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Gene replacement therapy in Bietti crystalline corneoretinal dystrophy:an open-label,single-arm,exploratory trial

Signal Transduction and Targeted Therapy 2024年第5期9卷 2275-2284页

作者： Jinyuan Wang Jinlu Zhang Shicheng Yu Hongyan Li shaohong chen Jingting Luo Haibo Wang Yuxia Guan Haihan Zhang Shiyi Yin Huili Wang Heping Li Junle Liu Jingyuan Zhu Qiong Yang Ying Sha Chuan Zhang Yuhang Yang Xuan Yang Xifang Zhang Xiuli Zhao Likun Wang Liping Yang Wenbin Wei Beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology&Visual Sciences Key LabMedical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information TechnologyBeijing Tongren HospitalCapital Medical University100730 BeijingChina School of Clinical Medicine Tsinghua University100084 BeijingChina Chigenovo Co. Ltd.102206 BeijingChina Department of Ophthalmology Peking University Third HospitalBeijing Key Laboratory of Restoration of Damaged Ocular NervePeking University Third Hospital100191 BeijingChina Department of Ophthalmology The Third People’s Hospital of Dalian116091 DalianChina Department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available treatment.Here,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 days.This open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/8-hCYP4V2.Overall,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were observed.Compared with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the treatment.We conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).

关键词： cor dystrophy crystalline

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MicroRNAs recruit eIF4E2 to repress translation of target mRNAs

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Protein & Cell 2017年第10期8卷 750-761页

作者： shaohong chen Guangxia Gao CAS Key Laboratory of Infection and Immunity CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100101 China

MicroRNAs （miRNAs） recruit the RNA-induced silencing complex （RISC） to repress the translation of target mRNAs. While the 5＇ 7-methylguanosine cap of target mRNAs has been well known to be important for miRNA repression, the underlying mechanism is not clear. Here we show that TNRC6A interacts with elF4E2, a homo- Iogue of eIF4E that can bind to the cap but cannot interact with eIF4G to initiate translation, to inhibit the translation of target mRNAs. Downregulation of eIF4E2 relieved miRNA repression of reporter expression. Moreover, eIF4E2 downregulation increased the protein levels of endogenous IMP1, PTEN and PDCD4, whose expression are repressed by endogenous miRNAs. We further provide evidence showing that miRNA enhances elF4E2 association with the target mRNA. We propose that miRNAs recruit eI4E2 to compete with eIF4E to repress mRNA translation.

关键词： microRNAs translation repression 5＇ cap eIF4E2. TNRC6A

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Increased pathogenicity and aerosol transmission for one SARS-CoV-2 B.1.617.2 Delta variant over the wild-type strain in hamsters

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Virologica Sinica 2022年第6期37卷 796-803页

作者： Xinghai Zhang shaohong chen Zengguo Cao Yanfeng Yao Junping Yu Junhui Zhou Ge Gao Ping He Zhuo Dong Jie Zhong Jing Luo Hongping Wei Huajun Zhang State Key Laboratory of Virology Key Laboratory of Special Pathogens and BiosafetyWuhan Institute of VirologyChinese Academy of SciencesWuhan430071China University of Chinese Academy of Sciences Beijing101409China Hubei International Travel Healthcare Center(Wuhan Customs Port Outpatient Department) Wuhan430040China

During the two-year pandemic of coronavirus disease 2019(COVID-19), its causative agent, severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has been evolving. SARS-CoV-2 Delta, a variant of concern, has become the dominant circulating strain worldwide within just a few months. Here, we performed a comprehensive analysis of a new B.1.617.2 Delta strain(Delta630) compared with the early WIV04 strain(WIV04) in vitro and in vivo, in terms of replication, infectivity, pathogenicity, and transmission in hamsters. When inoculated intranasally, Delta630 led to more pronounced weight loss and more severe disease in hamsters. Moreover, 40%mortality occurred about one week after infection with 10^(4)PFU of Delta630, whereas no deaths occurred even after infection with 10^(5)PFU of WIV04 or other strains belonging to the Delta variant. Moreover, Delta630outgrew over WIV04 in the competitive aerosol transmission experiment. Taken together, the Delta630 strain showed increased replication ability, pathogenicity, and transmissibility over WIV04 in hamsters. To our knowledge, this is the first SARS-CoV-2 strain that causes death in a hamster model, which could be an asset for the efficacy evaluation of vaccines and antivirals against infections of SARS-CoV-2 Delta strains. The underlying molecular mechanisms of increased virulence and transmission await further analysis.

