inhibitor, cynaroside, that effectively suppressed the enzyme activity and DANCR in TNBC cells. Treatment with cynaroside inhibited the OXPHOS phenotype of TNBC cells, which severely impaired tumor formation. Taken together, our study provides mechanistic insights into the LIPG modulation of mitochondrial metabolism in TNBC and a proof-of-concept that targeting LIPG is a promising new therapeutic strategy for the treatment of TNBC.
ESTHER : Yang_2022_Cancers.(Basel)_14_3763
PubMedSearch : Yang_2022_Cancers.(Basel)_14_3763
PubMedID: 35954428
Gene_locus related to this paper: human-LIPG

Title : Identification of Novel Organophosphate Esters in Hydroponic Lettuces (Lactuca sativa L.): Biotransformation and Acropetal Translocation - Li_2022_Environ.Sci.Technol__
Author(s) : Li X , Yao Y , Chen H , Zhang Q , Li C , Zhao L , Guo S , Cheng Z , Wang Y , Wang L , Sun H
Ref : Environ Sci Technol , : , 2022
Abstract : The absorption, translocation, and biotransformation behaviors of organophosphate esters (OPEs) and diesters (OPdEs) in a hydroponic system were investigated. The lateral root was found as the main accumulation and biotransformation place of OPEs and OPdEs in lettuce. The nontarget analysis using high-resolution mass spectrometry revealed five hydroxylated metabolites and five conjugating metabolites in the OPE exposure group, among which methylation, acetylation, and palmitoyl conjugating OPEs were reported as metabolites for the first time. Particularly, methylation on phosphate can be a significant process for plant metabolism, and methyl diphenyl phosphate (MDPP) accounted for the majority of metabolites. The translocation factor values of most identified OPE metabolites are negatively associated with their predicted logarithmic octanol-water partitioning coefficient (log K(ow)) values (0.75-2.45), indicating that hydrophilicity is a dominant factor in the translocation of OPE metabolites in lettuce. In contrast, palmitoyl conjugation may lead to an enhanced acropetal translocation and those with log K(ow) values < 0 may have limited translocation potential. Additionally, OPE diesters produced from the biotransformation of OPEs in lettuce showed a higher acropetal translocation potential than those exposed directly. These results further emphasize the necessity to consider biotransformation as an utmost important factor in the accumulation and acropetal translocation potential of OPEs in plants.
ESTHER : Li_2022_Environ.Sci.Technol__
PubMedSearch : Li_2022_Environ.Sci.Technol__
PubMedID: 35849551

Title : Isolation, sequencing of the HvnHID gene and its role in the purple-grain colour development in Tibetan hulless barley - Yao_2021_Czech.J.Genet.Plant.Breed__
Author(s) : Yao X , Su L , Yao Y , An L , Bai Y , Li X , Wu K
Ref : _Czech J Genet Plant Breed , : , 2021
Abstract : 2-hydroxyisoflavanone dehydratase (HID) plays an important role in isoflavone biosynthesis. In this study, HID was isolated from the seeds of the purple-grained Tibetan hulless barley variety Nerumuzha and the white-grained variety Kunlun 10. The HvnHID gene includes the 981 bp open reading frame and encodes a protein of 327 amino acids. It has a typical Abhydrolase_3 domain (78-306) and belongs to the carboxylesterase (CXE) family of the Abhydrolase_3 (alpha/beta hydrolase) superfamily. There are eight nucleotide differences in the HvnHID coding sequence and two amino acid differences (one in the Abhydrolase_3 domain) between Nerumuzha and Kunlun 10. The HvnHID of hulless barley has the closest relationship with the HID in Hordeum vulgare, and the most distant relationship in Panicum hallii. At the early-mid stage of the seed colour development, the HvnHID expression levels in the purple and black seeds were significantly higher than in the white and blue ones (P < 0.01). During the seed colour development of purple-grained hulless barley, the expression of the key genes (HvnF3'H, HvnDRF, HvnANT1, and HvnGT) in the anthocyanidin biosynthetic pathway increased significantly, while the HvnHID expression decreased significantly (P < 0.01). Thus, it is likely that HvnHID negatively regulates the anthocyanidin biosynthesis. This result provides an important basis for further study of the biological functions of HvnHID in the anthocyanidin biosynthetic pathway.
ESTHER : Yao_2021_Czech.J.Genet.Plant.Breed__
PubMedSearch : Yao_2021_Czech.J.Genet.Plant.Breed__
PubMedID:
Gene_locus related to this paper: horvv-f2da29

Title : Improving the production of AHL lactonase AiiO-AIO6 from Ochrobactrum sp. M231 in intracellular protease-deficient Bacillus subtilis - Xia_2020_AMB.Express_10_138
Author(s) : Xia R , Yang Y , Pan X , Gao C , Yao Y , Liu X , Teame T , Zhang F , Hu J , Ran C , Zhang Z , Liu-Clarke J , Zhou Z
Ref : AMB Express , 10 :138 , 2020
Abstract : Quorum quenching (QQ) blocks bacterial cell-to-cell communication (i.e., quorum sensing), and is a promising antipathogenic strategy to control bacterial infection via inhibition of virulence factor expression and biofilm formation. QQ enzyme AiiO-AIO6 from Ochrobactrum sp. M231 has several excellent properties and shows biotherapeutic potential against important bacterial pathogens of aquatic species. AiiO-AIO6 can be secretory expressed in Bacillus subtilis via a non-classical secretion pathway. To improve AiiO-AIO6 production, four intracellular protease-deletion mutants of B. subtilis 1A751 were constructed by individually knocking out the intracellular protease-encoding genes (tepA, ymfH, yrrN and ywpE). The AiiO-AIO6 expression plasmid pWB-AIO6BS was transformed into the B. subtilis 1A751 and its four intracellular protease-deletion derivatives. Results showed that all recombinant intracellular protease-deletion derivatives (BStepA, BSymfH, BSyrrN and BSywpE) had a positive impact on AiiO-AIO6 production. The highest amount of AiiO-AIO6 extracellular production of BSywpE in shake flask reached 1416.47 U/mL/OD(600), which was about 121% higher than that of the wild-type strain. Furthermore, LC-MS/MS analysis of the degrading products of 3-oxo-C8-HSL by purification of AiiO-AIO6 indicated that AiiO-AIO6 was an AHL-lactonase which hydrolyzes the lactone ring of AHLs. Phylogenetic analysis showed that AiiO-AIO6 was classified as a member of the alpha/beta hydrolase family with a conserved "nucleophile-acid-histidine" catalytic triad. In summary, this study showed that intracellular proteases were responsible for the reduced yields of heterologous proteins and provided an efficient strategy to enhance the extracellular production of AHL lactonase AiiO-AIO6.
ESTHER : Xia_2020_AMB.Express_10_138
PubMedSearch : Xia_2020_AMB.Express_10_138
PubMedID: 32757095
Gene_locus related to this paper: ocha4-a6wx49

Title : Inhibition of LIPG phospholipase activity suppresses tumor formation of human basal-like triple-negative breast cancer - Lo_2020_Sci.Rep_10_8911
Author(s) : Lo PK , Yao Y , Zhou Q
Ref : Sci Rep , 10 :8911 , 2020
Abstract : The endothelial lipase LIPG possesses serine phospholipase activity and is involved in lipoprotein metabolism. Our previous studies have revealed that LIPG overexpression is required for tumor formation and metastasis of human basal-like triple-negative breast cancer (TNBC). We also demonstrated that LIPG differentially regulates TNBC malignancy through its enzymatic and non-enzymatic functions. The present studies were aimed at determining how XEN445, a specific inhibitor targeting LIPG phospholipase activity, impacts on TNBC tumor formation and malignant features. We established a cell-based LIPG enzymatic assay system to measure the inhibitory effect of XEN445 on LIPG phospholipase activity and determine its IC50. We found that XEN445 preferentially inhibited the proliferation of LIPG-expressing TNBC cells but not LIPG-negative luminal breast cancer cells. XEN445 inhibited the self-renewal of cancer stem cells (CSCs) in vitro and TNBC tumor formation in vivo. However, XEN445 had no inhibitory effect on the invasiveness and CSC stemness of TNBC cells. Our studies suggest that targeting both LIPG enzymatic and non-enzymatic functions is an important strategy for the treatment of TNBC.
ESTHER : Lo_2020_Sci.Rep_10_8911
PubMedSearch : Lo_2020_Sci.Rep_10_8911
PubMedID: 32488004

