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TRAF3 activates STING-mediated suppression of EV-A71 and target of viral evasion

Signal Transduction and Targeted Therapy 2023年第3期8卷 1296-1309页

作者： Wenwen zheng Zhenbang Zhou yajuan Rui Runxin Ye Fengyan Xia Fei Guo Xiaoman Liu Jiaming Su Meng Lou Xiao-Fang Yu Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China National Health Commission of the People’s Republic of China Key Laboratory of Systems Biology of Pathogens Institute of Pathogen Biology and Center for AIDS ResearchChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Cancer Center Zhejiang UniversityHangzhouZhejiang 310058China

Innate immunity represents one of the main host responses to viral infection.1,2,3 STING(Stimulator of interferon genes),a crucial immune adapter functioning in host cells,mediates cGAS(Cyclic GMP-AMP Synthase)sensing of exogenous and endogenous DNA fragments and generates innate immune responses.4 Whether STING activation was involved in infection and replication of enterovirus remains largely *** the present study,we discovered that human enterovirus A71(EV-A71)infection triggered STING activation in a cGAS dependent ***-A71 infection caused mitochondrial damage and the discharge of mitochondrial DNA into the cytosol of infected ***,during EV-A71 infection,cGAS-STING activation was ***-A71 ^(pro)teins were screened and the viral ^(pro)tease 2A^(pro) had the greatest capacity to inhibit cGAS-STING *** identified TRAF3 as an important factor during STING activation and as a target of 2A^(pro).Supplement of TRAF3 rescued cGAS-STING activation suppression by 2A^(pro).TRAF3 supported STING activation mediated TBK1 ***,we found that 2A^(pro) ^(pro)tease activity was essential for inhibiting STING ***,EV-D68 and CV-A16 infection also triggered STING *** viral ^(pro)tease 2A^(pro) from EV-D68 and CV-A16 also had the ability to inhibit STING *** STING activation prior to EV-A71 infection generated cellular resistance to EV-A71 replication,blocking EV-A71-mediated STING suppression represents a new anti-viral target.

关键词： mediated TRAF3 immunity

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TMEM16A inhibits angiotensin Ⅱ-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner

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Acta Pharmaceutica Sinica B 2021年第12期11卷 3994-4007页

作者： Huaqing zheng Xiaolong Li Xin Zeng Chengcui Huang Mingming Ma Xiaofei Lv yajuan Zhang Lu Sun Guanlei Wang Yanhua Du Yongyuan Guan Department of Pharmacology Cardiac&Cerebral Vascular Research CenterZhongshan School of MedicineSun Yat-sen UniversityGuangzhou 510080China

Vascular smooth muscle cell(VSMC) migration plays a critical role in the pathogenesis of many cardiovascular *** recently showed that TMEM16 A is involved in hypertensioninduced cerebrovascular ***,it is unclear whether this effect is related to the regulation of VSMC ***,we investigated whether and how TMEM16 A contributes to migration in basilar artery smooth muscle cells(BASMCs).We observed that AngⅡ increased the migration of cultured BASMCs,which was markedly inhibited by overexpression of TMEM16 ***16 A overexpression inhibited AngⅡ-induced RhoA/ROCK2 activation,and myosin light chain phosphatase(MLCP)and myosin light chain(MLC20) *** AnsⅡ-induced myosin light chain kinase(MLCK)activation was not affected by TMEM16 ***,a suppressed activation of integrinβ3/FAK pathway,determined by reduced integrinβ3 expression,FAK phosphorylation and F-actin rearrangement,was observed in TMEM16 A-overexpressing BASMCs upon AngⅡ *** to the results of TMEM16 A overexpression,silencing of TMEM16 A showed the opposite *** in vitro results were further demonstrated in vivo in basilar arteries from VSMC-specific TMEM10 A transgenic mice during AngⅡ-induced ***,we observed that the inhibitory effect of TMEM16 A on BASMC migration was mediated by decreasing the activation of WNK1,a Cl^(-)-sensitive serine/threonine *** conclusion,this study demonstrated that TMEM16 A suppressed AnsⅡ-induced BASMC migration,thus contributing to the protection against cerebrovascular remodeling during AngⅡ-infused ***16 A may exert this effect by suppressing the RhoA/ROCK2/MLCP/MLC20 and integrinβ3/FAK signaling pathways via inhibiting *** results suggest that TMEM16 A may serve as a novel therapeutic target for VSMC migration-related diseases,such as vascular remodeling.

