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Hepatocyte nuclear factor 1A suppresses innate immune response by inducing degradation of TBK1 to inhibit steatohepatitis

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Genes & Diseases 2023年第4期10卷 1596-1612页

作者： Jinyong He Cong Du Xuyun Peng Weilong Hong Dongbo Qiu Xiusheng Qiu Xingding Zhang yunfei qin Qi Zhang Cell-gene Therapy Translational Medicine Research Center The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510630China Biotherapy Center The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510630China Guangdong Province Key Laboratory of Liver Disease Research The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510630China Molecular Cancer Research Center School of Medicine Sun Yat-sen UniversityShenzhenGuangdong 518107China Department of Emergency The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong 510630China

Non-alcoholic steatohepatitis(NASH),a progressive form of non-alcoholic fatty liver disease(NAFLD),is characterised by chronic liver inflammation,which can further prog-ress into complications such as liver cirrhosis and NASH-associated hepatocellular carcinoma(HCC)and therefore has become a growing health problem *** type I interferon(IFN)signaling pathway plays a pivotal role in chronic inflammation;however,the molecular mechanisms underlying NAFLD/NASH from the perspective of innate immune response has not yet been fully *** this study,we elucidated the mechanisms of how innate im-mune response modulates NAFLD/NASH pathogenesis,and demonstrated that hepatocyte nu-clear factor-1alpha(HNF1A)was suppressed and the typeⅠIFN production pathway was activated in liver tissues of patients with NAFLD/*** experiments suggested that HNF1A negatively regulates the TBK1-IRF3 signaling pathway by promoting autophagic degra-dation of phosphorylated-TBK1,which constrains IFN production,thereby inhibiting the activa-tion of type I IFN ***,HNF1A interacts with the phagophore membrane protein LC3 through its LIR-docking sites,and mutations of LIRs(LIR2,LIR3,LIR4,and LIRs)block the HNF1A-LC3 *** addition,HNF1A was identified not only as a novel autop-hagic cargo receptor but also to specifically induce K33-linked ubiquitin chains on TBK1 at Lys670,thereby resulting in autophagic degradation of ***,our study illustrates the crucial function of the HNF1A-TBK1 signaling axis in NAFLD/NASH pathogenesis via cross-talk between autophagy and innate immunity.

关键词： HNF1A IFN signaling pathway Innate immunity NAFLD TBK1

Molecular simulation study on the evolution process of hydrate residual structures into hydrate

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Chinese Journal of Chemical Engineering 2024年第5期69卷 79-91页

作者： Liwei Cheng yunfei Li Jinlong Cui Huibo qin Fulong Ning Bei Liu Guangjin Chen Faculty of Engineering China University of GeosciencesWuhan 430074China State Key Laboratory of Heavy Oil Processing China University of PetroleumBeijing 102249China College of Science Nanchang Institute of TechnologyNanchang 330099China School of Chemical Engineering Guangdong University of Petrochemical TechnologyMaoming 525000China National Center for International Research on Deep Earth Drilling and Resource Development China University of Geosciences(Wuhan)Wuhan 430074China

The clathrate hydrate memory effect is a fascinating phenomenon with potential applications in carbon capture,utilization and storage(CCUS),gas separation,and gas storage as it can accelerate the secondary formation of clathrate ***,the underlying mechanism of this effect remains *** gain a better understanding of the mechanism,we conducted molecular dynamic simulations to simulate the initial formation and reformation processes of methane *** this work,we showed the evolution process of hydrate residual structures into hydrate *** simulation results indicate that the residual structures are closely related to the existence of hydrate memory effect,and the higher the contribution of hydrate dissociated water to the hydrate nucleation process,the faster the hydrate *** hydrate dissociation,the locally ordered structures still exist after hydrate dissociation and can promote the formation of cluster structures,thus accelerating hydrate ***,the nucleation process of hydrate and the formation process of clusters are *** size of clusters composed of cup-cage structures is critical for hydrate *** residence time at high temperature after hydrate decomposition will affect the strength of the hydrate memory *** simulation results provide microscopic insights into the occurrence of the hydrate memory effect and shed light on the hydrate reformation process at the molecular scale.