关键词： SARS-CoV-2 B.1.617.2 Delta variant Syrian hamsters Pathogenicity Transmission

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Methods for Private College Counselors to Carry Out Implicit Ideological and Political Education

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Journal of Contemporary Educational Research 2022年第9期6卷 120-125页

作者： shaohong chen Chao Zhang Institute of Foreign Languages Guangzhou Huashang CollegeGuangzhou 511300Guangdong ProvinceChina

With the continuous progress of the society,the new media network has proposed new conditions and provided new means for implicit ideological and political education in private colleges and universities.This article discusses the launching of the e-class platform for private college counselors to develop the feasibility of implicit ideological and political education for private colleges.The involved methods of education are deeply explored,in order to improve the implicit ideological and political education work ability of private college counselors.

关键词： Private colleges and universities E-class Implicit Ideological and political education

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Investigation and Analysis on the Status Quo of College Students’Network Entrepreneurship in Private University

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Journal of Contemporary Educational Research 2022年第8期6卷 81-90页

作者： shaohong chen Chao Zhang Lingling Dai Institute of Foreign Languages Guangzhou Huashang CollegeGuangzhou 511300Guangdong ProvinceChina

This year,the number college graduates in China surpassed tens of millions for the first time.The employment rate of fresh graduates has been concerning.In view of this,network entrepreneurship has become an important channel and platform to solve the problem of college students’employment.The government,society and universities has been actively encouraging college students'network entrepreneurship as the value of college students'network entrepreneurship is significant.This paper analyzes the current situation of college students'network entrepreneurship and the problems faced through the survey data and thus suggests corresponding countermeasures.

关键词： Private university College students Network entrepreneurship Suggestions

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A potent neutralizing antibody provides protection against SARS-CoV-2 Omicron and Delta variants via nasal delivery

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3584-3591页

作者： Xinghai Zhang Huajun Zhang Tingting Li shaohong chen Feiyang Luo Junhui Zhou Peiyi Zheng Shuyi Song Yan Wu Tengchuan Jin Ni Tang Aishun Jin chengyong Yang Guofeng cheng Rui Gong Sandra Chiu Ailong Huang CAS Key Laboratory of Special Pathogens and Biosafety Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430o71 HubeiChina Department of Immunology College of Basic MedicineChongqing Medical UniversityChongqing 400010China Chongqing Key Laboratory of Basic and Translational Research of Tumor Immunology Chongqing Medical UniversityChongqing 400010China University of Chinese Academy of Sciences 100049 BeijingChina Division of Life Sciences and Medicine University of Science and Technology of ChinaHefei 230026 AnhuiChina Key Laboratory of Molecular Biology on Infectious Diseases Ministry of EducationChongqing Medical UniversityChongqing 400010China Mindao Haoyue Co LtdSQ0042 Lanyuan HallNo.61 Daxuecheng Middle RoadChongqing 400042China

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is still rapidly spreading worldwide.Many drugs and vaccines have been approved for clinical use show efficacy in the treatment and prevention of SARS-CoV-2 infections.However,the emergence of SARS-CoV-2 variants of concern(VOCs),such as Delta(B.1.617.2)and the recently emerged Omicron(B.1.1.529),has seriously challenged the application of current therapeutics.Therefore,there is still a pressing need for identification of new broad-spectrum antivirals.Here,we further characterized a human antibody(58G6),which we previously isolated from a patient,with a broadly authentic virus-neutralizing activity that inhibits the Delta and Omicron variants with half-maximal inhibitory concentrations(ICso)of 1.69 ng/ml and 54.31 ng/ml,respectively.58G6 shows prophylactic and therapeutic effcacy in hamsters challenged with the Delta and Omicron variants through nasal delivery.Notably,a very low dosage(2 mg/kg daily)of 58G6 efficiently prevented Omicron variant replication in the lungs.These advantages may overcome the efficacy limitation of currently approved neutralizing antibodies that can be administered only by intravenous injection.In general,58G6 is a promising prophylactic and therapeutic candidate against current circulating VOCs and even future emerging mutants.To the best of our knowledge,58G6 is one of the most potent neutralizing antibodies against Omicron,with a broader spectrum than those approved for clinical use.58G6 could be developed as a nebulized therapy,which would be more cost effective and user friendly and enhance the clinical outcome comparedto thatobtainedwithdirect nasaldelivery.

