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Inhibition of gasdermin D-dependent pyroptosis attenuates the progression of silica-induced pulmonary inflammation and fibrosis

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1213-1224页

作者： Meiyue Song Jiaxin wang Youliang Sun Junling Pang Xiaona Li Yuan Liu Yitian Zhou Peiran Yang tianhui Fan Ying Liu Zhaoguo Li Xianmei Qi Baicun Li Xinri Zhang Jing wang Chen wang State Key Laboratory of Medical Molecular Biology Department of PhysiologyInstitute of Basic Medical Sciences Chinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijing 100730China Tsinghua-Peking Center for Life Sciences Department of BiologyCollege of MedicineTsinghua UniversityBeijing 100084China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Department of Pulmonary and Critical Care Medicine Center of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China National Clinical Research Center for Respiratory Diseases Beijing 100029China Peking Union Medical College Chinese Academy of Medical SciencesBeijing 100730China Peking Union Medical College MD ProgramBeijing 100730China Department of Respiratory the Second Affiliated Hospital of Harbin Medical UniversityHarbin 150086China Department of Pulmonary and Critical Care Medicine the First Hospital of Shanxi Medical UniversityTaiyuan 030001China

Silicosis is a leading cause of occupational disease-related morbidity and mortality worldwide,but the molecular basis underlying its development remains unclear.An accumulating body of evidence supports gasdermin D(GSDMD)-mediated pyroptosis as a key component in the development of various pulmonary diseases.However,there is little experimental evidence connecting silicosis and GSDMD-driven pyroptosis.In this work,we investigated the role of GSDMD-mediated pyroptosis in silicosis.Single-cell RNA sequencing of healthy and silicosis human and murine lung tissues indicated that GSDMD-induced pyroptosis in macrophages was relevant to silicosis progression.Through microscopy we then observed morphological alterations of pyroptosis in macrophages treated with silica.Measurement of interleukin-1βrelease,lactic dehydrogenase activity,and real-time propidium iodide staining further revealed that silica induced pyroptosis of macrophages.Additionally,we verified that both canonical(caspase-1-mediated)and non-canonical(caspase-4/5/11-mediated)signaling pathways mediated silica-induced pyroptosis activation,in vivo and in vitro.Notably,Gsdmd knockout mice exhibited dramatically alleviated silicosis phenotypes,which highlighted the pivotal role of pyroptosis in this disease.Taken together,our results demonstrated that macrophages underwent GSDMD-dependent pyroptosis in silicosis and inhibition of this process could serve as a viable clinical strategy for mitigating silicosis.

关键词： Silicosis Gasdermin D Pyroptosis Macrophage Pulmonary fibrosis

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Probability Analysis of the Wave-Slamming Pressure Values of the Horizontal Deck with Elastic Support

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Journal of Ocean University of China 2018年第3期17卷 507-515页

作者： ZUO Weiguang LIU Ming FAN tianhui wang Pengtao North China University of Water Resources and Electric Power Zhengzhou 450045 China CCCC First Harbor Engineering Company Ltd. Tianjin 300461 China South China University of Technology Guangzhou 510640 China

This paper presents the probability distribution of the slamming pressure from an experimental study of regular wave slamming on an elastically supported horizontal deck. The time series of the slamming pressure during the wave impact were first obtained through statistical analyses on experimental data. The exceeding probability distribution of the maximum slamming pressure peak and distribution parameters were analyzed, and the results show that the exceeding probability distribution of the maximum slamming pressure peak accords with the three-parameter Weibull distribution. Furthermore, the range and relationships of the distribution parameters were studied. The sum of the location parameter D and the scale parameter L was approximately equal to 1.0, and the exceeding probability was more than 36.79% when the random peak was equal to the sample average during the wave impact. The variation of the distribution parameters and slamming pressure under different model conditions were comprehensively presented, and the parameter values of the Weibull distribution of wave-slamming pressure peaks were different due to different test models. The parameter values were found to decrease due to the increased stiffness of the elastic support. The damage criterion of the structure model caused by the wave impact was initially discussed, and the structure model was destroyed when the average slamming time was greater than a certain value during the duration of the wave impact. The conclusions of the experimental study were then described.

