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Knockdown of insulin-like growth factor 2 gene disrupts mitochondrial functions in the liver

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Journal of Molecular Cell Biology 2021年第8期13卷 543-555页

作者： Weiwei Gui yiyi Zhu Shuiya Sun Weifen Zhu Bowen Tan Hanxin zhao Chengxin Shang Fenping Zheng Xihua Lin Hong Li Department of Endocrinology The Affiliated Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhouChina Peking Union Medical College Chinese Academy of Medical SciencesBeijingChina College of Medicine Zhejiang UniversityHangzhouChina Biomedical Research Center and Key Laboratory of Biotherapy of Zhejiang Province The Affiliated Sir Run Run Shaw HospitalZhejiang UniversityHangzhouChina

Even though insulin-like growth factor 2(IGF2)has been reported to be overexpressed in nonalcoholic fatty liver disease(NAFLD),its role in the progression of NAFLD and the potential mechanism remain largely *** in vitro models,we found that IGF2 was the key overexpressed gene in steatosis,suggesting a possible association between IGF2 and ***,loss-of-function experiments revealed that inhibition of IGF2 protein impaired mitochondrial biogenesis and *** additionally disrupted the expression changes of mitochondrial fusion and fission-related proteins necessary in maintaining mitochondrial ***,IGF2 knockdown reduced the mitochondrial membrane potential and increased the production of reactive oxygen ***,IGF2 regulates mitochondrial functions by modulating the expression of SIRT1 and its downstream gene *** research opens a new frontier on the role of IGF2 in energy metabolism,which potentially participates in the development of *** such,IGF2 is a potential therapeutic target against NAFLD.

关键词： insulin-like growth factor 2 mitochondrial function nonalcoholic fatty liver

Growth Kinetics of γ′ Particles in Incoloy 907

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Journal of Materials Science & Technology 1994年第2期10卷 127-130页

作者： Xu zhao Dongfa LI Ke YANG Cungan FAN and yiyi LI (Institute of Metal Research, Academia Sinica, Shenyang, 110015, China)(To whom correspondence should be addressed) Acad Sinica Shenyang China

The kinetics of growth of the γ' precipitate in an lncoloy 907 alloy have been studied. The kinetics of particle growth obeyed the tirne law predicted by the Lifshitz-Wagner theory. The distribution of γ'particle sizes was found to be significantly broader than the theoretical distribution of LifshitZ-Wagner theory. It is suggested that this is due to the relatively large lattice parameter mismatch between γ' and the Fe-Ni-Co matrix

关键词： Ni Growth Kinetics of Particles in Incoloy 907

SMAD7 expression in CAR-T cells improves persistence and safety for solid tumors

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Cellular & Molecular Immunology 2024年第3期21卷 213-226页

作者： Sixin Liang Rui Zheng Baile Zuo Jia Li yiyi Wang Yujie Han Hao Dong Xiaojuan zhao Yiting Zhang Pengju Wang Ruotong Meng Lintao Jia Angang Yang Bo Yan State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Department of Biochemistry and Molecular BiologyFourth Military Medical UniversityXi’anShaanxi710032China School of Medicine Technology Xinxiang Medical UniversityXinxiangHenan453003China Department of Obstetrics and Gynecology Xijing Hospital of Fourth Military Medical UniversityXi’anShaanxi710032China College of Life Science Yan’an UniversityYan’anShaanxi716000China Department of Immunology Fourth Military Medical UniversityXi’anShaanxi710032China

Despite the tremendous progress of chimeric antigen receptor T(CAR-T)cell therapy in hematological malignancies,their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment(TME)and systemic toxicity caused by excessive cytokine *** a key regulator of the immunosuppressive TME,TGF-βpromotes cytokine synthesis via the NF-κB ***,we coexpressed SMAD7,a suppressor of TGF-βsignaling,with a HER2-targeted CAR in engineered T *** novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-β-triggered exhaustion,which enabled sustained tumoricidal capacity after continuous antigen ***,SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T ***,SMAD7 downregulated TGF-βreceptor I and abrogated the interplay between the TGF-βand NF-κB pathways in CAR-T *** a result,these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-β.SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor ***,our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.

