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| 1 | Salmonella flagella confer anti-tumor immunological effect via activating Flagellin/TLR5 signalling within tumor microenvironment显示文摘Salmonella:mediated cancer therapy has achieved remarkable anti-tumor effects in experimental animal models,but the detailed mechanism remains unsolved.In this report,the active involvement of the host immune response in this process was confirmed by comparing the tumor-suppressive effects of Salmonella in immunocompetent and immunodeficient mice bearing melanoma allografts.Since flagella are key inducers of the host immune response during bacterial infection,flagella were genetically disrupted to analyse their involvement in Salmonella-mediated cancer therapy.The results showed that flagellum-deficient strains failed to induce significant anti-tumor effects,even when more bacteria were administered to offset the difference in invasion efficiency.Flagella mainly activate immune cells via Flagellin/Toll-like receptor 5(TLR5)signalling pathway.Indeed,we showed that exogenous activation of TLR5 signalling by recombinant Flagellin and exogenous expression of TLR5 both enhanced the therapeutic efficacy of flagellum-deficient Salmonella against melanoma.Our study highlighted the therapeutic value of the interaction between Salmonella and the host immune response through Flagellin/TLR5 signalling pathway during Salmonella-mediated cancer therapy,thereby suggesting the potential application of TLR5 agonists in the cancer immune therapy. | Jianxiang Chen Yiting Qiao Guo Chen Cunjie Chang Heng Dong Bo Tang Xiawei Cheng Xiufeng Liu Zichun Hua | 2021 | Acta Pharmaceutica Sinica B2021，11，10： | 6 |
| 2 | Acidity of Aerosols during Winter Heavy Haze Events in Beijing and Gucheng, China显示文摘We investigated the acidity and concentrations of water-soluble ions in PM_(2.5) aerosol samples collected from an urban site in Beijing and a rural site in Gucheng, Hebei Province from November 2016 to January 2017 to gain an insight into the formation of secondary inorganic species. The average SO_4^(2–), NO_3~–, and NH_4^+ concentrations were 8.3,12.5, and 14.1 μg m^(–3), respectively, at the urban site and 14.0, 14.2, and 24.2 μg m^(–3), respectively, at the rural site.The nitrogen and sulfur oxidation ratios in urban Beijing were correlated with relative humidity(with correlation coefficient r = 0.79 and 0.67, respectively) and the aerosol loadings. Based on a parameterization model, we found that the rate constant of the heterogeneous reactions for SO_2 on polluted days was about 10 times higher than that on clear days, suggesting that the heterogeneous reactions in the aerosol water played an essential role in haze events.The ISORROPIA II model was used to predict the aerosol pH, which had a mean(range) of 5.0(4.9–5.2) and 5.3(4.6–6.3) at the urban and rural site, respectively. Under the conditions with this predicted pH value, oxidation by dissolved NO_2 and the hydrolysis of N_2O_5 may be the major heterogeneous reactions forming SO_4^(2–) and NO_3~– in haze.We also analyzed the sensitivity of the aerosol p H to changes in the concentrations of SO_4^(2–), NO_3~–, and NH_4^+ under haze conditions. The aerosol p H was more sensitive to the SO_4^(2–) and NH_4^+ concentrations with opposing trends, than to the NO_3~– concentrations. The sensitivity of the p H was relatively weak overall, which was attributed to the buffering effect of NH_3 partitioning. | Xiyuan CHI Pengzhen HE Zhuang JIANG Xiawei YU Fange YUE Longquan WANG Bokun LI Hui KANG Cheng LIU Zhouqing XIE | 2018 | Journal of Meteorological Research2018，32，1： | 4 |
| 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 | Ecological functions of uncultured microorganisms in the cobaltrich ferromanganese crust of a seamount in the central Pacific are elucidated by fosmid sequencing显示文摘Cobalt-rich ferromanganese is an important seafloor mineral and is abundantly present in the seamount crusts.Such crusts form potential hotspots for biogeochemical activity and microbial diversity, yet our understanding of their microbial communities is lacking. In this study, a cultivation-independent approach was used to recover genomic information and derive ecological functions of the microbes in a sediment sample collected from the cobalt-rich ferromanganese crust of a seamount region in the central Pacific. A total of 78 distinct clones were obtained by fosmid library screening with a 16 SrRNA based PCR method. Proteobacteria and MGI Thaumarchaeota dominated the bacterial and archaeal 16 SrRNA gene sequence results in the microbial community. Nine fosmid clones were sequenced and annotated. Numerous genes encoding proteins involved in metabolic functions and heavy metal resistance were identified, suggesting alternative metabolic pathways and stress responses that are essential for microbial survival in the cobalt-rich ferromanganese crust. In addition, genes that participate in the synthesis of organic acids and exoploymers were discovered. Reconstruction of the metabolic pathways revealed that the nitrogen cycle is an important biogeochemical process in the cobalt-rich ferromanganese crust. In addition, horizontal gene transfer(HGT) events have been observed, and most of them came from bacteria, with some occurring in archaea and plants. Clone W4-93 a, belonging to MGI Thaumarchaeota, contained a region of gene synteny. Comparative analyses suggested that a high frequency of HGT events as well as genomic divergence play important roles in the microbial adaption to the deep-sea environment. | HUO Yingyi CHENG Hong Anton F.Post WANG Chunsheng JIANG Xiawei PAN Jie WU Min XU Xuewei | 2015 | Acta Oceanologica Sinica2015，34，4： | 2 |
