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Heat Treatment Promotes Ubiquitin-Mediated Proteolysis of SARS-CoV-2 RNA Polymerase and Decreases Viral Load

Research 2022年第2期2022卷 41-45页

作者： Yasen Maimaitiyiming Tao Yang Qian Qian Wang Yan Feng Zhi Chen Mikael Bjorklund Fudi Wang Chonggao Hu Chih-Hung Hsu hua naranmandura Deparment of Public Healh and Department of Hematology of First Afilated Hospital Zhejiang Unvrsity Schoo of MedicineHangzhou 310058China Zhejiang University Cancer Cenler Hangzhou 310058China Deparment of Neurobiology and Depariment of Neurology of the First Afiliated Hospital Zhejiang University School of Medicire.NHC and CAMS Key Laboratory of Medical Neurobiology School of Brain Science and Brain MedicineZhejiang UniversityHangzhou 310058China Zhejing Provincial Center for Disease Control and Prevention Hangzhou 310051China State Key Laboratory for Diagrosis and Treatment of Infectious Diseases Collaborative Innovation Center for DigHosis and Treatment of Infectious DiseaseThe First filiated HospitalZhejiang University School of MedicineHangzhouChina Zhejing Unversity-Univrsity of Edinburgh(ZJU-UoE)Institute Haining 314499ZhejiangChina The First Afiliated Hospital Institute of Trarslational MedicineSchoo of Public HealthZhejiang University School of Medicine.Hangzhou 310058Chima Hengvang Medical School University of South ChinaHengvang 421001China Women's Hospital Institut of Gencticsand Departmrent of Enwironmental Medicine.Zhejiang Universty School of MedicineHangzhou 310006China

Despite extensive eforts,COVID-19 pandemic caused by the SARS-CoV-2 virus is still at *** is an eftive approach to curb virus spread,but several variants(***,delta plus,omicron,and IHU)appear to weaken or possibly escape immune ***,novel and quickly scalable approaches to restrain SARS-CoV-2 are urgently *** evidences showed thermal sensitivity of SARS-CoV-2 and negative correlation between environmental temperature and COVID-19 transmission with unknown *** reveal a potential mechanism by which mild heat treatment destabilizes the wild-type RNA-dependent RNA polymerase(also known a nonstructural protein 12(NSP12))of SARS-CoV-2 as well as the P323L mutant commonly found in SARS-CoV-2 variants,including omicron and ***,heat treatment promotes E3 ubiquitin ligase ZNF598-dependent NSP12 ubiquitination leading to proteasomal degradation and significantly decreases SARS-CoV-2 RNA copy number and viral titer.A mild daily heat Ireatment maintains low levels of both wild-type and P323L mutant of NSP12,sugesting clinical ***',this novel mechanism,heat-induced NSP12 degradation,suggests a prospective heat-based intervention against SARS-CoV-2.

关键词： NSP1 mechanism delta

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Release of Cyt c from mitochondria by methylated arsenic occurs through interaction with voltage dependent anion channel in vitro

Release of Cyt c from mitochondria by methylated arsenic occ...

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2014线粒体毒性与基于毒性通路的安全性评价新策略学术...

作者： hua naranmandura School of Medicine and Public Health Zhejiang University

＜正＞Arsenic is known to be a human carcinogen as well as one of the most effective drugs for treatment of patients with acute promyelocytic leukemia（APL）.Although it has been reported that arsenic intermediate metabolites monomethylarsonous acid（MMAIII）and dimethylarsinous acid（DMAIII）,which transformed by methylation reactions are more reactive and toxic than that of inorganic precursor

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Metabolism,Toxicity and Anticancer Activities of Arsenicals

