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| 1 | Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection显示文摘Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined.Here,we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2.On the basis of our previously identified humanized cross-neutralizing antibody H014,we systematically an a lyzed a fully human n aive antibody library and rationally identified a potent neutralizing antibody partner,P17,which confers effective protection in animal model.Cryo-EM studies dissected the nature of the P17 epitope,which is SARS-CoV-2 specific and distinctly different from that of HOI4.High-resolution structure of the SARS-CoV-2 spike in complex with HOM and P17,together with functional investigations revealed that in a two-antibody cocktail,synergistic neutralization was achieved by S1 shielding and conformational locking,thereby blocking receptor attachment and viral membrane fusion,conferring high potency as well as robustness against viral mutation escape.Furthermore,cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics. | Hangping Yao Yao Sun Yong-Qiang Deng Nan Wang Yongcong Tan Na-Na Zhang Xiao-Feng Li Chao Kong Yan-Peng Xuc Qi Chen Tian-Shu Cao Hui Zhao Xintian Yan Lei Cao Zhe Lv Dandan Zhu Rui Feng Nanping Wu Wenhai Zhang Yuhao Hu Keda Chen Rong-Rong Zhang Qingyu Lv Shihui Sun Yunhua Zhou Run Yan Guan Yang Xinglu Chanjuan Liu Xiangyun Lu Linfang Cheng Hongying Qiu Xing-Yao Huang Tianhao Weng Danrong Shi Weidong Jiang Junbin Shao Lei Wang Jie Zhang Tao Jiang Guojun Lang Cheng-Feng Qinc Lanjuan Li Xiangxi Wang | 2021 | Cell Research2021，31，1： | 5 |
| 2 | Volitinib, a potent and highly selective c-Met inhibitor, effectively blocks c-Met signaling and growth in c-MET amplified gastric cancer patient-derived tumor xenograft models显示文摘 | Paul R. Gavine Yongxin Ren Lu Han Jing Lv Shiming Fan Wei Zhang Wen Xu Yuan Jie Liu Tianwei Zhang Haihua Fu Yongjuan Yu Huiying Wang Shirlian Xu Feng Zhou Xinying Su XiaoLu Yin Liang Xie Linfang Wang Weiguo Qing Longxian Jiao Weiguo Su Q. May Wang | 2014 | Molecular Oncology2014，，： | 1 |
| 3 | RING finger 138 deregulation distorts NF-κB signaling and facilities colitis switch to aggressive malignancy显示文摘Prolonged activation of nuclear factor(NF)-кB signaling significantly contributes to the development of colorectal cancer(CRC).New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction.Here,we discovered the critical role of RING finger 138(RNF138)in CRC tumorigenesis through regulating the NF-кB signaling,which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response.RNF138^(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy,which coincided with sustained aberrant NF-кB signaling in the colonic cells.Furthermore,RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein(NIBP)to the cytoplasm,which requires the ubiquitin interaction motif(UIM)domain.More importantly,we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings,raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling.Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients,we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth.Overall,our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression,and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation. | Yalan Lu Rong Huang Jianming Ying Xingchen Li Tao Jiao Lei Guo Haitao Zhou Han Wang Amannisa Tuersuntuoheti Jianmei Liu Qichen Chen Yanhong Wang Luying Su Changyuan Guo Fu Xu Ziyi Wang Yan Lu Kai Li Junbo Liang Zhen Huang Xiao Chen Jinjie Yao Hanjie Hu Xiaowen Cheng Yufeng Wan Xinyan Chen Ning Zhang Shiying Miao Jianqiang Cai Linfang Wang Changzheng Liu Wei Song Hong Zhao | 2022 | Signal Transduction and Targeted Therapy2022，7，7： | 0 |
| 4 | Retinoblastoma binding protein 4 represses HIV-1 long terminal repeat–mediated transcription by recruiting NR2F1 and histone deacetylase显示文摘Human immunodeficiency virus (HIV) transcription is closely associated with chromatin remodeling. Retinoblastoma binding protein 4 (RBBP4) is a histone chaperone implicated in chromatin remodeling. However, the role of RBBP4 in HIV-1 infection and the underlying mechanism remain elusive. In the present study, we showed that RBBP4 plays a negative regulatory role during HIV-1 infection. RBBP4 expression was significantly increased in HIV-1–infected T cells. RBBP4 binds to the HIV-1 long terminal repeat (LTR), represses HIV-1 LTR-mediated transcription through recruiting nuclear receptor subfamily 2 group F member 1(NR2F1) and histone deacetylase 1 and 2 (HDAC1/2) to HIV-1 LTR, and further controls local histone 3 (H3) deacetylation and chromatin compaction. Furthermore, the occupancy of RBBP4, HDAC1/2, and NR2F1 on LTR in HIV-latent J-lat cells was significantly higher than that in HIV-1–activated cells. In conclusion, our results establish RBBP4 as a new potent antiretroviral factor, which may provide theoretical basis for the treatment of HIV in the future. | Juan Wang Zongxing Yang Linfang Cheng Lingna Lu Kenv Pan Jin Yang Nanping Wu | 2019 | Acta Biochimica et Biophysica Sinica2019，51，9： | 0 |
