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Lnc-EST12,which is negatively regulated by mycobacterial EST12,suppresses antimycobacterial innate immunity through its interaction with FUBP3

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Cellular & Molecular Immunology 2022年第8期19卷 883-897页

作者： Qili Yao Yan Xie Dandan Xu Zilu Qu Jian Wu Yuanyuan Zhou Yuying Wei Huan Xiong xiao-lian zhang Hubei Province Key Laboratory of Allergy and Immunology Department of ImmunologyWuhan University TaiKang Medical School(School of Basic Medical Sciences)WuhanChina State Key Laboratory of Virology Frontier Science Center for Immunology and MetabolismWuhan UniversityWuhanChina Department of Allergy Zhongnan HospitalWuhan UniversityWuhanChina Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhanChina.

Long noncoding RNAs (lncRNAs) have been implicated in the pathogenesis of intracellular pathogens. However, the role andmechanism of the important lncRNAs in Mycobacterium tuberculosis (M.tb) infection remain largely unexplored. Recently, we foundthat a secreted M.tb Rv1579c (an early secreted target with a molecular weight of 12 kDa, named EST12) protein activates NLRP3-gasdermin D (GSDMD)-mediated pyroptosis and plays a pivotal role in M.tb-induced immunity. In the present study, M.tb and theEST12 protein negatively regulated the expression of a key lncRNA (named lnc-EST12) in mouse macrophages by activating theJAK2-STAT5a signaling pathway. Lnc-EST12, with a size of 1583 bp, is mainly expressed in immune-related organs (liver, lung andspleen). Lnc-EST12 not only reduces the expression of the proinflammatory cytokines IL-1β, IL-6, and CCL5/8 but also suppressesthe NLRP3 inflammasome and GSDMD pyroptosis-IL-1β immune pathway through its interaction with the transcription factor farupstream element-binding protein 3 (FUBP3). The KH3 and KH4 domains of FUBP3 are the critical sites for binding to lnc-EST12.Deficiency of mouse lnc-EST12 or FUBP3 in macrophages increased M.tb clearance and inflammation in mouse macrophages ormice. In conclusion, we report a new immunoregulatory mechanism in which mouse lnc-EST12 negatively regulates anti-M.tbinnate immunity through FUBP3.

关键词： Mycobacterium tuberculosis lncRNA Pyroptosis Cytokines

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Neamine-heterocycle conjugates as potential anti-HIV agents

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Chinese Chemical Letters 2013年第4期24卷 273-278页

作者： Ri-Bai Yan Yan-Fen Wu Jun Liu xiao-lian zhang Xin-Shan Ye State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking University State Key Laboratory of Virology Department of ImmunologyHubei Province Key Laboratory of Allergy and ImmunologyWuhan University School of Medicine

A series of neamine-heterocycle conjugates were designed and synthesized. All new compounds displayed more potent inhibitory effect on HIV replication than neamine, among them two compounds displayed stronger anti-HIV activity than neomycin B. The results suggested that it might be a promising approach to modify neamine for the discovery of new anti-HIV agents.

关键词： Aminoglycoside Anti-HIV Neamine Synthesis

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Serum ficolin-2 concentrations are significantly changed in patients with hepatitis B virus infection and liver diseases

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Virologica Sinica 2015年第4期30卷 249-260页

作者： Tielong Chen Yilan Hu Quanquan Ding Jing Yu Fubing Wang Fengling Luo xiao-lian zhang State Key Laboratory of Virology and Department of Immunology and Hubei Province Key Laboratory of Allergy and Immunology Wuhan University School of Medicine Zhongnan Hospital of Wuhan University Department of Immunology Wuhan University of Science and Technology School of Medicine Hubei Cancer Hospital

Human ficolin-2 is an important lectin complement pathway activator that is secreted from liver cells and has been implicated as an anti-infection innate immune molecule. However, the role of ficolin-2 protein and its dynamic changes over the course of and in the prognosis of chronic hepatitis B(CHB) and hepatocellular carcinoma(HCC) remain unclear. In this study, we analyzed ficolin-2 protein expression in a cohort of individuals with CHB infection, HCC and cirrhosis. A sandwich enzyme-linked immunosorbent assay(ELISA) method was used to measure serum ficolin-2 concentrations. Ficolin-2 expression in liver tissues was detected by immunohistochemical staining. Serum ficolin-2 concentrations in CHB patients were significantly higher than in healthy controls and HBV carriers. After 48 weeks of routine amelioration liver function treatment, serum ficolin-2 concentrations decreased and were positively correlated with favorable alanine aminotransferase(ALT), HBV DNA and HBe Ag-seroconversion outcomes. Interestingly, we observed much lower expression of serum and intrahepatic ficolin-2 in HCC and cirrhosis compared with healthy controls. Our findings suggest that serum and intrahepatic ficolin-2 levels may be considered one of the indicators for the response of chronic HBV infection, HCC and cirrhosis.