关键词： TGF-βpathway SMAD7 NF-κB pathway CAR-T-cell therapy Cytokine release syndrome(CRS)

Development and Diagnosis Performance of IgM-Based Rapid Antigen Test for Early Detection of SARS-CoV-2 Infection in a Large Cohort of Suspected COVID-19 Cases—USA,Poland,and Sweden,2021-2022

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China CDC weekly 2024年第37期6卷 953-961,I0009,I0010页

作者： Yihua Huang yiyi Pu Youhong Weng Yahan Wu Qing He Sofia Litchev Longyou zhao Haojie Ding Yunru Lai Jie Li Xiaojun Zheng Jinshu Chen XianqinXiong Shaohong Lu Fei Gao Meng Gao Qingming Kong Department of Laboratory Medicine Lishui Second People's Hospital Affiliated to Wenzhou Medical UniversityLishui CityZhejiang ProvinceChina Key Laboratory of Biomarkers and In Vitro Diagnosis Translation of Zhejiang province School of Laboratory Medicine and BioengineeringHangzhou Medical CollegeHangzhou CityZhejiang ProvinceChina School of Basic Medicine and Forensics Key Laboratory of Bio-tech Vaccine of Zhejiang ProvinceEngineering Research Center of Novel Vaccine of Zhejiang ProvinceHangzhou Medical CollegeHangzhou CityZhejiang ProvinceChina The Fifth Affiliated Hospital of Wenzhou Medical University Lishui CityZhejiang ProvinceChina Baylor College of Medicine HoustonTXUSA Department of Research and Development Hangzhou AllTest Biotech Co.LtdHangzhou CityZhejiang ProvinceChina

Introduction:Antigen testing has been crucial in effectively managing the coronavirus disease 2019(COVID-19)*** study evaluated the clinical performance of a nasopharyngeal swab(NPS)-based antigen rapid diagnostic test(Ag-RDT)compared to the gold standard real-time reverse transcription-polymerase chain reaction(RT-PCR)for early detection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).Methods:We developed an IgM-based rapid antigen test for early detection of SARS-CoV-2 *** July 2021 and January 2022,we analyzed 1,030 NPS samples from participants at three centers in different countries,using both antigen rapid diagnostic tests(Ag-RDT)and ***:The Ag-RDT demonstrated minimal detection limits as low as 0.1 ng/mL for recombinant N antigen and 100 TCID50/mL for heat-inactivated SARS-CoV-2 *** assessments involving four human coronaviruses and 13 other respiratory viruses showed no *** Ag-RDT assay(ALLtest)exhibited high sensitivity(93.18%-100%)and specificity(99.67%-100%)across all *** such as cycle threshold(Ct)values and the timing of symptoms since onset were influential,with sensitivity increasing at lower Ct values(<30)and within the first week of ***:The ALLtest Ag-RDT demonstrated high reliability and significant potential for diagnosing suspected COVID-19 cases.

关键词： Antigen specificity centers

Oxidized galectin-1 in SLE fails to bind the inhibitory receptor VSTM1 and increases reactive oxygen species levels in neutrophils

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Cellular & Molecular Immunology 2023年第11期20卷 1339-1351页

作者： Xu Jiang Xinyue Xiao Hao Li yiyi Gong Min Wang Huaxia Yang Lidan zhao Ying Jiang Yanping Wei Chongchong zhao Jin Li Yuling Chen Shan Feng Haiteng Deng Shiliang Ma Yue Xu Yudong Liu George C.Tsokos Minghong Jiang Xuan Zhan Medical Research Center State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalDepartment of RheumatologyBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijingChina Department of Rheumatology Key Laboratory of MyositisChina-Japan Friendship HospitalBeijingChina Department of Medicine Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMAUSA Medical Research Center Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina Department of Rheumatology Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineClinical Immunology CenterChinese Academy of Medical SciencesBeijingChina Department of Rheumatology and Clinical Immunology Peking Union Medical College HospitalClinical Immunology CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeThe Ministry of Education Key LaboratoryBeijingChina Department of Rheumatology Xiangya HospitalCentral South UniversityHunanChina MOE Key Laboratory of Bioinformatics Center for Synthetic&Systems BiologySchool of Life SciencesTsinghua UniversityBeijingChina Key Laboratory of Structural Biology of Zhejiang Province School of Life SciencesWestlake UniversityHangzhouZhejiangChina State Key Laboratory of Common Mechanism Research for Major Diseases Institute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina

Inhibitory immune receptors set thresholds for immune cell activation,and their deficiency predisposes a person to autoimmune ***,the agonists of inhibitory immune receptors remain largely unknown,representing untapped sources of treatments for autoimmune ***,we show that V-set and transmembrane domain-containing 1(VSTM1)is an inhibitory receptor and that its binding by the competent ligand soluble galectin-1(Gal1)is essential for maintaining neutrophil viability mediated by downregulated reactive oxygen species ***,in patients with systemic lupus erythematosus(SLE),circulating Gal1 is oxidized and cannot be recognized by VSTM1,leading to increased intracellular reactive oxygen species levels and reduced neutrophil *** neutrophil function or death contributes significantly to the pathogenesis of SLE by providing danger molecules and autoantigens that drive the production of inflammatory cytokines and the activation of autoreactive ***,serum levels of glutathione,an antioxidant able to convert oxidized Gal1 to its reduced form,were negatively correlated with SLE disease *** together,our findings reveal failed inhibitory Gal1/VSTM1 pathway activation in patients with SLE and provide important insights for the development of effective targeted therapies.

关键词： Systemic lupus erythematosus ROS VSTM1 Galectin-1 Glutathione

平面K型圆钢管搭接节点有限元参数分析与极限承载力计算公式

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建筑结构学报 2006年第4期27卷 30-36页

作者：陈誉赵宪忠陈以一同济大学土木工程学院上海200092

以平面K型圆钢管搭接节点的试验数据为基础,从节点极限承载力、变形过程和破坏模式等方面对搭接节点的非线性有限元建模方法进行了校验。重点考察了贯通腹杆受压且内隐蔽部分焊接的搭接节点的应力分布、塑性区扩展和破坏模式,以及几何... 详细信息

以平面K型圆钢管搭接节点的试验数据为基础,从节点极限承载力、变形过程和破坏模式等方面对搭接节点的非线性有限元建模方法进行了校验。重点考察了贯通腹杆受压且内隐蔽部分焊接的搭接节点的应力分布、塑性区扩展和破坏模式,以及几何参数、腹杆搭接顺序变化、内隐蔽部分焊接与否对各类搭接节点性能的影响。有限元参数分析结果表明,腹弦杆壁厚比的变化对搭接节点的破坏模式和承载性能影响较大;内隐蔽部分未焊接对贯通腹杆受压的节点极限承载力影响很小,但对贯通腹杆受拉的节点极限承载力影响很大。最后,在零间隙节点承载力计算公式的基础上,应用多元线性回归方法拟合出搭接节点的极限承载力计算公式;该公式与试验结果吻合良好,且具有较好的适用性。

关键词： K型圆钢管搭接节点极限承载力有限元分析参数分析

The global registry of COVID-19 clinical trials: indicating the design of traditional Chinese medicine clinical trials

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TMR Modern Herbal Medicine 2020年第3期3卷 140-146页

作者： Xuxu Wei Mengzhu zhao Chen zhao Xiaoyu Zhang Ruijin Qiu yiyi Lin Yang Sun Manke Guan Hongcai Shang The Key Laboratory of Chinese Internal Medicine of the Ministry of Education Dongzhimen Hospital Affiliated to Beijing University of Chinese MedicineBeijingChina First Teaching Hospital of Tianjin University of traditional Chinese medicine Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences College of Traditional Chinese Medicine Beijing University of Chinese Medicine International Institute of evidence-based traditional Chinese Medicine Beijing University of Chinese Medicine

