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STUB1 regulates antiviral RNAi through inducing ubiquitination and degradation of Dicer and AGO2 in mammals

Virologica Sinica 2022年第4期37卷 569-580页

作者： Shumin zhang xuhua zhang Yuanyuan Bie Jing Kong An Wang Yang Qiu Xi Zhou State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhan 430071China University of Chinese Academy of Sciences Beijing 100049China

RNA interference(RNAi)is an intrinsic antiviral immune mechanism conserved in diverse eukaryotic organisms.However,the mechanism by which antiviral RNAi in mammals is regulated is poorly understood.In this study,we uncovered that the E3 ubiquitin ligase STIP1 homology and U-box-containing protein 1(STUB1)was a new regulator of the RNAi machinery in mammals.We found that STUB1 interacted with and ubiquitinated AGO2,and targeted it for degradation in a chaperon-dependent manner.STUB1 promoted the formation of Lys48(K48)-linked polyubiquitin chains on AGO2,and facilitated AGO2 degradation through ubiquitin-proteasome system.In addition to AGO2,STUB1 also induced the protein degradation of AGO1,AGO3 and AGO4.Further investigation revealed that STUB1 also regulated Dicer's ubiquitination via K48-linked polyubiquitin and induced the degradation of Dicer as well as its specialized form,termed antiviral Dicer(avi Dicer)that expresses in mammalian stem cells.Moreover,we found that STUB1 deficiency up-regulated Dicer and AGO2,thereby enhancing the RNAi response and efficiently inhibiting viral replication in mammalian cells.Using the newborn mouse model of Enterovirus A71(EV-A71),we confirmed that STUB1 deficiency enhanced the virus-derived si RNAs production and antiviral RNAi,which elicited a potent antiviral effect against EV-A71 infection in vivo.In summary,our findings uncovered that the E3 ubiquitin ligase STUB1 was a general regulator of the RNAi machinery by targeting Dicer,avi Dicer and AGO1–4.Moreover,STUB1 regulated the RNAi response through mediating the abundance of Dicer and AGO2 during viral infection,thereby providing novel insights into the regulation of antiviral RNAi in mammals.

关键词： Antiviral RNAi STIP1 homology and U-box-containing protein 1(STUB1) Argonaute 2(AGO2) Dicer

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Novel T cells with improved in vivo anti-tumor activity generated by RNA electroporation

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Protein & Cell 2017年第7期8卷 514-526页

作者： Xiaojun Liu Shuguang Jiang Chongyun Fang Hua Li xuhua zhang Fuqin zhang Carl H. June Yangbing Zhao Key Laboratory for Experimental Teratology of Ministry of Education and Department of Immunology School of Basic Medical Sciences Shandong University Jinan 250012 China Center for Cellular Immunotherapies University of Pennsylvania Cancer Center Philadelphia PA 19104 USA Department of Pathology and Laboratory Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA 19104-5156 USA

The generation of T cells with maximal anti-tumor activities will significantly impact the field of T-cell- based adoptive immunotherapy. In this report, we found that OKT3/IL-2-stimulated T cells were phenotypically more heterogeneous, with enhanced anti-tumor activity in vitro and when locally administered in a solid tumor mouse model. To further improve the OKT3/IL-2-based T cell manufacturing procedure, we developed a novel T cell stimulation and expansion method in which peripheral blood mononuclear cells were electroporated with mRNA encoding a chimeric membrane protein consisting of a single-chain variable fragment against CD3 and the intracellular domains of CD28 and 4-1BB （OKT3-28BB）. The expanded T cells were phenotypically and functionally similar to T cells expanded by OKT3/IL-2. Moreover, co-electroporation of CD86 and 4-1BBL could further change the phenotype and enhance the in vivo anti-tumor activity. Although T cells expanded by the co- electroporation of OKT3-28BB with CD86 and 4-1BBL showed an increased central memory phenotype, the T cells still maintained tumor lytic activities as potent as those of OKT3/IL-2 or OKT3-28BB-stimulated T cells. In different tumor mouse models, T cells expanded by OKT3-28BB RNA electroporation showed anti-tumor activities superior to those of OKT3/IL-2 T cells. Hence, T cells with both a less differentiated phenotype and potent tumor killing ability can be generated by RNA electroporation, and this T cell manufacturing procedure can be further optimized by simply co-delivering other splices of RNA, thus providing a simple and cost-effec- tive method for generating high-quality T cells for adop- tive immunotherapy.

