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Drug resistance mutation profiles of the drug-nave and first-line regimen-treated HIV-1-infected population of Suzhou, China

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Virologica Sinica 2017年第4期32卷 271-279页

作者： Tingting Li Feng Qian Ting Yuan Weilu Xu Li Zhu Jinlong Huang Haiyan Wang Yueping Zhu Yinling Wang Xiaohong Li Saihong Gu Zhuqing Tan Hui Chen Xiangrong Luo Wei Zhu Weniuan Lu Ping Xu Ming Li Yuying Chen Yong Gao Rongge Yang Chuanwu Zhu Binlian Sun Research Group of HIV-1 molecular Epidemiology and virology The State Key Laboratory of Virology Wuhan Institute of Virology Chinese Academy of Sciences University of Chinese Academy of Sciences division of HIV-1/AIDS the Fifth People's Hospital of Suzhou Department of Microbiology and Immunology Schulich School of Medicine & Dentistry University of Western Ontario

Little is known about the prevalence of drug-resistant mutations in HIV-1-positive individuals in Suzhou, China. To elucidate the transmitted drug resistance(TDR) and acquired drug resistance mutation(ADR) profiles, we collected blood specimens from 127 drug-naive and 117 first-line drugtreated HIV-1-infected individuals sampled from 2014 to 2016 in Suzhou. We successfully amplified po/fragments from 100 drug-naive and 20 drug-treated samples. We then determined the drugresistant mutations to protease(PR) and reverse-transcriptase(RT) inhibitors according to the Stanford drug resistance database. Overall, 11 and 13 individuals had transmitted(drug-naive group) and acquired(treated group) resistance mutations, respectively. Six transmitted drugresistant mutations were found, including two mutations(L33F and L76V) in the protease region and four(K70N/E and V179D/E) in the RT region. Only L76 V was a major mutation, and K70N/E and V179D/E are known to cause low-level resistance to RT inhibitors. All 13 treated participants who had major drug resistance mutations demonstrated intermediate to high resistance to efavirenz and nevirapine, and six had a treatment duration of less than three months. No major mutations to RT inhibitors were found, implying that the epidemic of transmitted resistance mutations was not significant in this area. Our results suggest that more frequent virus load and drug resistance mutation tests should be conducted for individuals receiving antiretroviral treatment, especially for newly treated patients. Our research provides insights into the occurrence of HIV-1 drug resistance in Suzhou and will help to optimize the treatment strategy for this population.

关键词： HIV-1 drug resistance mutation first-line regimen China

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Organization of microtubule plus-end dynamics by phase separation in mitosis

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Journal of molecular Cell Biology 2024年第2期16卷 24-35页

作者： Fengrui Yang Mingrui Ding Xiaoyu Song Fang Chen Tongtong Yang Chunyue Wang Chengcheng Hu Qing Hu Yihan Yao Shihao Du Phil YYao Peng Xia Gregory Adams Jr Chuanhai Fu Shengqi Xiang Dan Liu Zhikai Wang Kai Yuan Xing Liu MOE Key Laboratory for Membraneless Organelles&Cellular Dynamics Hefei National Research Center for Cross-disciplinary SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science&Technology of ChinaHefei 230027China Anhui Key Laboratory for Cellular Dynamics and Chemical Biology University of Science&Technology of ChinaHefei 230027China Keck Center for Organoids Plasticity Morehouse School of MedicineAtlantaGA 30310USA Hunan Key Laboratory of molecular Precision Medicine Central South UniversityChangsha 410083China

In eukaryotes,microtubule polymers are essential for cellular plasticity and fate ***-binding(EB)proteins serve as scaffolds for orchestrating microtubule polymer dynamics and are essential for cellular dynamics and chromosome segregation in ***,we show that EB1 forms molecular condensates with TIP150 and MCAK through liquid–liquid phase separation to compartmentalize the kinetochore–microtubule plus-end machinery,ensuring accurate kinetochore–microtubule interactions during chromosome segregation in *** of EB1–TIP150 polymer formation by a competing peptide prevents phase separation of the EB1-mediated complex and chromosome alignment at the metaphase equator in both cultured cells and Drosophila ***220 of EB1 is dynamically acetylated by p300/CBP-associated factor in early mitosis,and persistent acetylation at Lys220 attenuates phase separation of the EB1-mediated complex,dissolves droplets in vitro,and harnesses accurate chromosome *** data suggest a novel framework for understanding the organization and regulation of eukaryotic spindle for accurate chromosome segregation in mitosis.

