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Serum Glypican 4 Levels Are Associated with Metabolic Syndrome in a Han Population from Guizhou Province, china

Biomedical and Environmental Sciences 2019年第5期32卷 383-388页

作者： NING Dong Ping xu Ke zhu Hui Juan SHAN Guang Liang {2. Ding Ming PING Bo YU Yang Wen PAN Hui GONG Feng Ying Key Laboratory of Endocrinology of National Health Commission Dept. of EndocrinologyPeking Union Medical College HospitalTranslation Medicine CentreCAMS & PUMCBeijing 100730China Graduate school Hebei North UniversityZhangjiakou 075000HebeiChina Linfen Central Hospital Linfen 041000ShanxiChina Dept. of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityZhejiang Provincial First Hospital of WenzhouWenzhou 325000ZhejiangChina Dept. of Epidemiology and Health Statistics Institute of Basic Medical SciencesCAMS & PUMCBeijing 100005China Guizhou Provincial Center for Disease Control and Prevention Guiyang 550004GuizhouChina Longli Center for Disease Control and Prevention Longli 551200GuizhouChina

Metabolic syndrome (MetS) is the presence of a battery of cardiovascular risk factors including abdominal obesity, hypertension, dyslipidemia, and disturbed carbohydrate metabolism[1]. MetS affects 2.% of adults in the Western world and 33% of adults in china[2. and has become a serious public health problem worldwide. However, the mechanism underlying the occurrence and progression of MetS is still largely unclear. It is now well established that excess fat deposition leads to abdominal obesity, which plays a vital role in the underlying mechanism. Adipose tissue can function as an endocrine organ that secretes various adipokines. The dysregulated expression of adipokines caused by excess adiposity and adipocyte dysfunction, has been linked to the pathogenesis of MetS[3]. Some serum adipokines such as leptin, adiponectin, interleukin 6 (IL-6), and tumour necrosis factor-α(TNF-α), might be potential markers for MetS development.

关键词： Serum Glypican 4 Levels Metabolic Syndrome

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生髓健骨胶囊对酒精性骨质疏松症患者的血清IL-6、TNF-α因子的影响

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时珍国医国药 2024年第7期35卷 1670-1672页

作者：田圣雨谭福柱申意伟耿慧春杨春雨王龙飞徐西林任树军黑龙江中医药大学研究生院黑龙江哈尔滨150040 黑龙江中医药大学附属第一医院黑龙江哈尔滨150040 北京中医药大学深圳医院(龙岗) 广东深圳518172 黑龙江中医药大学附属第三医院黑龙江哈尔滨150030

目的探讨生髓健骨胶囊对治疗酒精性骨质疏松症患者的IL-6、TNF-α因子水平的影响。方法收集黑龙江中医药大学附属第一医院骨伤科2.2.年6月至2.2.年8月54例符合AOP的患者作为研究对象,并且采用随机数字表法分为治疗组和对照组,每组各2.... 详细信息

目的探讨生髓健骨胶囊对治疗酒精性骨质疏松症患者的IL-6、TNF-α因子水平的影响。方法收集黑龙江中医药大学附属第一医院骨伤科2.2.年6月至2.2.年8月54例符合AOP的患者作为研究对象,并且采用随机数字表法分为治疗组和对照组,每组各2.例。治疗组予患者口服碳酸钙维D3、生髓健骨胶囊治疗;对照组予患者口服碳酸钙维D3与阿仑膦酸钠片,3个月为1个疗程,连续治疗3个疗程。比较两组患者治疗前后腰椎和左髋BMD骨密度及血清肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平变化。结果治疗后,治疗组腰椎和左髋BMD骨密度分别为(0.757±0.018)、(0.646±0.02.)g/cm^(2.,明显高于对照组的(0.743±0.02.)、(0.632.0.014)g/cm^(2.,差异均有统计学意义(P10.16)、(59.53±9.35)n g/L,明显低于对照组的(59.97±10.48)、(77.89±10.61)ng/L,差异均有统计学意义(P<0.05)。结论生髓健骨胶囊对于治疗酒精性骨质疏松的临床疗效明确,可以明显改善患者腰椎和左髋BMD骨密度,其机制可能是通过调节血清中IL-6和TNF-α的浓度从而影响骨吸收。

关键词：生髓健骨胶囊酒精性骨质疏松症骨密度肿瘤坏死因子-α 白细胞介素-6

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Identification and validation of key biomarkers and potential therapeutic targets for primary open-angle glaucoma

