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| 1 | A two-step lineage reprogramming strategy to generate functionally competent human hepatocytes from fibroblasts显示文摘Terminally differentiated cells can be generated by lineage reprogramming,which is,however,hindered by incomplete conversion with residual initial cell identity and partial functionality. Here, we demonstrate a new reprogramming strategy by mimicking the natural regeneration route, which permits generating expandable hepatic progenitor cells and functionally competent human hepatocytes. Fibroblasts were first induced into human hepatic progenitor-like cells (hHPLCs), which could robustly expand in vitro and efficiently engraft in vivo. Moreover, hHPLCs could be efficiently induced into mature human hepatocytes (hiHeps) in vitro, whose molecular identity highly resembles primary human hepatocytes (PHHs). Most importantly, hiHeps could be generated in large quantity and were functionally competent to replace PHHs for drug-metabolism estimation, toxicity prediction and hepatitis B virus infection modeling. Our results highlight the advantages of the progenitor stage for successful lineage reprogramming. This strategy is promising for generating other mature human cell types by lineage reprogramming. | Bingqing Xie Da Sun Yuanyuan Du Jun Jia Shicheng Sun Jun Xu Yifang Liu Chengang Xiang Sitong Chen Huangfan Xie Qiming Wang Guangya Li Xuehui LYU Hui Shen Shiyu Li Min Wu Xiaonan Zhang Yue Pu Kuanhui Xiang Weifeng Lai Peng Du Zhenghong Yuan Cheng Li Yan Shi Shichun Lu Hongkui Deng | 2019 | Cell Research2019，29，9： | 9 |
| 2 | Interplay between hepatitis B virus and the innate immune responses:implications for new therapeutic strategies显示文摘Hepatitis B virus(HBV) infection is still a worldwide health problem;however,the current antiviral therapies for chronic hepatitis B are limited in efficacy.The outcome of HBV infection is thought to be the result of complex interactions between the HBV and the host immune system.While the role of the adaptive immune responses in the resolution of HBV infection has been well characterized,the contribution of innate immune mechanisms remains elusive until recent evidence implicates that HBV appears to activate the innate immune response and this response is important for controlling HBV infection.Here,we review our current understanding of innate immune responses to HBV infection and the multifaceted evasion by the virus and discuss the potential strategies to combat chronic HBV infection via induction and restoration of host innate antiviral responses. | Jieliang Chen Zhenghong Yuan | 2014 | Virologica Sinica2014，29，1： | 9 |
| 3 | Plasma membrane proteome analysis of the early effect of alcohol on liver: implications for alcoholic liver disease显示文摘在人,酒精的在消费上能导致严肃的肝疾病。在肝疾病上检验酒精的早效果,老鼠被给足够的乙醇开发肝肝硬化。在纤维变性的发作前的老鼠在这个工作被学习。肝的血浆膜(下午) 被提取由两次蔗糖密度坡度 centrifugation。从对待乙醇的老鼠和控制的下午的 proteome 侧面为相对、绝对的 quantitation (iTRAQ ) 用二维的胶化电气泳动(2-DE ) 和等压的标签被分析技术。乙醇处理改变了 15 不同的肝蛋白质的数量:他们中的 10 个被 2-DE 检测并且 5 由 iTRAQ。角质素 8 被两个方法检测。这些差别的基因本体论分析检测了显示的蛋白质他们的那个大多数涉及象有约束力的活动那样的重要房间函数(包括离子, DNA, ATP 绑定,等等) ,房间结构,或酶活动。在这些之中, annexin A2,角质素 8,和角质素 18 进一步用西方的污点分析被验证, annexin A2 被 immunohistochemistry 验证。我们的结果建议酒精有潜力由在 PM 改变几相关蛋白质的表示层次影响房间结构,粘附和酶活动。就我们的知识而言,这是第一次在肝下午 proteome 上学习酒精的效果,它可能对理解导致白酒的肝疾病的可能的机制有用。 | Lijun Zhang Xiaofang Jia Yanling Feng Xia Peng Zhiyong Zhang Wenjiang Zhou Zhanqing Zhang Fang Ma Xiaohui Liu Ye Zheng Pengyuan Yang Zhenghong Yuan | 2011 | Acta Biochimica et Biophysica Sinica2011，43，1： | 8 |
| 4 | RBD-Fc-based COVID-19 vaccine candidate induces highly potent SARS-CoV-2 neutralizing antibody response显示文摘The pandemic of coronavirus disease 2019(COVID-19)caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has posed serious threats to global health and economy,thus calling for the development of safe and effective vaccines.The receptorbinding domain(RBD)in the spike protein of SARS-CoV-2 is responsible for its binding to angiotensin-converting enzyme 2(ACE2)receptor.It contains multiple dominant neutralizing epitopes and serves as an important antigen for the development of COVID-19 vaccines.Here,we showed that immunization of mice with a candidate subunit vaccine