| 5 | Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro显示文摘Dear Editor,The coronavirus disease 2019(COVID-19)outbreak,has spread across the world(Wu et al.,2020).The causative agent of COVID-19,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),is highly pathogenic and infectious,which become a major public health hazard that has had a devastating social and economic impact worldwide(Li Q.Q.et al.,2020).Variants of the virus have emerged that behave differently(CDC2021;Gobeil et al.,2020;Leung et al.,2021).Some of them show increased infectivity(Li Q.et al.,2020;Zhang et al.,2020)and may escape from neutralizing antibodies(Weisblum et al.,2020). | Danrong Shi Keda Chen Xiangyun Lu Linfang Cheng Tianhao Weng Fumin Liu Nanping Wu Lanjuan Li Hangping Yao | 2022 | Virologica Sinica2022，37，2： | 0 |
| 6 | Lrrc34 Is Highly Expressed in SSCs and Is Necessary for SSC Expansi on In Vitro显示文摘Objective To discover critical genes contributing to the sternness and maintenance of spermatogonial stem cells(SSCs)and provide new insights into the function of the leucine-rich repeat(LRR)family member Lrrc34(leudne-rich repeat-containing 34)in SSCs from mice.Methods Bioinformatic methods,including differentially expressed gene(DEG),gene ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses,were used to uncover latent pluripotency-related genes.Reverse transcription-polymerase chain reaction(RT-PCR)and immunofluorescence analyses were utilized to verify the mRNA and protein expression levels,respectively.RNA interference of Lrrc34 using siRNA was performed to detect its transient impact on SSCs.Results Eight DEGs between ID4-EGFP+(G)and ID4-EGFP+/TSPAN8Hig11(TH),eight DEGs between G and ID4-EGFP+/TSPAN8Uw(TL)and eleven DEGs between TH and TL were discovered,and eleven proteinprotein interaction(PPI)modules were found to be significant in the PPI network of DEGs.One of the DEGs,Lrrc34,was selected as a potential pluripotency?related gene due to its differential expression among ID4-EGFP+spermatogonia subsets and its interaction with fibroblast growth factor 2 in the fifth module.Immunofluorescence experiments exhibited specific expression of Lrrc34 in a subpopulation of undifferentiated spermatogonia marked by LIN28A,and RT-PCR experiments confirmed the high expression of Lrrc34 in SSCs from P7 and adult mice.The transient knockdown of Lrrc34 in SSCs resulted in reduced colony sizes and significant changes in the transcriptome and apoptotic pathways.Conclusion Lrrc34 is highly expressed in mouse SSCs and is required for SSC proliferation in vitro through effects on transcriptome and signaling transduction pathways. | Jinhuan Ou Yiran Li Zhipeng Wang Cheng Jin Kai Li Yan Lu Dingfeng Zou Pengyu Li Mengzhen Li Shiying Miao Linfang Wang Wei Song | 2020 | Chinese Medical Sciences Journal2020，35，1： | 0 |
| 7 | SARS-CoV-2-specific antibody response characteristics in COVID-19 patients of different ages显示文摘Age has been found to be one of the main risk factors for the severity and outcome of COVID-19.However,differences in SARS-CoV-2 specific antibody responses among COVID-19 patients of different age groups remain largely unknown.In this study,we analyzed the IgG/IgM responses to 21 SARS-CoV-2 proteins and 197 peptides that fully cover the spike protein against 731 sera collected from 731 COVID-19 patients aged from 1 to 92 years.We show that there is no overall difference in SARS-CoV-2 antibody responses in COVID-19 patients in the 4 age groups.By antibody response landscape maps,we find that the IgG response profiles of SARS-CoV-2 proteins are positively correlated with age.The S protein linear epitope map shows that the immunogenicity of the S-protein peptides is related to peptide sequence,disease severity and age of the COVID-19 patients.Furthermore,the enrichment analysis indicates that low S1 IgG responses are enriched in patients aged<50 and high S1 IgG responses are enriched in mild COVID-19 patients aged>60.In addition,high responses of non-structural/accessory proteins are enriched in severe COVID-19 patients aged>70.These results suggest the distinct immune response of IgG/IgM to each SARS-CoV-2 protein in patients of different age,which may facilitate a deeper understanding of the immune responses in COVID-19 patients. | Linfang Lu Siqi Yu Min Liu Yang Li Qing Lei Mingxi Lin Danyun Lai Shujuan Guo Hewei Jiang Hongyan Hou Yunxiao Zheng Xuening Wang Mingliang Ma Bo Zhang Hong Chen Junbiao Xue Hainan Zhang Huan Qi Ziyong Sun Feng Wang Xionglin Fan Zhaowei Xu | 2022 | Acta Biochimica et Biophysica Sinica2022，54，4： | 0 |
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