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Science china(Life Sciences) 2023年第12期66卷 2837-2850页

作者： Jian Wu Caixia Lin Chenlong Yang Lijie Pan Hongyi Liu Sirui zhu Shuwen Wei xu Jia Qi Zhang Ziyu Yu Xiaofang Zhao Weihai Liu Yehong zhuo Ningli wang beijing Institute of Ophthalmology Beijing Tongren Eye CenterBeijing Tongren HospitalCapital Medical UniversityBeijing Key Laboratory of Ophthalmology and Visual SciencesBeijing 100730China beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Department of Neurosurgery Peking University Third HospitalCenter for Precision Neurosurgery and Oncology of Peking University Health Science CenterBeijing 100191China North America Medical Education Foundation Union City CA 94539USA State Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China Spencer Center for Vision Research Byers Eye InstituteSchool of MedicineStanford UniversityPalo Alto CA 94304USA

Primary open-angle glaucoma(POAG)is a prevalent cause of blindness worldwide,resulting in degeneration of retinal ganglion cells and permanent damage to the optic ***,the underlying pathogenetic mechanisms of POAG are currently indistinct,and there has been no effective nonsurgical treatment *** objective of this study is to identify novel biomarkers and potential therapeutic targets for *** mRNA expression microarray datasets GSE2.2.6 and GSE13812.,as well as the single-cell high-throughput RNA sequencing(sc RNA-seq)dataset GSE148371 were utilized to screen POAGrelated differentially expressed genes(DEGs).Functional enrichment analyses,protein-protein interaction(PPI)analysis,and weighted gene co-expression network analysis(WGCNA)of the DEGs were ***,the hub genes were validated at a single-cell level,where trabecular cells were annotated,and the mRNA expression levels of target genes in different cell clusters were *** and quantitative real-time PCR(q PCR)were performed for further *** analysis identified 43 downregulated and 32.upregulated genes in POAG,which were mainly enriched in immune-related pathways,oxidative stress,and endoplasmic reticulum(ER)*** networks showed that FN1 and DUSP1 were the central hub nodes,while GPX3 and VAV3 were screened out as hub genes through WGCNA and subsequently validated by q ***,FN1,GPX3,and VAV3 were determined to be pivotal core genes via single-cell *** relevant biomarkers involved in the pathogenesis of POAG,may serve as potential therapeutic *** studies are necessary to unveil the mechanisms underlying the expression variations of these genes in POAG.

关键词： primary open-angle glaucoma biomarkers immune response oxidative stress endoplasmic reticulum stress

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The repression of oncoprotein SET by the tumor suppressor p53 reveals a p53-SET-PP2. feedback loop for cancer therapy

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Science china(Life Sciences) 2023年第1期66卷 81-93页

作者： Han Yao Wenbin xu Yajing Liu Zhijie Cao Jia Wen Mi Zhang Zhen Wu Xiaojun Yan Zishan Jiao Zijing Zhang Jianyuan Chen Meng Zhang Wei-Guo zhu Donglai {2. State Key Laboratory of Medical Molecular Biology&Department of Medical Genetics Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China Department of Anatomy Histology and EmbryologySchool of Basic MedicineChina Medical UniversityShenyang 110122China Department of Biochemistry and Molecular Biology Shenzhen University School of MedicineShenzhen 518060China

The oncoprotein SET is frequently overexpressed in many types of tumors and contributes to malignant initiation and progression through multiple mechanisms,including the hijacking of the tumor suppressors p53 and *** aberrant SET represents a promising strategy for cancer ***,the mechanism by which endogenous SET is regulated in cancer cells remains largely ***,we identified the tumor suppressor p53 as a key regulator that transcriptionally repressed the expression of SET in both normal and cancer *** addition,p53 stimulated PP2. phosphatase activity via p53-mediated transcriptional repression of SET,whereby SET-mediated inhibition of PP2. was ***,targeting the interaction between SET and PP2. catalytic subunit(PP2.c)with FTY72. enhanced stress-induced p53 activation via PP2.-mediated dephosphorylation of p53 on threonine 55(Thr55).Therefore,our findings uncovered a previously unknown p53-SETPP2. regulatory feedback *** functionally potentiate this feedback loop,we designed a combined therapeutic strategy by simultaneously administrating a p53 activator and SET antagonist in cancer cells and observed a dramatic synergistic effect on tumor *** study reveals mechanistic insight into the regulation of the oncoprotein SET and raises a potential strategy for cancer therapy by stimulating the p53-SET-PP2. feedback loop.