Title : Candidate detoxification-related genes in brown planthopper, Nilaparvata lugens, in response to beta-asarone based on transcriptomic analysis - Xu_2019_Ecotoxicol.Environ.Saf_185_109735
Author(s) : Xu X , Li X , Wang F , Han K , Liu Z , Fan L , Hua H , Cai W , Yao Y
Ref : Ecotoxicology & Environmental Safety , 185 :109735 , 2019
Abstract : Nilaparvata lugens(Stal) is a serious pest of rice and has evolved different levels of resistance against most chemical pesticides. beta-asarone is the main bioactive insecticidal compound of Acorus calamus L. that shows strong insecticidal activity against pests. In this study, we conducted a bioassay experiment to determine the contact toxicity of beta-asarone to N. lugens nymphs. The LD30 sublethal dose was 0.106mug per nymph, with 95% confidence limits of 0.070-0.140mug. We applied the LD30 concentration of beta-asarone to nymphs for 24h or 72h and then performed a transcriptome sequence analysis by referencing the N. lugens genome to characterize the variation. The transcriptomic analysis showed that several GO terms and KEGG pathways presented significant changes. Individually, 126 differentially expressed genes (DEGs), including 72 upregulated and 54 downregulated genes, were identified at 24h, and 1771 DEGs, including 882 upregulated and 889 downregulated genes, were identified at 72h. From the DEGs, we identified a total of 40 detoxification-related genes, including eighteen Cytochrome P450 monooxygenase genes (P450s), three Glutathione S-transferase genes, one Carboxylesterase gene, twelve UDP-glucosyltransferases and six ATP-binding cassette genes. We selected the eighteen P450s for subsequent verification by quantitative PCR. These findings indicated that beta-asarone presented strong contact toxicity to N. lugens nymphs and induced obvious variation of detoxification-related genes that may be involved in the response to beta-asarone.
ESTHER : Xu_2019_Ecotoxicol.Environ.Saf_185_109735
PubMedSearch : Xu_2019_Ecotoxicol.Environ.Saf_185_109735
PubMedID: 31586846

Title : A highly sensitive and low-background fluorescence assay for pesticides residues based on hybridization chain reaction amplification assisted by magnetic separation - Yao_2019_Methods.Appl.Fluoresc_7_035006
Author(s) : Yao Y , Liu Y , Zhang H , Wang X
Ref : Methods Appl Fluoresc , 7 :035006 , 2019
Abstract : Due to the concern over food safety, it is important to detect the pesticides residues in agricultural products. Here, a highly sensitive and low background fluorescent strategy for the detection of pesticides residues has been developed. The fluorescence intensity of N-methyl mesoporphyrin IX (NMM) binding G-quadruplex could be turn off because of inhibiting effect of the pesticides on the acetylcholinesterase (AChE) activity. For that, four single-stranded DNAs (named linker, trigger, H1 and H2, respectively) are rational designed and T-Hg-T mismatches duplex DNAs as a recognizer combined with the separation of magnetic beads. The design of hybridization chain reaction (HCR) amplification strategy assisted by magnetic separation has been adopted to improve the detection sensitivity. In the presence of pesticides, the amount of the thiol group generated by hydrolysis reaction of acetylcholine (ACh) is reduced, lead to release of less trigger DNA. Therefor subsequent HCR process is retarded with decreased fluorescence intensity. The reduced fluorescence intensity has a quantitative relationship with the pesticide concentration. The limit of detection of chlorpyrifos was estimated to be 2.0 ng ml(-1). It has been applied to detect the pesticides residues in real samples.
ESTHER : Yao_2019_Methods.Appl.Fluoresc_7_035006
PubMedSearch : Yao_2019_Methods.Appl.Fluoresc_7_035006
PubMedID: 31042679

Title : Insights into the improvement of the enzymatic hydrolysis of bovine bone protein using lipase pretreatment - Yao_2019_Food.Chem_302_125199
Author(s) : Yao Y , Wang M , Liu Y , Han L , Liu X
Ref : Food Chem , 302 :125199 , 2019
Abstract : Animal bones are a high-quality source of protein and comprehensive nutrients and improper handling can cause resource wasting and environmental issues. Pretreatment before enzymatic hydrolysis of bone could significantly improve the enzymolytic efficiency, which is an essential step to achieve high value-added utilization of bones. This study investigated the effect of lipase pretreatment on the enzymatic hydrolysis of bones. The degree of hydrolysis after lipase pretreatment was 12.58%, which was 8.19% higher than that without pretreatment. Lipase pretreatment was optimal at 9% substrate concentration and initial pH 7.5, with 0.08% lipase, followed by 4h incubation at 40 degrees C. Mechanism analysis indicated that lipase pretreatment improved the enzymolytic efficiency by significantly decreasing the lipid content, and changing the surface structure and surface element content of C, N, and O, promoting the attachment of alkaline protease onto the sample. Overall, lipase pretreatment was an effective method to reduce the costs of production.
ESTHER : Yao_2019_Food.Chem_302_125199
PubMedSearch : Yao_2019_Food.Chem_302_125199
PubMedID: 31400699

Title : Self-reduction bimetallic nanoparticles on ultrathin MXene nanosheets as functional platform for pesticide sensing - Zhao_2019_J.Hazard.Mater_384_121358
Author(s) : Zhao F , Yao Y , Jiang C , Shao Y , Barcelo D , Ying Y , Ping J
Ref : J Hazard Mater , 384 :121358 , 2019
Abstract : Two-dimensional (2D) transition metal carbides and nitrides, named MXene, appear promising application prospects in sensor filed. Metal nanoparticles, especially bimetallic nanoparticles, are the superior nanocatalyst, which process excellent features due to the high specific surface area and synergistic catalytic capacity. Using ultrathin MXene nanosheets as the natural reducing agent and support, we prepare the shape-controlled Au-Pd bimetallic nanoparticles via a self-reduction process at room temperature in a short time, which can well enhance the catalytic performance and are benefit for the acetylcholinesterase immobilization. Based on their desired properties, we propose a disposable electrochemical biosensor for the detection of organophosphorus pesticide using the multi-dimensional nanocomposites (MXene/Au-Pd) as the functional platform. Under the optimized conditions, our fabricated biosensor exhibits a favorable linear relationship with the concentration of paraoxon from 0.1 to 1000mugL(-1), with a low detection limit of 1.75ng L(-1). Furthermore, the biosensor can be applied for paraoxon detection in pear and cucumber samples, providing an effective and useful avenue for the applicability of novel 2D nanomaterials in biosensing field.
ESTHER : Zhao_2019_J.Hazard.Mater_384_121358
PubMedSearch : Zhao_2019_J.Hazard.Mater_384_121358
PubMedID: 31600694

Title : Time-dependent Expression and Distribution of AChE during the Skin Incised Wound Healing in Mice - Zhao_2019_Fa.Yi.Xue.Za.Zhi_35_143
Author(s) : Zhao JX , Jin X , Huang JJ , Yao Y , Yu LS , Fan YY
Ref : Fa Yi Xue Za Zhi , 35 :143 , 2019
Abstract : Abstract: Objective To study the time-dependent expression and distribution of acetylcholinesterase AChE during skin incised wound healing in mice, and discuss its effect in wound healing as well as the feasibility of using it as a reference index for wound age estimation. Methods A total of 45 C57BL/KsJ mice were randomly divided into one control group and eight incised groups. The skin incised wound model was established in the incised groups with samples of skin wounds taken at 6 h, 12 h, 1 d, 3 d, 5 d, 7 d, 10 d and 14 d post-injury respectively, while the uninjured skin tissue was extracted in the control group. Expression and distribution of AChE in skin samples were detected by immunohistochemistry, double immunofluorescence and Western blotting. Results Immunohistochemistry results indicated that AChE was mainly detected in infiltrating polymorphonuclear cells PMNs 6 to 12 h post-injury. A large number of AChE-positive mononuclear cells MNCs were observed 1 to 3 d post-injury. The AChE-positive cells were mainly fibroblastic cells FBCs 5 to 14 d post-injury. The ratio of the AChE-positive cells increased initially 6 h post-injury, and reached the peak at 1 d post-injury. Double immunofluorescent staining showed that the majority of AChE-positive MNCs and FBCs expressed macrophage marker and myofibroblast marker, respectively. Western blotting results showed that the relative expression level of AChE in the incised group was higher than that in the control group averagely, reached the peak at 1 d post-injury, then reached a second peak at 7 d post-injury. Conclusion The expression of AChE is found in PMNs, macrophages and myofibroblast during skin wound healing, which indicates it might be involved in the adjustment of inflammatory response and fibrotic repair after injury. Moreover, combined use of various methods for the detection of the expression of AChE would provide reference for skin wound age estimation.
ESTHER : Zhao_2019_Fa.Yi.Xue.Za.Zhi_35_143
PubMedSearch : Zhao_2019_Fa.Yi.Xue.Za.Zhi_35_143
PubMedID: 31135106