关键词： phase separation mitosis microtubule dynamics EB1 acetylation

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Dietary Green Tea Extract and Antioxidants Improve Insulin Secretory Functions of Pancreatic β-Cells in Mild and Severe Experimental Rodent Model of Chronic Pancreatitis

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Open Journal of Endocrine and Metabolic Diseases 2024年第2期14卷 53-72页

作者： Galande Sheethal Ranjeet K. Tokala Pavan Pondugala Krishna Vemula Vijayalakshmi Venkatesan Pothani Suresh Surya Satyanarayana Singh Guduru Venkat Rao Duvvur Nageshwar Reddy Mitnala Sasikala Basic Science and Translational Research division Asian Healthcare Foundation AIG Hospitals Hyderabad India division of Cell and molecular Biology National institute of Nutrition Hyderabad India National Animal Resource Facility for Biomedical Research Hyderabad India Department of Biochemistry Osmania University Hyderabad India Department of Surgical Gastroenterology Asian Institute of Gastroenterology Hyderabad India Department of Gastroenterology Asian Institute of Gastroenterology Hyderabad India

Chronic pancreatitis (CP) is a progressive inflammatory disorder of the pancreas. It is predominantly idiopathic (with an unknown cause) in India and mostly due to alcohol in the West. Diabetes that occur secondary to chronic pancreatitis (T3c Diabetes) is often brittle, and is difficult to attain normoglycemia with conventional treatment requiring multiple doses of insulin. Mild and severe model of CP was induced in mice by repeated intraperitoneal injections of cerulein and L-arginine respectively with an intent to study islet dysfunction and develop therapeutic strategy in animal models of CP. Dietary intervention of epigallocatechin-3-gallate (EGCG) was tested in both the models of CP for its beneficial effects on insulin secretory functions. Pancreata collected upon euthanasia were used to study alterations in the morphology of pancreatic parenchyma and inflammation by staining with H&E and fibrotic changes by Masson’s trichrome and picrosirius staining. Insulin secretory functions of islets were evaluated to test the efficacy of the dietary intervention on β-cell functions. Intraperitoneal glucose tolerance test was performed to monitor the glucose homeostasis before and after the dietary intervention. Both the models resulted in CP with dispersed acini, inflammation and fibrosis. The loss of acini and extent of fibrosis was more in L-arginine model. 2-fold improvement in glucose-stimulated insulin secretory functions of islets was observed with 0.5% EGCG dietary intervention in cerulein model of CP and 1.6-fold in L-arginine model of CP. A further improvement in insulin secretion by 3.2-fold was observed with additional dietary supplements like N-acetyl cysteine, curcumin in combination with EGCG. Our results thus demonstrate and highlight the therapeutic potential of dietary green tea (EGCG) supplementation in reversing islet dysfunction and improving glucose homeostasis in experimental chronic pancreatitis in mice.

关键词： Dietary Intervention C57BL6/J Mice Epigallocatechin-3-Gallate N-Acetyl Cysteine Curcumin Chronic Pancreatitis Islets Glucose Stimulated Insulin Secretion

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Th17 Cells in autoimmune diseases

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Frontiers of Medicine 2015年第1期9卷 10-19页

作者： Lei Han Jing Yang Xiuwen Wang Dan Li Ling Lv Bin Li division of Rheumatology Huashan Hospital Fudan University Shanghai 200040 China Key Laboratory of molecular virology and Immunology Unit of Molecular Immunology Institut Pasteur of Shanghai Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai 200032 China

Th17 cells are a new subset of CD4^＋ T cells fungi. Accumulating evidence suggests that Tb17 cells involved in the clearance of extracellular pathogens and and their signature cytokines have a pivotal role in the pathogenesis of multiple autoimmune-mediated inflammatory diseases. Here, we summarize recent research progress on Th17 function in the development and pathogenesis of autoimmune diseases. We also propose to identify new small molecule compounds to manipulate Th17 function for potential therapeutic application to treat human autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjogren＇s syndrome, inflammatory bowel disease, and multiple sclerosis.