关键词： p53 SET PP2. FTY72. feedback loop tumor suppression

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Structural and functional analysis of a potent human neutralizing antibody against enterovirus A71

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Science china(Life Sciences) 2022年第12期65卷 2517-2526页

作者： Zhe Chen Linlin Bao Bin zhu Hua Fu Shuangli zhu Tianjiao Ji Ying {2.e Chuan Liu {2.rong wang Fengdi Li Qi Lv Feifei Qi Pin Yu Wei Deng Wenbo {2. Chuan Qin Hongrong Liu Qi Jin MOH Key Laboratory of Systems Biology of Pathogens Institute of Pathogen BiologyChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases NHC Key Laboratory of Human Disease Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China school of Computer Science and Engineering Hunan University of Science and TechnologyXiangtan 411201China National Institute for Viral Disease Control and Prevention China CDCBeijing 102206China Ministry of Education Key Laboratory of Protein Sciences Beijing Advanced Innovation Center for Structural BiologyTsinghua UniversityBeijing 100084China Key Laboratory for Matter Microstructure and Function of Hunan Province Key Laboratory of Low-dimensional Quantum Structures and Quantum ControlSchool of Physics and ElectronicsHunan Normal UniversityChangsha 410081China Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases Hangzhou 310058China

Enterovirus A71(EV-A71) causes major outbreaks of hand,foot,and mouth disease(HFMD) in many countries,most frequently affecting children,and a small proportion of cases may lead to ***,no vaccine is available in most endemic regions,and no licenced treatments for EV-A71 infection are ***,we characterize a human monoclonal antibody(Hu MAb),E1,by screening a Fab antibody phage library derived from patients who recovered from EV-A71 infection.E1 exhibits strong neutralizing activity against EV-A71 virus in *** cryo-electron microscopy(cryo-EM) structures of the EV-A71 virion in complex with E1 Fab fragments demonstrated that E1 recognized an epitope formed by residues in the BC and HI loops of *** a mouse model,E1 effectively protected against lethal EV-A71 challenge in both prophylactic and therapeutic *** particular,E1 significantly reduces virus titers and muscle damage.E1 might represent a potential adjunct to EV-A71 treatment.

关键词： enterovirus A71 antibody mouse models cryo-electron microscopy

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Trim2. depletion alleviates bone loss in osteoporosis via activation of YAP1/β-catenin signaling

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Bone Research 2023年第4期11卷 819-833页

作者： Ri-xu Liu Rong-He Gu Zhi-Peng Li Zhi-Quan Hao Qin-Xiao Hu Zhen-Yan Li Xiao-Gang wang wang Tang Xiao-He wang Yu-Kai Zeng Zhen-Wei Li Qiu Dong Xiao-Feng zhu Di Chen Ke-Wei Zhao Rong-Hua Zhang Zhen-Gang Zha Huan-Tian Zhang Department of Bone and Joint Surgery the First Affiliated Hospital of Jinan UniversityKey Laboratory of Regenerative Medicine of Ministry of EducationJinan UniversityGuangzhou 510630 GuangdongChina Department of Orthopedic and Spine Surgery The First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120 GuangdongChina school of Basic Medical Sciences of Guangxi Medical university the Fifth Affiliated Hospital of Guangxi Medical UniversityNanning 530022 GuangxiChina Key Laboratory of Big Data-Based Precision Medicine School of Engineering MedicineBeihang University100191 BeijingChina Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization College of PharmacyJinan UniversityGuangzhou 510630 GuangdongChina Research Center for Computer-aided Drug Discovery Shenzhen Institute of Advanced TechnologyChinese Academy of Sciences518005 ShenzhenChina Guangzhou Key Laboratory of Chinese Medicine Research on Prevention and Treatment of Osteoporosis the Third Affiliated Hospital of Guangzhou University of Chinese Medicine510375 GuangzhouChina