关键词： ficolin-2 chronic hepatitis B(CHB) hepatocellular

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Neural Dynamics for Cooperative Motion Control of Omnidirectional Mobile Manipulators in the Presence of Noises: A Distributed Approach

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IEEE/CAA Journal of Automatica Sinica 2024年第7期11卷 1605-1620页

作者： Yufeng lian Xingtian xiao Jiliang zhang Long Jin Junzhi Yu Zhongbo Sun the Department of Control Engineering Changchun University of TechnologyChangchun 130012China IEEE the College of Information Science and Engineering Northeastern UniversityShenyang 110819 the National Mobile Communications Research Laboratory Southeast UniversityNanjing 210096China the School of Information Science and Engineering Lanzhou UniversityLanzhou 730000China the State Key Laboratory for Turbulence and Complex Systems Department of Advanced Manufacturing and RoboticsCollege of EngineeringPeking UniversityBeijing 100871China

This paper presents a distributed scheme with limited communications, aiming to achieve cooperative motion control for multiple omnidirectional mobile manipulators(MOMMs).The proposed scheme extends the existing single-agent motion control to cater to scenarios involving the cooperative operation of MOMMs. Specifically, squeeze-free cooperative load transportation is achieved for the end-effectors of MOMMs by incorporating cooperative repetitive motion planning(CRMP), while guiding each individual to desired poses. Then, the distributed scheme is formulated as a time-varying quadratic programming(QP) and solved online utilizing a noise-tolerant zeroing neural network(NTZNN). Theoretical analysis shows that the NTZNN model converges globally to the optimal solution of QP in the presence of noise. Finally, the effectiveness of the control design is demonstrated by numerical simulations and physical platform experiments.

关键词： Cooperative motion control noise-tolerant zeroing neural network(NTZNN) omnidirectional mobile manipulator(OMM) repetitive motion planning

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Simulation of gas-solids heat transfer in cyclone pyrolyzer using CFD-DEM model

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Particuology 2024年第2期85卷 155-166页

作者： Nan zhang Xueer Pan Jingxuan Yang Qian Liu Wenhao lian xiao Du Zhonglin zhang xiaogang Hao Guoqing Guan College of Chemical Engineering and Technology Taiyuan University of TechnologyTaiyuan030024China School of Chemistry and Chemical Engineering North University of ChinaTaiyuan030051China Shanxi Jinke Technology Service Company Limited Taiyuan030000China Labraory of Eey onveron Engineerng Institute f Rgional Innvation(RI)Hosaki Univerty3-BunkychoHiroak036-8561Japan

Fast heat transfer in the pyrolyzer can increase the yield of pyrolysis gas and tar,and improve the quality of tar.Compared with the downer pyrolyzer,the cyclone pyrolyzer can simultaneously achieve high solids holdup and violent turbulence,and correspondingly faster heat transfer.In this work,the heat transfer behavior in the cyclone pyrolyzer is specifically studied using the computational fluid dynamics-discrete element method.The simulation results reveal that the gas-solids heat convection contributes mainly to the heat transfer process,and the heat radiation and conduction are relatively small and almost negligible,respectively.Compared with the downer pyrolyzer under the same operating conditions,the heating rate is significantly increased in the cyclone pyrolyzer.By analyzing the flow characteristics in the cyclone pyrolyzer,it is found that the region of high convective heat transfer rate coincides with that of natural cyclone length.Additionally,the final coal temperature increases with the increase of gas velocity and exists a maximum value.These results can offer some qualitative understanding of the heat transfer behavior in the cyclone pyrolyzer.

