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AAV mediated carboxyl terminus of Hsp70 interacting protein overexpression mitigates the cognitive and pathological phenotypes of APP/PS1 mice

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Neural Regeneration Research 2025年第1期20卷 253-264页

作者： Zhengwei Hu Jing Yang Shuo zhang Mengjie Li Chunyan Zuo Chengyuan Mao zhongxian zhang Mibo Tang Changhe Shi Yuming Xu Department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Academy of Medical Sciences of Zhengzhou University ZhengzhouHenan ProvinceChina NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Henan Key Laboratory of Cerebrovascular Diseases The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina Institute of Neuroscience Zhengzhou UniversityZhengzhouHenan ProvinceChina Sino-British Research Centre for Molecular Oncology National Centre for International Research in Cell and Gene TherapySchool of Basic Medical SciencesAcademy of Medical SciencesZhengzhou UniversityZhengzhouHenan ProvinceChina Department of Gerontology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou UniversityZhengzhouHenan ProvinceChina

The E3 ubiquitin ligase,carboxyl terminus of heat shock protein 70(Hsp70)interacting protein(CHIP),also functions as a co-chaperone and plays a crucial role in the protein quality control *** this study,we aimed to investigate the neuroprotective effect of overexpressed CHIP on Alzheimer’s *** used an adeno-associated virus vector that can cross the blood-brain barrier to mediate CHIP overexpression in APP/PS1 mouse *** overexpression significantly ameliorated the performance of APP/PS1 mice in the Morris water maze and nest building tests,reduced amyloid-βplaques,and decreased the expression of both amyloid-βand phosphorylated *** also alleviated the concentration of microglia and astrocytes around *** APP/PS1 mice of a younger age,CHIP overexpression promoted an increase in ADAM10 expression and inhibitedβ-site APP cleaving enzyme 1,insulin degrading enzyme,and neprilysin *** of HSP70 and HSP40,which have functional relevance to CHIP,were also *** nuclei transcriptome sequencing in the hippocampus of CHIP overexpressed mice showed that the lysosomal pathway and oligodendrocyte-related biological processes were up-regulated,which may also reflect a potential mechanism for the neuroprotective effect of *** research shows that CHIP effectively reduces the behavior and pathological manifestations of APP/PS1 ***,overexpression of CHIP could be a beneficial approach for the treatment of Alzheimer’s disease.

关键词： adeno-associated virus Alzheimer’s disease APP/PS1 mice carboxyl terminus of Hsp70 interacting protein gene therapy

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Rapid identification of full-length genome and tracing variations of monkeypox virus in clinical specimens based on mNGS and amplicon sequencing

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Virologica Sinica 2024年第1期39卷 134-143页

作者： Changcheng Wu Ruhan A Sheng Ye Fei Ye Weibang Huo Roujian Lu Yue Tang Jianwei Yang Xuehong Meng Yun Tang Shuang Chen Li Zhao Baoying Huang zhongxian zhang Yuda Chen Dongfang Li Wenling Wang Ke-jia Shan Jian Lu Wenjie Tan NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing100052China Chongqing Municipal Key Laboratory for High Pathogenic Microbes Chongqing Center for Disease Control and PreventionChongqing400042China MGI BGI-ShenzhenShenzhen518083China Thermo Fisher Scientific Beijing100013China School of Public Health Baotou Medical CollegeBaotou014030China BGI PathoGenesis Pharmaceutical Technology Shenzhen518000China State Key Laboratory of Protein and Plant Gene Research Center for BioinformaticsSchool of Life SciencesPeking UniversityBeijing100871China College of Life Sciences University of Chinese Academy of SciencesBeijing100049China