Despite the diverse roles of tripartite motif(Trim)-containing proteins in the regulation of autophagy,the innate immune response,and cell differentiation,their roles in skeletal diseases are largely *** recently demonstrated that Trim2. plays a crucial role in regulating osteoblast(OB)differentiation in ***,how Trim2. contributes to skeletal degenerative disorders,including osteoporosis,remains ***,human and mouse bone specimens were evaluated,and the results showed that Trim2. expression was significantly elevated in bone tissues obtained from osteoporosis ***,we found that global knockout of the Trim2. gene(KO,Trim2.(1-/-))resulted in higher bone mass compared to that of the control *** further demonstrated that loss of Trim2. promoted bone formation by enhancing the osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs)and elevating the activity of OBs;moreover,Trim2. depletion suppressed osteoclast(OC)formation of RAW2.4.7 *** addition,the differentiation of OCs from bone marrow-derived macrophages(BMMs)isolated from Trim2.^(-/-)and Ctsk-cre;Trim2.^(f/f)mice was largely compromised compared to that of the littermate control ***,YAP1/β-catenin signaling was identified and demonstrated to be required for the Trim2.-mediated osteogenic differentiation of *** importantly,the loss of Trim2. prevented ovariectomy(OVX)-and lipopolysaccharide(LPS)-induced bone loss in vivo by orchestrating the coupling of OBs and OCs through YAP1 *** current study demonstrated that Trim2. is crucial for regulating OB-mediated bone formation and OC-mediated bone resorption,thereby providing a basis for exploring Trim2. as a novel dual-targeting approach for treating osteoporosis and pathological bone loss.

关键词： YAP1 osteoporosis depletion

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New innovations in pavement materials and engineering:A review on pavement engineering research 2.2.

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Journal of Traffic and Transportation Engineering(English Edition) 2021年第6期8卷 815-999页

作者： JTTE Editorial Office Jiaqi Chen Hancheng Dan Yongjie Ding Yangming Gao Meng Guo Shuaicheng Guo Bingye Han Bin Hong Yue Hou Chichun Hu Jing Hu Ju Huyan Jiwang Jiang Wei Jiang Cheng Li Pengfei Liu Yu Liu zhuangzhuang Liu Guoyang Lu Jian Ouyang Xin Qu Dongya Ren Chao wang Chaohui wang Dawei wang Di wang Hainian wang Haopeng wang Yue Xiao Chao Xing Huining xu Yu Yan xu Yang Lingyun You Zhanping You Bin Yu Huayang Yu Huanan Yu Henglong Zhang Jizhe Zhang Changhong Zhou Changjun Zhou Xingyi zhu Editorial Office of Journal of Traffic and Transportation Engineering(English Edition) Chang’an UnivieristyXi’an 710064China school of Civil Engineering Central South UniversityChangsha 410075China school of Civil Engineering Chongqing Jiaotong UniversityChongqing 400074China Department of Structural Engineering Faculty of Civil Engineering and GeosciencesDelft University of TechnologyDelft 2628 CNthe Netherlands The Key Laboratory of Urban Security and Disaster Engineering of Ministry of Education Beijing University of TechnologyBeijing 100124China College of Civil Engineering Hunan UniversityChangsha 410082China school of Civil and Transportation Engineering Beijing University of Civil Engineering and ArchitectureBeijing 100044China school of Transportation Science and Engineering Harbin Institute of TechnologyHarbin 150090China College of Metropolitan Transportation Beijing University of TechnologyBeijing 100124China school of Civil Engineering&Transportation South China University of TechnologyGuangzhou 510641China school of Transportation Southeast UniversityNanjing 211189China Department of Civil&Environmental Engineering University of WaterlooWaterlooON N2L 3G1Canada Department of Civil and Environmental Engineering The Hong Kong Polytechnic UniversityHong KongChina school of Highway Chang’an UniversityXi’an 710064China Institute of Highway Engineering RWTH Aachen UniversityAachen 52074Germany school of Transportation&Logistics Dalian University of TechnologyDalian 116024China school of Civil Engineering Southwest Jiaotong UniversityChengdu 611756China Faculty of Architecture Civil and Transportation EngineeringBeijing University of TechnologyBeijing 100124China Department of Civil Engineering Aalto UniversityEspoo 02150Finland Nottingham Transportation Engineering Center(NTEC) University of NottinghamNottingham NG72RDUK State Key Laboratory of Silicate Materials for Architectures Wuhan University of TechnologyWuhan 430070China College of Transportation Engineer

Sustainable and resilient pavement infrastructure is critical for current economic and environmental *** the past 10 years,the pavement infrastructure strongly supports the rapid development of the global social *** theories,new methods,new technologies and new materials related to pavement engineering are *** of pavement infrastructure is a typical multi-physics *** of actual coupled behaviors of traffic and environmental conditions,predictions of pavement service life become more and more complicated and require a deep knowledge of pavement material *** order to summarize the current and determine the future research of pavement engineering,Journal of Traffic and Transportation Engineering(English Edition)has launched a review paper on the topic of"New innovations in pavement materials and engineering:A review on pavement engineering research 2.2.".Based on the joint-effort of 43 scholars from 2. well-known universities in highway engineering,this review paper systematically analyzes the research status and future development direction of 5 major fields of pavement engineering in the *** content includes asphalt binder performance and modeling,mixture performance and modeling of pavement materials,multi-scale mechanics,green and sustainable pavement,and intelligent ***,this review paper is able to provide references and insights for researchers and engineers in the field of pavement engineering.

