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MFN2 suppresses clear cell renal cell carcinoma progression by modulating mitochondria-dependent dephosphorylation of EGFR

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Cancer Communications 2023年第7期43卷 808-833页

作者： Li Luo Denghui Wei yihui pan Qiu-Xia Wang Jian-Xiong Feng Bing Yu Tiebang Kang Junhang Luo Jiefeng Yang Song Gao State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdongP.R.China Department of Urology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Department of Urology The Third Affiliated Hospital of Soochow UniversityChangzhouJiangsuP.R.China

Background:Clear cell renal cell carcinoma(ccRCC)is the most lethal renal cancer.An overwhelming increase of patients experience tumor progression and unfavorable prognosis.However,the molecular events underlying ccRCC tumorigenesis and metastasis remain unclear.Therefore,uncovering the underlying mechanisms will pave the way for developing novel therapeutic targets for ccRCC.In this study,we sought to investigate the role of mitofusin-2(MFN2)in supressing ccRCC tumorigenesis and metastasis.Methods:The expression pattern and clinical significance of MFN2 in ccRCC were analyzed by using the Cancer Genome Atlas datasets and samples from our independent ccRCC cohort.Both in vitro and in vivo experiments,including cell proliferation,xenograft mouse models and transgenic mouse model,were used to determine the role of MFN2 in regulating the malignant behaviors of ccRCC.RNA-sequencing,mass spectrum analysis,co-immunoprecipitation,bio-layer interferometry and immunofluorescence were employed to elucidate the molecular mechanisms for the tumor-supressing role of MFN2.Results:we reported a tumor-suppressing pathway in ccRCC,characterized by mitochondria-dependent inactivation of epidermal growth factor receptor(EGFR)signaling.This process was mediated by the outer mitochondrial membrane(OMM)protein MFN2.MFN2 was down-regulated in ccRCC and associated with favorable prognosis of ccRCC patients.in vivo and in vitro assays demonstrated thatMFN2 inhibited ccRCC tumor growth and metastasis by suppressing the EGFR signaling pathway.In a kidney-specific knockout mouse model,loss of MFN2 led to EGFR pathway activation and malignant lesions in kidney.Mechanistically,MFN2 preferably binded small GTPaseRab21 in its GTPloading form,which was colocalized with endocytosed EGFR in ccRCC cells.Through this EGFR-Rab21-MFN2 interaction,endocytosed EGFR was docked to mitochondria and subsequently dephosphorylated by the OMM-residing tyrosine-protein phosphatase receptor type J(PTPRJ).Conclusions:Our findings uncover an important non-canonica

关键词： ccRCC EGFR signaling pathway MFN2 PTPRJ Rab21

The Role of Soft Vein Joints in Dragonfly Flight

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Journal of Bionic Engineering 2017年第4期14卷 738-745页

作者： Dan Hou Zheng Zhong Yajun Yin yihui pan Hongxiao Zhao Department of Mechanical Engineering Shanghai Maritime University Shanghai 201306 China School of Aerospace Engineering and Applied Mechanics Tongji University Shanghai 200092 China College of Science Harbin Institute of Technology Shenzhen 518055 China Department of Engineering Mechanics Tsinghua University Beijing 100084 China

Dragonflies are excellent flyers among insects and their flight ability is closely related to the architecture and material properties of their wings. The veins are main structure components of a dragonfly wing, which are found to be connected by resilin with high elasticity at some joints. A three-dimensional （3D） finite element model of dragonfly wing considering the soft vein joints is developed, with some simplifications. Passive deformation under aerodynamic loads and active flapping motion of the wing are both studied. The functions of soft vein joints in dragonfly flight are concluded. In passive deformation, the chordwise flexibility is improved by soft vein joints and the wing is cambered under loads, increasing the action area with air. In active flapping, the wing rigidity in spanwise direction is maintained to achieve the required amplitude. As a result, both the passive deformation and the active control of flapping work well in dragonfly flight. The present study may also inspire the design of biomimetic Flapping Micro Air Vehicles （FMAVs）.

关键词： dragonfly wing resilin soft vein joint bionics and mechanics flapping micro air vehicles

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江苏省灌区水生态文明建设评价指标体系研究

江苏科技信息 2024年第5期41卷 120-124页

作者：潘逸卉丰叶李帆张华芦荀朱天雅江苏省水利科学研究院江苏南京210017 河海大学设计研究院有限公司江苏南京210024

为了客观准确评价江苏省灌区水生态文明建设状况,为水美乡村建设和全国农业现代化发展提供重要保障,文章从资源节约、生产高效、生态自然、环境优美、意识文明5个方面初步构建了江苏省灌区水生态文明建设评价指标体系。通过查询文献、... 详细信息