The monkeypox virus(MPXV)has triggered a current outbreak *** sequencing of MPXV and rapid tracing of genetic variants will benefit disease diagnosis and *** is a significant challenge but necessary to optimize the strategy and application of rapid full-length genome identification and to track variations of MPXV in clinical specimens with low viral loads,as it is one of the DNA viruses with the largest genome and the most AT-biased,and has a significant number of tandem *** we evaluated the performance of metagenomic and amplicon sequencing techniques,and three sequencing platforms in MPXV genome sequencing based on multiple clinical specimens of five mpox cases in Chinese *** rapidly identified the full-length genome of MPXV with the assembly of accurate tandem repeats in multiple clinical *** sequencing enables cost-effective and rapid sequencing of clinical specimens to obtain high-quality MPXV ***-generation sequencing facilitates the assembly of the terminal tandem repeat regions in the monkeypox virus genome and corrects a common misassembly in published ***,several intra-host single nucleotide variations were identified in the first imported mpox *** study offers an evaluation of various strategies aimed at identifying the complete genome of MPXV in clinical *** findings of this study will significantly enhance the surveillance of MPXV.

关键词： Monkeypox virus(MPXV) Metagenomic Next generation sequencing Amplicon Third-generation sequencing

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Perspective on the application of genome sequencing for monkeypox virus surveillance

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Virologica Sinica 2023年第2期38卷 327-333页

作者： Yuda Chen Changcheng Wu Ruhan A Li Zhao zhongxian zhang Wenjie Tan School of Public Health Baotou Medical CollegeBaotou014040China NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing100052China

Monkeypox virus(MPXV),a DNA virus belonging to the Orthopoxvirus genus,causes a self-limiting zoonotic disease known as *** human monkeypox infection was first recorded in a 9-month-old child in the Republic of Congo in the 1970s(Ladnyj et al.,1972).For a long time,mpox was mainly prevalent in the humid forests of Central Africa and parts of West Africa(Kabugae and El Zowalaty,2019).In recent years,MPXV has been spread to other countries through trade and *** 2003,a group of rare pets carrying MPXV was exported from Africa to the United States,and an outbreak of animal-to-human transmission occurred(Di Giulio and Eckburg,2004).In 2018,two cases of mpox were confirmed in travelers from Nigeria to the United Kingdom and one case was confirmed in Israel(Vaughan et al.,2018;Erez et al.,2019).Then,in 2019,one case was confirmed in Singapore(Ng et al.,2019).The outbreak of mpox in multiple non-endemic countries in North America and Europe started in May 2022(WHO,2022b).On July 23,2022,the WHO declared MPXV a Public Health Emergency of International Concern(PHEIC)(WHO,2022a).As of March 5,2023,86,309 confirmed mpox cases have been reported from 107 countries/regions worldwide(WHO,2023).In the mainland of China,the first imported case was confirmed by the Chinese Center for Disease Control and Prevention(Zhao et al.,2022),making this the fifth confirmed mpox infection in *** zoonotic mpox has been restricted in Africa but now it is back in the spotlight worldwide(Tan and Gao,2022).

关键词： fir mainland Israel

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新型冠状病毒Beta变异株感染C57BL/6小鼠肺组织转录组分析及趋化因子实验验证

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病毒学报 2024年第2期40卷 255-265页

作者：张高倩吴长城黄保英李涵霍恕婷叶飞赵莉阿茹罕张钟贤沈晓玲谭文杰内蒙古医科大学基础医学院微生物学教研室呼和浩特010010 中国疾病预防控制中心病毒病预防控制所国家卫生健康委员会生物安全重点实验室北京102206 包头医学院公共卫生学院包头014030

研究旨在通过从转录组水平分析新冠病毒Beta变异株感染C57BL/6小鼠肺部的基因表达变化,以揭示引发轻症肺部损伤的关键宿主因子。首先构建Beta变异株感染C57BL/6小鼠模型,并对感染和未感染第3天(3d)小鼠的肺组织进行病原检测、病理分析... 详细信息

