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Loss of LBP triggers lipid metabolic disorder through H3K27 acetylation-mediated C/EBPβ-SCD activation in non-alcoholic fatty liver disease

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Zoological Research 2024年第1期45卷 79-94页

作者： Ya-Ling Zhu Lei-Lei Meng Jin-Hu Ma Xin Yuan Shu-Wen Chen Xin-Rui Yi Xin-Yu Li Yi Wang Yun-Shu Tang Min Xue Mei-Zi Zhu Jin Peng Xue-Jin Lu Jian-Zhen Huang Zi-Chen Song chong wu Ke-Zhong Zheng Qing-Qing Dai Fan Huang Hao-Shu Fang Department of Pathophysiology Anhui Medical UniversityHefeiAnhui 230032China Laboratory Animal Research Center School of Basic Medical SciencesAnhui Medical UniversityHefeiAnhui 230032China Department of Hepatobiliary Surgery First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230022China College of Animal Science and Technology Jiangxi Agricultural UniversityNanchangJiangxi 330045China

Non-alcoholic fatty liver disease(NAFLD)is associated with mutations in lipopolysaccharide-binding protein(LBP),but the underlying epigenetic mechanisms remain understudied.Herein,LBP^(-/-)rats with NAFLD were established and used to conduct integrative targetingactive enhancer histone H3 lysine 27 acetylation(H3K27ac)chromatin immunoprecipitation coupled with high-throughput and transcriptomic sequencing analysis to explore the potential epigenetic pathomechanisms of active enhancers of NAFLD exacerbation upon LBP deficiency.Notably,LBP^(-/-)reduced the inflammatory response but markedly aggravated high-fat diet(HFD)-induced NAFLD in rats,with pronounced alterations in the histone acetylome and regulatory transcriptome.In total,1128 differential enhancer-target genes significantly enriched in cholesterol and fatty acid metabolism were identified between wild-type(WT)and LBP^(-/-)NAFLD rats.Based on integrative analysis,CCAAT/enhancer-binding proteinβ(C/EBPβ)was identified as a pivotal transcription factor(TF)and contributor to dysregulated histone acetylome H3K27ac,and the lipid metabolism gene SCD was identified as a downstream effector exacerbating NAFLD.This study not only broadens our understanding of the essential role of LBP in the pathogenesis of NAFLD from an epigenetics perspective but also identifies key TF C/EBPβand functional gene SCD as potential regulators and therapeutic targets.

关键词： Non-alcoholic fatty liver disease C/EBPβ Lipopolysaccharide-binding protein H3K27ac Integrative analysis Enhancer

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From ancient wisdom to modern science:Gut microbiota sheds light on property theory of traditional Chinese medicine

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Journal of Integrative Medicine 2024年第4期22卷 413-444页

作者： Ya-nan Yang Jia-guo Zhan Ying Cao chong-ming wu School of Chinese Materia Medica Tianjin University of Traditional Chinese Medicine Tianjin Key Laboratory of Therapeutic Substance of Traditional Chinese Medicine

The property theory of traditional Chinese medicine(TCM) has been practiced for thousands of years,playing a pivotal role in the clinical application of TCM. While advancements in energy metabolism,chemical composition analysis, machine learning, ion current modeling, and supercritical fluid technology have provided valuable insight into how aspects of TCM property theory may be measured, these studies only capture specific aspects of TCM property theory in isolation, overlooking the holistic perspective inherent in TCM. To systematically investigate the modern interpretation of the TCM property theory from multidimensional perspectives, we consulted the Chinese Pharmacopoeia(2020 edition) to compile a list of Chinese materia medica(CMM). Then, using the Latin names of each CMM and gut microbiota as keywords, we searched the PubMed database for relevant research on gut microbiota and CMM. The regulatory patterns of different herbs on gut microbiota were then summarized from the perspectives of the four natures, the five flavors and the meridian tropism. In terms of the four natures, we found that warm-natured medicines promoted the colonization of specific beneficial bacteria,while cold-natured medicines boosted populations of some beneficial bacteria while suppressing pathogenic bacteria. Analysis of the five flavors revealed that sweet-flavored and bitter-flavored CMMs positively influenced beneficial bacteria while inhibiting harmful bacteria. CMMs with different meridian tropism exhibited complex modulative patterns on gut microbiota, with Jueyin(Liver) and Taiyin(Lung) meridian CMMs generally exerting a stronger effect. The gut microbiota may be a biological indicator for characterizing the TCM property theory, which not only enhances our understanding of classic TCM theory but also contributes to its scientific advancement and application in healthcare.