为了客观准确评价江苏省灌区水生态文明建设状况,为水美乡村建设和全国农业现代化发展提供重要保障,文章从资源节约、生产高效、生态自然、环境优美、意识文明5个方面初步构建了江苏省灌区水生态文明建设评价指标体系。通过查询文献、规范、标准等确定评级标准,采用层次分析法(AHP)和综合指数评价法构建了评价模型,并对江苏省渠南灌区进行了综合评价实证研究。渠南灌区水生态文明综合评价指数为3.812,属于Ⅱ级灌区,资源节约、生产高效和生态自然状况好,环境优美和意识文明评价指数不高,分析了渠南灌区建设的薄弱环节。文章为江苏省灌区水生态文明建设提供了理论依据与技术支撑。

关键词：灌区评价指标水生态文明建设

基于NOX5-ERK1/2信号通路探讨健脾祛痰化瘀方对动脉粥样硬化小型猪炎症反应的影响

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中国中医药信息杂志 2024年第3期31卷 105-112页

作者：陆翼陈向心郝秀炜张铜五周媛媛潘奕卉杨关林孔德昭辽宁中医药大学辽宁沈阳110847 辽宁中医药大学附属医院辽宁沈阳110000 中国医学科学院北京100730

目的观察健脾祛痰化瘀方对动脉粥样硬化(AS)小型猪氧化应激和炎症反应的影响,基于NOX5-ERK1/2信号通路探讨其作用机制。方法将12只巴马小型猪随机分为对照组、模型组和健脾祛痰化瘀方低、高剂量组,每组3只。采用高脂饮食饲养24周构建... 详细信息

目的观察健脾祛痰化瘀方对动脉粥样硬化(AS)小型猪氧化应激和炎症反应的影响,基于NOX5-ERK1/2信号通路探讨其作用机制。方法将12只巴马小型猪随机分为对照组、模型组和健脾祛痰化瘀方低、高剂量组,每组3只。采用高脂饮食饲养24周构建动脉粥样硬化模型,给药组同时在饲料中添加健脾祛痰化瘀方。分别于给药0、16、24周检测小型猪一般体征(体长、腹围、体质量、食物摄入量和粪便含水量),HE染色观察主动脉形态,油红O染色观察主动脉和心肌组织脂质沉积,透射电镜观察胸主动脉组织超微结构,全自动生化分析仪检测血清总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)含量,ELISA检测血清活性氧(ROS)、白细胞介素(IL)-6、IL-10、肿瘤坏死因子(TNF)-α、超敏C反应蛋白(hs-CRP)、血管细胞黏附分子-1(VCAM-1)、细胞间黏附分子-1(ICAM-1)含量,Western blot检测主动脉组织NADPH氧化酶5(NOX5)、细胞外信号调节激酶1/2(ERK1/2)、p-ERK1/2、VCAM-1、增殖细胞核抗原(PCNA)蛋白表达。结果与正常组比较,模型组小型猪16、24周腹围、体质量、食物摄入量增加(P<0.01),主动脉内膜明显增厚,内皮细胞破坏,脂质沉积,平滑肌细胞水肿,线粒体肿胀明显,血清TC、LDL-C含量及ROS、IL-6、IL-10、TNF-α、hs-CRP、VCAM-1、ICAM-1含量升高,HDL-C含量降低(P<0.01);主动脉组织NOX5、p-ERK1/2、VCAM-1、PCNA蛋白表达升高(P<0.01)。与模型组比较,健脾祛痰化瘀方低、高剂量组16、24周腹围、体质量、食物摄入量减少(P<0.05,P<0.01),斑块面积和脂质沉积减少,内皮细胞破坏减轻,血清TC、LDL-C含量及ROS、IL-6、IL-10、TNF-α、hs-CRP、VCAM-1、ICAM-1含量降低,HDL-C含量升高(P<0.01,P<0.05);主动脉组织NOX5、p-ERK1/2、VCAM-1、PCNA蛋白表达降低(P<0.01,P<0.05)。结论健脾祛痰化瘀方可减轻小型猪AS,其机制可能与抑制NOX5-ERK1/2信号通路激活、减轻氧化应激诱导的炎症反应有关。

关键词：动脉粥样硬化健脾祛痰化瘀方氧化应激炎症 NOX5-ERK1/2信号通路小型猪

1954—2020年太湖水位变化的时空差异特征分析

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江苏水利 2024年第2期 42-45页

作者：蔡文美陈少颖孙玉莹陆昊陈黎明潘逸卉南京水利科学研究院水灾害防御全国重点实验室江苏南京210029 江苏省水利科学研究院江苏南京210017 河海大学水文水资源学院江苏南京210098

为探究太湖水位变化的时空差异特征,基于太湖1954—2020年实测水位数据,对太湖的年平均水位、年最高水位、年最低水位以及逐年水位空间变化,采用M-K突变检验等方法开展研究并结合太湖进出水量变化分析原因。结果表明,随着太湖湖体入湖... 详细信息

为探究太湖水位变化的时空差异特征,基于太湖1954—2020年实测水位数据,对太湖的年平均水位、年最高水位、年最低水位以及逐年水位空间变化,采用M-K突变检验等方法开展研究并结合太湖进出水量变化分析原因。结果表明,随着太湖湖体入湖水量的增加,太湖年平均水位及年最低水位均呈上升趋势,且在突变年份之后显著上升;年最高水位也呈上升趋势,但在突变年份后变化不明显。

关键词：太湖流域时空差异突变检验水位

Effects of nuclear chimney on climate

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Journal of Environmental Sciences 1990年第4期2卷 111-116页

作者： Gao Suhua, Ding yihui, pan Yaru and Zhang QingchenAcademy of Meteorological Science State Meteorological Administration,Beijing 100081,China

In this paper, according to the data from several single nuclear explosion experiments of an equivalent to magnitude of million tons, and combined with meteorological data, their effects on the regional climate nave b... 详细信息

关键词： nuclear chimney nuclear explosion temperature change.