Title : Efficient molecular evolution to generate enantioselective enzymes using a dual-channel microfluidic droplet screening platform - Ma_2018_Nat.Commun_9_1030
Author(s) : Ma F , Chung MT , Yao Y , Nidetz R , Lee LM , Liu AP , Feng Y , Kurabayashi K , Yang GY
Ref : Nat Commun , 9 :1030 , 2018
Abstract : Directed evolution has long been a key strategy to generate enzymes with desired properties like high selectivity, but experimental barriers and analytical costs of screening enormous mutant libraries have limited such efforts. Here, we describe an ultrahigh-throughput dual-channel microfluidic droplet screening system that can be used to screen up to ~10(7) enzyme variants per day. As an example case, we use the system to engineer the enantioselectivity of an esterase to preferentially produce desired enantiomers of profens, an important class of anti-inflammatory drugs. Using two types of screening working modes over the course of five rounds of directed evolution, we identify (from among 5 million mutants) a variant with 700-fold improved enantioselectivity for the desired (S)-profens. We thus demonstrate that this screening platform can be used to rapidly generate enzymes with desired enzymatic properties like enantiospecificity, chemospecificity, and regiospecificity.
ESTHER : Ma_2018_Nat.Commun_9_1030
PubMedSearch : Ma_2018_Nat.Commun_9_1030
PubMedID: 29531246

Title : Unexpected protonation state of Glu197 discovered from simulations of tacrine in butyrylcholinesterase - Wan_2018_Phys.Chem.Chem.Phys_20_14938
Author(s) : Wan X , Yao Y , Fang L , Liu J
Ref : Phys Chem Chem Phys , 20 :14938 , 2018
Abstract : Butyrylcholinesterase (BChE) has been actively involved in drug discoveries from many fields for decades. In the crystal structure of the BChE-tacrine complex, there is an unanticipated formyl-proline molecule resolved very close to tacrine, raising an essential question on how reliable it is to apply the binding pose in a crystal structure to analyze related experimental observations, in which no formyl-proline is actually involved. In this study, by performing a series of 100 ns molecular dynamics simulations, we demonstrate that it is safe to employ the structural information from this crystal structure to analyze related experimental observations. Surprisingly, Glu197 needs to be protonated to have the structures simulated appropriately. It should be noted that Glu197 has been commonly considered as deprotonated in diverse analyses due to its low pKa in aqueous solution, for which some interpretations are inconsistent or unclear. Our further investigation shows that the protonated Glu197 plays a very important role in preserving His438 within the catalytic triad through stabilizing a highly conserved water molecule. Interestingly, the catalytic triad and Glu197 have been long recognized for possibly deviating largely from the crystal structure, which might be catalytically deficient and is generally considered to result from the difference between the crystal and aqueous environment. Herein, our results suggest that the large deviations of the catalytic triad and Glu197 from the crystal structure are caused by the inappropriate protonation state of Glu197. This finding shall provide an important clue that has been long missing for a better understanding of BChE-related puzzles or even reconsideration of some BChE-catalyzed reaction mechanisms.
ESTHER : Wan_2018_Phys.Chem.Chem.Phys_20_14938
PubMedSearch : Wan_2018_Phys.Chem.Chem.Phys_20_14938
PubMedID: 29786716

Title : Recipient treatment with acetylcholinesterase inhibitor donepezil attenuates primary graft failure in rats through inhibiting post-transplantational donor heart ischaemia\/reperfusion injury - Yuan_2018_Eur.J.Cardiothorac.Surg_53_400
Author(s) : Yuan X , Teng X , Wang Y , Yao Y
Ref : Eur J Cardiothorac Surg , 53 :400 , 2018
Abstract : OBJECTIVES: Ischaemia/reperfusion injury may have deleterious consequences on heart transplantation. The underlying causes such as inflammation may also contribute to the pathogenesis of primary or chronic graft failure. We hypothesize that donepezil (DO), a reversible acetylcholinesterase inhibitor that increases cholinergic receptor activation, may protect the transplanted heart through increasing the level of acetylcholine, which in turn inhibits systemic inflammation in the recipients. METHODS: First, Lewis-Lewis heart transplantation model was successfully established, and 75 rats were randomly assigned into 3 groups: the DO group (received single dose of intragastric DO treatment), the donepezil + methyllycaconitine group (alpha7 nicotinic acetylcholine receptor inhibitor) and the control group. Ten rats per group were sacrificed at 24 h after drug administration, whereas the rest of the groups were observed 1 month after surgery. The status of inflammation, survival of the graft and function of the graft were examined. RESULTS: Serum tumour necrosis factor alpha level was significantly lower in the donepezil group when compared with the control group 24 h after first drug administration; this trend was maintained for 1 month (P < 0.001). Furthermore, DO inhibited CD11b/18-positive cell infiltration (P < 0.001) and myocardiocyte apoptosis (as shown by the percentage of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick-end labelling-positive nuclei, P = 0.039) in the recipient rats at 24 h after the first drug administration. The percentage of cardiac grafts that survived for 1 month in rats given DO alone was significantly higher (80.0%, 33.3% and 26.7% in the DO, donepezil + methyllycaconitine and control groups, respectively, P = 0.014); the fractional shortening value of the DO group was significantly higher than that in the other 2 groups (29.25 +/- 1.84%, 17.92 +/- 3.69% and 17.07 +/- 2.99% in the DO, donepezil + methyllycaconitine and control group, respectively, P < 0.001). The collagen volume fraction was lower in the DO group than in the other 2 groups (P < 0.001). CONCLUSIONS: Our results reveal that treatment of the recipient with DO protects the donor hearts for 1 month after transplantation through suppressing the signalling pathway of inflammation. These results suggest that DO is a novel and clinically feasible strategy to protect the donor heart in transplantation in the long term.
ESTHER : Yuan_2018_Eur.J.Cardiothorac.Surg_53_400
PubMedSearch : Yuan_2018_Eur.J.Cardiothorac.Surg_53_400
PubMedID: 28950359

Title : LIPG signaling promotes tumor initiation and metastasis of human basal-like triple-negative breast cancer - Lo_2018_Elife_7_e31334
Author(s) : Lo PK , Yao Y , Lee JS , Zhang Y , Huang W , Kane MA , Zhou Q
Ref : Elife , 7 : , 2018
Abstract : Current understanding of aggressive human basal-like triple-negative breast cancer (TNBC) remains incomplete. In this study, we show endothelial lipase (LIPG) is aberrantly overexpressed in basal-like TNBCs. We demonstrate that LIPG is required for in vivo tumorigenicity and metastasis of TNBC cells. LIPG possesses a lipase-dependent function that supports cancer cell proliferation and a lipase-independent function that promotes invasiveness, stemness and basal/epithelial-mesenchymal transition features of TNBC. Mechanistically, LIPG executes its oncogenic function through its involvement in interferon-related DTX3L-ISG15 signaling, which regulates protein function and stability by ISGylation. We show that DTX3L, an E3-ubiquitin ligase, is required for maintaining LIPG protein levels in TNBC cells by inhibiting proteasome-mediated LIPG degradation. Inactivation of LIPG impairs DTX3L-ISG15 signaling, indicating the existence of DTX3L-LIPG-ISG15 signaling. We further reveal LIPG-ISG15 signaling is lipase-independent. We demonstrate that DTX3L-LIPG-ISG15 signaling is essential for malignancies of TNBC cells. Targeting this pathway provides a novel strategy for basal-like TNBC therapy.
ESTHER : Lo_2018_Elife_7_e31334
PubMedSearch : Lo_2018_Elife_7_e31334
PubMedID: 29350614
Gene_locus related to this paper: human-LIPG