关键词： Five flavors Four natures Gut microbiota Meridian tropism Property theory Traditional Chinese medicine

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Salicylic acid inhibits gibberellin signaling through receptor interactions

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Molecular Plant 2022年第11期15卷 1759-1771页

作者： Xiaodong Yu Xiaoyu Cui chong wu Shixi Shi Shunping Yan Hubei Hongshan Laboratory Wuhan 430070China College of Life Science and Technology Huazhong Agricultural UniversityWuhan 430070China Shenzhen Institute of Nutrition and Health Huazhong Agricultural UniversityShenzhen 518000China Shenzhen Branch Guangdong Laboratory for Lingnan Modern AgricultureShenzhen 518000China Agricultural Genomics Institute at Shenzhen Chinese Academy of Agricultural SciencesShenzhen 518000China

It is well known that plants activate defense responses at the cost of growth.However,the underlying molecular mechanisms are not well understood.The phytohormones salicylic acid(SA)and gibberellin(GA)promote defense response and growth,respectively.Here we show that SA inhibits GA signaling to repress plant growth.We found that the SA receptor NPR1 interacts with the GA receptor GID1.Further biochemical studies revealed that NPR1 functions as an adaptor of ubiquitin E3 ligase to promote the polyubiquitination and degradation of GID1,which enhances the stability of DELLA proteins,the negative regulators of GA signaling.Genetic analysis suggested that NPR1,GID1,and DELLA proteins are all required for the SA-mediated growth inhibition.Collectively,our study not only uncovers a novel regulatory mechanism of growth-defense trade-off but also reveals the interaction of hormone receptors as a new mode of hormonal crosstalk.

关键词： salicylic acid gibberellin trade-off receptor growth inhibition

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The shikimate pathway regulates programmed cell death

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Journal of Genetics and Genomics 2022年第10期49卷 943-951页

作者： Xuerui Lu Shixi Shi chong wu Xueao Zheng Chenkun Yang Jie Luo Shunping Yan Hubei Hongshan Laboratory WuhanHubei 430070China College of Life Science and Technology Huazhong Agricultural UniversityWuhanHubei 430070China National Key Laboratory of Crop Genetic Improvement Huazhong Agricultural UniversityWuhanHubei 430070China

Programmed cell death(PCD)is essential for both plant development and stress responses including immunity.However,how plants control PCD is not well-understood.The shikimate pathway is one of the most important metabolic pathways in plants,but its relationship to PCD is unknown.Here,we show that the shikimate pathway promotes PCD in Arabidopsis.We identify a photoperiod-dependent lesion-mimic mutant named Lesion in short-day(lis),which forms spontaneous lesions in short-day conditions.Mapbased cloning and whole-genome resequencing reveal that LIS encodes MEE32,a bifunctional enzyme in the shikimate pathway.Metabolic analysis shows that the level of shikimate is dramatically increased in lis.Through genetic screenings,three suppressors of lis(slis)are identified and the causal genes are cloned.SLISes encode proteins upstream of MEE32 in the shikimate pathway.Furthermore,exogenous shikimate treatment causes PCD.Our study uncovers a link between the shikimate pathway and PCD,and suggests that the accumulation of shikimate is an alternative explanation for the action of glyphosate,the most successful herbicide.

关键词： Programmed cell death Shikimate pathway Lesion-mimic mutant Immunity Photoperiod Arabidopsis

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Cause–Effect Relationship between Meso-γ-Scale Rotation and Extreme Short-Term Precipitation:Observational Analyses at Minute and Sub-Kilometer Scales

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Journal of Meteorological Research 2022年第4期36卷 539-552页

作者： Qiuyang ZHANG Yali LUO Ying TANG Xin XU Shuting YU chong wu School of Atmospheric Sciences Chengdu University of Information TechnologyChengdu 610225 State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing 100081 Collaborative Innovation Center on Forecast and Evaluation of Meteorological Disasters Nanjing University of Information Science&TechnologyNanjing 210044 Nanjing Marine Radar Institute Nanjing 211153 School of Atmospheric Sciences Nanjing UniversityNanjing 210023

The cause–effect relationship between meso-γ-scale rotation and extreme short-term precipitation events remains elusive in mesoscale meteorological research.We aimed to elucidate this relationship by analyzing a rainstorm over the Pearl River Delta during the nocturnal hours of 15 May 2017 based on 6-min radar observations and 1-min rain gauge data.This rainstorm had a maximum hourly rainfall of 100.1 mm,with 26 stations recording hourly rainfall>60 mm h^(−1) in 5 h.Extreme heavy precipitation was produced in association with a convergence zone along the southern side of a synoptic low-level shear line,where southwesterly warm,humid airflows with precipitable water of>60 mm,little convection inhibition(100 mm h^(−1)),reached its peak intensity after the peak of the collocated 6-min rainfall accumulation,and then weakened rapidly after the extreme rainfall region moved away.The radar-retrieved liquid water path was about five to seven times the ice water path and the specific differential phase(Kdp)below 0°C increased sharply downward during the lifetime of the vortex,suggesting the presence of active warm rain microphysical processes.These results indicate that the release of the latent heat of condensation induced by extreme rainfall could have contributed to the formation of the vortex in an environment with a weak 0–1-km vertical wind shear(about 4–5 m s^(−1))through enhanced lowlevel convergence,although the strengthening of low-level updrafts by rotational dynamic effects and short-term rainfall cannot be ruled out.