consisting of SARS-CoV-2 RBD and Fc fragment of human IgG,as an immunopotentiator,elicited high titer of RBD-specific antibodies with robust neutralizing activity against both pseudotyped and live SARS-CoV-2 infections.The mouse antisera could also effectively neutralize infection by pseudotyped SARS-CoV-2 with several natural mutations in RBD and the IgG extracted from the mouse antisera could also show neutralization against pseudotyped SARS-CoV and SARS-related coronavirus(SARSr-CoV).Vaccination of human ACE2 transgenic mice with RBD-Fc could effectively protect mice from the SARS-CoV-2 challenge.These results suggest that SARS-CoV-2 RBD-Fc has good potential to be further developed as an effective and broad-spectrum vaccine to prevent infection of the current SARS-CoV-2 and its mutants,as well as future emerging SARSr-CoVs and re-emerging SARS-CoV. | Zezhong Liu Wei Xu Shuai Xia Chenjian Gu Xinling Wang Qian Wang Jie Zhou Yanling Wu Xia Cai Di Qu Tianlei Ying Youhua Xie Lu Lu Zhenghong Yuan Shibo Jiang | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 7 |
| 5 | Development and validation of a liquid chromatography-mass spectrometry metabonomic platform in human plasma of liver failure caused by hepatitis B virus显示文摘 | Lijun Zhang Xiaofang Jia Xia Peng Qiang Ou Zhengguo Zhang Chao Qiu Yamin Yao Fang Shen Hua Yang Fang Ma Jiefei Wang Zhenghong Yuan | 2010 | Acta Biochimica et Biophysica Sinica2010，42，10： | 6 |
| 6 | New insights into hepatitis B virus biology and implications for novel antiviral strategies显示文摘Hepatitis B virus(HBV), a small DNA virus with a unique replication mode, can cause chronic hepatitis(CHB), which is characterized by the persistence of the viral covalently closed circular DNA that serves as the template for HBV replication and the production of large amounts of secreted HBV surface antigen(HBs Ag) that is present in excess of the levels of infectious virus. Despite the success of currently approved antiviral treatments for CHB patients, including interferon and nucleotide analogs, which suppress HBV replication and reduce the risk of CHB-related liver diseases, these therapies fail to eradicate the virus in most of the patients. With the development of the cell and animal models for HBV study, a beter understanding of the HBV life cycle has been achieved and a series of novel antiviral strategies that target diferent stages of HBV replication have been designed to overcome the viral factors that contribute to HBV persistence. Such basic HBV research advancements and therapeutic developments are the subject of this review. | Jieliang Chen Min Wu Kuancheng Liu Wen Zhang Yaming Li Xiaohui Zhou Lu Bai Zhenghong Yuan | 2015 | National Science Review2015，2，3： | 6 |
| 7 | A novel STING agonist-adjuvanted pan-sarbecovirus vaccine elicits potent and durable neutralizing antibody and T cell responses in mice,rabbits and NHPs显示文摘The emergence of SARS-CoV-2 variants and potentially other highly pathogenic sarbecoviruses in the future highlights the need for pan-sarbecovirus vaccines.Here,we discovered a new STING agonist,CF501,and found that CF501-adjuvanted RBD-FC vaccine(CF501/RBD-FC)elicited significantly stronger neutralizing antibody(nAb)and T cell responses than Alum-and cGAMP-adjuvanted RBD-FC in mice.Vaccination of rabbits and rhesus macaques(nonhuman primates,NHPs)with CF501/RBD-FC elicited exceptionally potent nAb responses against SARS-CoV-2 and its nine variants and 41 S-mutants,SARS-CoV and bat SARSr-CoVs.CF501/RBD-FC-immunized hACE2-transgenic mice were almost completely protected against SARS-CoV-2 challenge,even 6 months after the initial immunization.NHPs immunized with a single dose of CF501/RBD-FC produced high titers of nAbs.The immunized macaques also exhibited durable humoral and cellular immune responses and showed remarkably reduced viral load in the upper and lower airways upon SARS-CoV-2 challenge even at 108 days post the final immunization.Thus,CF501/RBD-Fc can be further developed as a novel pan-sarbecovirus vaccine to combat current and future outbreaks of sarbecovirus diseases. | Zezhong Liu Jie Zhou Wei Xu Wei Deng Yanqun Wang Meiyu Wang Qian Wang Ming Hsieh Jingming Dong Xinling Wang Weijin Huang Lixiao Xing Miaoling He Chunlin Tao Youhua Xie Yilong Zhang Youchun Wang Jincun Zhao Zhenghong Yuan Chuan Qin Shibo Jiang Lu Lu | 2022 | Cell Research2022，32，3： | 5 |