Title : Metallic Transition Metal Dichalcogenide Nanosheets as an Effective and Biocompatible Transducer for Electrochemical Detection of Pesticide - Zhao_2018_Anal.Chem_90_11658
Author(s) : Zhao F , Yao Y , Li X , Lan L , Jiang C , Ping J
Ref : Analytical Chemistry , 90 :11658 , 2018
Abstract : Owing to their large specific surface, favorable electrical conductivity, and excellent electrocatalytic capabilities, two-dimensional transition metal dichalcogenides have received considerable attention in the field of biosensors. On the basis of these properties, we developed a portable and disposable enzyme-based biosensor for paraoxon detection using a metallic MoS2 nanosheets modified screen-printed electrode (SPE). The exfoliated ultrathin metallic MoS2 nanosheets can accelerate the electron transfer on electrode surface and contribute to the immobilization of acetylcholinesterase (AChE) via the cross-linking of glutaraldehyde. Electrodeposited gold nanoparticles (AuNPs) on SPE were used to immobilize MoS2 nanosheets through the interaction between Au atoms on AuNPs and S atoms on MoS2. Using acetylcholine as the substrate, AChE can catalyze the formation of electroactive thiocholine and further generate the redox current. In the presence of paraoxon, the activity of AChE can be inhibited, making the related electrochemical signals weaken. Under the optimized conditions, this electrochemical biosensor exhibited a favorable linear relationship with the concentration of paraoxon from 1.0 to 1000 mug L(-1), with the detection limit of 0.013 mug L(-1). Furthermore, this developed biosensor was successfully applied to detect paraoxon in pretreated apple and pakchoi samples, which can provide a reliable method for the rapid analysis of organophosphorus pesticides in agricultural products.
ESTHER : Zhao_2018_Anal.Chem_90_11658
PubMedSearch : Zhao_2018_Anal.Chem_90_11658
PubMedID: 30156095

Title : Transcriptional responses in the hepatopancreas of Eriocheir sinensis exposed to deltamethrin - Yang_2017_PLoS.One_12_e0184581
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
Ref : PLoS ONE , 12 :e0184581 , 2017
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.
ESTHER : Yang_2017_PLoS.One_12_e0184581
PubMedSearch : Yang_2017_PLoS.One_12_e0184581
PubMedID: 28910412

Title : Next-generation sequencing reveals lymph node metastasis associated genetic markers in colorectal cancer - Xie_2017_Exp.Ther.Med_14_338
Author(s) : Xie N , Yao Y , Wan L , Zhu T , Liu L , Yuan J
Ref : Exp Ther Med , 14 :338 , 2017
Abstract : Colorectal cancer is the third most prevalent type of cancer in the United States. Early diagnosis of lymph node metastases is essential to improve the prognosis for patients with colorectal cancer. Therefore, the present study aimed to screen genetic markers, including single nucleotide polymorphisms (SNPs), copy number variations (CNVs) and mRNA expression, associated with lymph node metastases in patients with colorectal cancer to enable an early diagnosis. Targeted next-generation sequencing was applied to capture SNPs and CNVs in tumor-related candidate genes within tumor tissues from 39 colorectal cancer patients; reverse transcription-quantitative polymerase chain reaction was used to detect the specific mRNA level of tumor-related candidate genes, including vascular endothelial growth factor C, cyclin-A2, Interleukin-2, ATP-binding cassette sub-family G member 2, epidermal growth factor (EGF) and nuclear factor kappa B subunit 1 (NFKB1) on chromosome 4. The SNPs in solute carrier family 28 member 3 (SLC28A3), breast cancer 1 (BRCA1), ribonucleotide reductase regulators subunit M2 (RRM2), PMS1 homolog 2 (PMS2), cytidine deaminase (CDA), epoxide hydrolase 1 (EPHX1), heterogenous ribonucleoprotein particle-associated with lethal yellow (RALY), Siglec-3 (CD33), B cell lymphoma 10 (BCL10), ETS variant 1 (ETV1), macrophage stimulating 1 receptor 1 (MST1R), lysine methyltransferase 2B (KMT2B), B cell lymphoma 2 (BCL2), U6 small nuclear RNA-associated Sm-like protein 3 (LSM3), thyroid transcription factor 1 (TTF1) and mitogen-activated protein 3 kinase 1 (MAP3K1) were significantly associated with lymphatic metastasis (P<0.05). EGF and NFKB1 were both observed to be significantly downregulated in the lymph node metastases group (P<0.05). Although no association between CNVs and lymph node metastases in patients with colorectal cancer was observed in the present study, SNPs in SLC28A3, BRCA1, RRM2, PMS2, CDA, EPHX1, RALY, CD33, BCL10, ETV1, MST1R, KMT2B, BCL2, LSM3, TTF1 and MAP3K1 were significantly associated with colorectal cancer. Downregulation of EGF and NFKB1 was also identified to be associated with lymph node metastases in colorectal cancer. The findings of the current study provide a scientific basis for the clinical inspection of lymphatic metastasis and prognosis prediction, intervention and guidance therapy for patients with colorectal cancer.
ESTHER : Xie_2017_Exp.Ther.Med_14_338
PubMedSearch : Xie_2017_Exp.Ther.Med_14_338
PubMedID: 28672935

Title : Let-7f Regulates the Hypoxic Response in Cerebral Ischemia by Targeting NDRG3 - Yao_2017_Neurochem.Res_42_446
Author(s) : Yao Y , Wang W , Jing L , Wang Y , Li M , Hou X , Wang J , Peng T , Teng J , Jia Y
Ref : Neurochem Res , 42 :446 , 2017
Abstract : microRNAs are a class of non-coding RNAs including approximately 22 nucleotides in length and play a pivotal role in post-transcriptional gene regulation. Currently, the role of miRNAs in the pathophysiology of ischemic stroke has been the subject of recent investigations. In particular, antagomirs to microRNA (miRNA) let-7f have been found to be neuroprotective in vivo, although the detailed function of let-7f during cerebral ischemia has not been fully illustrated. NDRG3 is an N-myc downstream-regulated gene (NDRG) family member that has been observed in the nuclei in most brain cells. Recently, a NDRG3-mediated lactate signaling, in which stabilized NDRG3 protein can promote angiogenesis and cell growth by activating the Raf-ERK pathway in hypoxia was discovered. In this study, we preliminarily explored the change in the expression of the NDRG3 protein which indicated that NDRG3 protein is an oxygen-regulated protein in neurons in rat cerebral ischemia in vivo and in vitro. We further identified let-7f as an upstream regulator of NDRG3 by the lentiviral transfection of rat cortical neurons and the dual luciferase analysis of human genes. In addition, a dual-color fluorescence in situ hybridization assay showed that when the expression of let-7f was elevated, the expression of NDRG3 mRNA was accordingly reduced in rat cerebral ischemia. Taken together, our results identify a new regulatory mechanism of let-7f on NDRG3 expression in the hypoxic response of cerebral ischemia and raise the possibility that the let-7f/NDRG3 pathway may serve as a potential target for the treatment of ischemic stroke.
ESTHER : Yao_2017_Neurochem.Res_42_446
PubMedSearch : Yao_2017_Neurochem.Res_42_446
PubMedID: 27812761