关键词：撞击压力概率分析波浪价值弹性水准甲板 Weibull

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Berberine might block colorectal carcinogenesis by inhibiting the regulation of B-cell function by Veillonella parvula

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Chinese Medical Journal 2023年第22期136卷 2722-2731页

作者： Yun Qian Ziran Kang Licong Zhao Huimin Chen Chengbei Zhou Qinyan Gao Zheng wang Qiang Liu Yun Cui Xiaobo Li Yingxuan Chen tianhui Zou Jingyuan Fang Division of Gastroenterology and Hepatology Shanghai Institute of Digestive DiseaseNHC Key Laboratory of Digestive DiseasesState Key Laboratory for Oncogenes and Related GenesRenji HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Department of General Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China Department of Pathology Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200001China

Background:Colorectal carcinogenesis and progression are related to the gut microbiota and the tumor immune microenvironment.Our previous clinical trial demonstrated that berberine(BBR)hydrochloride might reduce the recurrence and canceration of colorectal adenoma(CRA).The present study aimed to further explore the mechanism of BBR in preventing colorectal cancer(CRC).Methods:We performed metagenomics sequencing on fecal specimens obtained from the BBR intervention trial,and the differential bacteria before and after medication were validated using quantitative polymerase chain reaction.We further performed Apc Min/+animal intervention tests,RNA sequencing,flow cytometry,immunohistochemistry,and enzyme-linked immunosorbent assays.Results:The abundance of fecal Veillonella parvula(V.parvula)decreased significantly after BBR administration(P=0.0016)and increased through the development from CRA to CRC.Patients with CRC with a higher V.parvula abundance had worse tumor staging and a higher lymph node metastasis rate.The intestinal immune pathway of Immunoglobulin A production was activated,and the expression of TNFSF13B(Tumor necrosis factor superfamily 13b,encoding B lymphocyte stimulator[BLyS]),the representative gene of this pathway,and the genes encoding its receptors(interleukin-10 and transforming growth factor beta)were significantly upregulated.Animal experiments revealed that V.parvula promoted colorectal carcinogenesis and increased BLyS levels,while BBR reversed this effect.Conclusion:BBR might inhibit V.parvula and further weaken the immunomodulatory effect of B cells induced by V.parvula,thereby blocking the development of colorectal tumors.Trial Registraion:ClinicalTrials.gov,No.NCT02226185.

关键词： Colorectal cancer Berberine Gut microbiota Intestinal immune pathway B Lymphocytes

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Genomic convergence underlying high-altitude adaptation in alpine plants

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Journal of Integrative Plant Biology 2023年第7期65卷 1620-1635页

作者： Xu Zhang tianhui Kuang Wenlin Dong Zhihao Qian Huajie Zhang Jacob BLandis Tao Feng Lijuan Li Yanxia Sun Jinling Huang Tao Deng Hengchang wang Hang Sun CAS Key Laboratory of Plant Germplasm Enhancement and Specialty Agriculture The Chinese Academy of SciencesWuhan Botanical GardenWuhan 430074China Center of Conservation Biology Core Botanical GardensThe Chinese Academy of SciencesWuhan 430074China Yunnan International Joint Laboratory for Biodiversity of Central Asia Key Laboratory for Plant Diversity and Biogeography of East AsiaKunming Institute of BotanyThe Chinese Academy of SciencesKunming 650201China University of Chinese Academy of Sciences Beijing 100049China School of Integrative Plant Science Section of Plant Biology and the L.H.Bailey HortoriumCornell UniversityIthacaNew York 14850USA BTI Computational Biology Center Boyce Thompson InstituteIthacaNew York 14853USA State Key Laboratory of Crop Stress Adaptation and Improvement School of Life SciencesHenan UniversityKaifeng 475004China Department of Biology East Carolina UniversityGreenvilleNorth Carolina 27858USA

Evolutionary convergence is one of the most striking examples of adaptation driven by natural selection.However, genomic evidence for convergent adaptation to extreme environments remains scarce.Here, we assembled reference genomes of two alpine plants, Saussurea obvallata(Asteraceae)and Rheum alexandrae(Polygonaceae), with 37,938 and 61,463 annotated protein-coding genes. By integrating an additional five alpine genomes,we elucidated genomic convergence underlying high-altitude adaptation in alpine plants. Our results detected convergent contractions of diseaseresistance genes in alpine genomes, which might be an energy-saving strategy for surviving in hostile environments with only a few pathogens present.We identified signatures of positive selection on a set of genes involved in reproduction and respiration(e.g., MMD1, NBS1, and HPR), and revealed signatures of molecular convergence on genes involved in self-incompatibility, cell wall modification,DNA repair and stress resistance, which may underlie adaptation to extreme cold, high ultraviolet radiation and hypoxia environments. Incorporating transcriptomic data, we further demonstrated that genes associated with cuticular wax and flavonoid biosynthetic pathways exhibit higher expression levels in leafy bracts, shedding light on the genetic mechanisms of the adaptive “greenhouse” morphology. Our integrative data provide novel insights into convergent evolution at a high-taxonomic level,aiding in a deep understanding of genetic adaptation to complex environments.

