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TRPC6 Knockout Alleviates Renal Fibrosis through PI3K/AKT/GSK3B Pathway

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Current Medical Science 2024年第3期44卷 589-602页

作者： An-bang SUN fang-hua LI Lin ZHU Xi-xi ZENG Min ZHU Qing-hua LEI Yan-hong LIAO Department of Anatomy School of Basic MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Transfusion Medicine Wuhan Hospital of Traditional Chinese and Western MedicineTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Department of Nephrology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450052China Department of Thoracic Surgery Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China National Basic Medical Teaching Demonstration Center Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China Key Laboratory of Neurological Diseases of Ministry of Education Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective Renal fibrosis is the ultimate pathway of various forms of acute and chronic kidney damage.Notably,the knockout of transient receptor potential channel 6(TRPC6)has shown promise in alleviating renal fibrosis.However,the regulatory impact of TRPC6 on renal fibrosis remains unclear.Methods In vivo,TRPC6 knockout(TRPC6−/−)mice and age-matched 129 SvEv(WT)mice underwent unilateral renal ischemia-reperfusion(uIR)injury surgery on the left renal pedicle or sham operation.Kidneys and serum were collected on days 7,14,21,and 28 after euthanasia.In vitro,primary tubular epithelial cells(PTECs)were isolated from TRPC6−/−and WT mice,followed by treatment with transforming growth factorβ1(TGFβ1)for 72 h.The anti-fibrotic effect of TRPC6−/−and the underlying mechanisms were assessed through hematoxylin-eosin staining,Masson staining,immunostaining,qRT-PCR,and Western blotting.Results Increased TRPC6 expression was observed in uIR mice and PTECs treated with TGFβ1.TRPC6−/−alleviated renal fibrosis by reducing the expression of fibrotic markers(Col-1,α-SMA,and vimentin),as well as decreasing the apoptosis and inflammation of PTECs during fibrotic progression both in vivo and in vitro.Additionally,we found that the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/glycogen synthase kinase 3 beta(GSK3β)signaling pathway,a pivotal player in renal fibrosis,was down-regulated following TRPC6 deletion.Conclusion These results suggest that the ablation of TRPC6 may mitigate renal fibrosis by inhibiting the apoptosis and inflammation of PTECs through down-regulation of the PI3K/AKT/GSK3βpathway.Targeting TRPC6 could be a novel therapeutic strategy for preventing chronic kidney disease.

关键词： transient receptor potential channel 6 ischemia-reperfusion injury renal fibrosis renal tubular epithelial cells

Protein acylation:mechanisms,biological functions and therapeutic targets

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Signal Transduction and Targeted Therapy 2023年第1期8卷 220-249页

作者： Shuang Shang Jing Liu fang hua CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis State Key Laboratory of Bioactive Substance and Function of Natural MedicinesInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical College100050 BeijingP.R.China

Metabolic reprogramming is involved in the pathogenesis of not only cancers but also neurodegenerative diseases,cardiovascular diseases,and infectious diseases.With the progress of metabonomics and proteomics,metabolites have been found to affect protein acylations through providing acyl groups or changing the activities of acyltransferases or deacylases.Reciprocally,protein acylation is involved in key cellular processes relevant to physiology and diseases,such as protein stability,protein subcellular localization,enzyme activity,transcriptional activity,protein–protein interactions and protein–DNA interactions.Herein,we summarize the functional diversity and mechanisms of eight kinds of nonhistone protein acylations in the physiological processes and progression of several diseases.We also highlight the recent progress in the development of inhibitors for acyltransferase,deacylase,and acylation reader proteins for their potential applications in drug discovery.

关键词： diseases cardiovascular mechanisms

Early Triassic Legoupil Formation in Schmidt Peninsula,Antarctic Peninsula:Provenance and Depositional Settings

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Journal of Earth Science 2024年第2期35卷 317-331页

作者： Chao Zhang Ying-Chun Cui Chen-Guang Liu fang-hua Cui Lu-Yuan Wang Wei-Qiang Zhang School of Resources and Environmental Engineering Shandong University of TechnologyZibo255049China MNR Key Laboratory for Polar Science Polar Research Institute of ChinaShanghai201209China Key Laboratory of Marine Sedimentology and Environmental Geology First Institute of OceanographyState Oceanic AdministrationQingdao266061China Laboratory for Marine Geology Qingdao National Laboratory for Marine Science and TechnologyQingdao266061China Key Laboratory of Mineral Resources Evaluation in Northeast Asia Ministry of Land and ResourcesChangchun130061China

Geochemical compositions can be used to determine the tectonic setting of sedimentary basins,while where the link of source to sink is no longer preserved,detrital zircon age patterns can aid in resolving the original basin setting.The metasedimentary Legoupil Formation,located at Cape Legoupil and the Schmidt Peninsula,could give a hint for the tectonic evolution of Antarctic Peninsula.In this contribution,we constrain the sedimentary provenance of the Legoupil Formation through geochemistry and detrital zircon U-Pb geochronology.The petrography and geochemical features indicate that the provenance of the Legoupil Formation could be felsic rocks.Detrital zircon grains record a steady supply of Permian and Ordovician material into the Legoupil Formation.The youngest concordant zircon ages of 262 Ma suggest that the depositional time of Legoupil Formation is no older than Late Permian.The detrital zircon age spectrum of Legoupil Formation suggests that the Legoupil Formation sediments should be derived from regional sources endemic to western Gondwana prior to its breakup.Together with the previous studies,geochemistry and detrital zircons reflect an active continental margin tectonic setting and the detrital zircon spectra of Legoupil Formation are similar to the ones deposited in forearc tectonic setting.

