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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 | New partial cooperation model for bilevel programming problems显示文摘Partial cooperation models are studied for many years to solve the bilevel programming problems where the follower’s optimal reaction is not unique. However, in these existed models, the follower’s cooperation level does not depend on the leader’s decision. A new model is proposed to solve this deficiency. It is proved the feasibility of the new model when the reaction set of the lower level is lower semicontinuous. And the numerical results show that the new model has optimal solutions when the reaction set of the lower level is discrete, lower semi-continuous and non-lower semi-continuous. | Shihui Jia Zhongping Wan Yuqiang Feng Guangmin Wang | 2011 | Journal of Systems Engineering and Electronics2011，22，2： | 4 |
| 3 | Single-cell transcriptomic landscape of human blood cells显示文摘High throughput single-cell RNA-seq has been successfully implemented to dissect the cellular and molecular features underlying hematopoiesis.However,an elaborate and comprehensive transcriptome reference of the whole blood system is lacking.Here,we profiled the transcriptomes of 7551 human blood cells representing 32 immunophenotypic cell types,including hematopoietic stem cells,progenitors and mature blood cells derived from 21 healthy donors.With high sequencing depth and coverage,we constructed a single-cell transcriptional atlas of blood cells(ABC) on the basis of both protein-coding genes and long noncoding RNAs(lncRNAs),and showed a high consistence between them.Notably,putative lncRNAs and transcription factors regulating hematopoietic cell differentiation were identified.While common transcription factor regulatory networks were activated in neutrophils and monocytes,lymphoid cells dramatically changed their regulatory networks during differentiation.Furthermore,we showed a subset of nucleated erythrocytes actively expressing immune signals,suggesting the existence of erythroid precursors with immune functions.Finally,a web portal offering transcriptome browsing and blood cell type prediction has been established.Thus,our work provides a transcriptional map of human blood cells at single-cell resolution,thereby offering a comprehensive reference for the exploration of physiological and pathological hematopoiesis. | Xiaowei Xie Mengyao Liu Yawen Zhang Bingrui Wang Caiying Zhu Chenchen Wang Qing Li Yingying Huo Jiaojiao Guo Changlu Xu Linping Hu Aiming Pang Shihui Ma Una Wang Wenbin Cao Shulian Chen Qiuling Li Sudong Zhang Xueying Zhao Wen Zhou Hongbo Luo Guoguang Zheng Erlie Jiang Sizhou Feng Lixiang Chen Lihong Shi Hui Cheng Sha Hao Ping Zhu Tao Cheng | 2021 | National Science Review2021，8，3： | 3 |
| 4 | IntegrinαEβ7^(+)T cells direct intestinal stem cell fate decisions via adhesion signaling显示文摘Intestinal stem cell(ISC)differentiation is regulated precisely by a niche in the crypt,where lymphocytes may interact with stem and transient amplifying(TA)cells.However,whether and how lymphocyte–stem/TA cell contact affects ISC differentiation is largely unknown.Here,we uncover a novel role of T cell–stem/TA cell contact in ISC fate decisions.We show that intestinal lymphocyte depletion results in skewed ISC differentiation in mice,which can be rescued by T cell transfer.Mechanistically,integrinαEβ7 expressed on T cells binds to E-cadherin on ISCs and TA cells,triggering E-cadherin endocytosis and the consequent Wnt and Notch signaling alterations.BlockingαEβ7−E-cadherin adhesion suppresses Wnt signaling and promotes Notch signaling in ISCs and TA cells,leading to defective ISC differentiation.Thus,αEβ7^(+)T cells regulate ISC differentiation at single-cell level through cell–cell contact-mediatedαEβ7−E-cadherin adhesion signaling,highlighting a critical role of the T cell–stem/TA cell contact in maintaining intestinal homeostasis. | Shiyang Chen Yajuan Zheng Xiaojuan Ran Hui Du Hua Feng Lei Yang Yating Wen Changdong Lin Shihui Wang Mengwen Huang Zhanjun Yan Dianqing Wu Hongyan Wang Gaoxiang Ge An Zeng Yi Arial Zeng Jianfeng Chen | 2021 | Cell Research2021，31，12： | 3 |