关键词： adaptation alpine plants evolutionary rates genomic convergence “greenhouse”morphology high altitude

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Efficacy and safety of ixekizumab in Chinese patients with plaque psoriasis

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Chinese Medical Journal 2023年第3期136卷 360-361页

作者： He Huang Min Chen Wenjuan Wu tianhui Yang Hao Liu Zhengwei Zhu Wenjun wang Sen Yang Xian Ding Hui wang Yujun Sheng Yaohua Zhang Min Li Xuejun Zhang Department of Dermatology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230031China Ferry Institute of Dermatology HefeiAnhui 230000China Boao Super Hospital Dermatology Center QionghaiHainan 571437China Department of Dermatology Dushu Lake Hospital Affiliated to Soochow University(Medical Center of Soochow UniversitySuzhou Dushu Lake Hospital)SuzhouJiangsu 215125China Department of Dermatology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215006China Department of Dermatology Institute of DermatologyHuashan HospitalFudan UniversityShanghai 200040China

To the Editor:Psoriasis is a common,chronic papulosquamous skin disease occurring worldwide,presenting at any age,and leading to a substantial burden for individuals and society.Interleukin(IL)-17A is considered the key effector cytokine inducing psoriatic inflammation and tissue damage.[1]Ixekizumab is a humanized monoclonal immunoglobulin G specifically binding to and inhibiting IL-17A.The efficacy and safety of ixekizumab in patients with psoriasis have been clearly demonstrated in several randomized clinical trials,namely UNCOVER-1,UNCOVER-2,UNCOVER-3,and UNCOVER-J.[2,3]However,the clinical research data on ixekizumab in Chinese psoriasis patients remain limited.

关键词： patients psoriasis clinical

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广东海域风电场风浪联合分布研究

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中国造船 2022年第6期63卷 273-284页

作者：王凯万远琛刘天辉樊天慧麦志辉吴韩中山大学海洋工程与技术学院珠海519082 华南理工大学土木与交通学院广州510641 广东精铟海洋工程股份有限公司佛山528000

为了对风电场海况进行评估,以2010-2019年广东海域平均风浪时均数据为基础,选取5个风电站点的风况、波浪参数进行了长期联合分布拟合。采用双参数韦布尔分布模型计算平均风速的边缘分布,并采用Lonowe模型计算波高的边缘分布,以此为基础... 详细信息

为了对风电场海况进行评估,以2010-2019年广东海域平均风浪时均数据为基础,选取5个风电站点的风况、波浪参数进行了长期联合分布拟合。采用双参数韦布尔分布模型计算平均风速的边缘分布,并采用Lonowe模型计算波高的边缘分布,以此为基础结合正态分布得出波浪周期的分布以及平均风速、波高和波浪周期三者的联合概率密度分布,最后结合罗森布拉特变换得到50年重现周期的轮廓面。所开发的风浪联合概率分布模型及其分布轮廓面为广东海域风电场风力机结构在极端海况下的动力响应分析提供环境输入参数,并为广东海域风电场建设、评估提供有效的指导。

关键词：广东海域风电场建设长期统计风浪联合分布

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传统的会计评价指标和经济增加值的比较研究

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管理观察 2017年第32期 152-154页

作者：王天会北京林业大学经济管理学院北京100083

净利润、资产报酬率、剩余收益等传统的财务评价指标一直作为上市公司评价公司绩效的首要指标,然而随着越来越多公司目标由利润最大化向股东利益最大化和企业价值最大化转变,以上传统的绩效评价指标已经不能准确的评价公司经营是否向着... 详细信息

净利润、资产报酬率、剩余收益等传统的财务评价指标一直作为上市公司评价公司绩效的首要指标,然而随着越来越多公司目标由利润最大化向股东利益最大化和企业价值最大化转变,以上传统的绩效评价指标已经不能准确的评价公司经营是否向着自身目标发展。经济增加值EVA的出现克服了传统经济指标的缺陷,更加准确地反映了公司的价值和股东所获得的收益。

关键词：经济增加值资本成本税后经营利润

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Upregulation of long noncoding RNA MEG3 Induced by Heat Stress Contributes to Apoptosis of Rat Cardiomyocytes via Promoting TR3 Transcription

Upregulation of long noncoding RNA MEG3 Induced by Heat Stre...