| 5 | Ketogenic diet for human diseases:the underlying mechanisms and potential for clinical implementations显示文摘The ketogenic diet(KD)is a high-fat,adequate-protein,and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies.The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade,subject to emerging evidence of the promising therapeutic potential of the KD for various diseases,besides epilepsy,from obesity to malignancies.In this review,we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases,and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels.We emphasize that the KD may function through multiple mechanisms,which remain to be further elucidated.The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed.We suggest that,with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action,randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD. | Huiyuan Zhu Dexi Bi Youhua Zhang Cheng Kong Jiahao Du Xiawei Wu Qing Wei Huanlong Qin | 2022 | Signal Transduction and Targeted Therapy2022，7，2： | 2 |
| 6 | Method of Humanity Design for Numerical Control Machine Tool 显示文摘 | Xiawei Jiang Xiaochun Cheng | 2012 | Energy Procedia2012，，17： | 1 |
| 7 | Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials显示文摘Epigenetic alternations concern heritable yet reversible changes in histone or DNA modifications that regulate gene activity beyond the underlying sequence.Epigenetic dysregulation is often linked to human disease,notably cancer.With the development of various drugs targeting epigenetic regulators,epigenetic-targeted therapy has been applied in the treatment of hematological malignancies and has exhibited viable therapeutic potential for solid tumors in preclinical and clinical trials.In this review,we summarize the aberrant functions of enzymes in DNA methylation,histone acetylation and histone methylation during tumor progression and highlight the development of inhibitors of or drugs targeted at epigenetic enzymes. | Yuan Cheng Cai He Manni Wang Xuelei Ma Fei Mo Shengyong Yang Junhong Han Xiawei Wei | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 1 |
| 8 | Cationic nanocarriers as potent adjuvants for recombinant S-RBD vaccine of SARS-CoV-2显示文摘Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity.Therefore,to improve the efficacy of the vaccine and seek a novel adjuvant that can stimulate both humoral and cellular immunity,we investigated the potential of series of cationic nanocarriers as adjuvants of the recombinant S-RBD vaccine for SARS-CoV-2.As the surface charge of a nanocarrier might dramatically affect the immunogenicity of a vaccine and enhance and/or shape antigen-specific immune responses,we also used anionic nanocarriers and neutral nanocarriers as controls(Supplementary Table S1).S-RBD vaccines with adjuvant candidates were administered intranasally or intramuscularly in the present study. | Hong Lei Aqu Alu Jingyun Yang Cai He Weiqi Hong Zesheng Cheng Li Yang Jiong Li Zhenling Wang Wei Wang Guangwen Lu Xiawei Wei | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 0 |
| 9 | Cationic nanocarriers as potent adjuvants for recombinant S-RBD vaccine of SARS-CoV-2显示文摘Dear Editor,The worldwide outbreak of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has urged the investigation of preventive vaccines.Recently,our team has developed a recombinant protein vaccine,targeting receptor binding domain(RBD)of the spike protein(S-RBD)of SARS-CoV-2,which could induce a potent antibody response and protect non-human primates from SARS-CoV-2 challenge.1 The recombinant RBD protein is proved as a potent antigen and a novel adjuvant is in demand for the effective stimulation of adaptive immunity. | Hong Lei Aqu Alu Jingyun Yang Cai He Weiqi Hong Zesheng Cheng Li Yang Jiong Li Zhenling Wang Wei Wang Guangwen Lu Xiawei Wei | 2021 | Signal Transduction and Targeted Therapy2021，6，1： | 0 |
| 10 | Pacer通过与Stx17相互作用把PI3KC3和HOPS复合物亚基招募到自噬膜泡显示文摘文章简介自噬是基于溶酶体的胞内降解途径,对维持细胞的稳态维持有重要作用。自噬参与生物体发育、免疫反应、代谢调节、细胞凋亡和衰老等多种过程。自噬异常与神经退行性疾病、免疫紊乱等发生密切相关。 | Xiawei Cheng Xiuling Ma Xianming Ding Lin Li Xiao Jiang Zhirong Shen She Chen Wei Liu 龚渭华 孙启明 | 2018 | 科学新闻2018，0，4： | 0 |
| 11 | Deciphering the regulatory and catalytic mechanisms of an unusual SAM-dependent enzyme显示文摘S-adenosyl-1-methionine(SAM)-dependent enzymes regulate various disease-related behaviors in all organisms.Recently,the leporin biosynthesis enzyme LepI,a SAM-dependent enzyme,was reported to catalyze pericyclic reactions in leporin biosynthesis;however,the mechanisms underlying LepI activation and catalysis remain unclear.This study aimed to investigate the molecular mechanisms of LepI.Here,we reported crystal structures of LepI bound to SAM/5′-deoxy-5′-(methylthio)adenosine(MTA),S-adenosyl-homocysteine(SAH),and SAM/substrate states.Structural and biochemical analysis revealed that MTA or SAH inhibited the enzyme activities,whereas SAM activated the enzyme.The analysis of the substrate-bound structure of LepI demonstrated that this enzymatic retro-Claisen rearrangement was primarily driven by three critical polar residues His133,Arg197,Arg295 around the active site and assisted by SAM with unclear mechanism.The present studies indicate that the unique mechanisms underlying regulatory and catalysis of the unusual SAM-dependent enzyme LepI,not only strengthening current understanding of the fundamentally biochemical catalysis,but also providing novel insights into the design of SAM-dependent enzyme-specific small molecules. | Qiu Sun Yuehong Hu Yijun Gu Jiangkun Huang Jun He Lan Luo Yi Yang Shuo Yin Chao Dou Tianqi Wang Xianghui Fu Ling He Shiqian Qi Xiaofeng Zhu Shengyong Yang Xiawei Wei Wei Cheng | 2019 | Signal Transduction and Targeted Therapy2019，4，1： | 0 |
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