关键词： Cyclone pyrolyzer Rapidly heating Heat convection Natural cyclone length CFD-DEM

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Immunotherapy by targeting pathogen-surface glycans–induced immunosuppression

Immunotherapy by targeting pathogen-surface glycans–induced...

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中国生物化学与分子生物学会第十一次会员代表大会暨201...

作者： xiao-lian zhang State Key Laboratory of Virology Department of ImmunologyWuhan University School of Medicine

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Immunotherapy by targeting pathogens-surface glycansinduced immunosuppression

Immunotherapy by targeting pathogens-surface glycansinduced ...

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第九届全国免疫学学术大会

作者： xiao-lian zhang State Key Laboratory of Virology Department of ImmunologyWuhan University School of Medicine

Many pathogens including RNA viruses(e.g.Hepatitis C Virus)and intracellular bacteria(e.g.Mycobacterium tuberculosis and Salmonella)usually cause chronic or latent infection in humans.These pathogens-surface glycans have been implicated as an immunosuppressive epitopes of pathogens and might contribute to chronic or latent infection.In this study,we have found that human innate immune molecule serum ficolin-2 binds to these pathogen-surface glycans and mediates anti-infection response.Ficolin-2 also activates JNK phosphorylation and stimulation of IFN-γ,IL-17,IL-6,TNF-αand nitric oxide(NO)production by macrophages.This data provide a new immunotherapeutic strategy against pathogens based on the innate immune molecule ficolin-2 and indicate that ficolin-2 insufficiency is associated with high susceptibility to infection in humans.Apolipoprotein E3(ApoE3),which is enriched in the low-density fractions of HCVRNA-containing particles,promotes HCV infection promotes HCV infection,blocks the effect of ficolin-2 and mediates an immune escape mechanism during chronic HCV infection.ApoE3 may be a new target to combat infection.Highaffinity aptamers against ManLAM of M.Tb were generated by SELEX.Conclusion:Our data demonstrate that both ficolin-2 and aptamers against pathogen-surface glycans can be used as new anti-pathogens drug candidate without cross-resistance with known anti-microbe agents.

关键词： ficolin Immunotherapy glycans pathogens immunosuppression aptamer

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Succinylation modification:a potential therapeutic target in stroke

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Neural Regeneration Research 2024年第4期19卷 781-787页

作者： Jie lian Wenwu Liu Qin Hu xiaohua zhang Department of Neurosurgery Ren Ji HospitalShanghai Jiao Tong University School of Medicine Department of Diving and Hyperbaric Medicine Naval Medical CenterNaval Medical University

Stroke is a leading cause of mortality and disability worldwide.Ischemic cell death triggered by the compromised supply of blood oxygen and glucose is one of the major pathophysiology of strokeinduced brain injury.Impaired mitochondrial energy metabolism is observed minutes after stroke and is closely associated with the progression of neuropathology.Recently,a new type of posttranslational modification,known as lysine succinylation,has been recognized to play a significant role in mitochondrial energy metabolism after ischemia.However,the role of succinylation modification in cell metabolism after stroke and its regulation are not well understood.We aimed to review the effects of succinylation on energy metabolism,reactive oxygen species generation,and neuroinflammation,as well as Sirtuin 5 mediated desuccinylation after stroke.We also highlight the potential of targeting succinylation/desuccinylation as a promising strategy for the treatment of stroke.The succinylation level is dynamically regulated by the nonenzymatic or enzymatic transfer of a succinyl group to a protein on lysine residues and the removal of succinyl catalyzed by desuccinylases.Mounting evidence has suggested that succinylation can regulate the metabolic pathway through modulating the activity or stability of metabolic enzymes.Sirtuins,especially Sirtuin 5,are characterized for their desuccinylation activity and have been recognized as a critical regulator of metabolism through desuccinylating numerous metabolic enzymes.Imbalance between succinylation and desuccinylation has been implicated in the pathophysiology of stroke.Pharmacological agents that enhance the activity of Sirtuin 5 have been employed to promote desuccinylation and improve mitochondrial metabolism,and neuroprotective effects of these agents have been observed in experimental stroke studies.However,their therapeutic efficacy in stroke patients should be validated.