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中国生物化学与分子生物学会第十二届全国会员代表大会暨2...

作者： Xinxing wang Zhaoli Chen Weili Liu Tianhui Wang Ruifeng Duan Yingying Li Lingling Pu Bingnan Deng Environmental Medicine Laboratory Tianjin Institute of Environmental and Operational Medicine

Mitochondria play a key role in cardiomyocytes apoptosis induced by heat stress.Our previous study indicate that TR3 binding to mitochondria and induces apoptosis under stress.However,the alteration of TR3 responding environmental heat stress is far from fully understood.Our present study,for the first time to the best of our knowledge,discovered that environmental thermal exposure led to MEG3 upregulation,consequently upregulate ELK1 transcription and increasing TR3 transcription,in turn resulting in decline of mitochondria membrane potential(ΔΨm) and apoptosis of cardiomyocytes.Mechanistically,MEG3 upregulation was attributed to heat stress-induced c-Myc expression,while ELK1 upregulation was due to the increasing translation of c-Jun induced by MEG3.Moreover,TR3 transcription was upregulated via increasing its transcription factor ELK1 the resultant from c-jun upregulation in heat stress responses.Collectively,we uncover that heat stress exposure results in c-Myc induction and MEG3 expression elevation,further promotes c-Jun translation and in turn initiates ELK1 transcripton,leading to increase of TR3 protein trancription,and decline of mitochondria membrane potential(ΔΨm) as well as apoptosis of cardiomyocytes.Our present study provided a significant insight into understanding the alteration and role of TR3 in heat stress cardiomyocytes.

关键词： TR3 ELK1 c-Myc MPTP Heat Stress

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THALES DVOR 432全向信标初装调试方法及关键点探讨

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电子测试 2021年第14期32卷 80-81页

作者：王天汇民航中南空管局技术保障中心广东广州510410

本文开展THALES DVOR432全向信标初装调试方法及技巧探讨,在分析全向信标原理、THALES DVOR432设备结构基础上,对THALES DVOR432全向信标调试准备工作、调试流程做出阐释,随后围绕天线系统、发射机调整这两个步骤进行调试方法与关键点... 详细信息

本文开展THALES DVOR432全向信标初装调试方法及技巧探讨,在分析全向信标原理、THALES DVOR432设备结构基础上,对THALES DVOR432全向信标调试准备工作、调试流程做出阐释,随后围绕天线系统、发射机调整这两个步骤进行调试方法与关键点探讨。

关键词：全向信标天线调试发射机调试

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运动诱导生理性心肌肥厚的非编码RNA调节机制

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上海大学学报（自然科学版） 2019年第3期25卷 425-434页

作者：王天慧肖俊杰上海大学生命科学学院

大量研究表明运动训练对心脏具有保护作用.运动可诱导生理性心肌肥厚,对于心力衰竭具有保护作用.心肌肥厚可分为生理性和病理性心肌肥厚,后者可导致心脏功能受损、心力衰竭以及高死亡率.近几十年来,非编码RNA 包括微小RNA (microRNA, mi... 详细信息

大量研究表明运动训练对心脏具有保护作用.运动可诱导生理性心肌肥厚,对于心力衰竭具有保护作用.心肌肥厚可分为生理性和病理性心肌肥厚,后者可导致心脏功能受损、心力衰竭以及高死亡率.近几十年来,非编码RNA 包括微小RNA (microRNA, miRNAs)、长链非编码RNA (long noncodingRNA, lncRNAs)和环状RNA (circularRNA, circRNAs)等,引起了研究者的极大关注,非编码RNA 的失调被证实与多种心血管疾病密切相关.综述了心肌肥厚,尤其是生理性心肌肥厚中miRNAs, lncRNAs和circRNAs的特征、功能和分子机制.同向调控这些运动影响的非编码RNA 可以防治心力衰竭.

关键词：非编码RNA 运动生理性心肌肥厚病理性心肌肥厚

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