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3,6-dichlorobenzo[b]thiophene-2-carboxylic acid alleviates ulcerative colitis by suppressing mammalian target of rapamycin complex 1 activation and regulating intestinal microbiota

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World Journal of Gastroenterology 2022年第46期28卷 6522-6536页

作者： Qiong-Zi He Peng Wei Jun-Zhi Zhang Tong-Tong Liu Kun-Qun shi Huan-Huan Liu Jing-Wei Zhang shi-Jia Liu Affiliated Hospital of Nanjing University of Chinese Medicine Jiangsu Province Hospital of Chinese MedicineNanjing 210029Jiangsu ProvinceChina College of The First Clinical Medicine Nanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina School of Life Science and Technology China Pharmaceutical UniversityNanjing 211198Jiangsu ProvinceChina

BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin complex 1(mTORC1)activation.Previous studies have demonstrated the therapeutic effects of BT2 on arthritis,liver cancer,and kidney injury.However,the effects of BT2 on ulcerative colitis(UC)are unknown.AIM To investigate the anti-UC effects of BT2 and the underlying mechanism.METHODS Mouse UC models were created through the administration of 3.5%dextran sodium sulfate(DSS)for 7 d.The mice in the treated groups were administered salazosulfapyridine(300 mg/kg)or BT2(20 mg/kg)orally from day 1 to day 7.At the end of the study,all of the mice were sacrificed,and colon tissues were removed for hematoxylin and eosin staining,immunoblot analyses,and immunohistochemical assays.Cytokine levels were measured by flow cytometry.The contents of BCAAs including valine,leucine,and isoleucine,in mouse serum were detected by liquid chromatography-tandem mass spectrometry,and the abundance of intestinal flora was analyzed by 16S ribosomal DNA sequencing.RESULTS Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in mice.BT2 also reduced the production of the proinflammatory cytokines interleukin 6(IL-6),IL-9,and IL-2 and increased the anti-inflammatory cytokine IL-10 level.In addition,BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC mice.Furthermore,highthroughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with colitis.Compared with the DSS group,BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and Escherichia-shigella.CONCLUSION Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the latent mechanism involved the suppression of BCAA-as

关键词： 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid Ulcerative colitis Mechanistic target of rapamycin complex 1 Intestinal flora Dextran sodium sulfate Cyclooxygenase-2

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基于GAMIT/GLOBK大陆构造单元稳定性研究

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河南科学 2016年第9期34卷 1481-1485页

作者：牛群施昆昆明理工大学国土资源与工程学院昆明650093

中国大陆板块内部构造变形复杂,火山、地震等活动频繁,这导致各构造单元运动剧烈.因此研究今中国大地构造格局以及构造单元的相对移动趋势具有重要的意义.利用GAMIT/GLOBK软件对近几年某些构造单元的位移方向和位移量进行分析,提出了一... 详细信息

中国大陆板块内部构造变形复杂,火山、地震等活动频繁,这导致各构造单元运动剧烈.因此研究今中国大地构造格局以及构造单元的相对移动趋势具有重要的意义.利用GAMIT/GLOBK软件对近几年某些构造单元的位移方向和位移量进行分析,提出了一套完整的大陆构造单元稳定性分析的方法和流程,并通过IGS站数据进行了验证,结果表明该方法可行.基于GAMIT/GLOBK的GPS定位方法为大陆构造单元变化分析提供了先进、高效的手段和方法.

关键词：构造单元 GAMIT/GLOBK GPS 位移方向

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Bus passengers’anger scale and expression in anger-provoking situations

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Transportation Safety and Environment 2023年第1期5卷 18-30页

作者： Zhili Yuan qun Chen shi Ye School of Traffic and Transportation Engineering Central South UniversityChangsha 410075HunanChina.