关键词： nasal dosage prevention

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Assessment on the Diagnostic Capacity for Parasitic Diseases of Health Facilities—China,2019

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China CDC weekly 2021年第35期3卷 731-735页

作者： Qiang Wang Jing Xu Yuwan Hao Tian Tian Zelin Zhu Xueqiang Zhang Liying Wang shaohong chen Jiaxu chen Ning Xiao Shizhu Li National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention(Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector BiologyWHO Collaborating Centre for Tropical DiseasesNational Center for International Research on Tropical DiseasesShanghaiChina.

What is already known about this topic?Morbidity and prevalence of several major parasitic diseases have been declining in China.To reduce the disease burden of parasitic diseases and protect public health security,conducting accurate diagnoses following timely treatment is important.What is added by this report?In the national competition held in 2019.

关键词： China. conducting burden

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旋毛虫新生幼虫细胞外囊泡的分离鉴定及组学分析

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中国寄生虫学与寄生虫病杂志 2024年第2期42卷 225-233页

作者：刘毅蔡玉春陈家旭陈韶红俞英昉中国疾病预防控制中心寄生虫病预防控制所(国家热带病研究中心) 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寄生虫病原与媒介生物学重点实验室世界卫生组织热带病合作中心科技部国家级热带病国际研究中心上海200025 上海健康医学院医学技术学院上海201318

目的分离并鉴定旋毛虫新生幼虫分泌的细胞外囊泡(EV)主要成分,了解新生幼虫EV的功能。方法消化旋毛虫保种小鼠肌肉,手机旋毛虫肌幼虫,昆明小鼠灌胃感染肌幼虫(2000条/鼠)后5 d取小肠,网筛法收集旋毛虫成虫,成虫置于RPMI 1640培养液中培... 详细信息

目的分离并鉴定旋毛虫新生幼虫分泌的细胞外囊泡(EV)主要成分,了解新生幼虫EV的功能。方法消化旋毛虫保种小鼠肌肉,手机旋毛虫肌幼虫,昆明小鼠灌胃感染肌幼虫(2000条/鼠)后5 d取小肠,网筛法收集旋毛虫成虫,成虫置于RPMI 1640培养液中培养48 h后收集新生幼虫。采用差速超速离心法提取旋毛虫新生幼虫培养液中的EV,透射电子显微镜观察EV形态,使用纳米颗粒跟踪分析技术检测EV的粒径,蛋白质免疫印迹(Western blotting)验证EV蛋白。对新生幼虫及其EV进行蛋白组质谱分析和miRNA测序分析,采用t检验比较新生幼虫及其EV之间蛋白和miRNA的表达差异。差异表达蛋白和miRNA靶基因进行基因本体论(GO)功能条目富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。使用WoLFPSORT分析蛋白的亚细胞定位。结果透射电子显微镜和纳米颗粒跟踪分析结果显示,旋毛虫新生幼虫分泌的EV为“杯盘”形膜性囊泡,平均粒径为(101.7±1.8)nm。Western blotting结果显示,新生幼虫EV能与旋毛虫感染小鼠血清产生特异性条带,相对分子质量约为65000。蛋白组质谱分析结果显示,新生幼虫及其EV样品中分别检测到1424和231种蛋白,有220种蛋白在两组样品中均有表达,其中116种表达有差异(在EV中31种表达上调、85种表达下调)。蛋白亚细胞定位分析结果显示,差异蛋白主要分布于细胞质(30.2%,35/116)、细胞核(19.0%,22/116)和细胞膜(17.2%,20/116)。miRNA测序结果显示,新生幼虫及其EV样品分别检测到183和117种miRNA,有46种miRNA在两组样品中均有表达,其中40种表达有差异(在EV中10种表达上调、30种表达下调)。在EV中表达上调的10种miRNA中,let-7-5p表达最高。GO功能条目富集分析结果显示,差异蛋白有57种属于细胞组成、73种具有分子功能、63种参与生物过程,差异miRNA的靶基因主要与自噬相关12基因转移酶活性、胞质泛素连接酶复合物、细胞对紫外线A的响应和钙离子稳态等条目有关。KEGG通路富集分析结果显示,差异蛋白主要富集在代谢途径、内质网中的蛋白质加工等相关通路,差异miRNA的靶基因仅涉及自噬-其他1条途径。结论本研究分离并鉴定了旋毛虫新生幼虫分泌的EV,检测到新生幼虫及其EV间差异表达的116种蛋白和40种miRNA,主要参与代谢、自噬等途径,推测新生幼虫EV可能在旋毛虫感染早期逃避宿主免疫防御的过程中发挥重要作用。