Metabolism,Toxicity and Anticancer Activities of Arsenicals

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第五届全国原子光谱及相关技术学术会议

作者： hua naranmandura School of Medicine and Public Health Zhejiang University

A variety of studies indicated that inorganic arsenic and its methylated metabolites have paradoxical effects,namely,carcinogenic and anticancer ***,arsenic trioxide(AsO) is successfully used in the treatment of refractory or relapsed acute promyelocytic leukemia(APL),but its exact antileukemic mechanism in APL is still under *** probable explanation for AsO-induced cell differentiation is the direct targeting of PML-RARα oncoprotein by AsO,which results in initiation of PML-RARα ***,after injection,AsO is able toy methylated in body to different intermediate metabolites such as trivalent monomethylarsonous acid(MMA) and dimethylarsinous acid(DMA),therefore,it remains unknown that which arsenic specie is actually responsible for the therapeutic effects against *** we have shown the role of iAs and its intermediate metabolites(i.e.,MMA/DMA) in NB4 *** iAs predominantly showed induction of cell differentiation,while MMA and DMA specifically showed to induce ***,our results also found that the binding of arsenicals to PML proteins is not associated with the degradation of PML-RARα fusion protein.

关键词： Arsenic trioxide Acute promyelocytic leukemia PML-RARα Cell differentiation

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YTHDF2-mediated regulations bifurcate BHPF-induced programmed cell deaths

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National Science Review 2023年第12期10卷 83-97页

作者： Jiebo Lin Guankai Zhan Jinfeng Liu Yasen Maimaitiyiming Zhiping Deng Baohua Li Kunhui Su Jiafeng Chen Siqi Sun Wanlin Zheng Xianghui Yu Feng He Xiaodong Cheng Lingfang Wang Bin Shen Ziqin Yao Xinquan Yang Jian Zhang Wentao He Hengyu Wu hua naranmandura Kao-Jung Chang Junxia Min Jun Ma Mikael Bj?rklund Peng-Fei Xu Fudi Wang Chih-Hung Hsu State Key Laboratory of Reproductive Medicine Center for Global HealthGusu School Women's Hospital of Nanjing Medical University Nanjing Maternity and Child Health Care Hospital Nanjing Medical University The First Affiliated Hospital Basic Medical SciencesSchool of Public HealthSchool of Pharmaceutical Science Hengyang Medical School University of South China Department of Medical Research Taipei Veterans General Hospital The First Affiliated Hospital Institute of Translational MedicineCancer Center Zhejiang University School of Medicine Zhejiang University-University of Edinburgh (ZJU-UoE) Institute University of Edinburgh Medical School Biomedical SciencesCollege of Medicine & Veterinary MedicineUniversity of Edinburgh Women's Hospital The Fourth Affiliated Hospitaland Department of Environmental MedicineZhejiang University School of Medicine Institute of Genetics International School of MedicineZhejiang University The Second Affiliated Hospital School of Public Health State Key Laboratory of Experimental Hematology Zhejiang University School of Medicine Department of Hematology of First Affiliated Hospital and Department of Public Health Zhejiang University School of Medicine State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products Institute of Virology and Biotechnology Zhejiang Academy of Agricultural Sciences Department of Obstetrics Women's Hospital School of Medicine Zhejiang University Women's Hospital and Institute of Genetics Zhejiang University School of Medicine Zhejiang Provincial Key Lab of Genetic and Developmental Disorders Zhejiang Provincial Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine

N6-methyladenosine(m6A) is a critical regulator in the fate of RNA, but whether and how m6A executes its functions in different tissues remains largely obscure. Here we report downregulation of a crucial m6A reader, YTHDF2, leading to tissue-specific programmed cell deaths(PCDs) upon fluorene-9-bisphenol(BHPF) exposure. Currently, Bisphenol A(BPA) substitutes are widely used in plastic *** eight common BPA substitutes, we detected BHPF in 14% serum samples of pregnant participants. In a zebrafish model, BHPF caused tissue-specific PCDs triggering cardiac and vascular ***, BHPF-mediated downregulation of YTHDF2 reduced YTHDF2-facilitated translation of m6A-gch1 for cardiomyocyte ferroptosis, and decreased YTHDF2-mediated m6A-sting1 decay for caudal vein plexus(CVP) apoptosis. The two distinct YTHDF2-mediated m6A regulations and context-dependent co-expression patterns of gch1/ythdf2 and tnfrsf1a/ythdf2 contributed to YTHDF2-mediated tissue-specific PCDs, uncovering a new layer of PCD regulation. Since BHPF/YTHDF2-medaited PCD defects were also observed in mammals, BHPF exposure represents a potential health threat.