This paper investigates the scale and expression of passengers’anger arising from disputes between drivers and passengers,and between passengers,by surveying a sample of 757 undergraduate students.The bus passengers’anger scale and expression inventory(BPASX),a newly-designed questionnaire battery,is used to analyse the anger levels and resulting behaviour expression of passengers in 6-item anger-provoking situations.The analysis shows that a positive correlation exists between the frequency or duration of bus rides and anger levels/external anger expression,while self-adaptive expression is only correlated with frequency.Gender differs only in the violent external expression,where males display a greater preference.Meanwhile,the correlations of anger levels between anger-provoking situations are significantly positive.Moreover,anger expression patterns gradually shift from self-adaptation to external expression as anger levels grow in general,but the variation rules of expression frequency are different.Overall,this study provides a newly effective tool to explore characteristics of the anger expression of bus passengers in different anger-provoking scenarios and demonstrates its variation features when anger levels change.

关键词： anger bus passengers expression bus passengers’anger and expression inventory(BPASX)

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Clinical characteristic and fecal microbiota responses to probiotic or antidepressant in patients with diarrhea-predominant irritable bowel syndrome with depression comorbidity: a pilot study

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Chinese Medical Journal 2019年第3期132卷 346-351页

作者： Lu Zhang Yi-Xuan Liu Zhe Wang Xiao-Qi Wang Jing-Jing Zhang Rong-Huan Jiang Xiang-qun Wang shi-Wei Zhu kun Wang Zuo-Jing Liu Huai-Qiu Zhu Li-Ping Duan Department of Gastroenterology Peking University Third HospitalBeijing 100191China Department of Biomedical Engineering College of Engineeringand Center for Quantitative BiologyPeking UniversityBeijing 100871China Department of Psychiatry Institute of Mental HealthPeking UniversityBeijing 100191China Department of Psychological Medicine Chinese People's Liberation Army (PLA)General HospitalBeijing 100853China

To the Editor: Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder that presents as abdominal pain with altered bowel habits. The pathophysiologic mechanism of IBS is not well understood, although many hypotheses have been proposed, including visceral hypersensitivity, gastrointestinal dysmotility, lowgrade inflammation of the intestinal mucosa, and dysfunction of the brain-gut interaction. Dysfunction of the braingut interaction is thought to be involved in IBS because a considerable proportion of patients with IBS have some form of psychologic comorbidity, such as depression or anxiety. In addition, mental and psychologic problems increase the risk for IBS and the symptom severity of IBS. Recently, changes in the gut microbiota have also been suggested to contribute to both IBS and depression. Our previous study demonstrated significant altered gut microbiota profiles in patients with diarrhea-predominant IBS (IBS-D) and depression.

关键词： fecal microbiota responses depression comorbidity diarrhea-predominant irritable bowel syndrome

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Engineering nano-clustered multivalent agonists to cross-link TNF receptors for cancer therapy

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Aggregate 2023年第6期4卷 209-220页

作者： Yue Zhang Gui Zhao Yi-Fang Chen shi-kun Zhou Yue Wang Yi-qun Sun Song Shen Cong-Fei Xu Jun Wang School of Biomedical Sciences and Engineering South China University of TechnologyGuangzhou International CampusGuangzhouP.R.China National Engineering Research Center for Tissue Restoration and Reconstruction South China University of TechnologyGuangzhouP.R.China Guangdong Provincial Key Laboratory of Biomedical Engineering South China University of TechnologyGuangzhouP.R.China Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education South China University of TechnologyGuangzhouP.R.China

Tumor necrosis factor receptors(TNFRs)are promising targets for cancer therapy.However,activating their downstream signaling requires cross-linking of TNFRs.Herein,to devise strong agonists of TNFRs,ligands targeting TNFRs,such as OX40L and tumor necrosis factor-related apoptosis-inducing ligand(TRAIL),were fused with a multivalent protein scaffold(MV)to prepare multivalent agonists for cross-linking TNFRs.The nano-clustered multivalent-OX40L(MV-OX40L)and MV-TRAIL could promote T cell activation and directly induce tumor cell apoptosis.Moreover,to develop a universal nano-adaptor for the rapid preparation of multivalent agonists of different TNFRs,the Fc receptor that could immobilize antibodies was fused with MV to prepare MV-FcR,which could multimerize commercial agonist antibodies targeting TNFRs,such as anti-OX40 antibody(αOX40).Simply incubatingαOX40 with MV-FcR could prepare MV-αOX40 to enhance its antitumor efficacy.In addition,MV-FcR could multimerize with other therapeutic antibodies,such as anti-PD-L1 antibody,to enhance their valency.This study provides a promising strategy for engineering multivalent antitumor protein drugs.