关键词：旋毛虫新生幼虫细胞外囊泡蛋白组学 miRNA测序

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Spreading of Human Babesiosis in China:Current Epidemiological Status and Future Challenges

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China CDC weekly 2020年第33期2卷 634-637页

作者： Muxin chen Qin Liu Jingbo Xue shaohong chen Dana Huang Yingfang Yu Yuchun Cai Yan Lu Peng Song Renli Zhang Lin Ai Jiaxu chen National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention/Chinese Center for Tropical Diseases Research/Key Laboratory of Parasite and Vector BiologyMinistry of Health/National Center for International Research on Tropical DiseasesMinistry of Science and Technology/WHO Collaborating Center for Tropical DiseasesShanghaiChina Shenzhen Center for Disease Control and Prevention ShenzhenChina National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention-Shenzhen Center for Disease Control and Prevention Joint Laboratory for Imported Tropical Disease ControlShanghaiChina

Human babesiosis is an infection caused by intraerythrocytic protozoa of the genus Babesia and is a worldwide emerging tick-borne disease(1).Babesia is mainly parasitized in erythrocytes of human or other vertebrates and transmitted by the bite of ticks,blood transfusion,or organ transplantation(1).Humans are generally susceptible to Babesia,especially those who are immunocompromised with conditions such as splenectomy or splenic dysfunction,as well as those of old age,with infirmity,or with other severe diseases.

关键词： (1) Human transfusion

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Effects of a combination of Japanese Raisin Tree Seed and Flower of Lobed Kudzuvine against acute alcohol-induced liver injury in mice

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Journal of Traditional Chinese Medical Sciences 2020年第1期7卷 59-67页

作者： Wan Xu shaohong chen Gansheng Zhong Haiyan Liu Linlin Xiu Xue Yu Feng chen Na Li Yanmin Lv School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing100029China

Objective:The Flower of Lobed Kudzuvine[Pueraria lobata(Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed(Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ)are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases.We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury,and to elucidate the mechanisms involved.Methods:Male ICR mice were randomly allocated to six groups:a control group,an alcohol-administered group,and groups that were administered alcohol and one of silibinin,the GH,the ZJZ or a GH-ZJZ combination(at a ratio of 2:1).Animals were orally administered 56%alcohol(Er Guo-tou white spirit,0.12 mL/10 g/d)for 10 days and at the end of this period,hepatic biochemical indicators,antioxidant parameters,alcohol metabolic enzymes,and histopathologic changes were evaluated.Moreover,the expression of the signaling molecules KEAP1,NRF2,and AQP9 were measured by qRT-PCR and western blotting.Results:Compared with the model group,GH-ZJZ(2:1)had lower serum ALT(12.15±0.39,P紏.003),AST(104.07±1.03,P紏.001),and ALP(148.09±2.55,P紏.010)activities,and lower TC(1.97±0.05,P紏.001)and TG(1.54±0.07,P?.002)concentrations.GH-ZJZ(2:1)also significantly increased the hepatic activities of SOD and GSH(4.24±0.25 and 1.57±0.06,respectively;both P<.01),reduced the ROS and MDA concentrations(97.50±3.00 and 2.39±0.19,respectively;both P<.01),and upregulated Nrf2 expression(P<.01).GH-ZJZ(2:1)significantly reduced the expression of KEAP1 and AQP9 in the liver,compared with alcohol-administered mice(P<.01).Importantly,the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.Conclusion:We have demonstrated protective effects of GH-ZJZ(2:1)against acute alcohol-induced hepatic injury,and shown that these effects may be associated with improvements in lipid and alcohol metabolism,antioxidant capacity,and lipid peroxidation.

关键词： GH-ZJZ combination Acute alcohol-induced liver injury Oxidative stress AQP9 KEAP1-NRF2-ARE

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