关键词： RNA m6A modification programmed cell deaths bifurcation role of YTHDF2 environmental stress and m6A regulation fluorene-9-bisphenol (BHPF)

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热激诱导新冠病毒RNA聚合酶NSP12降解及抑制病毒复制分子机制研究

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中国医药导刊 2022年第3期24卷 197-203页

作者：那仁满都拉浙江大学医学院浙江杭州310058

据美国约翰斯霍普金斯大学的实时统计数据显示,截至2022年3月,全球新冠肺炎(COVID-19)累计确诊病例已近4.88亿例,死亡近610万例。疫情的全球肆虐已持续两年多,给世界带来了巨大影响,大多数国家的国民健康、经济和生活等诸多方面都遭受... 详细信息

据美国约翰斯霍普金斯大学的实时统计数据显示,截至2022年3月,全球新冠肺炎(COVID-19)累计确诊病例已近4.88亿例,死亡近610万例。疫情的全球肆虐已持续两年多,给世界带来了巨大影响,大多数国家的国民健康、经济和生活等诸多方面都遭受了重创。2022年年初,浙江大学那仁满都拉教授团队联合许志宏研究员团队,首次发现相对温和的热激(40℃)能显著地诱导新冠病毒(SARS-CoV-2)RNA依赖的RNA聚合酶(又名NSP12)及其突变体的降解,并进一步抑制新冠病毒复制。该研究结果提示,科学合理温度下的热激治疗(热疗)或许能通过降解病毒RNA聚合酶而减少病毒复制,阻止其感染和传播,进一步抑制新冠肺炎患者的病情恶化。本研究着重从分子机制及潜在应用等方面介绍该研究成果,旨在为热疗后续更广泛、更精准的临床应用提供理论支持和指导。

关键词：热激新冠病毒新冠肺炎 RNA依赖的RNA聚合酶(NSP12) 病毒复制

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On the Pathwise Uniqueness of Solutions of One-dimensional Reflected Stochastic Differential Equations with Jumps

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Acta Mathematicae Applicatae Sinica 2024年第1期40卷 149-163页

作者： hua Zhang School of Statistics and Data Science&Key Laboratory of Data Science in Finance and Economics Jiangxi University of Finance and EconomicsNanchang330013China

In this paper, we are concerned with the problem of the pathwise uniqueness of one-dimensional reflected stochastic differential equations with jumps under the assumption of non-Lipschitz continuous coefficients whose... 详细信息

关键词： reflected diffusion processes with jumps pathwise uniqueness local time Meyer It?'s formula

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Goal-Oriented Control Systems(GOCS):From HOW to WHAT

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IEEE/CAA Journal of Automatica Sinica 2024年第4期11卷 816-819页

作者： Wen-hua Chen the Department of Aeronautical and Automotive Engineering Loughborough UniversityLeicestershireLE113TUU.K.

Brief:New control theory is required to underpin safe design and deployment of future highly automated systems to deal with uncertain environments and complicated tasks,enabled by AI and other advanced ***-Oriented Control Systems offer potential to transform the control system design from currently instructing a control system how to perform a task to specifying what is to be achieved.

关键词： automated instru system

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Reliability of a Multicomponent Stress-strength Model Based on a Bivariate Kumaraswamy Distribution with Censored Data

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Acta Mathematicae Applicatae Sinica 2024年第2期40卷 478-507页

作者： Cong-hua CHENG School of Mathematics and Statistics Zhaoqing UniversityZhaoqing 526061China