关键词： antibody cancer therapy drug delivery nanoparticle TNFR

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Epidemiology and evolution of Middle East respiratory syndrome coronavirus, 2012-2020

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Infectious Diseases of Poverty 2021年第3期10卷 1-13页

作者： An-Ran Zhang Wen-Qiang shi kun Liu Xin-Lou Li Ming-Jin Liu Wen-Hui Zhang Guo-Ping Zhao Jin-Jin Chen Xiao-Ai Zhang Dong Miao Wei Ma Wei Liu Yang Yang Li-qun Fang Department of Epidemiology School of Public HealthCheeloo College of MedicineShandong University44 West Wenhua RoadJinanPeople's Republic of China State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology20 Dong-Da StreetFengtai DistrictBeijing 100071People's Republic of China Department of Biostatistics College of Public Health and Health Professionsand Emerging Pathogens InstituteUniversity of FloridaGainesvilleFLUSA Department of Epidemiology Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational EnvironmentSchool of Public HealthAir Force Medical UniversityxranPeople's Republic of China Department of Medical Research Key Laboratory of Environmental Sense Organ Stress and Health of the Ministry of Environmental ProtectionPLA Stragetic Support Force Characteristic Medical CenterBeijingPeople's Republic of China Logistics College of Chinese People's Armed Police Forces TianjinPeople's Republic of China.

Background:The ongoing transmission of the Middle East respiratory syndrome coronavirus(MERS-CoV)in the Middle East and its expansion to other regions are raising concerns of a potential pandemic.An in-depth analysis about both population and molecular epidemiology of this pathogen is needed.Methods:MERS cases reported globally as of June 2020 were collected mainly from World Health Organization official reports,supplemented by other reliable sources.Determinants for case fatality and spatial diffusion of MERS were assessed with Logistic regressions and Cox proportional hazard models,respectively.Phylogenetic and phylogeographic analyses were performed to examine the evolution and migration history of MERS-CoV.Results:A total of 2562 confirmed MERS cases with 150 case clusters were reported with a case fatality rate of 32.7%(95%Cl:30.9-34.6%).Saudi Arabia accounted for 83.6%of the cases.Age of>65 years old,underlying conditions and>5 days delay in diagnosis were independent risk factors for death.However,a history of animal contact was associated with a higher risk(adjusted OR=297,95%Cl:1」0-7.98)among female cases65 years old.Diffusion of the disease was fastest from its origin in Saudi Arabia to the east,and was primarily driven by the transportation network.The most recent subclade C5.1(since 2013)was associated with non-synonymous mutations and a higher mortality rate.Phylogeographic analyses pointed to Riyadh of Saudi Arabia and Abu Dhabi of the United Arab Emirates as the hubs for both local and international spread of MERS-CoV.Conclusions:MERS-CoV remains primarily locally transmitted in the Middle East,with opportunistic exportation to other continents and a potential of causing transmission clusters of human cases.Animal contact is associated with a higher risk of death,but the association differs by age and sex.Transportation network is the leading driver for the spatial diffusion ofthe disease.These findings how this patho

关键词： Middle East respiratory syndrome MERS-CoV Case fatality rate Spatial diffusion Phylogeny Phylogeographic dynamic

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公安应急管理教育定位与教育实践探索

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广西警察学院学报 2018年第5期31卷 113-118页

作者：石琨石向群王君君南京森林警察学院江苏南京212300

公安应急管理教育内容具有政治法律、系统整合、过程控制、现场行动及转机塑形等属性,其价值、目标、功能、标准和效益定位与日常警务有所差异。公安应急管理教育人才培养目标定位,决定于教育本身具有多学科融合、实践操作和系统协同三... 详细信息

