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| 1 | NAD+metabolism:pathophysiologic mechanisms and therapeutic potential显示文摘Nicotinamide adenine dinucleotide(NAD^(+))and its metabolites function as critical regulators to maintain physiologic processes,enabling the plastic cells to adapt to environmental changes including nutrient perturbation,genotoxic factors,circadian disorder,infection,inflammation and xenobiotics.These effects are mainly achieved by the driving effect of NAD^(+)on metabolic pathways as enzyme cofactors transferring hydrogen in oxidation-reduction reactions.Besides,multiple NAD^(+)-dependent enzymes are involved in physiology either by post-synthesis chemical modification of DNA,RNA and proteins,or releasing second messenger cyclic ADPribose(cADPR)and NAADP^(+).Prolonged disequilibrium of NAD^(+)metabolism disturbs the physiological functions,resulting in diseases including metabolic diseases,cancer,aging and neurodegeneration disorder.In this review,we summarize recent advances in our understanding of the molecular mechanisms of NAD^(+)-regulated physiological responses to stresses,the contribution of NAD^(+)deficiency to various diseases via manipulating cellular communication networks and the potential new avenues for therapeutic intervention. | Na Xie Lu Zhang Wei Gao Canhua Huang Peter Ernst Huber Xiaobo Zhou Changlong Li Guobo Shen Bingwen Zou | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 5 |
| 2 | Structural basis of the Norrin-Frizzled 4 interaction显示文摘 | Guobo Shen Jiyuan Ke Zhizhi Wang Zhihong Cheng Xin Gu Yuquan Wei Karsten Melcher H Eric Xu Wenqing Xu | 2015 | Cell Research2015，25，9： | 3 |
| 3 | Histones released by NETosis enhance the infectivity of SARS-CoV-2 by bridging the spike protein subunit 2 and sialic acid on host cells显示文摘Neutrophil extracellular traps(NETs)can capture and kill viruses,such as influenza viruses,human immunodeficiency virus(HIV),and respiratory syncytial virus(RSV),thus contributing to host defense.Contrary to our expectation,we show here that the histones released by NETosis enhance the infectivity of SARS-CoV-2,as found by using live SARS-CoV-2 and two pseudovirus systems as well as a mouse model.The histone H3 or H4 selectively binds to subunit 2 of the spike(S)protein,as shown by a biochemical binding assay,surface plasmon resonance and binding energy calculation as well as the construction of a mutant S protein by replacing four acidic amino acids.Sialic acid on the host cell surface is the key molecule to which histones bridge subunit 2 of the S protein.Moreover,histones enhance cell-cell fusion.Finally,treatment with an inhibitor of NETosis,histone H3 or H4,or sialic acid notably affected the levels of sgRNA copies and the number of apoptotic cells in a mouse model.These findings suggest that SARS-CoV-2 could hijack histones from neutrophil NETosis to promote its host cell attachment and entry process and may be important in exploring pathogenesis and possible strategies to develop new effective therapies for COVID-19. | Weiqi Hong Jingyun Yang Jun Zou Zhenfei Bi Cai He Hong Lei Xuemei He Xue Li Aqu Alu Wenyan Ren Zeng Wang Xiaohua Jiang Kunhong Zhong Guowen Jia Yun Yang Wenhai Yu Qing Huang Mengli Yang Yanan Zhou Yuan Zhao Dexuan Kuang Junbin Wang Haixuan Wang Siyuan Chen Min Luo Ziqi Zhang Tiangi Lu Li Chen Haiying Que Zhiyao He Qiu Sun Wei Wang Guobo Shen Guangwen Lu Zhiwei Zhao Li Yang Jinliang Yang Zhenling Wang Jiong Li Xiangrong Song Lunzhi Dai Chong Chen Jia Geng Maling Gou Lu Chen Haohao Dong Yong Peng Canhua Huang Zhiyong Qian Wei Cheng Changfa Fan Yuquan Wei Zhaoming Su Aiping Tong Shuaiyao Lu Xiaozhong Peng Xiawei Wei | 2022 | Cellular & Molecular Immunology2022，19，5： | 2 |