In this paper,we consider a system which has k statistically independent and identically distributed strength components and each component is constructed by a pair of statistically dependent elements with doubly type-II censored *** elements(X1,Y1),(X2,Y2),…,(Xk,Yk)follow a bivariate Kumaraswamy distribution and each element is exposed to a common random stress T which follows a Kumaraswamy *** system is regarded as operating only if at least s out of k(1≤s≤k)strength variables exceed the random *** multicomponent reliability of the system is given by Rs,k=P(at least s of the(Z1,…,Zk)exceed T)where Zi=min(Xi,Yi),i=1,…,*** Bayes estimates of Rs,k have been developed by using the Markov Chain Monte Carlo methods due to the lack of explicit *** uniformly minimum variance unbiased and exact Bayes estimates of Rs,k are obtained analytically when the common second shape parameter is *** asymptotic confidence interval and the highest probability density credible interval are constructed for Rs,*** reliability estimators are compared by using the estimated risks through Monte Carlo simulations.

关键词： stress-strength model bivariate Kumaraswamy distribution multicomponent reliability doubly Type-II censored scheme interval estimation

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Nuclear charge radius predictions by kernel ridge regression with odd-even effects

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Nuclear Science and Techniques 2024年第2期35卷 94-102页

作者： Lu Tang Zhen-hua Zhang Mathematics and Physics Department North China Electric Power UniversityBeijing 102206China Hebei Key Laboratory of Physics and Energy Technology North China Electric Power UniversityBaoding 071000China

The extended kernel ridge regression(EKRR)method with odd-even effects was adopted to improve the description of the nuclear charge radius using five commonly used nuclear *** are:(i)the isospin-dependent A^(1∕3) formula,(ii)relativistic continuum Hartree-Bogoliubov(RCHB)theory,(iii)Hartree-Fock-Bogoliubov(HFB)model HFB25,(iv)the Weizsacker-Skyrme(WS)model WS*,and(v)HFB25**** the last two models,the charge radii were calculated using a five-parameter formula with the nuclear shell corrections and deformations obtained from the WS and HFB25 models,*** each model,the resultant root-mean-square deviation for the 1014 nuclei with proton number Z≥8 can be significantly reduced to 0.009-0.013 fm after considering the modification with the EKRR *** best among them was the RCHB model,with a root-mean-square deviation of 0.0092 *** extrapolation abilities of the KRR and EKRR methods for the neutron-rich region were examined,and it was found that after considering the odd-even effects,the extrapolation power was improved compared with that of the original KRR *** strong odd-even staggering of nuclear charge radii of Ca and Cu isotopes and the abrupt kinks across the neutron N=126 and 82 shell closures were also calculated and could be reproduced quite well by calculations using the EKRR method.

关键词： Nuclear charge radius Machine learning Kernel ridge regression method

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Cardiovascular computed tomography in cardiovascular disease:An overview of its applications from diagnosis to prediction

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Journal of Geriatric Cardiology 2024年第5期21卷 550-576页

作者： Zhong-hua SUN Discipline of Medical Radiation Science Curtin Medical SchoolCurtin UniversityPerthAustralia Curtin Health Innovation Research Institute(CHIRI) Curtin UniversityPerth 6012Australia

Cardiovascular computed tomography angiography(CTA)is a widely used imaging modality in the diagnosis of cardiovascular *** in CT imaging technology have further advanced its applications from high diagnostic value to minimising radiation exposure to *** addition to the standard application of assessing vascular lumen changes,CTA-derived applications including 3D printed personalised models,3D visualisations such as virtual endoscopy,virtual reality,augmented reality and mixed reality,as well as CT-derived hemodynamic flow analysis and fractional flow reserve(FFRCT)greatly enhance the diagnostic performance of CTA in cardiovascular *** widespread application of artificial intelligence in medicine also significantly contributes to the clinical value of CTA in cardiovascular *** value of CTA has extended from the initial diagnosis to identification of vulnerable lesions,and prediction of disease extent,hence improving patient care and *** this review article,as an active researcher in cardiovascular imaging for more than 20 years,I will provide an overview of cardiovascular CTA in cardiovascular *** is expected that this review will provide readers with an update of CTA applications,from the initial lumen assessment to recent developments utilising latest novel imaging and visualisation *** will serve as a useful resource for researchers and clinicians to judiciously use the cardiovascular CT in clinical practice.

关键词： diagnosis cardiovascular prediction

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