关键词： Memory effect Molecular simulation Hydrate reformation Residual structures

Glycogen metabolism-mediated intercellular communication in the tumor microenvironment influences liver cancer prognosis

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Oncology Research 2024年第3期32卷 563-576页

作者： YANG ZHANG NANNAN qin XIJUN WANG RUI LIANG QUAN LIU RUOYI GENG TIANXIAO JIANG yunfei LIU JINWEI LI Graduate School Kunming Medical UniversityKunming650000China Depatment of Vascular Surgery Fuwai Yunnan Cardiovascular HospitalAfliated Cardiovascular Hospital of Kunming Medical UniversityKunming650000China Department of Neurosurgery West China HospitalSichuan UniversityChengdu610000China Department of Neurosurgery The Fourth Afiliated Hospital of Guangxi Medical UniversityLiuzhou545000China Depatment of Gynecology Oncology The Fourth Afliated Hospital of Guangxi Medical UniversityLiuzhou545000China School of Basic Medical Sciences Xianning Medical CollegeHubei University of Science and TechnologyXianning437100China College of Bioengineering Chongqing UniversityChongqing400030China Department of General Visceraland Transplant SurgeryLudwig Maximilians University MunichMunich81377Germany

Glycogen metabolism plays a key role in the development of hepatoellular carcinoma(HCC),but the function of glycogen metabolism genes in the tumor microenvironment(TME)is still to be *** cell RNA-seq data were obtained from ten HCC tumor samples totaling 64,545 cells and 65 glycogen metabolism genes were analyzed bya nonnegative matrix factorization(NMF).The prognosis and immune response of new glycogen TME cell dusters were predicted by using HCC and immunotherapy cohorts from public *** single cell analysis was divided into fibroblasts,NT T cells,macrophages,endothelial clls,and B cells,which were separately divided into new cell clusters by glycogen metabolism gene *** temporal trajectory analysis demonstrated the temporal differentiation trajectory of different glycogen subtype cell *** communication analysis revealed extensive interactions between endothelial cells with glycogen metabolizing TME *** subtypes and diferent glycogen subtype cell *** analysis of transcription factors upstream of TME cell clusters with different glycogen *** addition,TME cell dusters of glycogen metabolism were found to be enriched in expression in CAF subtypes,CD8 depleted,M1,and M2 *** seq analysis showed the prognostic signifcance of glycogen *** TME cell dusters in HCC,while a significant immune response was found in the immunotherapy cohort in patients treated with immune checkpoint blockade(ICB),especially for CAFs,T cells,and macrophages In summary,our study reveals for the first time that glycogen metabolism mediates intercellular communication in the hepatocellular carcinoma microenvironment while elucidating the anti-tumor mechanisms and immune prognostic responses of different subtypes of cell dusters.

关键词： Glycogen metabolism Metabolic map Single cell Tumor microenvironment Liver cancer Prognosis Immunotherapy

SKP2 attenuates NF-κB signaling by mediating IKKβ degradation through autophagy

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Journal of Molecular Cell Biology 2018年第3期10卷 205-215页

作者： Kunpeng Liu Lei Zhang Qiang Zhao Zhiyao Zhao Feng Zhi yunfei qin Jun Cui Key Laboratory of Gene Engineering of the Ministry of Education State Key Laboratory of Biocontrol School of Life Sciences Sun Yat-sen University Guangzhou 510006 China Organ Transplant Center The First Affiliated Hospital Sun Yat-sen University Guangzhou 510080 China Modern Medical Research Center Department of Neurosurgery The Third Affiliated Hospital of Soochow University Changzhou 213000 China Guangdong Provincial Key Laboratory of Liver Disease CeU-Gene Therapy Translational Medicine Research Center The Third Affiliated Hospital of Sun Yat-Sen University Guangzhou 510630 China

NF-κB signaling controls a large set of physiological processes ranging from inflammatory responses to cell death. Its activation is tightly regulated through controlling the activity and stability of multiple signaling components. Here, we identify that NF-κB activation is suppressed by an F-box protein, S-phase kinase associated protein 2 （SKP2）. SKP2 deficiency enhanced NF-κB activation as well as the production of inflammatory cytokines. In addition, SKP2 potently blocked the NF-κB activation at the κB kinase （IKIO level. Mechanistic study further revealed that SKP2 functions as an adaptor to promote an interaction between active IKKβ and the autophagic cargo receptor p62 to mediate IKKβ degradation via selective autophasy. These findings identify a previously unrecognized role of SKP2 in NF-κB activation by which SKP2 acts as a secondary receptor to assist IKKβ delivery to autophagosomes for degradation in a p62-dependent manner.