公安应急管理教育内容具有政治法律、系统整合、过程控制、现场行动及转机塑形等属性,其价值、目标、功能、标准和效益定位与日常警务有所差异。公安应急管理教育人才培养目标定位,决定于教育本身具有多学科融合、实践操作和系统协同三大属性,其认知、能力和情感目标也有一定特点。应采用理论讲授、实践训练和案例研讨三结合的教学模式,为总体国家安全提供基础、稳固的人才保障。

关键词：应急管理教育定位目标定位实践借鉴

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高压纳秒脉冲电场的细胞器生物电效应综述

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物理学报 2022年第6期71卷 422-433页

作者：郭雨怡石富坤王群季振宇庄杰中国科学技术大学生物医学工程学院(苏州)生命科学与医学部苏州215000 中国科学院苏州生物医学工程技术研究所苏州215000 空军军医大学军事生物医学工程学系西安710032

纳秒级高压脉冲电场的生物医学应用是近年来新兴的交叉学科研究领域,相比于微秒和毫秒级脉冲电场,高压纳秒脉冲电场不仅能够导致细胞膜结构极化和介电击穿,产生膜电穿孔,还可以穿透至细胞内部,引发诸如细胞骨架解聚、胞内钙离子释放及... 详细信息

纳秒级高压脉冲电场的生物医学应用是近年来新兴的交叉学科研究领域,相比于微秒和毫秒级脉冲电场,高压纳秒脉冲电场不仅能够导致细胞膜结构极化和介电击穿,产生膜电穿孔,还可以穿透至细胞内部,引发诸如细胞骨架解聚、胞内钙离子释放及线粒体膜电位耗散等细胞器生物电效应,吸引了学术界的广泛关注.本文首先介绍高压纳秒脉冲电场及其细胞器生物电作用的物理模型;然后对高压纳秒脉冲电场与细胞骨架、线粒体、内质网、细胞核等亚细胞结构的相互作用研究进行综述和总结;强调高压纳秒脉冲电场的细胞器作用与细胞死亡、细胞间通信等生物效应之间的联系;最后,凝练当前高压纳秒脉冲电场在生物医学研究中的关键技术问题,并对未来潜在的研究方向进行展望.

关键词：纳秒脉冲电场电穿孔生物电效应细胞器

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基于两岸四地警务合作的警学研讨话语体系之建构

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福建警察学院学报 2010年第1期24卷 31-35页

作者：石向群石琨南京森林公安学院治安系江苏南京210046 中国人民公安大学北京100038

两岸四地警学研讨机制需要梳理、研究和改进,科学建构警学研讨话语体系是系统解决相关问题的重要条件。可通以过规划话语主题,整合合作目标;巩固话语基础,营造合作环境;构建话语平台,推动合作深入;形成话语成果,促进推广应用,使两岸四... 详细信息

两岸四地警学研讨机制需要梳理、研究和改进,科学建构警学研讨话语体系是系统解决相关问题的重要条件。可通以过规划话语主题,整合合作目标;巩固话语基础,营造合作环境;构建话语平台,推动合作深入;形成话语成果,促进推广应用,使两岸四地警学研讨在更广阔的领域有更科学、持久的发展,为深化两岸四地警务合作和促进经济社会繁荣稳定服务。

关键词：警务合作两岸四地警学研讨话语体系建构设想

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Recollections of the COVID-19 Epidemiological Intelligence Task Force in China CDC, July 2021 to March 2022

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China CDC weekly 2022年第37期4卷 835-840页

作者： Lei Zhou Guoqing shi Hao Li Yanping Zhang qun Li Chinese Center for Disease Control and Prevention BeijingChina

INTRODUCTION The coronavirus disease 2019(COVID-19)pandemic has been going on for nearly three years since the coronavirus outbreak was first reported(1–3).China managed to control the unexpected first wave in Wuhan City,Hubei Province by using strictly compulsory measures(4–5).Later,to prevent imported infections and control subsequent local transmission,China adjusted and implemented a proactive strategy widely known as the Dynamic COVID-Zero Strategy(6–7).

关键词： COV measures collection

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