关键词： IL-17 Thl 7 cells RORγt autoimmune diseases posttranslational modification inhibitors

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Ellagic acid inhibits gastric cancer cells by modulating oxidative stress and inducing apoptosis

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Asian Pacific Journal of Tropical Biomedicine 2024年第4期14卷 162-169页

作者： Jian Zheng Chun-Feng Li Department of Diagnostic Radiology division Harbin Medical University Cancer HospitalHeilongjiangChina Department of Gastrointestinal Surgical Ward Harbin Medical University Cancer HospitalHeilongjiangChina

Objective:To evaluate the anticancer effect of ellagic acid on gastric cancer ***:MTT assay was used to evaluate the effect of ellagic acid at different concentrations(0.5-100μg/mL)on gastric cancer AGS ***-qPCR and Western blot analyses were applied to assess apoptosis(BCL-2,CASP-3,and BAX)and autophagy(LC3,ATG5,and BECN1)in AGS cells treated with ellagic *** expression of invasion-related markers including TP53,CDKN2A,and PTEN was *** addition,cell cycle markers including cyclin A,B,D,and E were measured by *** stress markers were evaluated using ***:Ellagic acid inhibited the proliferation of AGS cells in a concentration-and time-dependent *** expression of BCL-2 was significantly decreased(P0.05).Moreover,the oxidative stress markers including SOD,TAC,and MDA were increased by ellagic acid(Pmolecular studies are needed to verify its anticancer efficacy.

关键词： Ellagic acid Gastric cancer Apoptosis Autophagy Metastasis Proliferation

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Utilizing a metal-forging inspired chain combing strategy to enhance properties and expand applications of Nylon 66 plastic via heat inducing

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Nano Research 2024年第3期17卷 2164-2171页

作者： Junyu Yang Jiangwei Zhang Nan Wang Guangyuan Zhou division of Energy Materials Daglian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Innovation Center of Energy Material and Chemistry College of Chemistry and Chemical EngineeringInner Mongolia UniversityHohhot 010021China

The mechanical properties of engineering plastics can be enhanced through effective surface mechanical treatment(SMT),which can be applied to various types of engineering plastics,eliminating the limitations of conventional polymer processing and could potentially extend their applications and improve their performance and reliability as structural-functional *** by metal forging,this work proposes a simple and effective SMT strategy to enhance the mechanical properties of polyamide 66(PA66).Tensile tests have shown that SMTed PA66 samples exhibit significant improvements in both Young’s modulus and ultimate tensile strength(UTS),with a 2104 MPa Young’s modulus,almost double that of the pristine samples,and a 35.56%increase in UTS,reaching 183 ***,the modulus within the localized SMTed surface layer could reach up to 14 GPa,which is approximately 14 times higher than that of the pristine *** Vickers hardness within the localized SMTed surface layer can be doubled,reaching 10.72 Hv,and the crystallinity can increase by approximately 20%compared to the untreated ***,force field molecular dynamics(FFMD)simulations were conducted to investigate the ternary relationship between the SMT method,PA66’s molecular structure,and its *** combination of MD simulations and versatile structural characterizations provides evidence that the SMT method’s mechanism,under heat induction,results in a chain-combing procedure that changes the polymer’s molecular morphology microscopically and enhances its mechanical properties macroscopically.

关键词： Nylon 66 mechanical properties hardness crystallinity structural characterizations molecular dynamics simulation

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New perspectives on biology,disease progression,and therapy response of head and neck cancer gained from single cell RNA sequencing and spatial transcriptomics

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Oncology Research 2024年第1期32卷 1-17页

作者： GERWIN HELLER THORSTEN FUEREDER ALEXANDER MICHAEL GRANDITS ROTRAUD WIESER division of Oncology Department of Medicine IMedical University of ViennaVienna1090Austria Ludwig Boltzmann Institute for Hematology and Oncology Medical University of ViennaVienna1090Austria

Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent cancers *** main risk factors are consumption of tobacco products and alcohol,as well as infection with human papilloma *** therapeutic options comprise surgery,radiation,chemotherapy,targeted therapy through epidermal growth factor receptor inhibition,and immunotherapy,but outcome has remained unsatisfactory due to recurrence rates of~50%and the frequent occurrence of second *** availability of the human genome sequence at the beginning of the millennium heralded the omics era,in which rapid technological progress has advanced our knowledge of the molecular biology of malignant diseases,including HNSCC,at an unprecedented ***,microarray-based methods,followed by approaches based on next-generation sequencing,were applied to study the genetics,epigenetics,and gene expression patterns of bulk *** recently,the advent of single-cell RNA sequencing(scRNAseq)and spatial transcriptomics methods has facilitated the investigation of the heterogeneity between and within different cell populations in the tumor microenvironment(e.g.,cancer cells,fibroblasts,immune cells,endothelial cells),led to the discovery of novel cell types,and advanced the discovery of cell-cell communication within *** review provides an overview of scRNAseq,spatial transcriptomics,and the associated bioinformatics methods,and summarizes how their application has promoted our understanding of the emergence,composition,progression,and therapy responsiveness of,and intercellular signaling within,HNSCC.

关键词： Head and neck squamous cell carcinoma Tumor microenvironment Immunotherapy Gene expression Omics

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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical Research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan division of molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center Research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Three novel umami peptides derived from the alcohol extract of the Pacific oyster(Crassostrea gigas):identification,characterizations and interactions with T1R1/T1R3 taste receptors

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Food Science and Human Wellness 2024年第1期13卷 146-153页

作者： Baifeng Fu Di Wu Shuzhen Cheng Xianbing Xu Ling Zhang Lishu Wang Heshanm REl-Seedi Hanxiong Liu Ming Du School of Food Science and Technology Dalian Polytechnic UniversityDalian 116034China Collaborative Innovation Center of Seafood Deep Processing Dalian Polytechnic UniversityDalian 116034China National Engineering Research Center of Seafood Dalian Polytechnic UniversityDalian 116034China division of Hematology and Oncology Department of MedicineMedical College of WisconsinMilwaukee 53226USA division of Pharmacognosy Department of Medicinal ChemistryBiomedical CentreUppsala UniversityUppsala SE-75123Sweden

Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami *** this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their *** threshold of the three peptides ranged from 0.38 to 0.55 mg/m *** with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces ***,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami *** with two Glu residues at the terminus had stronger umami,especially at the *** results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.

关键词： Oyster umami peptides iUmami-SCM Taste characterization molecular docking

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Disease clearance in ulcerative colitis:A new therapeutic target for the future

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World Journal of Gastroenterology 2024年第13期30卷 1801-1809页

作者： Syed Adeel Hassan Neeraj Kapur Fahad Sheikh Anam Fahad Somia Jamal division of Digestive Disease and Nutrition University of KentuckyLexingtonKY 40536United States Department of Pathology and Laboratory Medicine Montefiore Medical CenterAlbert Einstein College of MedicineNew YorkNY 10461United States division of Primary Care Essen HealthcareNew YorkNY 10457United States Department of Internal Medicine Karachi Medical and Dental CollegeKarachi 74700SindhPakistan

Advancements in murine modeling systems for ulcerative colitis have diversified our understanding of the pathophysiological factors involved in disease onset and *** has fueled the identification of molecular targets,resulting in a rapidly expanding therapeutic ***,management strategies have evolved from symptomatic resolution to well-defined objective endpoints,including clinical remission,endoscopic remission and mucosal *** the incorporation of these assessment modalities has permitted targeted intervention in the context of a natural disease history and the prevention of complications,studies have consistently depicted discrepancies associated with ascertaining disease status through clinical and endoscopic *** recommendations lack consideration of histological *** simultaneous achievement of clinical,endoscopic,and histologic remission has not been fully *** has laid the groundwork for a novel therapeutic outcome termed disease clearance(DC).This article summarizes the concept of DC and its current evidence.

关键词： Inflammatory bowel disease Ulcerative colitis Clinical remission Endoscopic remission Histological remission Mucosal healing Disease clearance

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