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| 1 | Deregulation of brain insulin signaling in Alzheimer's disease显示文摘Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease(AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss defi ciencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders. | Yanxing Chen Yanqiu Deng Baorong Zhang Cheng-Xin Gong | 2014 | Neuroscience Bulletin2014，30，2： | 15 |
| 2 | Regulating surface state of WO3 nanosheets by gamma irradiation for suppressing hydrogen evolution reaction in electrochemical N2 fixation显示文摘Realizing the reduction of N2 to NH3 at low temperature and pressure is always the unremitting pursuit of scientists and then electrochemical nitrogen reduction reaction offers an intriguing alternative.Here,we develop a feasible way,gamma irradiation,for constructing defective structure on the surface of WO3 nanosheets,which is clearly observed at the atomic scale by high-angle annular dark-field scanning transmission electron microscopy(HAADF-STEM).The abundant oxygen vacancies ensure WO3 nanosheets with a Faradaic efficiency of 23%at−0.3 V vs.RHE.Moreover,we start from the regulation of the surface state to suppress proton availability towards hydrogen evolution reaction(HER)on the active site and thus boost the selectivity of nitrogen reduction. | Yanqiu Du Cheng Jiang Li Song Bin Gao Hao Gong Wei Xia Lei Sheng Tao Wang Jianping He | 2020 | Nano Research2020，13，10： | 4 |
| 3 | A recombinant receptor-binding domain in trimeric form generates protective immunity against SARSCoV-2 infection in nonhuman primates显示文摘A safe and effective vaccine is critical to combat the COVID-19 pandemic.Here,we developed a trimeric SARS-CoV-2 receptor-binding domain(RBD)subunit vaccine candidate that simulates the natural structure of the spike(S)trimer glycoprotein.Immunization with the RBD trimer-induced robust humoral and cellular immune responses,and a high level of neutralizing antibodies was maintained for at least 4.5 months.Moreover,the antibodies that were produced in response to the vaccine effectively cross-neutralized the SARS-CoV-2501Y.V2 variant(B.1.351).Of note,when the vaccine-induced antibodies dropped to a sufficiently low level,only one boost quickly activated the anamnestic immune response,conferring full protection against a SARSCoV-2 challenge in rhesus macaques without typical histopathological changes in the lung tissues.These results demonstrated that the SARS-CoV-2 RBD trimer vaccine candidate is highly immunogenic and safe,providing long-lasting,broad,and significant immunity protection in nonhuman primates,thereby offering an optimal vaccination strategy against COVID-19. | Limin Yang Deyu Tian Jian-bao Han Wenhui Fan Yuan Zhang Yunlong Li Wenqiang Sun Yanqiu Wei Xiaodong Tian Dan-dan Yu Xiao-li Feng Gong Cheng Yuhai Bi Yong-tang Zheng Wenjun Liu | 2021 | The Innovation2021，2，3： | 3 |
| 4 | Structural and functional insights into sorting nexin 5/6 interaction with bacterial effector IncE显示文摘The endosomal trafficking pathways are essential for many cellular activities.They are also important targets by many intracellular pathogens.Key regulators of the endosomal trafficking include the retromer complex and sorting nexins(SNXs).Chlamydia trachomatis effector protein IncE directly targets the retromer components SNX5 and SNX6 and suppresses retromer-mediated transport,but the exact mechanism has remained unclear.We present the crystal structure of the PX domain of SNX5 in complex with IncE,showing that IncE binds to a highly conserved hydrophobic groove of SNX5.The unique helical hairpin of SNX5/6 is essential for binding,explaining the specificity of SNX5/6 for IncE.The SNX5/6–IncE interaction is required for cellular localization of IncE and its inhibitory function.Mechanistically,IncE inhibits the association of CI-MPR cargo with retromer-containing endosomal subdomains.Our study provides new insights into the regulation of retromer-mediated transport and illustrates the intricate competition between host and pathogens in controlling cellular trafficking. | Qingxiang Sun Xin Yong Xiaodong Sun Fan Yang Zhonghua Dai Yanqiu Gong Liming Zhou Xia Zhang Dawen Niu Lunzhi Dai Jia-Jia Liu Da Jia | 2017 | Signal Transduction and Targeted Therapy2017，2，1： | 1 |