| 8 | Genome Size of Alexandrium catenella and Gracilariopsis lemaneiformis Estimated by Flow Cytometry显示文摘Flow cytometry(FCM) technique has been widely applied to estimating the genome size of various higher plants. However, there is few report about its application in algae. In this study, an optimized procedure of FCM was exploited to estimate the genome size of two eukaryotic algae. For analyzing Alexandrium catenella, an important red tide species, the whole cell instead of isolated nucleus was studied, and chicken erythrocytes were used as an internal reference. The genome size of A. catenella was estimated to be 56.48 ± 4.14 Gb(1C), approximately nineteen times larger than that of human genome. For analyzing Gracilariopsis lemaneiformis, an important economical red alga, the purified nucleus was employed, and Arabidopsis thaliana and Chondrus crispus were used as internal references, respectively. The genome size of Gp. lemaneiformis was 97.35 ± 2.58 Mb(1C) and 112.73 ± 14.00 Mb(1C), respectively, depending on the different internal references. The results of this research will promote the related studies on the genomics and evolution of these two species. | DU Qingwei SUI Zhenghong CHANG Lianpeng WEI Huihui LIU Yuan MI Ping SHANG Erlei Zeeshan Niaz QUE Zhou | 2016 | Journal of Ocean University of China2016，15，4： | 2 |
| 9 | Structural and functional basis for pan-CoV fusion inhibitors against SARS-CoV-2 and its variants with preclinical evaluation显示文摘The COVID-19 pandemic poses a global threat to public health and economy.The continuously emerging SARS-CoV-2 variants present a major challenge to the development of antiviral agents and vaccines.In this study,we identified that EK1 and cholesterol-coupled derivative of EK1,EK1C4,as pan-CoV fusion inhibitors,exhibit potent antiviral activity against SARS-CoV-2 infection in both lung-and intestine-derived cell lines(Calu-3 and Caco2,respectively).They are also effective against infection of pseudotyped SARS-CoV-2 variants B.1.1.7(Alpha)and B.l.1.248(Gamma)as well as those with mutations in S protein,including N417T,E484K,N501Y,and D614G,which are common in South African and Brazilian variants.Crystal structure revealed that EK1 targets the HR1 domain in the SARS-CoV-2 S protein to block virus-cell fusion and provide mechanistic insights into its broad and effective antiviral activity.Nasal administration of EK1 peptides to hACE2 transgenic mice significantly reduced viral titers in lung and intestinal tissues.EK1 showed good safety profiles in various animal models,supporting further clinical development of EK1-based pan-CoV fusion inhibitors against SARS-CoV-2 and its variants. | Shuai Xia Qiaoshuai Lan Yun Zhu Chao Wang Wei Xu Yutang Li Lijue Wang Fanke Jiao Jie Zhou Chen Hua Qian Wang Xia Cai Yang Wu Jie Gao Huan Liu Ge Sun Jan Munch Frank Kirchhoff Zhenghong Yuan Youhua Xie Fei Sun Shibo Jiang Lu Lu | 2021 | Signal Transduction and Targeted Therapy2021，6，8： | 2 |
| 10 | Genome Sequence of Shigella flexneri 2a, Insights into pathogenicity through comparison with genomes of Escherichia coli K-12 and O157显示文摘 | Qi Jin Zhenghong Yuan Jianguo Xu | 2002 | Nuel Acids Res2002，30，20： | 1 |
| 11 | Hydrogen-rich gas production from biomass air and oxygen/steam gasification in a downdraft gasifier显示文摘 | Pengmei Lv Zhenghong Yuan Longlong Ma | 2006 | Renewable Energy2006，32，10： | 1 |
| 12 | Expression profiles and function of Toll-like receptors 2 and 4 in peripheral blood mononuclear cells of chronic hepatitis B patients显示文摘 | Zhiao Chen Yuming Cheng Yongfen Xu Jing Liao Xiaonan Zhang Yunwen Hu Qin Zhang Jiefei Wang Zhanqing Zhang Fang Shen Zhenghong Yuan | 2008 | Clinical Immunology2008，，3： | 1 |
| 13 | Hepatitis B virus polymerase impairs interferon‐α–induced STA T activation through inhibition of importin‐α5 and protein kinase C‐δ显示文摘 | Jieliang Chen Min Wu Xiaonan Zhang Wen Zhang Zhanqing Zhang Lixiang Chen Jing He Ye Zheng Cuncun Chen Fan Wang Yunwen Hu Xiaohui Zhou Cong Wang Yang Xu Mengji Lu Zhenghong Yuan | 2013 | Hepatology2013，，2： | 1 |