Title : Middle East Respiratory Syndrome Coronavirus Efficiently Infects Human Primary T Lymphocytes and Activates the Extrinsic and Intrinsic Apoptosis Pathways - Chu_2016_J.Infect.Dis_213_904
Author(s) : Chu H , Zhou J , Wong BH , Li C , Chan JF , Cheng ZS , Yang D , Wang D , Lee AC , Yeung ML , Cai JP , Chan IH , Ho WK , To KK , Zheng BJ , Yao Y , Qin C , Yuen KY
Ref : J Infect Dis , 213 :904 , 2016
Abstract : Middle East respiratory syndrome (MERS) is associated with a mortality rate of >35%. We previously showed that MERS coronavirus (MERS-CoV) could infect human macrophages and dendritic cells and induce cytokine dysregulation. Here, we further investigated the interplay between human primary T cells and MERS-CoV in disease pathogenesis. Importantly, our results suggested that MERS-CoV efficiently infected T cells from the peripheral blood and from human lymphoid organs, including the spleen and the tonsil. We further demonstrated that MERS-CoV infection induced apoptosis in T cells, which involved the activation of both the extrinsic and intrinsic apoptosis pathways. Remarkably, immunostaining of spleen sections from MERS-CoV-infected common marmosets demonstrated the presence of viral nucleoprotein in their CD3(+) T cells. Overall, our results suggested that the unusual capacity of MERS-CoV to infect T cells and induce apoptosis might partly contribute to the high pathogenicity of the virus.
ESTHER : Chu_2016_J.Infect.Dis_213_904
PubMedSearch : Chu_2016_J.Infect.Dis_213_904
PubMedID: 26203058

Title : Is it possible to reverse aged acetylcholinesterase inhibited by organophosphorus compounds? Insight from the theoretical study - An_2016_Phys.Chem.Chem.Phys_18_9838
Author(s) : An Y , Zhu Y , Yao Y , Liu J
Ref : Phys Chem Chem Phys , 18 :9838 , 2016
Abstract : The main treatment for organophosphorus (OP) compound poisoning in clinics is to restore the activity of acetylcholinesterase (AChE) through oxime-induced reactivation of the phosphorylated OP-AChE adduct. It suffers from a competitive and irreversible aging reaction of the phosphorylated OP-AChE adduct, resulting in permanent inactivity of AChE. However, it was recently reported that N-methyl-2-methoxypyridinium species can act as methylating agents to methylate the methyl methane-phosphonate monoanion, in which the reaction mimics the reverse of the aging reaction of the phosphorylated OP-AChE adduct. If the aging reaction could be really reversed, the efficiency for the OP detoxification should be significantly improved, bringing up the possibility to develop an agent to reverse the aging process of the phosphorylated OP-AChE adduct. However, such a reaction with the N-methyl-2-methoxypyridinium species in the enzyme is still not reported so far. It is of great interest to know whether or not this reaction is observable in the enzyme, and more importantly, if it turns out to be not observable in the enzyme, why such a reaction proceeds quickly in aqueous solution but not in the enzyme. In the present study, we performed DFT calculations and quantum mechanical/molecular mechanical (QM/MM) calculations to reveal the fundamental mechanism for the methylation of both the methyl methane-phosphonate monoanion and the aged sarin-AChE adduct by N-methyl-2-methoxypyridinium species, respectively. The obtained results support the SN2 reaction mechanism, not the stepwise mechanism, for the methylation of the methyl methane-phosphonate monoanion by 9 reported N-methyl-2-methoxypyridinium compounds. The calculated free energy barriers are in good agreement with the experimental data. The methylation of the aged sarin-AChE adduct by one N-methyl-2-methoxypyridinium compound (labeled as compound 2) also employs the SN2 reaction mechanism with an extremely high free energy barrier of 30.4 +/- 3.5 (or 26.6) kcal mol(-1), implying that this reaction in the enzyme hardly occurs. Our results clearly show that compound 2 forms a strong pi-pi stacking interaction with the aromatic ring of the W86 residue of AChE, making itself unable to approach sarin for the reverse of the aging process. On the basis of the structure and mechanism, several possible strategies have been suggested for designing methylating agents with higher activity against the aged sarin-AChE adduct.
ESTHER : An_2016_Phys.Chem.Chem.Phys_18_9838
PubMedSearch : An_2016_Phys.Chem.Chem.Phys_18_9838
PubMedID: 27000635

Title : Structural insights into the specific recognition of N-heterocycle biodenitrogenation-derived substrates by microbial amide hydrolases - Wu_2014_Mol.Microbiol_91_1009
Author(s) : Wu G , Chen D , Tang H , Ren Y , Chen Q , Lv Y , Zhang Z , Zhao YL , Yao Y , Xu P
Ref : Molecular Microbiology , 91 :1009 , 2014
Abstract : N-heterocyclic compounds from industrial wastes, including nicotine, are environmental pollutants or toxicants responsible for a variety of health problems. Microbial biodegradation is an attractive strategy for the removal of N-heterocyclic pollutants, during which carbon-nitrogen bonds in N-heterocycles are converted to amide bonds and subsequently severed by amide hydrolases. Previous studies have failed to clarify the molecular mechanism through which amide hydrolases selectively recognize diverse amide substrates and complete the biodenitrogenation process. In this study, structural, computational and enzymatic analyses showed how the N-formylmaleamate deformylase Nfo and the maleamate amidase Ami, two pivotal amide hydrolases in the nicotine catabolic pathway of Pseudomonas putida S16, specifically recognize their respective substrates. In addition, comparison of the alpha-beta-alpha groups of amidases, which include Ami, pinpointed several subgroup-characteristic residues differentiating the two classes of amide substrates as containing either carboxylate groups or aromatic rings. Furthermore, this study reveals the molecular mechanism through which the specially tailored active sites of deformylases and amidases selectively recognize their unique substrates. Our work thus provides a thorough elucidation of the molecular mechanism through which amide hydrolases accomplish substrate-specific recognition in the microbial N-heterocycles biodenitrogenation pathway.
ESTHER : Wu_2014_Mol.Microbiol_91_1009
PubMedSearch : Wu_2014_Mol.Microbiol_91_1009
PubMedID: 24397579
Gene_locus related to this paper: psep6-f8g0m2

Title : Chrysin attenuates experimental autoimmune neuritis by suppressing immuno-inflammatory responses - Xiao_2014_Neurosci_262_156
Author(s) : Xiao J , Zhai H , Yao Y , Wang C , Jiang W , Zhang C , Simard AR , Zhang R , Hao J
Ref : Neuroscience , 262 :156 , 2014
Abstract : Guillain-Barre syndrome (GBS) is an acute, post-infectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. Experimental autoimmune neuritis (EAN) is an animal model of GBS. Chrysin, which is a naturally occurring flavonoid, exhibits various biological activities. This study was designed to investigate the anti-inflammatory and neuroprotective properties of preventative and therapeutic chrysin treatment in EAN rats. For preventative treatment, chrysin was administered orally from day 1 to day 16 (50mg/kg once daily) while, for therapeutic treatment, rats received chrysin from day 7 to day 16 at the same dose once daily. Control animals received the same volume of the vehicle (phosphate-buffered saline/2% dimethylsulfoxide). Regardless of the treatment regimen, chrysin attenuated the severity and duration of the clinical course of EAN and reduced inflammatory cell infiltration and demyelination of sciatic nerves. In the sciatic nerves, the expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor kappa B was reduced. Furthermore, chrysin inhibited the splenic mononuclear cell secretion of interleukin-1beta, interleukin-2, interleukin-6, inteleukin-12, interferon gamma and tumor necrosis factor alpha, and elevated the level of inteleukin-4. In summary, our data demonstrate that chrysin is a potentially useful agent for the treatment of EAN with its anti-inflammatory and neuroprotective effects.
ESTHER : Xiao_2014_Neurosci_262_156
PubMedSearch : Xiao_2014_Neurosci_262_156
PubMedID: 24412705