研究旨在通过从转录组水平分析新冠病毒Beta变异株感染C57BL/6小鼠肺部的基因表达变化,以揭示引发轻症肺部损伤的关键宿主因子。首先构建Beta变异株感染C57BL/6小鼠模型,并对感染和未感染第3天(3d)小鼠的肺组织进行病原检测、病理分析以及差异表达基因分析。最后,筛选可能导致肺部损伤的5个炎症反应关键基因进行RT-qPCR验证。研究结果显示Beta变异株能感染C57BL/6小鼠肺部并导致轻度病理损伤。在感染的小鼠中,Beta变异株激活了肺组织的天然免疫应答,主要通路包括Toll样受体信号通路、Ⅰ和Ⅱ型干扰素反应、白细胞趋化反应和细胞因子反应等。通过对重症与轻症感染小鼠的肺组织转录组比较,筛选出与疾病严重程度相关的炎症反应趋化因子,包括Ccl2、Ccl7、Cxcl9、Cxcl10和Cxcl14。通过RT-qPCR验证,基因表达变化趋势与转录组结果一致,表明这些趋化因子过度激活与肺部病理表型损伤程度相关。本研究揭示了Beta变异株感染小鼠肺部激活宿主炎症反应通路关键因子,可能是引发小鼠肺部轻度病理损伤的主要诱因之一,这为预防和治疗新冠病毒感染提供了有利的研究靶点。

关键词：新型冠状病毒Beta变异株肺部损伤天然免疫炎症因子转录组

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广谱抗病毒药物吐根碱抑制HCoV-OC43的转录组分析

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病毒学报 2024年第3期40卷 458-468页

作者：李涵张高倩吴长城张钟贤牛军伟霍恕婷叶飞邓瑶黄保英赵莉沈晓玲谭文杰包头医学院公共卫生学院包头014040 传染病溯源预警与智能决策全国重点实验室中国疾病预防控制中心病毒病预防控制所国家卫生健康委员会生物安全重点实验室北京102206 内蒙古医科大学基础医学院微生物教研室呼和浩特010010

本研究旨在探索吐根碱对人冠状病毒OC43(Human coronavirus OC43, HCoV-OC43)的作用时相和抗病毒机制。首先,在MRC-5细胞上建立了HCoV-OC43病毒的体外感染复制动力学曲线,测定了药物的EC_(50)和CC_(50)。结果表明吐根碱能够在感染早期... 详细信息

本研究旨在探索吐根碱对人冠状病毒OC43(Human coronavirus OC43, HCoV-OC43)的作用时相和抗病毒机制。首先,在MRC-5细胞上建立了HCoV-OC43病毒的体外感染复制动力学曲线,测定了药物的EC_(50)和CC_(50)。结果表明吐根碱能够在感染早期有效地抑制HCoV-OC43病毒在MRC-5细胞中的复制。通过转录组分析,发现HCoV-OC43感染和吐根碱处理均导致宿主基因表达的紊乱,并且两者共同激活了抗病毒通路。吐根碱可能通过激活OASL、Mx1和IFIT2等抗病毒基因来增强宿主对病毒的抵抗能力。此外,吐根碱还可能通过抑制TMEM41B表达而进一步影响病毒复制过程。这些研究结果为深入探究吐根碱作为抗冠状病毒药物的机制和潜在靶点提供了重要线索。

关键词：吐根碱 HCoV-OC43 抗病毒作用转录组学基因表达紊乱

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Development of two multiplex real-time PCR assays for simultaneous detection and differentiation of monkeypox virus IIa,IIb,and I clades and the B.1 lineage

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Biosafety and Health 2022年第6期4卷 392-398页

作者： Shuting Huo Yuda Chen Roujian Lu zhongxian zhang Gaoqian zhang Li Zhao Yao Deng Changcheng Wu Wenjie Tan NHC Key Laboratory of Biosafety National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 100052China School of Public Health Baotou Medical CollegeBaotou 014030China Department of Microbiology Basic Medical CollegeInner Mongolia Medical UniversityHohhot 010010China

An ongoing multi-country outbreak of monkeypox was reported in May 2022 with several deaths,affecting 107 countries of all six World Health Organization(WHO)*** WHO has declared the current monkeypox outbreak to be a Public Health Emergency of International *** is,thus,necessary to rapidly and accurately detect and distinguish different monkeypox virus(MPXV)*** designed primers and probes based on the alignment of 138 complete genomes of *** Panel 1,we mixed one pair of primers and three probes to detect and differentiate the MPXV Western Africa(IIa,IIb clade)and Congo Basin(I clade)and other *** Panel 2,we mixed one pair of primers and two probes to detect the 2022 MPXV(B.1 lineage and its descendant lineages).In addition,we tested the specificity and sensitivity of the assay using real-time *** Panel 1,the assay reproducibly identified various concentrations of two plasmids of the monkeypox virus,whereas other orthopoxviruses did not *** Panel 2,the probe annealed well to MPXV B.1 and showed the expected *** two multiple real-time assays are inclusive and highly specific for identifying different clades of MPXV.