关键词： Asphalt binder Asphalt mixture Modeling of pavement materials Multi-scale mechanics Green and sustainable pavement Intelligent pavement

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Famitinib versus placebo in the treatment of refractory metastatic colorectal cancer:a multicenter,randomized,double-blinded,placebo-controlled,phaseⅡclinical trial

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Chinese Journal of Cancer 2017年第12期36卷 677-685页

作者： Rui-Hua xu Lin Shen Ke-Ming wang Gang Wu Chun-Mei Shi Ke-Feng Ding Li-{2. Lin Jin-Wan wang Jian-Ping Xiong Chang-Ping Wu Jin Li Yun-Peng Liu Dong wang Yi Ba Jue-Ping Feng Yu-Xian Bai Jing-wang Bi Li-Wen Ma Jian Lei Qing Yang Hao Yu Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060GuangdongP.R.China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Gastrointestinal OncologyPeking University Cancer Hospital&InstituteNo 52Fucheng RoadHaidian DistrictBeijing 100142P.R.China Department of Medical Oncology Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011JiangsuP.R.China Cancer Center of Union Hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030HubeiP.R.China Department of Medical Oncology Fujian Medical University Union HospitalFuzhou 350001FujianP.R.China Department of Surgical Oncology Second Hospital Affiliated to Zhejiang University School of MedicineHangzhou 310009ZhejiangP.R.China Department of Oncology First Affiliated Hospital of Guangzhou Medical University of Chinese MedicineGuangzhou 510405GuangdongP.R.China Department of Medical Oncology Chinese Academy of Medical Sciences Cancer HospitalBeijing 100021P.R.China Department of Medical Oncology First Affiliated Hospital of Nanchang UniversityNanchang 330006JiangxiP.R.China Department of Medical Oncology First People’s Hospital of ChangzhouChangzhou 213003JiangsuP.R.China Department of Medical Oncology Fudan University Cancer HospitalShanghai 200032P.R.China Department of Medical Oncology First Hospital of China Medical UniversityShenyang 110001LiaoningP.R.China Cancer Center Daping Hospital and Institute of Surgery ResearchThird Military Medical UniversityChongqing 400042P.R.China Department of Gastrointestinal Medical Oncology Tianjin Medical University Cancer Institute and HospitalTianjin 300060P.R.China Department of Oncology PuAi Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430032HubeiP.R.China Department of Medical Oncology Harbin Medical University Cancer Hospit

Background: Metastatic colorectal cancer(mCRC) patients with progressive disease after all available standard therapies need new medication for further treatment. Famitinib is a small-molecule multikinase inhibitor, with promising anticancer activities. This multicenter, randomized, double-blinded, placebo-controlled, phase II clinical trial was designed to evaluate the safety and efficacy of famitinib in ***: Famitinib or placebo was administered orally once daily. The primary endpoint was progression-free survival(PFS). Secondary endpoints included objective response rate(ORR), disease control rate(DCR), overall survival(OS), quality-of-life(QoL), and ***: Between July 18,2.12.and Jan 2.,2.14, a total of 167 patients were screened, and 154 patients were randomized in a 2.1 ratio to receive either famitinib(n = 99) or placebo(n = 55). The median PFS was 2.8 and 1.5 months in the famitinib and placebo groups(hazard ratio = 0.60,95% confidence interval = 0.41-0.86, P = 0.004). The DCR was 59.8% and 31.4%(P = 0.002. and the ORR was 2.2. and 0.0%(P = 0.540) in the famitinib and placebo groups,respectively. The most frequent grade 3-4 adverse events were hypertension(11.1%), hand-foot syndrome(10.1%),thrombocytopenia(10.1%) and neutropenia(9.1%). Serious adverse events occurred in 11(11.1%) patients in the famitinib group and 5(9.1%) in the placebo group(P = 0.788). The median OS of the famitinib and placebo groups was 7.4 and 7.2.months(P = 0.657).Conclusion: Famitinib prolonged PFS in refractory mCRC patients with acceptable *** registration This study was registered on ***(NCT01762.93) and was orally presented in the 2.15 ASCO-Gastrointestinal