关键词： mitochondria metabolism neuroprotection sirtuin 5 stroke succinylation modification

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Kinesin 26B modulates M2 polarization of macrophage by activating cancer-associated fibroblasts to aggravate gastric cancer occurrence and metastasis

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World Journal of Gastroenterology 2024年第20期30卷 2689-2708页

作者： lian-Meng Huang Ming-Jin zhang Department of General Surgery The 901st Hospital of PLAHefei 230031Anhui ProvinceChina

BACKGROUND The regulatory effects of KIF26B on gastric cancer(GC)have been confirmed,but the specific mechanism still needs further exploration.Pan-cancer analysis shows that the KIF26B expression is highly related to immune infiltration of cancerassociated fibroblasts(CAFs),and CAFs promote macrophage M2 polarization and affect cancers’progression.AIM To investigate the regulatory functions of KIF26B on immune and metastasis of GC.METHODS We analyzed genes’mRNA levels by quantitative real-time polymerase chain reaction.Expression levels of target proteins were detected by immunohistochemistry,ELISA,and Western blotting.We injected AGS cells into nude mice for the establishment of a xenograft tumor model and observed the occurrence and metastasis of GC.The degree of inflammatory infiltration in pulmonary nodes was observed through hematoxylin-eosin staining.Transwell and wound healing assays were performed for the evaluation of cell invasion and migration ability.Tube formation assay was used for detecting angiogenesis.M2-polarized macrophages were estimated by immunofluorescence and flow cytometry.RESULTS KIF26B was significantly overexpressed in cells and tissues of GC,and the higher expression of KIF26B was related to GC metastasis and prognosis.According to in vivo experiments,KIF26B promoted tumor formation and metastasis of GC.KIF26B expression was positively associated with CAFs’degree of infiltration.Moreover,CAFs could regulate M2-type polarization of macrophages,affecting GC cells’migration,angiogenesis,invasion,and epithelial-mesenchymal transition process.CONCLUSION KIF26B regulated M2 polarization of macrophage through activating CAFs,regulating the occurrence and metastasis of GC.

关键词： metastasis invasion macrophage

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Caffeic acid 3,4-dihydroxyphenethyl ester prevents colorectal cancer through inhibition of multiple cancer-promoting signal pathways in 1,2-Dimethylhydrazine/dextran sodium sulphate mouse model

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Journal of Traditional Chinese Medicine 2024年第1期44卷 70-77页

作者： JIN Tao ZHOU Qian SHEN Jichen zhang Zhizhong lian xiaoyuan College of Pharmaceutical Sciences Zhejiang UniversityHangzhou 310058China Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Ocean College Zhoushan Campus of Zhejiang UniversityZhoushan 316021China

OBJECTIVE:To elucidate the potential feature and mechanism of the caffeic acid 3,4-dihydroxyphenethyl ester(CADPE)molecule,which can prevent colorectal cancer(CRC)in the 1,2-Dimethylhydrazine(DMH)/dextran sodium sulphate(DSS)-induced mouse model.METHODS:Institute of cancer research(ICR)male mice were injected with 20 mg/kg DMH for a week.After that,2%DSS was administered in the drinking water for another 7 d.The CADPE treatment was given to the DMH/DSS induced male mice at three different periods until their sacrifice.Histopathological examination was used for observing the CRC development at colonic mucosa.Immunohistochemistry(IHC),blood cells smearing and crypt damage scoring methods were used for investigating the anti-inflammation feature of CADPE related to CRC.The reversing targets searching method was applied with artificial intelligence(AI),computeraided drug designing(CADD)and Ingenuity Pathway Analysis(IPA)techniques for predicting the potential targets and mechanism of CADPE highly related to CRC.RESULTS:The data indicated that CADPE inhibited CRC tumor development in the colitis-associated DMH/DSS induced mouse model after giving the early treatment.CADPE also impeded the acute inflammation by decreasing the infiltration of neutrophils significantly during the initial stage of CRC development.Finally,our data showed that CADPE prevented CRC by blocking active sites of three pivotal protein targets including epidermal growth factor receptor(EGFR),extracellular signal-regulated kinase(ERK)and mammalian target of rapamycin(m TOR)in two major cancer development pathways.CONCLUSIONS:CADPE effectively prevented CRC at early stage of tumor germination in the DMH/DSS mouse model highly likely due to its anti-acute inflammation characteristic and the ability of blocking EGFR,ERK and m TOR activities in two highly related CRC developing pathways.

关键词： caffeic acids colorectal neoplasms inflammation chemoprevention Sarcandra glabra

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