关键词： T lymphocytes CAR manufacture genetransfer RNA electroporation

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A New Cultivation-Evolution Technology of Accident Immune Function for a Petrochemical Enterprise

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China Petroleum Processing & Petrochemical Technology 2007年第1期9卷 41-46页

作者： Yang Zhenhong zhang xuhua Wang Xiangyao Wang Zhihu Liu Yank zhang Xuan School of Material Sci. and Eng. Xi＇an Univ. of Arch. ＆ Tech. Xi＇an 710055 School of Energy Eng. Xi＇an Univ. ofSci. ＆ Tech. Xi＇an 710054

为在一家石油化学的企业在生产事故上开发一个有免疫力的函数的目的，预防机制的一条新耕作进化途径被分析关于有免疫力的缺乏症候群的各种各样的因素建议，由指免疫，基因算法和相关概念在药science.Accident免疫系统申请了高度危险的... 详细信息

为在一家石油化学的企业在生产事故上开发一个有免疫力的函数的目的，预防机制的一条新耕作进化途径被分析关于有免疫力的缺乏症候群的各种各样的因素建议，由指免疫，基因算法和相关概念在药science.Accident免疫系统申请了高度危险的石油化学的企业，它由它的生产系统的安全 Organand 安全组织组成，典型地是为有免疫力的功能的进化耕作进步，新 Bimmune 房间在几层的家以后被产生屏蔽，克隆膨胀， receptored iting ，在石油化学的企业在工作事故的免疫系统组织。有有高本能的一个 B 有免疫力的房间，一个功利性的函数作为解决方案作为目标函数和有免疫力的抗体在工业为 accident-immunity.Taking 锁住事故的抗原，作者 scarried 外面为在抗原和抗体之间的本能的预言的一张计算图。

关键词：石化企业事故预防培养-进化技术免疫遗传算法

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Viromes of Haemaphysalis longicornis reveal different viral abundance and diversity in free and engorged ticks

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Virologica Sinica 2024年第2期39卷 194-204页

作者： Jian Xiao Xuan Yao xuhua Guan Jinfeng Xiong Yaohui Fang Jingyuan zhang You zhang Abulimiti Moming Zhengyuan Su Jiayin Jin Yingying Ge Jun Wang Zhaojun Fan Shuang Tang Shu Shen Fei Deng Key Laboratory of Virology and Biosafety and National Virus Resource Center Wuhan Institute of VirologyChinese Academy of SciencesWuhan430071China Hubei Provincial Center for Disease Control and Prevention Wuhan430070China University of Chinese Academy of Sciences Beijing101408China Hubei Jiangxia Laboratory Wuhan430200China Xinjiang Key Laboratory of Vector-borne Infectious Diseases Urumqi830002China Current address:Department of Medical Laboratory The Second Affiliated HospitalHainan Medical UniversityHaikou57000China

Haemaphysalis longicornis ticks,commonly found in East Asia,can transmit various pathogenic viruses,includingthe severe fever with thrombocytopenia syndrome virus(SFTSV)that has caused febrile diseases among humansin Hubei Province.However,understanding of the viromes of H.longicornis was limited,and the prevalence ofviruses among H.longicornis ticks in Hubei was not well clarified.This study investigates the viromes of bothengorged(fed)and free(unfed)H.longicornis ticks across three mountainous regions in Hubei Province from 2019to 2020.RNA-sequencing analysis identified viral sequences that were related to 39 reference viruses belonging tounclassified viruses and seven RNA viral families,namely Chuviridae,Nairoviridae,Orthomyxoviridae,Parvoviridae,Phenuiviridae,Rhabdoviridae,and Totiviridae.Viral abundance and diversity in these ticks were analysed,andphylogenetic characteristics of the Henan tick virus(HNTV),Dabieshan tick virus(DBSTV),Okutama tick virus(OKTV),and Jingmen tick virus(JMTV)were elucidated based on their full genomic sequences.Prevalenceanalysis demonstrated that DBSTV was the most common virus found in individual H.longicornis ticks(12.59%),followed by HNTV(0.35%),whereas JMTV and OKTV were not detected.These results improve our understanding of H.longicornis tick viromes in central China and highlight the role of tick feeding status and geographyin shaping the viral community.The findings of new viral strains and their potential impact on public health raisethe need to strengthen surveillance efforts for comprehensively assessing their spillover potentials.