关键词： Monkeypox virus Monkeypox virus B.1 lineage Real-time PCR Diagnostic accuracy

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Catalytic oxidation of toluene by manganese oxides:Effect of K^(+)doping on oxygen vacancy

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Journal of Environmental Sciences 2024年第8期142卷 43-56页

作者： Zhenzhen Huang Haiyang Li Xuejun zhang Yanli Mao Yinghan Wu Wei Liu Hongrun Gao Mengru zhang zhongxian Song Faculty of Environmental and Municipal Engineering Henan Key Laboratory of Water Pollution Control and Rehabilitation TechnologyHenan University of Urban ConstructionPingdingshan 467036China College of Environmental and Safety Engineering Shenyang University of Chemical TechnologyShenyang 110142China

Alkali metal potassium was beneficial to the electronic regulation and structural stability of transition metal ***,K ions were introduced into manganese oxides by different methods to improve the degradation efficiency of *** results of activity experiments indicated that KMnO_(4)-HT(HT:Hydrothermal method)exhibited outstanding low-temperature catalytic activity,and 90%conversion of toluene can be achieved at 243℃,which was 41℃and 43℃lower than that of KNO_(3)-HT and Mn-HT,*** largest specific surface area was observed on KMnO_(4)-HT,facilitating the adsorption of *** formation of cryptomelane structure over KMnO_(4)-HT could contribute to higher content of Mn^(3+)and lattice oxygen(Olatt),excellent low-temperature reducibility,and high oxygen mobility,which could increase the catalytic ***,two distinct degradation pathways were ***Ⅰ(KMnO_(4)-HT):toluene→benzyl→benzoic acid→carbonate→CO_(2)and H2O;PathwayⅡ(Mn-HT):toluene→benzyl alcohol→benzoic acid→phenol→maleic anhydride→CO_(2)and *** intermediates were detected on KMnO_(4)-HT,indicating its stronger oxidation capacity of toluene,which was originated from the doping of K^(+)and the interaction between *** intermediates were observed on Mn-HT,which can be attributed to the weaker oxidation ability of pure *** results indicated that the doping of K^(+)can improve the catalytic oxidation capacity of toluene,resulting in promoted degradation of intermediates during the oxidation of toluene.

关键词： Catalytic oxidation Preparation method Cryptomelane Mn^(3+)and lattice oxygen

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基于新一代测序技术精准确定复制缺陷型痘苗病毒天坛株全基因组序列及其开放阅读框组成

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中华微生物学和免疫学杂志 2024年第6期44卷 502-509页

作者：张钟贤吴长城李涵霍恕婷赵莉邓瑶孟昕陆柔剑田厚文王文玲黄保英谭文杰包头医学院公共卫生学院包头014040 中国疾病预防控制中心病毒病预防控制所传染病溯源预警与智能决策全国重点实验室国家卫生健康委员会生物安全重点实验室北京102206

目的应用新一代长读长测序技术精准确定复制缺陷型痘苗病毒天坛株(non-replicating Tiantan strain of vaccinia virus,NTV)全基因组序列及其开放阅读框(ORFs)组成。方法基于本实验室储备的NTV,在鸡胚成纤维细胞上进行扩增并纯化,提取NT... 详细信息