Objective:To analyze the registration information of Corona Virus Disease 2019(COVID-19)related clinical trials from all the clinical trial registry accepted by the International Committee of Medical Journal Editors(ICMJE).Methods:All the database of ICMJE-accepted clinical trial registry platform were searched for COVID-19 related clinical trials that registered from December 8,2019 to February 19,***:All the database totally contained data of 209 COVID-19 related clinical trials,including 66(31.6%)traditional Chinese medicine(TCM)related studies and 143(68.4%)non-TCM related studies.176(84.2%)clinical trials were registered in ChiCTR,as 33(15.8%)were registered in *** were 152(72.7%)intervention trials,including 9(4.3%in total)preventive trials,136(65.1%in total)therapeutic trials and 7(3.3%in total)convalescent ***:At the present stage,clinical studies are still aiming at exploring the effective treatment of COVID-19,and the existing treatments need more high-quality clinical evidence *** Chinese medicine may have played an important role in all stages of the epidemic preventing and control,and the enthusiasm of carrying out scientific research has also been greatly *** relevant policies of clinical trial registration should be popularized among researchers,including traditional Chinese medicine *** the methodological quality of clinical trials’design urges improving.

关键词： COVID-19 Clinical trial Register Data analysis

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空间网格结构连续性倒塌试验研究

建筑结构学报 2016年第6期37卷 1-8页

作者：赵宪忠闫伸陈以一同济大学土木工程学院上海200092 同济大学土木工程防灾国家重点实验室上海200092

为研究空间网格结构遭遇局部初始破坏后的结构响应、倒塌过程与倒塌机制,以单层球面网壳结构为研究对象,进行了1个直径为4.2 m,矢跨比为1/7的凯威特型网壳结构整体模型的连续性倒塌试验。施加节点集中荷载,采用自主研发的杆件破断触发... 详细信息

为研究空间网格结构遭遇局部初始破坏后的结构响应、倒塌过程与倒塌机制,以单层球面网壳结构为研究对象,进行了1个直径为4.2 m,矢跨比为1/7的凯威特型网壳结构整体模型的连续性倒塌试验。施加节点集中荷载,采用自主研发的杆件破断触发装置使网壳模型的1根经向杆件发生突然破断,并以采样频率100 Hz采集网壳模型各位置杆件的高频动应变响应,基于高速摄像测量技术(帧频200 fps)获取模型节点的高速动位移响应。初始破坏发生后,网壳模型呈现出自破坏局部向周围逐步扩展的连续性破坏,最终整个模型完全翻转并在一系列最外层杆件断裂后部分坠落。试验结果表明:尽管单层球面网壳结构杆件众多,但单根杆件的失效仍可能触发连锁反应,导致整体结构的连续性倒塌;单根杆件破坏后,局部内力重分布导致的杆端节点出现点失稳,并引发周围节点顺次向下运动,这也是单层球面网壳结构遭遇局部初始破坏后倒塌的主要模式。

关键词：空间网格结构连续性倒塌试验研究倒塌机制破坏模式

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超高层结构伸臂桁架的承载力及刚度简化计算

同济大学学报（自然科学版） 2014年第3期42卷 358-364页

作者：王斌陈以一赵宪忠同济大学土木工程防灾国家重点实验室上海200092 同济大学土木工程学院上海200092

对超高层结构体系中常用的伸臂桁架-单斜腹杆型式(N型)从桁架机制与刚架机制出发、依据伸臂桁架破坏模式建立了简化计算模型,揭示其受力机理.采用有限元模型对伸臂桁架的承载力和刚度指标进行了评估,得知斜腹杆是伸臂桁架主要的受力构件... 详细信息

对超高层结构体系中常用的伸臂桁架-单斜腹杆型式(N型)从桁架机制与刚架机制出发、依据伸臂桁架破坏模式建立了简化计算模型,揭示其受力机理.采用有限元模型对伸臂桁架的承载力和刚度指标进行了评估,得知斜腹杆是伸臂桁架主要的受力构件,对伸臂桁架整体承载力以及刚度均起着决定性作用.有限元计算值同简化模型计算结果较为接近,表明所提出的简化模型可以应用于伸臂桁架初步设计中的承载力及刚度的计算.

关键词：超高层结构伸臂桁架简化模型有限元计算承载力刚度