| 4 | Neoantigens:promising targets for cancer therapy显示文摘Recent advances in neoantigen research have accelerated the development and regulatory approval of tumor immunotherapies,including cancer vaccines,adoptive cell therapy and antibody-based therapies,especially for solid tumors.Neoantigens are newly formed antigens generated by tumor cells as a result of various tumor-specific alterations,such as genomic mutation,dysregulated RNA splicing,disordered post-translational modification,and integrated viral open reading frames.Neoantigens are recognized as non-self and trigger an immune response that is not subject to central and peripheral tolerance.The quick identification and prediction of tumor-specific neoantigens have been made possible by the advanced development of next-generation sequencing and bioinformatic technologies.Compared to tumor-associated antigens,the highly immunogenic and tumor-specific neoantigens provide emerging targets for personalized cancer immunotherapies,and serve as prospective predictors for tumor survival prognosis and immune checkpoint blockade responses.The development of cancer therapies will be aided by understanding the mechanism underlying neoantigen-induced anti-tumor immune response and by streamlining the process of neoantigen-based immunotherapies.This review provides an overview on the identification and characterization of neoantigens and outlines the clinical applications of prospective immunotherapeutic strategies based on neoantigens.We also explore their current status,inherent challenges,and clinical translation potential. | Na Xie Guobo Shen Wei Gao Zhao Huang Canhua Huang Li Fu | 2023 | Signal Transduction and Targeted Therapy2023，8，2： | 2 |
| 5 | Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection显示文摘The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants.In Chengdu,China,an infection wave was predominantly induced by the BA.5 subvariant.It is crucial to determine whether the hybrid anti-SARS-CoV-2 immunity following BA.5 infection. | Jingyun Yang Weiqi Hong Hong Lei Cai He Wenwen Lei Yanan Zhou Tingmei Zhao Aqu Alu Xuelei Ma Jiong Li Li Yang Zhenling Wang Wei Wang Guangwen Lu Guobo Shen Shuaiyao Lu Guizhen Wu Huashan Shi Xiawei Wei | 2023 | Signal Transduction and Targeted Therapy2023，8，7： | 1 |
| 6 | S19W,T27W,and N33OY mutations in ACE2 enhance SARS-CoV-2 S-RBD binding toward both wild-type and antibody-resistant viruses and its molecular basis显示文摘SARS-CoV-2 recognizes,via its spike receptor-binding domain(S-RBD),human angiotensin-converting enzyme 2(ACE2)to initiate infection.Ecto-domain protein of ACE2 can therefore function as a decoy.Here we show that mutations of S19W,T27W,and N330Y in ACE2 could individually enhance SARS-CoV-2 S-RBD binding.Y330 could be synergistically combined with either W19 or W27,whereas W19 and W27 are mutually unbeneficial.The structures of SARS-CoV-2S-RBD bound to the ACE2 mutants reveal that the enhan ced binding is mainly con tributed by the van der Waals interactio ns mediated by the aromatic side-chai ns from W19,W27,and Y330.While Y330 and W19/W27 are distantly located and devoid of any steric interference,W19 and W27 are shown to orient their side-chains toward each other and to cause steric conflicts,explai ning their in compatibility.Finally,using pseudotyped SARS-CoV-2 viruses,we dem on strate that these residue substitutions are associated with dramatically improved entry-inhibition efficacy toward both wild-type and antibody-resistant viruses.Taken together,our biochemical and structural data have delineated the basis for the elevated S-RBD binding associated with S19W,T27W,and N330Y mutations in ACE2,paving the way for potential application of these mutants in dinical treatment of COVID-19. | Fei Ye Xi Lin Zimin Che Fanli Yang Sheng Lin Jing Yang Hua Chen Honglu Sun Lingling Wang Ao Wen Xindan Zhang Yushan Dai Yu Cao Jingyun Yang Guobo Shen Li Yang Jiong Li Zhenling Wang Wei Wang Xiawei Wei Guangwen Lu | 2021 | Signal Transduction and Targeted Therapy2021，6，10： | 0 |
| 7 | Spike protein of SARS‐CoV‐2 Omicron(B.1.1.529)variant has a reduced ability to induce the immune response显示文摘Dear Editor,The severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)variant Omicron(B.1.1.529)has attracted great concerns since its identification in South Africa.Omicron is the fifth variant of concern(VOC)after Alpha(B.1.1.7),Beta(B.1.351),Gamma(P.1)and Delta(B.1.617.2),and set a record with the shortest duration from variants of interest(VOI)to VOC so far.Within 2 months after its first report,over 80%of global sequenced samples are verified as Omicron according to GISAID(http://gffzze725461255914afesn0kvp6wnbnn96o6o.ffgz.tsg.suse.edu.cn/explore/World/AllSamples/from=2021-12-15&to=2022-01-15/variants?pangoLineage=B.1.1.529*). | Cai He Xuemei He Jingyun Yang Hong Lei Weiqi Hong Xiangrong Song Li Yang Jiong Li Wei Wang Guobo Shen Guangwen Lu Xiawei Wei | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 0 |
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