关键词： Ticks Virome Haemaphysalis longicornis Phylogenetic analysis Viral abundance and diversity

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Prevalence and associated factors of chronic obstructive pulmonary disease in greenhouse working farmers among Liaoning Province in China A Large,Cross-sectional Survey

Prevalence and associated factors of chronic obstructive pul...

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中华医学会呼吸病学年会——2013（第十四次全国呼吸病...

作者： shuo liu deliang wen yu chen donghong chen liyun li xuhua zhang yibing zhang shuang fu zhenhua li shuyue xia dongliang wang hong chen jian zhao yangang ren xiaoge wang The Fourth Affiliated Hospital China Medical University The Second Affiliated Hospital The First Affiliated Hospital The Shenyang Military General Hospital The General Hospital of Fushun Mining Bureau Fengtian Hospital Shenyang Medical College 202 Hospital of Peoples Liberation Army The First People’s Hospital of Kazuo 205 Hospital of Peoples Liberation Army

Rationale The prevalence and associated factors of chronic obstructive pulmonary disease(COPD) in greenhouse working farmers in Liaoning Province of China is unclear. Objectives To record the prevalence and associated factors of chronic obstructive pulmonary disease in greenhouse working farmers in Liaoning Province of China. Methods Cross-sectional studies of random samples of

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恶性肿瘤患者合并感染的临床分析

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中南大学学报（医学版） 2010年第11期35卷 1183-1188页

作者：张旭华曹培国中南大学湘雅三医院肿瘤科长沙410013 河南省肿瘤医院中心实验室郑州450008

目的:探讨恶性肿瘤患者合并感染时病原菌的分布及年度动态变迁、病原菌对常用抗菌药物的耐药情况。方法:对489例恶性肿瘤患者合并感染的情况进行回顾性分析。结果:感染部位以呼吸道为主,占61.1%。感染的病原菌主要是条件致病菌,其中G-... 详细信息

目的:探讨恶性肿瘤患者合并感染时病原菌的分布及年度动态变迁、病原菌对常用抗菌药物的耐药情况。方法:对489例恶性肿瘤患者合并感染的情况进行回顾性分析。结果:感染部位以呼吸道为主,占61.1%。感染的病原菌主要是条件致病菌,其中G-菌占首位(46.3%),以铜绿假单胞菌、大肠埃希菌、鲍曼不动杆菌为主;其次为G+菌(29.9%),以金黄色葡萄球菌和表皮葡萄球菌为主;真菌居第3位(23.8%),以白色念珠菌为主。G-菌对青霉素类、头孢菌素类(除头孢他啶外)、磺胺类、四环素类、喹诺酮类抗生素耐药率较高;G+菌对青霉素类、大环内酯类、喹诺酮类抗生素耐药率较高;真菌对氟康唑、伊曲康唑耐药率较高。从5年感染率的变化趋势来看,真菌感染有明显上升趋势。结论:恶性肿瘤患者合并感染的病原菌大多为条件致病菌,并且对常用抗菌药物耐药情况严重。真菌感染上升趋势明显。

关键词：恶性肿瘤医院感染病原菌耐药性

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基于自适应上下文匹配网络的小样本知识图谱补全

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计算机科学 2024年第5期51卷 223-231页

作者：杨旭华张炼叶蕾浙江工业大学计算机科学与技术学院杭州310023

知识图谱在构建过程中需要面对繁杂的现实世界信息,无法建模所有知识,因此需要补全。真实的知识图谱中很多类型的关系通常只有少量的训练实体样本对。因此,如何进行小样本知识图谱补全是一个十分有价值的问题。目前基于嵌入的方法一般... 详细信息