Title : Synthesis and Biological Evaluation of Novel 10-Substituted-7-ethyl-10-hydroxycamptothecin (SN-38) Prodrugs - Zhou_2014_Molecules_19_19718
Author(s) : Zhou M , Liu M , He X , Yu H , Wu D , Yao Y , Fan S , Zhang P , Shi W , Zhong B
Ref : Molecules , 19 :19718 , 2014
Abstract : In an attempt to improve the antitumor activity and reduce the side effects of irinotecan (2), novel prodrugs of SN-38 (3) were prepared by conjugating amino acids or dipeptides to the 10-hydroxyl group of SN-38 via a carbamate linkage. The synthesized compounds completely generated SN-38 in pH 7.4 buffer or in human plasma, while remaining stable under acidic conditions. All prodrug compounds demonstrated much greater in vitro antitumor activities against HeLa cells and SGC-7901 cells than irinotecan. The most active compounds, 5h, 7c, 7d, and 7f, exhibited IC50 values that were 1000 times lower against HeLa cells and 30 times lower against SGC-7901 cells than those of irinotecan, and the inhibitory activities of these prodrugs against acetylcholinesterase (AchE) were significantly reduced, with IC50 values more than 6.8 times greater than that of irinotecan. In addition, compound 5e exhibited the same level of tumor growth inhibitory activity as irinotecan (CPT-11) in a human colon xenograft model in vivo.
ESTHER : Zhou_2014_Molecules_19_19718
PubMedSearch : Zhou_2014_Molecules_19_19718
PubMedID: 25438082

Title : Dual regulation of adipose triglyceride lipase by pigment epithelium-derived factor: A novel mechanistic insight into progressive obesity - Dai_2013_Mol.Cell.Endocrinol_377_123
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
Ref : Mol Cell Endocrinol , 377 :123 , 2013
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.
ESTHER : Dai_2013_Mol.Cell.Endocrinol_377_123
PubMedSearch : Dai_2013_Mol.Cell.Endocrinol_377_123
PubMedID: 23850519

Title : Systematic unraveling of the unsolved pathway of nicotine degradation in Pseudomonas - Tang_2013_PLoS.Genet_9_e1003923
Author(s) : Tang H , Wang L , Wang W , Yu H , Zhang K , Yao Y , Xu P
Ref : PLoS Genet , 9 :e1003923 , 2013
Abstract : Microorganisms such as Pseudomonas putida play important roles in the mineralization of organic wastes and toxic compounds. To comprehensively and accurately elucidate key processes of nicotine degradation in Pseudomonas putida, we measured differential protein abundance levels with MS-based spectral counting in P. putida S16 grown on nicotine or glycerol, a non-repressive carbon source. In silico analyses highlighted significant clustering of proteins involved in a functional pathway in nicotine degradation. The transcriptional regulation of differentially expressed genes was analyzed by using quantitative reverse transcription-PCR. We observed the following key results: (i) The proteomes, containing 1,292 observed proteins, provide a detailed view of enzymes involved in nicotine metabolism. These proteins could be assigned to the functional groups of transport, detoxification, and amino acid metabolism. There were significant differences in the cytosolic protein patterns of cells growing in a nicotine medium and those in a glycerol medium. (ii) The key step in the conversion of 3-succinoylpyridine to 6-hydroxy-3-succinoylpyridine was catalyzed by a multi-enzyme reaction consisting of a molybdopeterin binding oxidase (spmA), molybdopterin dehydrogenase (spmB), and a (2Fe-2S)-binding ferredoxin (spmC) with molybdenum molybdopterin cytosine dinucleotide as a cofactor. (iii) The gene of a novel nicotine oxidoreductase (nicA2) was cloned, and the recombinant protein was characterized. The proteins and functional pathway identified in the current study represent attractive targets for degradation of environmental toxic compounds.
ESTHER : Tang_2013_PLoS.Genet_9_e1003923
PubMedSearch : Tang_2013_PLoS.Genet_9_e1003923
PubMedID: 24204321

Title : IL-10-producing lymphocytes in inflammatory disease - Yao_2013_Int.Rev.Immunol_32_324
Author(s) : Yao Y , Simard AR , Shi FD , Hao J
Ref : Int Rev Immunol , 32 :324 , 2013
Abstract : IL-10 is an anti-inflammatory cytokine that plays a significant role in controlling inflammation and modulating adaptive immune responses that cause tissue damage. IL-10-producing lymphocytes contribute to the delicate balance between inflammation and immunoregulation, and are thus regarded as a kind of "regulatory cells." Dysregulation of these cells is linked with susceptibility to numerous inflammatory diseases. In this review, we summarized what is known about the regulatory effects of IL-10 produced by lymphocytes, including T cells, B cells and natural killer cells, in inflammatory diseases. We hope to augment immune responses or prevent immunopathology through making some small changes in the levels of IL-10 produced by lymphocytes, or in the cellular location where it is produced.
ESTHER : Yao_2013_Int.Rev.Immunol_32_324
PubMedSearch : Yao_2013_Int.Rev.Immunol_32_324
PubMedID: 23617759

Title : Iron(II)-dependent dioxygenase and N-formylamide deformylase catalyze the reactions from 5-hydroxy-2-pyridone to maleamate - Yao_2013_Sci.Rep_3_3235
Author(s) : Yao Y , Tang H , Ren H , Yu H , Wang L , Zhang W , Behrman EJ , Xu P
Ref : Sci Rep , 3 :3235 , 2013
Abstract : 5-Hydroxy-2-pyridone (2,5-DHP) is a central metabolic intermediate in catabolism of many pyridine derivatives, and has been suggested as a potential carcinogen. 2,5-DHP is frequently transformed to N-formylmaleamic acid (NFM) by a 2,5-DHP dioxygenase. Three hypotheses were formerly discussed for conversion of 2,5-DHP to maleamate. Based on enzymatic reactions of dioxygenase (Hpo) and N-formylamide deformylase (Nfo), we demonstrated that the dioxygenase does not catalyze the hydrolysis of NFM but rather that this activity is brought about by a separate deformylase. We report that the deformylase acts both on NFM and its trans-isomer, N-formylfumaramic acid (NFF), but the catalytic efficiency of Nfo for NFM is about 1,400 times greater than that for NFF. In addition, we uncover catalytic and structural characteristics of the new family that the Hpo belongs to, and support a potential 2-His-1-carboxylate motif (HX52HXD) by three-dimensional modeling and site-directed mutagenesis. This study provides a better understanding of 2,5-DHP catabolism.
ESTHER : Yao_2013_Sci.Rep_3_3235
PubMedSearch : Yao_2013_Sci.Rep_3_3235
PubMedID: 24241081

Title : Draft genome sequence of Aspergillus oryzae strain 3.042 - Zhao_2012_Eukaryot.Cell_11_1178
Author(s) : Zhao G , Yao Y , Qi W , Wang C , Hou L , Zeng B , Cao X
Ref : Eukaryot Cell , 11 :1178 , 2012
Abstract : Aspergillus oryzae is the most important fungus for the traditional fermentation in China and is particularly important in soy sauce fermentation. We report the 36,547,279-bp draft genome sequence of A. oryzae 3.042 and compared it to the published genome sequence of A. oryzae RIB40.
ESTHER : Zhao_2012_Eukaryot.Cell_11_1178
PubMedSearch : Zhao_2012_Eukaryot.Cell_11_1178
PubMedID: 22933657
Gene_locus related to this paper: aspor-q2uj83

Title : Why Does the G117H Mutation Considerably Improve the Activity of Human Butyrylcholinesterase against Sarin? Insights from Quantum Mechanical\/Molecular Mechanical Free Energy Calculations - Yao_2012_Biochemistry_51_8980
Author(s) : Yao Y , Liu J , Zhan CG
Ref : Biochemistry , 51 :8980 , 2012
Abstract : Human butyrylcholinesterase (BChE) is recognized as the most promising bioscavenger for organophosphorus (OP) warfare nerve agents. The G117H mutant of human BChE has been identified as a potential catalytic bioscavenger with a remarkably improved activity against OP nerve agents such as sarin, but it still does not satisfy the clinical use. For further design of the higher-activity mutants against OP nerve agents, it is essential to understand how the G117H mutation improves the activity. The reaction mechanisms and the free energy profiles for spontaneous reactivation of wild-type BChE and its G117H mutant phosphorylated by sarin have been explored, in this study, by performing first-principles quantum mechanical/molecular mechanical free energy calculations, and the remarkable role of the G117H mutation on the activity has been elucidated. For both the wild-type and G117H mutant enzymes, H438 acts as a general base to initiate the spontaneous reactivation that consists of two reaction steps: the nucleophilic attack at the phosphorus by a water molecule and decomposition of the pentacoordinated phosphorus intermediate. The calculated overall free energy barriers, i.e., 30.2 and 23.9 kcal/mol for the wild type and G117H mutant, respectively, are in good agreement with available experimental kinetic data. On the basis of the calculated results, the mutated residue (H117 in the G117H mutant) cannot initiate the spontaneous reactivation as a general base. Instead, it skews the oxyanion hole and makes the phosphorus more open to the nucleophilic water molecule, resulting in a remarkable change in the rate-determining step and significantly improved catalytic activity of human BChE.
ESTHER : Yao_2012_Biochemistry_51_8980
PubMedSearch : Yao_2012_Biochemistry_51_8980
PubMedID: 23092211