关键词： Schmidt Peninsula Legoupil Formation Trinity Peninsula Group detrital zircons Antarctic Peninsula geochemistry

Dietary oxidized cholesterol causes mucus barrier thinner via decreasing Muc2 expression in the proximal colon and increasing the abundance of mucus-degrading bacteria

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Food Science and Human Wellness 2024年

作者： Chi Yan Shou-He huang Zi-Xing Chen hua-fang Ding Zhen-Yu Chen School of Life Sciences Faculty of Science The Chinese University of Hong Kong

Oxidized cholesterol (OXC) is a harmful dietary substance. Although the consumption of OXC has been associated with colonic inflammation， related underlying mechanisms are still limited. We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model. Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC. Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon， accompanied by an increase in the abundance of two mucus-degrading bacteria， namely A. muciniphila and B. acidifaciens. Consistently， oral exposure of OXC promoted mucus barrier erosion in DSS-induced colitis mice and facilitated bacteria infiltration in the colon. The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice， suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis. Finally， the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins. These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.

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Solar-driven photothermal catalytic CO2 conversion:a review

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Rare Metals 2024年第7期43卷 2913-2939页

作者： Bachirou Guene Lougou Bo-Xi Geng Ru-Ming Pan Wei Wang Tian-Tian Yan fang-hua Li Hao Zhang Oraléou Sangué Djandja Yong Shuai Meisam Tabatabaei Daniel Sabi Takou School of Energy Science and Engineering Harbin Institute of Technology MIIT Key Laboratory of Critical Materials Technology for New Energy Conversion and Storage Harbin Institute of Technology State Key Laboratory of Urban Water Resource and Environment Harbin Institute of Technology School of Electrical Engineering and Automation Harbin Institute of Technology Guangdong Provincial Key Laboratory of Distributed Energy Systems Engineering Research Center of None-Food Biomass Efficient Pyrolysis and Utilization Technology of Guangdong Higher Education InstitutesDongguan University of Technology Higher Institution Centre of Excellence (HICoE) Institute of Tropical Aquaculture and Fisheries (AKUATROP)Universiti Malaysia Terengganu Department of Biomaterials Saveetha Dental CollegeSaveetha Institute of Medical and Technical Sciences école Polytechnique d'Abomey-Calavi University of Abomey-Calavi

It is highly desirable to seek green and sustainable technologies,such as employing photo thermal effects to drive energy catalysis processes to address the high energy demand and associated environmental impacts induced by the current methods.The photothermocatalysis process is an emerging research area with great potential in efficiently converting solar energy through various catalytic reactions.However,achieving simultaneously high conversion efficiency,cyclability,and durability is still a daunting challenge.Thus,tremendous work is still needed to enhance solar photo thermal catalytic conversion and promote its large-scale applications.This review developed the principles of coupling solar photon and thermal fields underlying the photothermal effect,exploration of efficient nanocatalysts,development of optofluidic reactor model,and photo thermal synergistic-driven CO2reduction mechanisms.The ultimate goal was to provide an effective approach that can effectively convert solar energy into photocarriers/hot-electrons and heat,and importantly,can couple them to regulate catalysis reaction pathways toward the production of value-added fuel and chemical energy.

关键词： Photochemistry Photothermal CO 2 catalytic conversion Nanomaterial Solar fuels and chemicals

丁酸钠对肉兔生长性能、肠道抗氧化指标及形态结构的影响

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中国饲料 2024年第10期 68-71页

作者：化芳莒南县十字路畜牧兽医站山东莒南276600

本研究旨在探究日粮添加丁酸钠对肉兔生长性能、肠道抗氧化指标及形态结构的影响。试验将600只30日龄断奶仔兔随机分为4组,每组5个重复,每重复30只。试验日粮分别向基础日粮中添加0.00%、0.05%、0.10%和0.20%的丁酸钠。试验为期42 d。... 详细信息

本研究旨在探究日粮添加丁酸钠对肉兔生长性能、肠道抗氧化指标及形态结构的影响。试验将600只30日龄断奶仔兔随机分为4组,每组5个重复,每重复30只。试验日粮分别向基础日粮中添加0.00%、0.05%、0.10%和0.20%的丁酸钠。试验为期42 d。试验结果表明,与对照组相比,添加0.1%~0.2%的丁酸钠肉兔终末体重分别显著提高8.98%和9.55%(P0.05)。日粮添加0.2%的丁酸钠后肉兔十二指肠绒毛高度及V/C值显著高于对照组(P0.05)。综上所述,丁酸钠能提高肉兔肠道抗氧化酶活性,改善其肠道形态,在本试验条件下,丁酸钠最适添加量为0.1%。