关键词： TMEM16A Integrin RhoA/ROCK VSMC migration Vascular remodeling WNK1 Hypertension FAK

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Zircon U-Pb Geochronology and Hf Isotopic Constraints on Petrogenesis of Plagiogranite from the Cuomuqu Ophiolite,Bangong Lake Area,North Tibet

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Acta Geologica Sinica(English Edition) 2015年第2期89卷 418-440页

作者： YIN zhengxin YUAN yajuan Lü Baofeng CAI Zhourong zheng Hao HUANG Qiangtai XIA Bin ZHONG Yun XIA Zhongyu SHI Xiaolong GUAN Yao School of Marine Sciences Sun Yat-sen University Key Laboratory of Offshore Oil Exploration and Development of Guangdong Higher Education Institutes Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering

Field observation, geochemical signatures and zircon Hf isotope data indicate that Cuomuqu ophiolite in the Bangonghu area was formed in a back-arc basin （BAB） above a supra- subduction zone （SSZ）. Zircon U-Pb dating of the diabase from the Cuomuqu massif yielded an age of 164.3±1.9 Ma, thus indicating that the ophiolite complex was formed in the Middle Jurassic during back-arc extension of the mature Bangonghu-Nujiang Ocean. The zircon εHf（t） and TDMC values of the plagiogranite are similar to the εHf（t） and TDM of the diabase, respectively. The mode of occurrence of plagiogranites and their bulk-rock and Hf isotope characteristics indicate that they were derived from the mantle, associated with the surrounding gabbro and diabase, and were formed by partial melting of altered and hydrated mafic rocks under shear conditions during lateral drifting of the oceanic crust. The zircon U-Pb age of the plagiogranite is 156.4±1.4 Ma, and it is 7.9 Ma younger than the hosting diabase. In this study, zircon chronological and Hf isotopic data were tentatively analyzed to determine the genesis of plagiogranites in the Cuomuqu ophiolite complex.

关键词： Bangonghu-Nujiang suture zone ophiolite plagiogranite zircon U-Pb dating zircon Hf isotope tectonic setting

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Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins

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Signal Transduction and Targeted Therapy 2021年第4期6卷 1320-1330页

作者： yajuan Rui Jiaming Su Si Shen Ying Hu Dingbo Huang Wenwen zheng Meng Lou Yifei Shi Meng Wang Shiqi Chen Na Zhao Qi Dong Yong Cai Rongzhen Xu Shu zheng Xiao-Fang Yu Cancer Institute Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina School of Life Science Jilin UniversityChangchunChina Department of Hematology Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouChina

The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic,leading to millions of infections and hundreds of thousands of human *** efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses,although the viral proteins responsible for this immune evasion are not *** this study,we identified SARS-CoV-2 structural proteins,accessory proteins,and the main viral protease as potent inhibitors of host innate immune responses of distinct *** particular,the main viral protease was a potent inhibitor of both the RLR and cGAS-STING *** accessory protein 0RF3a had the unique ability to inhibit STING,but not the RLR *** the other hand,structural protein N was a unique RLR inhibitor.0RF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-KB signaling.3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream *** vertebrate STINGs,including those from humans,mice,and chickens,could be inhibited by 0RF3a and 3CL of *** existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in *** evasion of host innate immune responses is essential for the survival of all viruses,our study provides insights into the design of therapeutic agents against SARS-CoV-2.

关键词： inhibited complementary hundreds

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Promotion of liquid-to-solid phase transition of cGAS by Baicalein suppresses lung tumorigenesis

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1392-1395页

作者： Tiansheng zheng Haipeng Liu Yifan Hong yajuan Cao Qing Xia Chengge Qin Ming Li Russel J.Reiter Yidong Bai Lihong Fan Department of Respiratory Medicine Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Department of Integrated Traditional Chinese&Western Medicine Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Clinical Translational Research Center Shanghai Pulmonary HospitalTongji University School of MedicineShanghai 200433China Institute of Energy Metabolism and Health Shanghai Tenth People’s HospitalTongji University School of MedicineShanghai 200072China Institute of Molecular Physiology Institue of Cancer ResearchShenzhen Bay LaboratoryShenzhen 518132China Medical School of Nantong University NantongJiangsu 22601China Department of Cell Systems and Anatomy University of Texas Health San AntonioSan AntonioTexas 78229USA