| 14 | Viperin inhibits hepatitis C virus replication by interfering with binding of NS5A to host protein hVAP-33显示文摘 | Shanshan Wang Xianfang Wu Tingting Pan Wuhui Song Yaohui Wang Fei Zhang Zhenghong Yuan | 2012 | J Gen Virol2012，93，1： | 1 |
| 15 | Self-healing of Cracks in Concrete with Various Crystalline Mineral Additives in Underground Environment显示文摘Cracks can deteriorate mechanical properties and/or durability of concrete. A few studies have shown that, cracks can autogenously heal under a certain conditions besides the traditional passive repair with a deliberate external intervention. For underground concrete structures, the presence of water, as a necessity for chemical reactions of the healing additives, is beneficial to healing concrete. In this paper, a natural healing method by mineral additives was developed according to the chemical and physical characteristics of underground environment. The healing capacity of three different crystalline mineral materials classified namely, carbonate, calcium sulphoaluminate expansive agent and natural metakaolin due to permeationcrystallization, expansion and pozzolanic reaction, has been assessed from the mechanical properties, referring to the relative elastic modulus, the strength restoration, and the water permeability of the healed specimens. In addition, the morphology of the healing products in the vicinity of the crack was observed. The results indicate that the specimens incorporated with the three mineral additives show different healing capacity according to the improved mechanical properties and permeability. The permeability of the host matrix decreased a lot after crack healing by natural metakaolin followed by carbonate whereas no noticeable improvement of water permeability has been observed for the specimens mixed with expansive agent. The specimens incorporated with carbonate show the best mechanical restoration in terms of relative elastic modulus and compressive strength. Although the dominate element is Ca CO3 by reaction of CO32-, either from the dissolved CO2 or from the additives, and Ca2+ in the cementitious system to fill the cracks, the healing capacity depends greatly on the morphology and the properties of the newly formed products. | 蒋正武 李文婷 YUAN Zhengzheng YANG Zhenghong | 2014 | Journal of Wuhan University of Technology(Materials Science)2014，29，5： | 1 |
| 16 | An ultrapotent pan-β-coronavirus lineage B(β-CoV-B)neutralizing antibody locks the receptor-binding domain in closed conformation by targeting its conserved epitope显示文摘New threats posed by the emerging circulating variants of SARS-CoV-2 highlight the need to find conserved neutralizing epitopes for therapeutic antibodies and efficient vaccine design.Here,we identified a receptorbinding domain(RBD)-binding antibody,XG014,which potently neutralizesβ-coronavirus lineage B(β-CoV-B),including SARS-CoV-2,its circulating variants,SARSCoV and bat SARSr-CoV WIV1.Interestingly,antibody family members competing with XG014 binding show reduced levels of cross-reactivity and induce antibodydependent SARS-CoV-2 spike(S)protein-mediated cellcell fusion,suggesting a unique mode of recognition by XG014.Structural analyses reveal that XG014 recognizes a conserved epitope outside the ACE2 binding site and completely locks RBD in the non-functional“down”conformation,while its family member XG005 directly competes with ACE2 binding and position the RBD“up”.Single administration of XG014 is effective in protection against and therapy of SARS-CoV-2 infection in vivo.Our findings suggest the potential to develop XG014 as pan-β-CoV-B therapeutics and the importance of the XG014 conserved antigenic epitope for designing broadly protective vaccines againstβ-CoV-B and newly emerging SARS-CoV-2 variants of concern. | Zezhong Liu Wei Xu Zhenguo Chen Wangjun Fu Wuqiang Zhan Yidan Gao Jie Zhou Yunjiao Zhou Jianbo Wu Qian Wang Xiang Zhang Aihua Hao Wei Wu Qianqian Zhang Yaming Li Kaiyue Fan Ruihong Chen Qiaochu Jiang Christian TMayer Till Schoofs Youhua Xie Shibo Jiang Yumei Wen Zhenghong Yuan Kang Wang Lu Lu Lei Sun Qiao Wang | 2022 | Protein & Cell2022，13，9： | 1 |