关键词： SKP2 IKKβ NF-κB activation autophagy inflammation

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安徽省宣城市宣州区土壤养分特征分析

资源信息与工程 2023年第6期38卷 111-114,120页

作者：刘广秦云飞安徽省地质矿产勘查局311地质队安徽安庆246003

基于安徽宣城市宣州区土地质量地球化学调查,研究土壤养分有机质、氮、磷、氧化钾等指标在不同成土母质、土壤类型、土地利用方式、地貌类型等分区单元的含量,划分研究区土壤养分(有机质、氮、磷、氧化钾)地球化学综合等级。结果表明:... 详细信息

基于安徽宣城市宣州区土地质量地球化学调查,研究土壤养分有机质、氮、磷、氧化钾等指标在不同成土母质、土壤类型、土地利用方式、地貌类型等分区单元的含量,划分研究区土壤养分(有机质、氮、磷、氧化钾)地球化学综合等级。结果表明:宣州区土壤在不同分区单元养分含量存在明显差异;养分一等土壤总面积30.30 km^(2),占比1.54%;养分二等土壤总面积250.62 km^(2),占比12.72%;养分三等土壤面积1001.64 km^(2),占比50.86%;养分四等土壤面积636.34 km^(2),占比32.31%;养分五等土壤面积50.56 km^(2),占比2.57%。

关键词：土壤养分地球化学地球化学等级宣州区

地铁车辆频繁启停工况加速钢轨滚动接触疲劳损伤行为

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铁道科学与工程学报 2023年第5期20卷 1645-1655页

作者：沈明学戴晓龙肖叶龙秦云飞华李成熊光耀华东交通大学轨道交通基础设施性能监测与保障国家重点实验室江西南昌330013 华东交通大学材料科学与工程学院江西南昌330013 宁波大学冲击与安全工程教育部重点实验室浙江宁波315211

列车启停过程中轮轨接触应力复杂交变,近站点附近车辆频繁启停运行工况加速了钢轨滚动接触疲劳损伤。为深入了解地铁车辆频繁启停工况下的钢轨滚动接触疲劳损伤特性,利用轮轨滚动接触疲劳/磨损试验台(JD-DRCF/M)开展频繁启停工况下轮轨... 详细信息

列车启停过程中轮轨接触应力复杂交变,近站点附近车辆频繁启停运行工况加速了钢轨滚动接触疲劳损伤。为深入了解地铁车辆频繁启停工况下的钢轨滚动接触疲劳损伤特性,利用轮轨滚动接触疲劳/磨损试验台(JD-DRCF/M)开展频繁启停工况下轮轨滚动接触疲劳试验。对比研究4种不同加/减速度工况下(0,400,800和1 200 r/min2)轮轨滚动接触界面黏着、钢轨磨耗和疲劳裂纹行为。研究结果表明:在干态环境中,加速工况显著降低了轮轨界面的黏着系数,其中:800 r/min2加速度下降幅最为明显;而进入水介质环境后,黏着系数出现瞬时极低值、加速度工况下的黏着系数降幅程度差异显著。加速度工况未引起钢轨的过高磨耗,但其对钢轨磨损形貌、表面粗糙度等的影响均较为显著,过高的加速度极易诱发钢轨以剥层机制失效并伴随表面粗糙度的大幅提升。钢轨磨耗与轮轨界面的剪切作用密切相关,加速度的存在往往不同程度地加剧了近表层钢轨材料的塑性变形和疲劳裂纹的萌生与扩展,使得裂纹扩展角、裂纹长度与数量均有不同程度地增加。因此,有必要开展实验条件下钢轨试样滚动接触损伤与实际现场钢轨损伤间的等效性评估,以利于指导近站点附近地铁车辆启停工况参数的优化。

关键词：频繁启停滚滑接触钢轨损伤表面剥落疲劳裂纹

安徽怀宁县富硒土壤分布、成因及硒元素水稻有效性浅析

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安徽地质 2022年第4期32卷 314-317页

作者：何振忠刘广秦云飞安徽省地质矿产勘查局311地质队安徽安庆246003

通过对怀宁县土壤硒含量的调查和研究,发现怀宁县富硒土壤主要分布在研究区中东部石镜、黄墩、清河至黄龙一带,南部腊树及雷埠乡以及研究区北部见有零星分布。表层土壤硒含量为0.053~40.802mg/kg,平均值为0.363 mg/kg。不同成土母质发... 详细信息