| 5 | Design,synthesis,and applications of stereospecific 1,3-diene carbonyls显示文摘The strategy toward the synthesis of various 1,3-dienals or 1,3-dienones is disclosed between diazo compounds and furans,which features metal-free,additive-free,broad functional group tolerance,and readily accessible starting materials.Notably,this strategy is applicable in both intramolecular and intermolecular protocols.Mechanistic studies suggested that the reactions undergo a cyclopropanation/rearrangement sequence.With an E/E-1,3-dienal,corresponding N-tosylhydrazones were readily prepared and subjected to phenylboronic acid to form a double bond migration product and indoles to construct a five-member ring via [3 + 2] annulation reaction. | Qiang Feng Shihui Wang Xingxing Ma Changqing Rao Qiuling Song | 2022 | Science China Chemistry2022，65，5： | 0 |
| 6 | EDVAM:a 3D eye-tracking dataset for visual attention modeling in a virtual museum显示文摘Predicting visual attention facilitates an adaptive virtual museum environment and provides a context-aware and interactive user experience.Explorations toward development of a visual attention mechanism using eye-tracking data have so far been limited to 2D cases,and researchers are yet to approach this topic in a 3D virtual environment and from a spatiotemporal perspective.We present the first 3D Eye-tracking Dataset for Visual Attention modeling in a virtual Museum,known as the EDVAM.In addition,a deep learning model is devised and tested with the EDVAM to predict a user’s subsequent visual attention from previous eye movements.This work provides a reference for visual attention modeling and context-aware interaction in the context of virtual museums. | Yunzhan ZHOU Tian FENG Shihui SHUAI Xiangdong LI Lingyun SUN Henry Been-Lirn DUH | 2022 | Frontiers of Information Technology & Electronic Engineering2022，23，1： | 0 |
| 7 | Rational design of Ruddlesden-Popper perovskite electrocatalyst for oxygen reduction to hydrogen peroxide显示文摘Although the oxygen reduction process to hydrogen peroxide(H_(2)O_(2))is a green option for H_(2)O_(2)generation,the low activity and selectivity hindered the industry's process.In recent years,the electrochemical synthesis of H_(2)O_(2)through a 2e-transfer method of oxygen reduction reaction(ORR)has piqued the interest of both academics and industry.Metal oxide catalysts have emerged as a novel family of electrochemical catalysts due to their unusual physical,chemical,and electrical characteristics.In this work,we first developed a Ruddlesden-Popper perovskite oxide(Pr_(2)NiO_(4+δ))as a highly selective and active catalyst for 2e-ORR to produce H_(2)O_(2).Molybdenum was introduced here to adjust the oxidation states of these transition metals with successful substitution into Ni-site to prepare Pr_(2)Ni1-xMoxO_(4+δ),and the molybdenum substitution improves the H_(2)O_(2)selectivity during the ORR process,in 0.1 M KOH,from 60%of Pr_(2)NiO_(4+δ)to 79%of Pr_(2)Ni_(0.8)Mo_(0.2)O_(4+δ)at 0.55 V versus RHE.A limiting H_(2)O_(2)concentration of_0.24 mM for Pr_(2)NiO_(4+δ)and 0.42 mM for Pr_(2)Ni_(0.8)Mo_(0.2)O_(4+δ)was obtained at a constant current of 10 mA/cm2 using a flow-cell reactor using a gas-diffusion electrode. | Ning Han Shihui Feng Wei Guo Omar Martinez Mora Xiaolin Zhao Wei Zhang Sijie Xie Zhenyu Zhou Zhiwei Liu Qiong Liu Kai Wan Xuan Zhang Jan Fransaer | 2022 | SusMat2022，2，4： | 0 |
| 8 | Inhibition of aryl hydrocarbon receptor signaling promotes the terminal differentiation of human erythroblasts显示文摘The aryl hydrocarbon receptor(AHR)plays an important role during mammalian embryo development.Inhibition of AHR signaling promotes the development of hematopoietic stem/progenitor cells.AHR also regulates the functional maturation of blood cells,such as T cells and megakaryocytes.However,little is known about the role of AHR modulation during the development of erythroid cells.In this study,we used the AHR antagonist StemRegenin 1(SR1)and the AHR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin during different stages of human erythropoiesis to elucidate the function of AHR.We found that antagonizing AHR signaling improved the production of human embryonic stem cell derived erythrocytes and enhanced erythroid terminal differentiation.RNA sequencing showed that SR1 treatment of proerythroblasts upregulated the expression of erythrocyte differentiation-related genes and downregulated actin organization-associated genes.We found that SR1 accelerated F-actin remodeling in terminally differentiated erythrocytes,favoring their maturation of the cytoskeleton and enucleation.We demonstrated that the effects of AHR inhibition on erythroid maturation were associated with F-actin remodeling.Our findings help uncover the mechanism for AHRmediated human erythroid cell differentiation.We also provide a new approach toward the large-scale production of functionally mature human pluripotent stem cell-derived erythrocytes for use in translational applications. | Yijin Chen Yong Dong Xulin Lu Wanjing Li Yimeng Zhang Bin Mao Xu Pan Xiaohong Li Ya Zhou Quanming An Fangxin Xie Shihui Wang Yuan Xue Xinping Cai Mowen Lai Qiongxiu Zhou Yan Yan Ruohan Fu Hong Wang Tatsutoshi Nakahata Xiuli An Lihong Shi Yonggang Zhang Feng Ma | 2022 | Journal of Molecular Cell Biology2022，14，2： | 0 |