Dear Editor,Kras and p53 mutation are among the most common gene mutations in lung cancer,which has both the highest incidence and mortality rate among cancers.1 Kras/p53 mutation also causes mitochondrial dysfunction,which has been implicated to promote the inflammation-to-cancer transition.2 We established a lung adenocarcinoma model by using conditional alleles of KrasLSLG12D/p53flox/flox in mice3 to evaluate the effect of Baicalein(5,6,7-trihydroxyflavone),a principal component of Scutellaria baicalensis in traditional Chinese medicine,4 on the initiation and progression of lung ***-mediated expression of KrasG12D and deletion of p53 caused obvious tumor lesions in the lung,which were strongly inhibited by the administration of Baicalein(Fig.1a,b and Supplementary Fig.1a,b),indicating that Baicalein is highly potent in inhibiting the progression of primary lung cancer.

关键词： lung Baicalein inhibited

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Preparation of Cu-SiO_2 composite aerogel by ambient drying and the influence of synthesizing conditions on the structure of the aerogel

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Chinese Science Bulletin 2011年第7期56卷 685-690页

作者： LI GuiAn, ZHU TingLiang, DENG ZhongXun, ZHANG yajuan, JIAO Fei & zheng HaiRong College of Physics and Information Technology, Shaanxi Normal University, Xi’an 710062, China College of Physics and Information Technology Shaanxi Normal University Xi’an China

A copper-doped silica composite aerogel with high specific surface area was prepared using a sol-gel method at ambient pressure. A drying control chemical additive (DCCA) N,N-dimethylformamide (DMF) was introduced to the composite sol of tetraethyl orthosilicate (TEOS) and copper nitrate (Cu(NO3)2·3H2O) during the synthesizing process. The influence of the preparation conditions including Cu loading, catalyst concentration and heat treatment on the structure of copper-doped silica was investigated. The results showed that the obtained aerogel particles were uniformly distributed. The pore diameter was in a range of 2 to 15 nm. Heavier Cu loading benefited the formation of CuO crystalline, and reduced the specific surface area and pore diameter. When the catalyst concentration was high, the aggregation of Si-O network was reduced with the increase of it. The composite aerogel exhibited a good thermal stability after the heat treatment at high temperature.

关键词：复合气凝胶铜掺杂凝胶结构合成条件 Si02 常压正硅酸乙酯溶胶凝胶法

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Clinical features and the traditional Chinese medicine therapeutic characteristics of 293 COVID-19 inpatient cases

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Frontiers of Medicine 2020年第6期14卷 760-775页

作者： Zixin Shu Yana Zhou Kai Chang Jifen Liu Xiaojun Min Qing Zhang Jing Sun yajuan Xiong Qunsheng Zou Qiguang zheng Jinghui Ji Josiah Poon Baoyan Liu Xuezhong Zhou Xiaodong Li Institute of Medical Intelligence School of Computer and Information TechnologyBeijing Jiaotong UniversityBeijing 100044China Hubei Provincial Hospital of Traditional Chinese Medicine Wuhan 430061China Institute of Liver Diseases Hubei Provincial Academy of Traditional Chinese MedicineWuhan 430061China School of Computer Science The University of SydneySydneyNew 2006Australia Analytic and Clinical Cooperative Laboratory for Integrative Medicine USYD&CUHKSydneyNSW 2006Australia China Academy of Chinese Medical Sciences Beijing 100700China

Coronavirus disease 2019 (COVID-19) is now pandemic worldwide and has heavily overloaded hospitals in Wuhan City, China during the time between late January and February. We reported the clinical features and therapeutic characteristics of moderate COVID-19 cases in Wuhan that were treated via the integration of traditional Chinese medicine (TCM) and Western medicine. We collected electronic medical record (EMR) data, which included the full clinical profiles of patients, from a designated TCM hospital in Wuhan. The structured data of symptoms and drugs from admission notes were obtained through an information extraction process. Other key clinical entities were also confirmed and normalized to obtain information on the diagnosis, clinical treatments, laboratory tests, and outcomes of the patients. A total of 293 COVID-19 inpatient cases, including 207 moderate and 86 (29.3%) severe cases, were included in our research. Among these cases, 238 were discharged, 31 were transferred, and 24 (all severe cases) died in the hospital. Our COVID-19 cases involved elderly patients with advanced ages (57 years on average) and high comorbidity rates (61%). Our results reconfirmed several well-recognized risk factors, such as age, gender (male), and comorbidities, as well as provided novel laboratory indications (e.g., cholesterol) and TCM-specific phenotype markers (e.g., dull tongue) that were relevant to COVID-19 infections and prognosis. In addition to antiviral/antibiotics and standard supportive therapies, TCM herbal prescriptions incorporating 290 distinct herbs were used in 273 (93%) cases. The cases that received TCM treatment had lower death rates than those that did not receive TCM treatment (17/273= 6.2% vs. 7/20= 35%, P = 0.0004 for all cases;17/77= 22% vs. 7/9= 77.7%, P = 0.002 for severe cases). The TCM herbal prescriptions used for the treatment of COVID-19 infections mainly consisted of Pericarpium Citri Reticulatae, Radix Scutellariae, Rhizoma Pinellia, and the