| 17 | A CRISPR activation screen identifies genes that enhance SARS-CoV-2 infection显示文摘Dear Editor,Identifying the host factors that are utilized for virus infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been devoted to the identification of SARS-CoV-2 infection-dependent host factors.CRISPR-based activation(Konermann et al.,2015). | Fei Feng Yunkai Zhu Yanlong Ma Yuyan Wang Yin Yu Xinran Sun Yuanlin Song Zhugui Shao Xinxin Huang Ying Liao Jingyun Ma Yuping He Mingyuan Wang Longhai Tang Yaowei Huang Jincun Zhao Qiang Ding Youhua Xie Qiliang Cai Hui Xiao Chun Li Zhenghong Yuan Rong Zhang | 2023 | Protein & Cell2023，14，1： | 0 |
| 18 | An approach for choosing discretization schemes and grid size based on the convection-diffusion equation显示文摘A new approach for selecting proper discretization schemes and grid size is presented.This method is based on the convection-diffusion equation and can provide insight for the Navier-Stokes equation.The approach mainly addresses two aspects,i.e.,the practical accuracy of diffusion term discretization and the behavior of high wavenumber disturbances.Two criteria are included in this approach.First,numerical diffusion should not affect the theoretical diffusion accuracy near the length scales of interest.This is achieved by requiring numerical diffusion to be smaller than the diffusion discretization error.Second,high wavenumber modes that are much smaller than the length scales of interest should not be amplified.These two criteria provide a range of suitable scheme combinations for convective flux and diffusive flux and an ideal interval for grid spacing.The effects of time discretization on these criteria are briefly discussed. | Lin ZHOU Zhenghong GAO Yuan GAO | 2018 | Applied Mathematics and Mechanics(English Edition)2018，39，6： | 0 |
| 19 | From Discovery to Cure, A Great Journey of the Hepatitis C Virus Study显示文摘Hepatitis C virus(HCV)causes chronic infection in over 75%of the HCV-infected individuals,resulting in liver cancer in substantial patients.Since its discovery in 1989,HCV experiences a journey from discovery to cure,largely due to the virology studies and success of direct antiviral agent(DAA)development.We reviewed the HCV research journey,from the discovery of this virus to the development of DAAs for cure.Learning the methodology used in HCV studies and the knowledge of developing DAAs against HCV may inspire the studies of other difficult-to-culture viruses,such as hepatitis E virus and norovirus,as well as the development of DAAs for other single-stranded positive-sense RNA viruses,including the pandemic-causing SARS-CoV-2 virus,which shares the common replication strategy of forming a membrane-bound viral replicase. | Zhigang Yi Zhenghong Yuan | 2022 | Infectious Diseases & Immunity2022，2，2： | 0 |
| 20 | Isolation and Expression Analysis of Growth-Related Genes at Different Growth Stages of Dinoflagellate Alexandrium pacificum显示文摘Based on the transcriptomic sequencing, three genes of Alexandrium pacificum encoding ubiquitin(UBI), telomerase(TEL) and glycine-rich protein(GRP) relating to cell division were isolated and characterized. The full-length cD NA of GRP was obtained through approach of rapid amplification of c DNA ends(RACE). Four conserved domains, including DNA-and RNAbinding sites or motifs, cold shock domain at the N-terminal, and zinc-finger structure of CCCH type at the C-terminal were idenrtified. Phylogenetic analysis revealed that the deduced amino acid sequence of GRP tends to cluster together with proteins harboring cold shock domain. The expressions of these three genes were analyzed with quantitative PCR(qPCR). It was found that the expressions of these three genes at the logarithmic growth phase and induced logarithmic growth phase were all higher than those at lagging growth phase(P < 0.05). The expression patterns of these three genes were coincident with the proliferative capacity of the algae, e.g., displaying increased expression level at log and induced growth phases. The functions of these genes and their possible roles during harmful algal blooms(HAB) were discussed. | LIU Yuan SUI Zhenghong ZHANG Shu MA Jinhua ZHONG Jie | 2019 | Journal of Ocean University of China2019，18，3： | 0 |
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