| 5 | Injectable cartilage matrix hydrogel loaded with cartilage endplate stem cells engineered to release exosomes for non-invasive treatment of intervertebral disc degeneration显示文摘Low back pain,mainly caused by intervertebral disc degeneration(IVDD),is a common health problem;however,current surgical treatments are less than satisfactory.Thus,it is essential to develop novel non-invasive surgical methods for IVDD treatment.Here,we describe a therapeutic strategy to inhibit IVDD by injecting hydrogels modified with the extracellular matrix of costal cartilage(ECM-Gels)that are loaded with cartilage endplate stem cells(CESCs).After loaded with CESCs overexpressing Sphk2(Lenti-Sphk2-CESCs)and injected near the cartilage endplate(CEP)of rats in vivo,ECM-Gels produced Sphk2-engineered exosomes(Lenti-Sphk2-Exos).These exosomes penetrated the annulus fibrosus(AF)and transported Sphk2 into the nucleus pulposus cells(NPCs).Sphk2 activated the phosphatidylinositol 3-kinase(PI3K)/p-AKT pathway as well as the intracellular autophagy of NPCs,ultimately ameliorating IVDD.This study provides a novel and efficient non-invasive combinational strategy for IVDD treatment using injectable ECM-Gels loaded with CESCs that express Sphk2 with sustained release of functional exosomes. | Liwen Luo Junfeng Gong Zhouguang Wang Yao Liu Jiaming Cao Jinghao Qin Rui Zuo Hongyu Zhang Shuai Wang Ping Zhao Di Yang Mengjie Zhang Yanqiu Wang Junfeng Zhang Yue Zhou Changqing Li Bing Ni Zhiqiang Tian MingHan Liu | 2022 | Bioactive Materials2022，7，9： | 1 |
| 6 | The glycosylation in SARS-CoV-2 and its receptor ACE2显示文摘Coronavirus disease 2019(COVID-19),a highly infectious disease caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2),has infected more than 235 million individuals and led to more than 4.8 million deaths worldwide as of October 52021.Cryo-electron microscopy and topology show that the SARS-CoV-2 genome encodes lots of highly glycosylated proteins,such as spike(S),envelope(E),membrane(M),and ORF3a proteins,which are responsible for host recognition,penetration,binding,recycling and pathogenesis.Here we reviewed the detections,substrates,biological functions of the glycosylation in SARS-CoV-2 proteins as well as the human receptor ACE2,and also summarized the approved and undergoing SARS-CoV-2 therapeutics associated with glycosylation.This review may not only broad the understanding of viral glycobiology,but also provide key clues for the development of new preventive and therapeutic methodologies against SARS-CoV-2 and its variants. | Yanqiu Gong Suideng Qin Lunzhi Dai Zhixin Tian | 2021 | Signal Transduction and Targeted Therapy2021，6，12： | 0 |
| 7 | The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response显示文摘Activation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications,including ubiquitination,SUMOylation,and phosphorylation;however,the underlying molecular mechanism is not fully understood.In this study,TRIM60 negatively regulated the formation and activation of the TAK1 signalosome.Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation,accompanied by elevated levels of proinflammatory cytokines but not IFN-I.Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination,resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways.The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562;substitution of these lysines with arginines abolished the SUMOylation of TAB2.In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock and L.monocytogenes infection.Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response,potentially paving the way for a new strategy to control antibacterial immune responses. | Zhiwen Gu Xueying Chen Wenyong Yang Yu Qi Hui Yu Xiaomeng Wang Yanqiu Gong Qianqian Chen Bo Zhong Lunzhi Dai Shiqian Qi Zhiqiang Zhang Huiyuan Zhang Hongbo Hu | 2021 | Cellular & Molecular Immunology2021，18，8： | 0 |
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