Title : Genome sequence of a novel nicotine-degrading strain, Pseudomonas geniculata N1 - Tang_2012_J.Bacteriol_194_3553
Author(s) : Tang H , Yu H , Tai C , Huang K , Liu Y , Wang L , Yao Y , Wu G , Xu P
Ref : Journal of Bacteriology , 194 :3553 , 2012
Abstract : A newly isolated bacterium, Pseudomonas geniculata N1, can efficiently degrade nicotine. Here we present a 4.51-Mb assembly of its genome, which is the first sequence of the P. geniculata group. The sequence contains the genes related to nicotine catabolism and may provide insights into its molecular mechanism for N-heterocyclic degradation.
ESTHER : Tang_2012_J.Bacteriol_194_3553
PubMedSearch : Tang_2012_J.Bacteriol_194_3553
PubMedID: 22689240
Gene_locus related to this paper: 9gamm-a0a0l8ag98

Title : Genomic analysis of Pseudomonas putida: genes in a genome island are crucial for nicotine degradation - Tang_2012_Sci.Rep_2_377
Author(s) : Tang H , Yao Y , Wang L , Yu H , Ren Y , Wu G , Xu P
Ref : Sci Rep , 2 :377 , 2012
Abstract : Nicotine is an important chemical compound in nature that has been regarded as an environmental toxicant causing various preventable diseases. Several bacterial species are adapted to decompose this heterocyclic compound, including Pseudomonas and Arthrobacter. Pseudomonas putida S16 is a bacterium that degrades nicotine through the pyrrolidine pathway, similar to that present in animals. The corresponding late steps of the nicotine degradation pathway in P. putida S16 was first proposed and demonstrated to be from 2,5-dihydroxy-pyridine through the intermediates N-formylmaleamic acid, maleamic acid, maleic acid, and fumaric acid. Genomics of strain S16 revealed that genes located in the largest genome island play a major role in nicotine degradation and may originate from other strains, as suggested by the constructed phylogenetic tree and the results of comparative genomic analysis. The deletion of gene hpo showed that this gene is essential for nicotine degradation. This study defines the mechanism of nicotine degradation.
ESTHER : Tang_2012_Sci.Rep_2_377
PubMedSearch : Tang_2012_Sci.Rep_2_377
PubMedID: 22530095

Title : Complete genome sequence of the nicotine-degrading Pseudomonas putida strain S16 - Yu_2011_J.Bacteriol_193_5541
Author(s) : Yu H , Tang H , Wang L , Yao Y , Wu G , Xu P
Ref : Journal of Bacteriology , 193 :5541 , 2011
Abstract : Pseudomonas putida S16 is an efficient degrader of nicotine. The complete genome of strain S16 (5,984,790 bp in length) includes genes related to catabolism of aromatic and heterocyclic compounds. The genes of enzymes in the core genome and a genomic island encode the proteins responsible for nicotine catabolism.
ESTHER : Yu_2011_J.Bacteriol_193_5541
PubMedSearch : Yu_2011_J.Bacteriol_193_5541
PubMedID: 21914868
Gene_locus related to this paper: psep6-f8g0m2 , psepu-PIP , psepu-PP4249 , psepu-PP4916 , psepu-q9wwz4

Title : A novel NADH-dependent and FAD-containing hydroxylase is crucial for nicotine degradation by Pseudomonas putida - Tang_2011_J.Biol.Chem_286_39179
Author(s) : Tang H , Yao Y , Zhang D , Meng X , Wang L , Yu H , Ma L , Xu P
Ref : Journal of Biological Chemistry , 286 :39179 , 2011
Abstract : Nicotine, the main alkaloid produced by Nicotiana tabacum and other Solanaceae, is very toxic and may be a leading toxicant causing preventable disease and death, with the rise in global tobacco consumption. Several different microbial pathways of nicotine metabolism have been reported: Arthrobacter uses the pyridine pathway, and Pseudomonas, like mammals, uses the pyrrolidine pathway. We identified and characterized a novel 6-hydroxy-3-succinoyl-pyridine (HSP) hydroxylase (HspB) using enzyme purification, peptide sequencing, and sequencing of the Pseudomonas putida S16 genome. The HSP hydroxylase has no known orthologs and converts HSP to 2,5-dihydroxy-pyridine and succinic semialdehyde, using NADH. (18)O(2) labeling experiments provided direct evidence for the incorporation of oxygen from O(2) into 2,5-dihydroxy-pyridine. The hspB gene deletion showed that this enzyme is essential for nicotine degradation, and site-directed mutagenesis identified an FAD-binding domain. This study demonstrates the importance of the newly discovered enzyme HspB, which is crucial for nicotine degradation by the Pseudomonas strain.
ESTHER : Tang_2011_J.Biol.Chem_286_39179
PubMedSearch : Tang_2011_J.Biol.Chem_286_39179
PubMedID: 21949128
Gene_locus related to this paper: psep6-f8g0m2

Title : [Molecular characterization and evolutional analysis of liportein lipase and hepatic lipase gene in Chinese Sturgeon and other six freshwater fishes] - Huang_2010_Dongwuxue.Yanjiu_31_239
Author(s) : Huang Y , Liang XF , Wang L , Li GZ , Liu XX , Yao Y
Ref : Dongwuxue Yanjiu , 31 :239 , 2010
Abstract : In order to study the structural, functional and molecular evolutional relationship of fish liportein lipase (LPL) and hepatic lipase (HL) genes, seven liver LPL and HL cDNA partial sequences were isolated from Acipenser sinensis, Hypophthalmichthys molitrix, Aristichthys nobilis, Ctenopharyngodon idellus, Cirrhinus molitorella, Oreochromis niloticus, Channa maculate by RT-PCR. Three full-length cDNA sequences of LPL, HL of Acipenser sinensis and LPL of Hypophthalmichthys molitrix were obtained by RACEs. From the sequence analysis and homologous results, the amino acid sequences of LPL and HL are relatively conserved in mammals, birds and fishes. Taken together with these obtained amino acid sequences and sequences of all known LPL, HL, EL and PL from other vertebrates, a phylogenetic tree was constructed by neighbor-joining method. The result supports that all of them belong to lipase family.
ESTHER : Huang_2010_Dongwuxue.Yanjiu_31_239
PubMedSearch : Huang_2010_Dongwuxue.Yanjiu_31_239
PubMedID: 20672411
Gene_locus related to this paper: acibe-a0a075ekg6 , oreni-i3j210 , hypmo-g7z072

Title : Mouse RIC-3, an endoplasmic reticulum chaperone, promotes assembly of the alpha7 acetylcholine receptor through a cytoplasmic coiled-coil domain - Wang_2009_J.Neurosci_29_12625
Author(s) : Wang Y , Yao Y , Tang XQ , Wang ZZ
Ref : Journal of Neuroscience , 29 :12625 , 2009
Abstract : RIC-3 (resistant to inhibitor of cholinesterase) is a transmembrane protein, found in invertebrates and vertebrates, that modulates the surface expression of a variety of nicotinic acetylcholine receptors (nAChRs) in neurons and other cells. To understand its mechanism of action, we investigated the cellular location, transmembrane topology and cellular mechanism by which RIC-3 facilitates alpha7 assembly and surface expression in cultured mammalian cells. We show that the mouse protein is targeted to the ER by the first 31 aa which act as a cleavable signal sequence. The mature protein is a single-pass type I transmembrane protein whose N terminus resides in the lumen of the ER with the coiled-coil domain in the cytoplasm. RIC-3, which binds both unfolded and folded alpha7 subunits, facilitates the surface expression of receptor principally by promoting the folding and assembly of the alpha7 subunits in the ER into fully polymerized receptor. Functional analysis shows that facilitation of surface expression of alpha7 in mammalian cells is reduced in RIC-3 mutants lacking the signal peptide, the lumenal segment or the coiled-coil domain, but not in mutants lacking the long C-terminal region downstream of the coiled-coil domain. We show that the coiled-coil domain of mRIC-3 is not required for the interaction of mRIC-3 with alpha7, but does mediate a homotypic interaction between molecules of mRIC-3. We suggest that efficient assembly of the homomeric alpha7 nAChR may thus require mRIC-3 self-association through the cytoplasmic coiled-coil domain and suggest a model by which this may occur.
ESTHER : Wang_2009_J.Neurosci_29_12625
PubMedSearch : Wang_2009_J.Neurosci_29_12625
PubMedID: 19812337

