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2-APQC,a small-molecule activator of Sirtuin-3(SIRT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2748-2764页

作者： Fu Peng Minru Liao Wenke Jin Wei Liu Zixiang Li zhichao fan Ling Zou Siwei Chen Lingjuan Zhu Qian Zhao Gu Zhan Liang Ouyang Cheng Peng Bo Han Jin Zhang Leilei Fu West China School of Pharmacy and Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan Engineering Research Center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Sirtuin 3(SIRT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAD^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP *** evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation ***,discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently ***,we identified a new small-molecule activator of SIRT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat ***,in SIRT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIRT3 for its protective ***,2-APQC was found to inhibit the mammalian target of rapamycin(mTOR)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial *** upon RNA-seq analyses,we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1(PYCR1)axis was closely assoiated with *** activating PYCR1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(ROS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative ***,activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced ***,our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

关键词： SIRT3 homeostasis metabolism

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区县级城市更新片区统筹模式研究——以四川省某县级市为例

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建设科技 2024年第1期 63-65页

作者：范志超筑福(北京)城市更新建设集团有限公司北京100043

城市更新是近年来城镇化升级的重要抓手。推动试点先行,标杆示范引领,探讨城市更新的可持续性、可复制模式,进而推动城市的高质量发展是国家的政策导向,也是城市更新的重要任务。本文主要深入分析了区县级城市更新现状,对片区统筹机制... 详细信息

城市更新是近年来城镇化升级的重要抓手。推动试点先行,标杆示范引领,探讨城市更新的可持续性、可复制模式,进而推动城市的高质量发展是国家的政策导向,也是城市更新的重要任务。本文主要深入分析了区县级城市更新现状,对片区统筹机制体制建立、模式的研究、实施落地,街区运营等方面进行了针对性实践研究,为片区统筹项目的创新性,落地性,持续性发展提供了参考,为区县级城市更新模式的研究起到了示范和推动作用。

关键词：片区统筹模式机制体制实施落地

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煤化工业园区土壤中多氯萘的浓度及来源分析

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环境污染与防治 2024年第2期46卷 200-207页

作者：范智超白昭张秦铭周弛陕西省环境监测中心站陕西西安710054 陕西省环境介质痕量污染物监测预警重点实验室陕西西安710054

为了解煤化工业园区表层土壤中多氯萘(PCNs)的污染水平、空间分布特征和来源,建立了同位素稀释气相色谱-三重四极杆质谱的检测方法,对陕西某煤化工业园区表层土壤中的PCNs含量进行检测分析。结果表明,煤化工业园区表层土壤中PCNs质量浓... 详细信息

为了解煤化工业园区表层土壤中多氯萘(PCNs)的污染水平、空间分布特征和来源,建立了同位素稀释气相色谱-三重四极杆质谱的检测方法,对陕西某煤化工业园区表层土壤中的PCNs含量进行检测分析。结果表明,煤化工业园区表层土壤中PCNs质量浓度为0.358~1.349 ng/g,相对于2,3,7,8-四氯二苯并二噁英(PCDD/Fs)的毒性当量(TEQ)为3.000×10^(-4)~0.197 pg/g,与国内外各地区土壤PCNs相比,煤化工业园区土壤PCNs的浓度和毒性均处于中等水平。煤化工业园区土壤PCNs以低氯代为主,其中二氯萘和三氯萘占比高,分别为23.7%(质量分数,下同)~43.0%和41.7%~56.8%,焦化生产热过程为该煤化工业园区土壤PCNs污染的主要来源。

关键词：多氯萘土壤煤化工业园区来源

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跨尺度复合织构化摩擦副端面密封性能分析

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润滑与密封 2024年第7期49卷 123-128页

作者：樊智超穆塔里夫·阿赫迈德张廷坤新疆大学电气工程学院新疆乌鲁木齐830047

在密封副的表面上引入大尺度的凹槽与小尺度微孔结合的跨尺度复合织构,提出椭圆形微孔与T形槽结合的复合织构化机械密封端面,并创建间隙液膜流体模型;根据质量守恒空化边界条件建立数学模型,采用有限单元法进行数值求解,研究不同长短轴... 详细信息

在密封副的表面上引入大尺度的凹槽与小尺度微孔结合的跨尺度复合织构,提出椭圆形微孔与T形槽结合的复合织构化机械密封端面,并创建间隙液膜流体模型;根据质量守恒空化边界条件建立数学模型,采用有限单元法进行数值求解,研究不同长短轴比的椭圆微孔分别与T形槽复合对密封性能的影响,确定最佳复合构型;对比分析不同工况参数下,不同织构化端面密封的开启力、泄漏量等密封性能的变化规律。结果表明:最佳复合构型为长短轴比1.8的椭圆微孔与T形槽复合,在相同工况参数下,相较单一织构,跨尺度复合织构化端面密封具有更强的动压润滑效应、更低的泄漏量、更高的开启力,综合密封性能最好。研究结果可应用于机械密封织构化摩擦副端面的设计及优化。