知识图谱在构建过程中需要面对繁杂的现实世界信息,无法建模所有知识,因此需要补全。真实的知识图谱中很多类型的关系通常只有少量的训练实体样本对。因此,如何进行小样本知识图谱补全是一个十分有价值的问题。目前基于嵌入的方法一般通过注意力机制等方法聚合实体上下文信息,通过学习关系嵌入的方式来补全知识图谱,仅考虑关系层面的匹配程度,虽然能够预测未知关系,但往往准确度不高。针对小样本知识图谱补全问题,提出了一个自适应上下文匹配网络(Adaptive Context Matching Network,ACMN)。首先提出一个共性邻居感知编码器,聚合参考集实体上下文,即一跳邻居实体,获得共性邻居感知编码;接着提出一个任务相关实体编码器,挖掘任务实体上下文与共性上下文的相似度信息,区分一跳邻居对当前任务的贡献,增强实体表征;然后提出一个上下文关系编码器获得动态关系表征;最后通过加权求和综合考虑实体上下文和关系的匹配程度,完成补全。ACMN从实体上下文相似度和关系匹配程度两个方面综合评价查询三元组是否成立,能够在小样本的背景下有效提高预测准确性。在两个公共数据集上和其他8个广泛使用的算法进行比较,ACMN在不同规模的小样本情况下,取得了目前最好的补全结果。

关键词：知识图谱补全小样本学习实体上下文关系预测表示学习

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曹魏九品中正制再探讨——与王晓毅先生商榷

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文史哲 2008年第6期 94-104页

作者：张旭华郑州大学历史学院

夏侯玄《时事议》的核心论旨,是要理顺中央吏部、台省长官与州郡中正三者之间的关系。文中所说"伦辈"、"辈类"诸语,是中正在品第人物时使用的专业术语,与曹魏三年一定品之制有关,意指列为同品。官品制度并非始于咸熙元年之后,而是创立... 详细信息

夏侯玄《时事议》的核心论旨,是要理顺中央吏部、台省长官与州郡中正三者之间的关系。文中所说"伦辈"、"辈类"诸语,是中正在品第人物时使用的专业术语,与曹魏三年一定品之制有关,意指列为同品。官品制度并非始于咸熙元年之后,而是创立于曹魏初年。上品二品与起家官品的对应关系并非是相差四品,而是表现为多层次性。自九品中正制一创立,中正之"品"就与"家世"有关,具有"门第"色彩。但"资品"之"资"不是指门资、世资,而是指资格、资历,与"家世"无关。

关键词：曹魏伦辈三年一定品官品制度中正品第家世

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Study on embedded length of piles for slope reinforced with one row of piles

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Journal of Rock Mechanics and Geotechnical Engineering 2011年第2期3卷 167-178页

作者： Shikou Yang, xuhua Ren, Jixun zhang College of Water Conservancy and Hydropower Engineering, Hohai University, Nanjing, 210098, China College of Water Conservancy and Hydropower Engineering Hohai University Nanjing 210098 China

The embedded length of anti-slide piles for slope is analyzed by three-dimensional elastoplastic shear strength reduction method. The effect of embedded pile length on the factor of safety and pile behavior is analyzed. Furthermore, the effects of pile spacing, pile head conditions, pile bending stiffness and soil properties on length and behavior of pile are also analyzed. The results show that the pile spacing and the pile head conditions have significant influences on the critical embedded length of pile. It is found that the critical embedded length of pile, beyond which the factor of safety does not increase, increases with the decrease in pile spacing. The smaller the pile spacing is, the larger the integrity of the reinforced slope will be. A theoretical analysis of the slip surface is also conducted, and the slip surface determined by the pressure on piles, considering the influences of both soil and piles for slope, is in agreement with the ones in previous studies.

关键词： slope stability factor of safety embedded pile length strength reduction method slip surface

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企业间技术合作的动因及利润影响:动态博弈观点

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科学学与科学技术管理 2005年第11期26卷 142-145页

作者：张旭华福建社会科学院决策科学研究中心福建福州350001

考察了企业之间的水平技术合作形式,并在定义了技术合作的市场效应和成本效应的基础上,运用二阶段动态博弈模型分析了两个具有同等技术含量的企业之间的技术合作为何发生、如何发生以及合作对企业的产品定价和利润究竟产生了怎样的影响。

关键词：技术合作博弈动态

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