关键词： extreme short-term precipitation meso-γ-scale vortex observational analysis minute-and kilometerscale resolution

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煤炭设计院设计质量管理评价体系构建研究

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煤炭工程 2024年第3期56卷 26-31页

作者：吴崇中煤科工集团武汉设计研究院有限公司湖北武汉430064

为提高煤炭设计院成果质量与质量管理能力,以Z煤炭设计院项目为研究对象,对影响设计成果的因素进行分析,以项目质量管理理论、方法及相关标准、规范为依据,结合4M1E方法,从人、机器、材料、方法、环境分析影响设计质量的指标因素,用层... 详细信息

为提高煤炭设计院成果质量与质量管理能力,以Z煤炭设计院项目为研究对象,对影响设计成果的因素进行分析,以项目质量管理理论、方法及相关标准、规范为依据,结合4M1E方法,从人、机器、材料、方法、环境分析影响设计质量的指标因素,用层次分析法构建了层次评价模型,并对模型进行评价分析,实证分析结果表明:基于4M1E方法和层次分析法所构建的煤炭设计院设计质量管理评价体系,能实现为科学有效地控制设计过程和提升设计质量提供关键路径。最后根据评价结果提出设计质量优化的对策和建议,包括加强设计团队管理、技术建设,加强信息化管理及硬件配套,加强设计质量过程管理体系。

关键词：煤炭设计院质量管理层次分析法 4M1E

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A Possible Dynamic Mechanism for Rapid Production of the Extreme Hourly Rainfall in Zhengzhou City on 20 July 2021

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Journal of Meteorological Research 2022年第1期36卷 6-25页

作者： Jinfang YIN Haodong GU Xudong LIANG Miao YU Jisong SUN Yanxin XIE Feng LI chong wu State Key Laboratory of Severe Weather Chinese Academy of Meteorological SciencesChina Meteorological AdministrationBeijing 100081 Research Center for Disastrous Weather over Hengduan Mountains&Low-Latitude Plateau China Meteorological AdministrationKunming 650034

In this study,the unprecedented extreme rainfall event during 19-20 July 2021,which caused devastating flooding in Zhengzhou City and its nearby areas,is examined based on observational data analysis and WRF model 40-h simulations on 1-km horizontal resolution.The results show that the model successfully reproduces(i)major synopticscale weather systems(i.e.,the western Pacific subtropical high,the Tibetan high,two typhoons,and the Huang-Huai cyclone),(ii)convective initiation along the east to north edge of the Songshan Mountain,where orographic lifting is obvious,and(iii)subsequent formation of the convective storm producing the extreme rainfall in Zhengzhou.In particular,the model generates the maximum rainfall rate of 233 mm h^(-1)and 40-h accumulated rainfall of 704 mm,corresponding well to the observed extreme values of 201.9 mm h^(-1)and 818 mm,at nearly observed timing and location.Importantly,the model reproduces an intense quasi-stationary,well-organized meso-γ-scale convective system,surrounded by an arc-shaped convergence zone,allowing the development of convective updrafts in a three-quarter circle around the convective system,in a way similar to“multidirectional pumping,”attracting all associated precipitation overlaid and concentrated into the same trailing region to generate the extreme hourly rainfall over Zhengzhou.Our study emphasizes the significant contribution of the unique dynamic structure of the well-organized meso-γ-scale convective system to the record-high hourly rainfall.A possible dynamic mechanism for short-time extreme rainfall production is proposed.That is,the arc-shaped convergence zone of the mesoscale convective system,acting like multidirectional lifting pumps,transports precipitation from different directions into the same region,and thus produces the extreme rainfall.The results gained herein may shed new light on better understanding and forecasting of short-time extreme rainfall.