通过对怀宁县土壤硒含量的调查和研究,发现怀宁县富硒土壤主要分布在研究区中东部石镜、黄墩、清河至黄龙一带,南部腊树及雷埠乡以及研究区北部见有零星分布。表层土壤硒含量为0.053~40.802mg/kg,平均值为0.363 mg/kg。不同成土母质发育的土壤硒含量差异较大,二叠系至三叠系灰岩类母质发育的土壤硒含量最高,达1.146 mg/kg。相关研究表明:硒的活性与氧化还原状态有关。硒的氧化还原状况能直接影响硒的价态变化,从而影响硒的生物可利用性。

关键词：富硒土壤成因有效性安徽怀宁

户外场地与体育活动设计对幼儿基本动作技能发展影响

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中国学校卫生 2021年第5期42卷 742-745,750页

作者：覃云飞张忠宁科广西体育高等专科学校体育与教育学院南宁530012 广西体育高等专科学校教务处陕西师范大学体育学院

目的了解幼儿在预设的户外场地进行一定时间、频次的结构化与自主体育活动对基本动作技能的影响效果,为促进儿童基本动作技能的发展提供参考。方法在南宁市主城区4所公立幼儿园随机抽取141名正常发育幼儿分为实验组(71名)和对照组(70名... 详细信息

目的了解幼儿在预设的户外场地进行一定时间、频次的结构化与自主体育活动对基本动作技能的影响效果,为促进儿童基本动作技能的发展提供参考。方法在南宁市主城区4所公立幼儿园随机抽取141名正常发育幼儿分为实验组(71名)和对照组(70名)。实验组儿童在预设的户外场地连续参加10周(每周3次,每次1 h)体育活动(每次体育活动由30 min自主身体活动和30 min结构化体育活动组成),对照组无场地预设和专门设计的活动干预。实验前后对每名受试儿童进行9项基本动作技能测试(包括3项精细动作技能和6项粗大动作技能)。结果干预后,实验组儿童6项粗大动作技能测试中双手抛掷实心球、单脚平衡(左)、单脚平衡(右)、荡桥平衡与平衡木行走与干预前差异均有统计学意义(t值分别为7.82,4.25,9.69,-10.01,-28.28,P值均0.05),投放硬币(右手)、投放硬币(左手)、方块堆砌3项精细动作技能测试均无明显改善(t值分别为0.91,1.03,0.42,P值均>0.05);对照组儿童除荡桥平衡(t=4.27,P0.05)。结论运动环境质量对幼儿基本动作技能有潜在影响作用。在预设的户外场地进行一定时间、频率的结构与自主化体育活动,幼儿的基本动作技可得到显著改善。

关键词：运动活动生长和发育运动技能随机对照试验儿童

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羲和卫星磁浮机构地面高精度分离测试研究

上海航天（中英文） 2023年第2期40卷 74-81页

作者：侯鹏秦云飞李志慧吴跃莺吴开祥黄亚忠上海卫星装备研究所上海200240 上海交通大学机械与动力工程学院上海200240

为满足“羲和”卫星在轨超高指向精度(优于5×10^(-4)(°))和超高姿态稳定度(5×10^(-4)(°)/s)要求,开展地面复杂环境下的磁浮机构高精度分离测试研究。分析地面测试的静态误差、动态误差和测量误差,以气浮系统变化、厂房环境和气浮平... 详细信息

为满足“羲和”卫星在轨超高指向精度(优于5×10^(-4)(°))和超高姿态稳定度(5×10^(-4)(°)/s)要求,开展地面复杂环境下的磁浮机构高精度分离测试研究。分析地面测试的静态误差、动态误差和测量误差,以气浮系统变化、厂房环境和气浮平台精度为主要影响因素,试验验证了分析结果。提出了一种基于地面超静环境下的磁浮机构高精度分离测试方法,解决了传统测试方法难以满足卫星高精度分离测试的难题。

关键词：羲和卫星磁浮机构指向精度测试误差分析超静环境