| 9 | Mutant rs189037 in ataxia-telangiectasia mutated gene had a negative association with metabolic syndrome but not cognitive decline in centenarians显示文摘Approximately 20%-25%of adults encounter metabolic syndrome(MetS)worldwide,and MetS is a riskfactorfor cognitive decline(CD)development.Patients with MetS have an 11.48-fold increased incidence of CD compared with those without Mets.^(1) Ataxia-telangiectasia mutated(ATM)gene encodes ATM kinase,which belongs to the phosphatidylinositol 3-hydroxy kinase family. | Long Feng Hongqi Huo Qun Li Tao Yang Yali Zhao Pei Zhang Ping Ping Shihui Fu | 2024 | Genes & Diseases2024，11，3： | 0 |
| 10 | Deciphering transcriptome alterations in bone marrow hematopoiesis at single-cell resolution in immune thrombocytopenia显示文摘Immune thrombocytopenia(ITP)is an autoimmune disorder,in which megakaryocyte dysfunction caused by an autoimmune reaction can lead to thrombocytopenia,although the underlying mechanisms remain unclear.Here,we performed single-cell transcriptome profiling of bone marrow CD34+hematopoietic stem and progenitor cells(HSPCs)to determine defects in megakaryopoiesis in ITP.Gene expression,cell-cell interactions,and transcriptional regulatory networks varied in HSPCs of ITP,particularly in immune cell progenitors.Differentially expressed gene(DEG)analysis indicated that there was an impaired megakaryopoiesis of ITP.Flow cytometry confirmed that the number of CD9+and HES1+cells from Lin−CD34+CD45RA−HSPCs decreased in ITP.Liquid culture assays demonstrated that CD9+Lin−CD34+CD45RA−HSPCs tended to differentiate into megakaryocytes;however,this tendency was not observed in ITP patients and more erythrocytes were produced.The percentage of megakaryocytes differentiated from CD9+Lin−CD34+CD45RA−HSPCs was 3-fold higher than that of the CD9−counterparts from healthy controls(HCs),whereas,in ITP patients,the percentage decreased to only 1/4th of that in the HCs and was comparable to that from the CD9−HSPCs.Additionally,when co-cultured with pre-B cells from ITP patients,the differentiation of CD9+Lin−CD34+CD45RA−HSPCs toward the megakaryopoietic lineage was impaired.Further analysis revealed that megakaryocytic progenitors(MkP)can be divided into seven subclusters with different gene expression patterns and functions.The ITP-associated DEGs were MkP subtype-specific,with most DEGs concentrated in the subcluster possessing dual functions of immunomodulation and platelet generation.This study comprehensively dissects defective hematopoiesis and provides novel insights regarding the pathogenesis of ITP. | Yan Liu Xinyi Zuo Peng Chen Xiang Hu Zi Sheng Anli Liu Qiang Liu Shaoqiu Leng Xiaoyu Zhang Xin Li Limei Wang Qi Feng Chaoyang Li Ming Hou Chong Chu Shihui Ma Shuwen Wang Jun Peng | 2022 | Signal Transduction and Targeted Therapy2022，7，11： | 0 |
| 11 | Crystal structure of the polyketide cyclase from Mycobacterium tuberculosis显示文摘About 40%of proteins are classified as conserved hypothetical proteins in Mycobacterium tuberculosis(TB).Identification and characterization of these proteins are beneficial to understand the pathogenesis of TB and exploiting novel drugs for TB treatments.The polyketide cyclase,a protein from M.tuberculosis(MtPC)has been annotated as a hypothetical protein in Uniprot database.Sequence analysis shows that the MtPC belongs to the NTF2-like superfamily proteins with diverse functions.Here,we determined the crystal structure of MtPC at a resolution of 2.4Åand measured backbone relaxation parameters for the MtPC protein.MtPC exists as a dimer in solution,and each subunit contains a six-stranded mixedβ-sheet and threeαhelixes which are arranged in the orderα1-α2-β1-β2-α3-β3-β4-β5-β6.The NMR dynamics analysis showed that the overall structure of MtPC is highly rigid on ps-ns time scales.Furthermore,we predicted the potential function of MtPC based on the crystal structure.Our results lay the basis for further exploiting and mechanistically understanding the biological functions of MtPC. | Jie Zhuang Shihui Fan Chenyun Guo Liubin Feng Huilin Wang Donghai Lin Xinli Liao | 2022 | Acta Biochimica et Biophysica Sinica2022，54，4： | 0 |
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