Title : Plasma F2A isoprostane levels in Alzheimer's and Parkinson's disease - Irizarry_2007_Neurodegener.Dis_4_403
Author(s) : Irizarry MC , Yao Y , Hyman BT , Growdon JH , Pratico D
Ref : Neurodegener Dis , 4 :403 , 2007
Abstract : BACKGROUND: Oxidative damage is implicated in the pathophysiology of Alzheimer's disease (AD). F2-isoprostane is a marker of lipid peroxidation which is elevated in AD CSF. Plasma F2-isoprostane has been proposed as a diagnostic marker for AD and mild cognitive impairment (MCI). OBJECTIVE: To determine whether plasma F2-isoprostane levels differ between nondemented control individuals and patients with AD, MCI, or Parkinson's disease (PD).
METHODS: We collected plasma from191 outpatients with a diagnosis of AD (49), MCI (47), nondemented PD (47), and no dementia (48). Plasma levels of the isoprostane iP2alpha-IV (F2A) were determined by gas chromatography/mass spectroscopy.
RESULTS: Mean plasma levels of F2A isoprostane did not differ significantly between the four diagnostic groups. Within the MCI and AD groups, F2A levels did not correlate with duration of memory impairment or with cognitive test scores. F2A levels were marginally lower in users of cholinesterase inhibitors and individuals with an APOE epsilon4 allele.
CONCLUSIONS: While CSF isoprostane levels are elevated in AD, plasma isoprostane measures were neither sensitive nor specific for the clinical diagnosis of MCI or AD.
ESTHER : Irizarry_2007_Neurodegener.Dis_4_403
PubMedSearch : Irizarry_2007_Neurodegener.Dis_4_403
PubMedID: 17934322

Title : Effect of molecular sieves on lipase-catalyzed esterification of rutin with stearic acid - Duan_2006_J.Agric.Food.Chem_54_6219
Author(s) : Duan Y , Du Z , Yao Y , Li R , Wu D
Ref : Journal of Agricultural and Food Chemistry , 54 :6219 , 2006
Abstract : Rutin was acylated with stearic acid in the esterification reaction catalyzed by immobilized Candida antarctica lipase B (Novozym 435) in tert-amyl alcohol with and without molecular sieves. The lipophilic rutin stearate was synthesized by this method, which had a potential use in food, cosmetics, and pharmacy. The structure of rutin stearate was characterized by spectral methods of 1H NMR and 13C NMR, Fourier transform infrared, and UV-vis. The results suggested that the regioselectivity of the lipase-catalyzed esterification of rutin was specific at the C(4''')-position of the rhamnose moiety. It was found that the addition of molecular sieves increased both the reaction rate and the yield. The time effect of adding molecular sieves in the reaction system on the conversion of rutin stearate was further examined. Instead of adding molecular sieves at the beginning of the reaction, the addition of molecular sieves at 5, 18, 24, 31, and 44 h after the beginning of the reaction was also applied. The final conversion for the case to add molecular sieves at 24 h after the beginning of reaction was the highest, with the conversion yield about 46%.
ESTHER : Duan_2006_J.Agric.Food.Chem_54_6219
PubMedSearch : Duan_2006_J.Agric.Food.Chem_54_6219
PubMedID: 16910711

Title : Aberrant development of motor axons and neuromuscular synapses in MyoD-null mice - Wang_2003_J.Neurosci_23_5161
Author(s) : Wang ZZ , Washabaugh CH , Yao Y , Wang JM , Zhang L , Ontell MP , Watkins SC , Rudnicki MA , Ontell M
Ref : Journal of Neuroscience , 23 :5161 , 2003
Abstract : Myogenic regulatory factors (MRFs), muscle-specific transcription factors, are implicated in the activity-dependent regulation of nicotinic acetylcholine receptor (AChR) subunit genes. Here we show, with immunohistochemistry, Western blotting, and electron microscopy that MyoD, a member of the MRF family, also plays a role in fetal synapse formation. In the diaphragm of 14.5 d gestation (E14.5) wild-type and MyoD-/- mice, AChR clusters (the formation of which is under a muscle intrinsic program) are confined to a centrally located endplate zone. This distribution persists in wild-type adult muscles. However, beginning at E15.5 and extending to the adult, innervated AChR clusters are distributed all over the diaphragm of MyoD-/- mice, extending as far as the insertion of the diaphragm into the ribs. In wild-type muscle, motor axons terminate on clusters adjacent to the main intramuscular nerve; in MyoD-/- muscle, axonal bundles form extensive secondary branches that terminate on the widely distributed clusters. The number of AChR clusters on adult MyoD-/- and wild-type diaphram muscles is similar. Junctional fold density is reduced at MyoD-/- endplates, and the transition from the fetal (alpha, beta, gamma, delta) to adult-type (alpha, beta, delta, epsilon) AChRs is markedly delayed. However, MyoD-/- mice assemble a complex postsynaptic apparatus that includes muscle-specific kinase (MuSK), rapsyn, erbB, and utrophin.
ESTHER : Wang_2003_J.Neurosci_23_5161
PubMedSearch : Wang_2003_J.Neurosci_23_5161
PubMedID: 12832540

Title : Yeast expression and NMR analysis of the extracellular domain of muscle nicotinic acetylcholine receptor alpha subunit - Yao_2002_J.Biol.Chem_277_12613
Author(s) : Yao Y , Wang J , Viroonchatapan N , Samson A , Chill J , Rothe E , Anglister J , Wang ZZ
Ref : Journal of Biological Chemistry , 277 :12613 , 2002
Abstract : The alpha subunit of the nicotinic acetylcholine receptor (AChR) from Torpedo electric organ and mammalian muscle contains high affinity binding sites for alpha-bungarotoxin and for autoimmune antibodies in sera of patients with myasthenia gravis. To obtain sufficient materials for structural studies of the receptor-ligand complexes, we have expressed part of the mouse muscle alpha subunit as a soluble, secretory protein using the yeast Pichia pastoris. By testing a series of truncated fragments of the receptor protein, we show that alpha211, the entire amino-terminal extracellular domain of AChR alpha subunit (amino acids 1-211), is the minimal segment that could fold properly in yeast. The alpha211 protein was secreted into the culture medium at a concentration of >3 mg/liter. It migrated as a 31-kDa polypeptide with N-linked glycosylation on SDS-polyacrylamide gel. The protein was purified to homogeneity by isoelectric focusing electrophoresis (pI 5.8), and it appeared as a 4.5 S monomer on sucrose gradient at concentrations up to 1 mm ( approximately 30 mg/ml). The receptor domain bound monoclonal antibody mAb35, a conformation-specific antibody against the main immunogenic region of the AChR. In addition, it formed a high affinity complex with alpha-bungarotoxin (k(D) 0.2 nm) but showed relatively low affinity to the small cholinergic ligand acetylcholine. Circular dichroism spectroscopy of alpha211 revealed a composition of secondary structure corresponding to a folded protein. Furthermore, the receptor fragment was efficiently (15)N-labeled in P. pastoris, and proton cross-peaks were well dispersed in nuclear Overhauser effect and heteronuclear single quantum coherence spectra as measured by NMR spectroscopy. We conclude that the soluble AChR protein is useful for high resolution structural studies.
ESTHER : Yao_2002_J.Biol.Chem_277_12613
PubMedSearch : Yao_2002_J.Biol.Chem_277_12613
PubMedID: 11812776