关键词：丁酸钠肉兔生长性能肠道抗氧化指标肠道形态

The cell cycle inhibitor P21 promotes the development of pulmonary fibrosis by suppressing lung alveolar regeneration

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Acta Pharmaceutica Sinica B 2022年第2期12卷 735-746页

作者： Xiaoxi Lv Chang Liu Shanshan Liu Yunxuan Li Wanyu Wang Ke Li fang hua Bing Cui Xiaowei Zhang Jiaojiao Yu Jinmei Yu ZhuoWei Hu Immunology and Cancer Pharmacology Group State Key Laboratory of Bioactive Substance and Function of Natural MedicinesInstitute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Drug Clinical Trial Institution Children’s HospitalCapital Institute of PediatricsBeijing 100020China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

The cell cycle inhibitor P21 has been implicated in cell senescence and plays an important role in the injury-repair process following lung injury.Pulmonary fibrosis(PF)is a fibrotic lung disorder characterized by cell senescence in lung alveolar epithelial cells.In this study,we report that P21 expression was increased in alveolar epithelial type 2 cells(AEC2 s)in a time-dependent manner following multiple bleomycin-induced PF.Repeated injury of AEC2 s resulted in telomere shortening and triggered P21-dependent cell senescence.AEC2 s with elevated expression of P21 lost their self-renewal and differentiation abilities.In particular,elevated P21 not only induced cell cycle arrest in AEC2 s but also bound to P300 andβ-catenin and inhibited AEC2 differentiation by disturbing the P300-β-catenin interaction.Meanwhile,senescent AEC2 s triggered myofibroblast activation by releasing profibrotic cytokines.Knockdown of P21 restored AEC2-mediated lung alveolar regeneration in mice with chronic PF.The results of our study reveal a mechanism of P21-mediated lung regeneration failure during PF development,which suggests a potential strategy for the treatment of fibrotic lung diseases.

关键词： P21 Cell senescence Alveolar epithelial type 2 cells Pulmonary fibrosis Alveolar regeneration Bleomycin Cell cycle arrest P300-β-catenin complex

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动态障碍物状态空间重构的无人车路径规划

机械设计与制造 2024年第3期 243-248页

作者：雷芳华袁小芳湖南大学电气与信息工程学院湖南长沙410082 郴州职业技术学院现代装备制造学院湖南郴州423000

为了保证无人驾驶汽车在动态障碍物的环境下,实现安全的避障路径规划,提出了一种基于动态障碍物状态空间重构的避障路径规划方法。该避障路径规划方法,以前轮偏角为控制量,运用模型预测控制(MPC)方法,忽略车身尺寸信息建立点质量模型,... 详细信息

为了保证无人驾驶汽车在动态障碍物的环境下,实现安全的避障路径规划,提出了一种基于动态障碍物状态空间重构的避障路径规划方法。该避障路径规划方法,以前轮偏角为控制量,运用模型预测控制(MPC)方法,忽略车身尺寸信息建立点质量模型,主要在规划层中利用车载传感器的采集信息,对动态障碍物状态空间信息进行重构,研究不同重构构型对避障效果以及“穿越”现象的影响问题。在特定行驶工况中,采用CarSim和Simulink进行联合仿真,以低中高三种速度进行动态障碍物避障稳定性分析,仿真结果表明,所提出的避障路径规划方法对于存在动态障碍物环境下是有效的,避免了由于忽略车身尺寸所导致的“穿越”现象,通过与传统人工势场法比较,验证了本方法规划的路径更短,避障曲率更优。基于动态障碍物状态空间重构的避障路径规划具有安全性和稳定性。

关键词：无人车动态障碍物状态空间重构路径规划

多维真值视角下主观化的实现机制研究——以“有2+vp”的复现为例

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外语学刊 2024年第4期 8-15页

作者：陈伟方华辉浙江工商大学人文与传播学院、文化产业创新发展研究院杭州310018 杭州市交通职业高级中学杭州310064

“有+vp”形式在现代汉语中的使用日渐频繁,其中尤以“有2+vp”频率的提升引人关注。与以往研究不同的是,本文不仅从历时层面来看“有2+vp”的演化过程,更是从多维真值视角来考察“有2+vp”的主观化进程。经研究发现,“有2+vp”形式在... 详细信息

“有+vp”形式在现代汉语中的使用日渐频繁,其中尤以“有2+vp”频率的提升引人关注。与以往研究不同的是,本文不仅从历时层面来看“有2+vp”的演化过程,更是从多维真值视角来考察“有2+vp”的主观化进程。经研究发现,“有2+vp”形式在现代汉语中复现以后,依次应用于话语的答句、问句以及陈述句之中,并分别产生焦点标记、倾向表述和存在强调的主观性含义。其主观化的实现机制包括系统缺位、构造类推、形式冗余、真值转移4个环节,在此过程中缺位的表达真值与类推产生的形式重新组合,完成语义从描述维度向表达维度的发展,其本质为形式与意义的再平衡。

关键词： “有2+vp” 多维语义学主观化描述表达