关键词： extreme rainfall meso-γ-scale convective system extreme hourly rainfall rate devastating flooding

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HTRA1 gene expression in gastric epithelial cells

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Asian Pacific Journal of Tropical Medicine 2014年第10期7卷 765-771页

作者： Hong-Xue wu Shi-Lun Tong chong wu Wei-Xing Wang Gastrointestinal Department People's Hospital Affiliated to Wuhan University

Objective:To explore HtrA1 gene expression aud its regulation in human gastric cancers.Methods:The HtrA1 mRNA levels were examined by QPCR analysis and coufirmed its expression with Northern blot analysis.The HtrA1 protein levels in all six gastric epithelial cell lines were investigated by Western blot analysis.Gene copy number was accessed and then sequenced the coding region from each mRNA in all six cell lines.The HtrA1 promoter region DNA methylation status was detected by using bisulfite sequeucing analysis.Effect of decitabine and TSA on HTRA1 expression in gastric cancer cell line was determined by RTPCR.Results:HIC analysis indicated that HtrA1 was highly expressed in normal epithelium,but dramatically down-regulated in gastric carcinoma tissues and variably expressed in tumor-adjacent tissues.HtrA1 gene expression was dramatically decreased in gastric carcinoma cells compared to nontumorigenic counterparts.The HtrA1 gene loss in any of the 4 breast cancer cell lines was not detected.Total 14 CpGs in this region were all methylated in gastric cancer cells,whereas two normal cells.GES-1 and HFI-145,were having several unmethylated cytosines in this region.HtrA1 showed as^Mr 44,000,Expression of HtrA1 protein was not observed in any of the four gastric caucer cell lines.BGC-823.MKN-45.SGC-7901and MKN-28.HtrA1 expression was observed in the HF1-145and GES-1 cell lines.Conclusions:The epigenetic silencing for HtrA1gene expression could provide a possible strategy for re-activating Htrt1 gene expression in gastric cancer cells.thus facilitating further investigation of HtrA1's role in chemotherapy.

关键词： HtrA 1 gene Gastric epithelial cells Gastric cancer

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Proteomics promises a new era of precision cancer medicine

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Signal Transduction and Targeted Therapy 2019年第1期4卷 562-563页

作者： chong wu Limin Zheng MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life SciencesSun Yat-sen University510275 GuangzhouChina

A study recently published in Nature provides new insights into the proteomic heterogeneity of early-stage hepatocellular carci-noma related to hepatitis B virus infection.1 Based on quantitative proteomic and phospho-proteomic profiling,early-stage hepato-cellular carcinoma can be stratified into subtypes with different clinical outcomes,and a druggable target has been identified.

关键词： clinical stratified cancer

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侧向冲击与静力加载下小剪跨比RC柱的剪切损伤行为

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中国公路学报 2024年第5期37卷 211-221页

作者：陈林周戴江冯非凡刘涛吴冲湖南科技大学土木工程学院湖南湘潭411201 湖南科技大学结构抗风与振动控制湖南省重点实验室湖南有湘潭411201

为深入研究小剪跨比条件下钢筋混凝土(RC)柱的抗冲击性能与剪切损伤行为,分别开展了6根RC柱的侧向摆锤冲击试验和8根RC柱的水平静力加载试验,考察了剪跨比、纵筋和箍筋用量以及轴压力等参数对试件抗剪性能的影响,并对冲击作用下各试件... 详细信息

为深入研究小剪跨比条件下钢筋混凝土(RC)柱的抗冲击性能与剪切损伤行为,分别开展了6根RC柱的侧向摆锤冲击试验和8根RC柱的水平静力加载试验,考察了剪跨比、纵筋和箍筋用量以及轴压力等参数对试件抗剪性能的影响,并对冲击作用下各试件的剪切损伤和弯曲损伤进行了等级划分。试验结果表明:动、静力作用下小剪跨比RC柱均易发生剪切破坏,箍筋对柱体抗变形能力和静态剪切承载力有较大贡献,但对冲击作用下试件剪切承载力的贡献较小;随着冲击能量的增大,柱身首次出现的斜裂缝与水平方向的夹角变小,而二次冲击下试件破坏形态受初次冲击损伤状态的影响较大;静力试验中,轴压力的增大延缓了试件前期弯曲和剪切损伤的发展,并提升试件承载能力,但会显著降低具有极小剪跨比(例如等于1.4)试件的延性。在试验基础上,采用冲击力峰值与试件剪切承载力(动态或静态)的比值作为损伤评估指标,对冲击作用下RC柱的剪切损伤状态进行了评估。分析结果表明:已有动态剪切承载力计算方法未能充分考虑不同剪跨比和柱体边界条件引起的惯性效应的差别,而试验所得静态剪切承载力也不能有效地反映动态剪切承载力随剪跨比变化的规律,因此目前采用冲击力峰值与剪切承载力的比值来对剪跨比存在变化的RC柱进行剪切损伤评估还存在困难。

关键词：桥梁工程 RC柱冲击试验剪切损伤小剪跨比

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