关键词： COVID-19 traditional Chinese medicine clinical features

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分段组合式厌氧生物反应器流态特性

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化工学报 2012年第10期63卷 3045-3051页

作者：季军远邢雅娟郑平浙江大学环境工程系浙江杭州310058

厌氧生物反应器高效性与稳定性取决于其流态特性的优良,采用示踪剂脉冲刺激响应技术研究了自主研发的分段组合式厌氧生物反应器的流态,以期揭示其高效机理,便于工程化开发与应用。试验结果表明:常负荷下该反应器的流态趋于平推流;以轴... 详细信息

厌氧生物反应器高效性与稳定性取决于其流态特性的优良,采用示踪剂脉冲刺激响应技术研究了自主研发的分段组合式厌氧生物反应器的流态,以期揭示其高效机理,便于工程化开发与应用。试验结果表明:常负荷下该反应器的流态趋于平推流;以轴向扩散模型表征,不产气与产气工况下的Peclet数分别为7.94和5.66;以多釜串联模型表征,不产气与产气工况下的串联釜数分别为4.55与3.44。高负荷与超高负荷下该反应器的流态趋于全混流,以轴向扩散模型表征,不产气与产气工况下的Peclet数分别为4.02、2.57和3.93、3.77;以多釜串联模型表征,不产气与产气工况下的串联釜数分别为2.66、2.00与2.62、2.51。反应器总死区的平均值为33.58%,其中水力死区的平均值为13.58%。建立了水力死区Vh(%)与容积水力负荷L(m3.m-3.d-1)和容积产气速率G(m3.m-3.d-1)之间的关联式。值得注意的是,在分段组合式厌氧反应器中,容积产气速率对水力死区的影响小于容积水力负荷。

关键词：厌氧反应器流态死区

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Author correction to“TMEM16A inhibits angiotensin Ⅱ-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner”[Acta Pharm Sin B 11(12)(2021)3994–4007]

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Acta Pharmaceutica Sinica B 2023年第9期13卷 1340-1343页

The authors regret that there were some picture errors in the Fig.1D,G,I,Fig.4L,Fig.6C,H and Supporting Information Fig.S1A owing to copy and paste mistakes when preparing the representative *** revisions do not affect the data value,significant difference,and conclusions of the current work and the description of the whole *** original data of this figure have been provided to the Editorial Office,and the Editorial Office or the corresponding authors can be contacted for original data access.

关键词： correction preparing paste

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发热通过Hsp90-α4整合素热感应信号通路促进T淋巴细胞迁移

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科学新闻 2020年第2期 57-57页

作者：陈剑峰林昶东张有华 Kun Zhang yajuan zheng Ling Lu HaiShuang Chang Hui Yang YanRong Yang YaoYing Wan ShiHui Wang MengYa Yuan ZhanJun Yan RongGuang Zhang YongNing He GaoXiang Ge Dianqing Wu 中科院分子细胞科学卓越创新中心、生物化学与细胞生物学研究所陈剑峰研究组

文章简介发热是机体受到病原体感染、产生损伤或者炎症后的一种复杂的生理应激反应。发热可以促进淋巴细胞迁移到次级淋巴器官或者炎症部位而促进免疫反应,对免疫稳态维持和免疫监视非常重要,但是目前对发热调控淋巴细胞黏附和迁移的机... 详细信息

文章简介发热是机体受到病原体感染、产生损伤或者炎症后的一种复杂的生理应激反应。发热可以促进淋巴细胞迁移到次级淋巴器官或者炎症部位而促进免疫反应,对免疫稳态维持和免疫监视非常重要,但是目前对发热调控淋巴细胞黏附和迁移的机制还不清楚。本研究中,课题组发现:发热可以通过热休克蛋白90(heat shock protein 90,Hsp90)诱导α4整合素活化

关键词：整合素信号通路淋巴细胞 Hsp90 热感应

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