妊娠早期和晚期棕色脂肪组织代谢能力与基因表达变化

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中华内分泌代谢杂志 2023年第7期39卷 588-595页

作者：肖文潘怡慧仲红崔县伟江苏第二师范学院南京211200 南京医科大学附属妇产医院(南京市妇幼保健院)医学研究中心 210004

目的探究不同妊娠时期棕色脂肪组织(brown adipose tissue, BAT)的基因表达及代谢能力变化。方法建立C57BL/6J小鼠正常妊娠动物模型, 以同周龄未妊娠小鼠为对照组, 观察妊娠各时期BAT组织形态变化, 检测产热标志物解偶联蛋白1(UCP1)表... 详细信息

目的探究不同妊娠时期棕色脂肪组织(brown adipose tissue, BAT)的基因表达及代谢能力变化。方法建立C57BL/6J小鼠正常妊娠动物模型, 以同周龄未妊娠小鼠为对照组, 观察妊娠各时期BAT组织形态变化, 检测产热标志物解偶联蛋白1(UCP1)表达, 揭示脂肪棕色化及线粒体标志基因的mRNA水平变化;此外选取妊娠早期和晚期小鼠BAT进行转录组测序(RNA sequencing, RNA-seq), 筛选随妊娠进程的差异表达基因, 并开展基因本体(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析。结果随妊娠进展, BAT脂滴显著增大, 产热标志蛋白UCP1表达下降(P<0.01), 脂肪棕色化标志基因Ucp1、2型脱碘酶(Dio2)、过氧化物酶增殖体激活受体γ辅激活因子1α(Pgc1α)以及线粒体标志基因细胞色素C(CytC)均显著下调(P<0.001), 以妊娠晚期组减弱最为显著。RNA-seq共筛选出差异表达基因1 298个, 其中906个基因在妊娠晚期上调、392个基因下调, GO及KEGG通路分析显示差异表达基因在脂质代谢、性类固醇激素、炎症因子等多种生物调节功能通路富集。结论小鼠妊娠晚期BAT出现脂滴变大、产热活性与代谢能力降低现象, BAT基因表达在妊娠不同时期存在显著差异, 因此BAT代谢能力降低可能是引发妊娠期代谢异常的重要原因。

关键词：妊娠棕色脂肪 RNA测序能量代谢

Influences of greenhouse effect on agricultural production in China

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Journal of Environmental Sciences 1990年第4期2卷 3-10页

作者： Gao Suhua, Ding yihui, pan Yaru and Zhao Zongci Academy of Meteorological Science,State Meteorological Administration,Beijing 100081,China

An obvious warming in China induced by doubled carbon, dioxide as simulated by the climatic models have been found. It is also noticed that there might be drying or wetting in some parts of China induced by doubled CO2 as simulated by the general circulation models(GCMs). Agricultural productivity mainly depends on the temperature, rainfall and soil moisture in China. The changes of agricultural productivity in the different parts of China induced by doubled CO2 have been estimated in this paper. It is shown that the greenhouse effect might cause increasing production in some parts of China and decreasing production in other parts of China.

关键词： greenhouse effect agricultural productivity doubled CO2 GCMs climatic productivity force.

基于光响应非均匀性的WhatsApp压缩视频来源识别

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应用光学 2024年第2期45卷 337-345页

作者：陈懿辉田妮莉潘晴苏开清广东工业大学信息工程学院广东广州510006

光响应非均匀噪声(photo response nonuniformity,PRNU)是光学成像传感器成像时引入的一种独特噪声,可有效识别压缩视频的来源。针对现有算法提取压缩视频的PRNU效果并不显著的问题,论文提出了一种改进PRNU提取算法。首先,去除视频编解... 详细信息

光响应非均匀噪声(photo response nonuniformity,PRNU)是光学成像传感器成像时引入的一种独特噪声,可有效识别压缩视频的来源。针对现有算法提取压缩视频的PRNU效果并不显著的问题,论文提出了一种改进PRNU提取算法。首先,去除视频编解码的环路滤波器,对视频帧使用双密度双树复小波变换进行分解;然后对高频子带使用基于贝叶斯阈值估计的双变量收缩算法进行估计,再使用自适应加窗维纳滤波进行二次估计,得到噪声残差;最后用基于量化参数值加权的最大似然估计法聚合噪声残差,再与视频帧估计得到PRNU。实验结果表明:该文提出的方法在20 s时WhatsApp视频的识别率为75%。

关键词：光响应非均匀性源相机识别压缩视频双密度双树复小波变换双变量收缩