目的应用新一代长读长测序技术精准确定复制缺陷型痘苗病毒天坛株(non-replicating Tiantan strain of vaccinia virus,NTV)全基因组序列及其开放阅读框(ORFs)组成。方法基于本实验室储备的NTV,在鸡胚成纤维细胞上进行扩增并纯化,提取NTV全长基因组核酸。PacBio HiFi测序从头组装获取NTV全长基因组序列。以同源注释的策略确定其ORF组成,并分析其与已知复制缺陷型痘苗病毒毒株ORF异同。结果NTV全长共171729 bp,GC含量为33%,其独特的倒置末端重复(ITR)区域包含发夹结构、两个串联重复区域及3个非重复区域。NTV共有166个ORFs,与第三代天花病毒疫苗改良安卡拉株(MVA-BN)和复制缺陷型哥本哈根株(NYVAC)株相比,主要差异位于ITR及其周围区域,3个毒株共同享有138个ORFs,NTV特有6个编码与病毒逃避宿主抗病毒反应相关的ORFs。结论通过三代测序技术精准确定NTV全基因组序列及ORFs组成,并揭示其与其他复制缺陷型痘苗病毒毒株的异同,为新一代猴痘疫苗和痘苗病毒载体研发应用提供重要参考。

关键词：复制缺陷型痘苗病毒天坛株三代测序全基因组测序开放阅读框

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Genomic Recombination of SARS-CoV-2 Subvariants BA.5.2.48 and BF.7.14—China,2023

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China CDC weekly 2023年第14期5卷 318-320页

作者： zhongxian zhang Han Li Hongxia Ma Wenling Wang Dawei Gao Fei Ye Weibang Huo Yuda Chen Changcheng Wu Wenjie Tan National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijingChina School of Public Health Baotou Medical CollegeBaotou CityInner Mongolia Autonomous RegionChina Henan Provincial Center for Disease Control and Prevention Zhengzhou CityHenan ProvinceChina Lu’an Municipal Center for Disease Control and Prevention Lu’an CityAnhui ProvinceChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),a single-stranded positive RNA virus,exhibits a high rate of genome mutation and recombination(1–2).Recombinant strains of this virus could potentially affect their binding ability to the ACE2 receptor,which may in turn diminish the protection offered by vaccines and neutralizing ***,the Delta and Omicron recombinations have been collectively referred to as Deltacron(3).Furthermore,XBB.1.5,a recombinant strain resulting from the combination of the BA.2 sublineages BA.2.10.1 and BA.2.75,has demonstrated enhanced transmissibility(4).As such,it is imperative to monitor the genome recombination of SARS-CoV-2 in order to provide valuable insights regarding epidemic and transmission trends.

关键词： acute respiratory collective

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痘苗病毒天坛株N1L基因表达调控序列的克隆与特性分析

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病毒学报 2024年第3期40卷 484-491页

作者：翟玉倩韩一泽吴长城张钟贤赵莉罗美惠豆亚美刘士元任皎田厚文王文玲谭文杰中国疾病预防控制中心病毒病预防控制所传染病溯源预警和智能决策全国重点实验室北京102206

本研究以痘苗病毒天坛株(Vaccinia Virus Tian Tan Strain,VTT)为对象,旨在明确N1L基因的表达调控序列。我们克隆了N1L起始密码子ATG上游不同长度的调控序列片段,构建了表达载体,并利用报告基因萤火虫荧光素酶(Firefly luciferase,Fluc... 详细信息

本研究以痘苗病毒天坛株(Vaccinia Virus Tian Tan Strain,VTT)为对象,旨在明确N1L基因的表达调控序列。我们克隆了N1L起始密码子ATG上游不同长度的调控序列片段,构建了表达载体,并利用报告基因萤火虫荧光素酶(Firefly luciferase,Fluc)的表达来确定N1L表达调控序列区域。通过PROMO在线预测网站,预测了与调控序列结合的转录因子。结果显示,VTT中N1L基因的表达受到上游调控序列的调控,其中以-404bp起始的片段启动的Fluc表达量最高。PROMO预测表明该区域存在多个转录因子结合位点。本研究为痘苗病毒基因表达特点的研究提供了实验依据,并为N1L基因功能及机制研究奠定了基础。

关键词：痘苗病毒天坛株 N1L基因基因表达与调控转录通读

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