关键词： Colorectal cancer Famitinib Efficacy Safety

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Maternal Eomesodermin regulates zygotic nodal gene expression for mesendoderm induction in zebrafish embryos

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Journal of Molecular Cell Biology 2014年第4期8卷 272-285页

作者： Pengfei xu Gaoyang zhu Yixia {2. Jiawei Sun Xingfeng Liu Ye-Guang Chen Anming Meng State Key Laboratory of Biomembrane and Membrane Engineering Tsinghua- Peking Center for Life Sciences School of Life Sciences Tsinghua University Beijing 100084 China

Development of animal embryos before zygotic genome activation at the mid blastula transition （MBT） is essentially supported by eggderived maternal products. Nodal proteins are crucial signals for mesoderm and endoderm induction after the MBT. It remains unclear which maternal factors activate zygotic expression of nodal genes in the ventrotateral blastodermal margin of the zebrafish blastulas. In this study, we show that loss of maternal Eomesodermin a （Eomesa）, a T-box transcription factor, impairs zygotic expression of the nodal genes ndr1 and ndr2.as well as mesodermal and endodermal markers, indicating an involvement in mesendoderm induction. Maternal Eomesa is also required for timely zygotic expression of the transcription factor gene mxtx2. a regulator of nodal gene expression. Eomesa directly binds to the Eomes-binding sites in the promoter or enhancer of ndr1, ndr2. and rnxtx2.to activate their transcrip- tion. Furthermore, human and mouse Nodal genes are also regulated by Eomes. Transfection of zebrafish eomesa into murine embryonic stem cells promotes mesendodermal differentiation with constant higher levels of endogenous Nodal expression, suggesting a conserved function of Eomes. Taken together, our findings reveal a conserved rote of maternal T-box transcription factors in regulating nodal gene expression and mesendoderm induction in vertebrate embryos.

关键词： Eomesodermin Nodal transcription mesoderm endoderm embryo zebrafish

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Evaluation of the Safety and Immune Efficacy of Recombinant Human Respiratory Syncytial Virus Strain Long Live Attenuated Vaccine Candidates

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Virologica Sinica 2021年第4期36卷 706-720页

作者： Li-Nan wang Xiang-Lei Peng Min xu Yuan-Bo Zheng Yue-Ying Jiao Jie-Mei Yu Yuan-Hui Fu Yan-Peng Zheng Wu-Yang {2. Zhong-Jun Dong Jin-Sheng He College of Life Sciences and Bioengineering School of ScienceBeijing Jiaotong UniversityBeijing100044China National Institute for Viral Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing102206China school of Medicine and Institute for Immunology Beijing Key Lab for Immunological Research on Chronic DiseasesTsinghua UniversityBeijing100084China

Human respiratory syncytial virus(RSV)infection is the leading cause of lower respiratory tract illness(LRTI),and no vaccine against LRTI has proven to be safe and effective in *** study assessed attenuated recombinant RSVs as vaccine candidates to prevent RSV infection in *** constructed recombinant plasmids harbored(5′to 3′)a T7 promoter,hammerhead ribozyme,RSV Long strain antigenomic cDNA with cold-passaged(cp)mutations or cp combined with temperature-sensitive attenuated mutations from the A2.strain(A2.pts)or further combined with SH gene deletion(A2.ptsΔSH),HDV ribozyme(δ),and a T7 *** vectors were subsequently co-transfected with four helper plasmids encoding N,P,L,and M2.1 viral proteins into BHK/T7-9 cells,and the recovered viruses were then passaged in Vero *** rescued recombinant RSVs(rRSVs)were named rRSV-Long/A2.p,rRSV-Long/A2.pts,and rRSV-Long/A2.ptsΔSH,respectively,and stably passaged in vitro,without reversion to wild type(wt)at sites containing introduced mutations or *** rRSV-Long/A2.pts and rRSV-Long/A2.ptsΔSH displayed temperature-sensitive(ts)phenotype in vitro and in vivo,all rRSVs were significantly attenuated in ***,BALB/c mice immunized with rRSVs produced Th1-biased immune response,resisted wtRSV infection,and were free from enhanced respiratory *** showed that the combination ofΔSH with attenuation(att)mutations of cpts contributed to improving att phenotype,efficacy,and gene stability of *** successfully introducing att mutations and SH gene deletion into the RSV Long parent and producing three rRSV strains,we have laid an important foundation for the development of RSV live attenuated vaccines.

关键词： Human respiratory syncytial virus(RSV) RSV long strain Live attenuated vaccine Safety Protective immunity

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