关键词：机械密封跨尺度复合织构空化算法密封性能

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Experimental and numerical studies of impact on filament-wound composite cylinder

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Acta Mechanica Solida Sinica 2017年第5期30卷 540-549页

作者： Qiaoguo Wu Xuedong Chen zhichao fan Yong Jiang Defu Nie National Safety Engineering Technology Research Center for Pressure Vessels and Pipelines Anhui Key Laboratory of Composite Technology for General Machinery Hefei General Machinery Research Institute Hefei 230031 China

This study focused on the impact behavior of carbon-fiber-wrapped composite cylinders subjected to impact from flat-ended, hemispherical-nosed and conical-nosed impactors. Damage morphologies of the cylinders and mechanisms of the damage were analyzed. Change laws of the maximum impact forces, durations of impact processes and energies absorbed by the cylinders after impact with different impactors and impact energies were obtained. A finite element model was developed and the simulation results were in reason- able agreement with the tests. Finally, taking the flat-ended impactor as an example, stress distributions of the cylinders under pressurization and impact were discussed.

关键词： Composite cylinderImpact testingNumerical simulationDamage behaviorImpact curve

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Creep-fatigue lives prediction and sensitivity study of 316H at 550 ℃

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Acta Metallurgica Sinica(English Letters) 2011年第2期24卷 132-140页

作者： zhichao fan David J Smith Xuedong CHEN Mike W Spindler Hefei General Machinery Research Institute Hefei 23-0031 China University of Bristol Bristol BS8 1TR UK British Energy Gloucester GL4 3RS UK

In Volume 2/3 of R5 ＂An assessment procedure for the high temperature response of structures＂, the strain based ductility exhaustion method is suggested to calculate the creep damage of stress concentration region, which involves description of creep dwell initial stress, stress drop and creep ductility. Considering lots of uncertainty existed in these assessment, some sensitivity analysis is required in R5 procedure to ensure the conservatism of assessment results. In this paper, laboratory creep-fatigue test data of 316H at 550 ℃ with different loading conditions are selected as a special case to investigate whether the basic R5 approach is conservative, and the different material data combinations of cyclic stress-strain, creep deformation and creep ductility are used to identify those significant parameters affecting the assessment results. The analytical results indicate that the creep deformation model and creep ductility data are more significant to the results comparing with cyclic stress-strain data. If the upper bound of creep deformation law and lower bound of creep ductility data are used to predict their creep-fatigue lives, the degree of conservatism can be as large as a factor of -300, but if the modified creep deformation model and cast specific ductility data are used, very well prediction results can be gained within a factor of ±2.0 although there is slight non-conservatism.

关键词： Creep Fatigue Damage Life prediction Sensitivity study

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STUDYING THE ROLE OF MACROPHAGES IN CIRCULATING PROSTATE CANCER CELLS BY IN VIVO FLOW CYTOMETRY

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Journal of Innovative Optical Health Sciences 2012年第4期5卷 39-47页

作者： JIN GUO zhichao fan ZHENGQIN GU XUNBIN WEI Department of Chemistry Fudan UniversityShanghaiP.R.China Institutes of Biomedical Sciences Fudan UniversityShanghaiP.R.China Med-X Research Institute Shanghai Jiao Tong University 1954Huashan RoadShanghai 200240P.R.China School of Biomedical Engineering Shanghai Jiao Tong University ShanghaiP.R.China Department of Urology Xinhua Hospital Shanghai Jiao Tong University 1665Kongjiang RoadShanghai 200092P.R.China

Metastasis is a very complicated multi-step process and accounts for the low survival rate of the cancerous *** metastasize,t he malignant cells must detach from the primary tumor and migrate to secondary sites in the body through either blood or lymph *** appear to be directly involved in tumor progression and ***,the role of macrophages in affecting cancer metast asis has not been fully ***,we have utilized an emerging technique,namely in vivo flow cytometry(IVFC)to study the depletion kinetics of circulating prostate cancer cells in mice and determine how depletion of macrophages by the liposome encapsulated clodronate affects the depletion *** results show diferent depletion kinetics of PC-3 cells between the macrophagedeficient group and the control *** number of circulating tumor cells(CTCs)in the macrophage-deficient group decreases in a slower manner compared to the control mice *** differences in depletion kinetics indicate that the absence of macrophages facilitates the stay of prostate cancer cells in *** addition,our imaging data suggest that macrophages might be able to arrest,phagocytose and digest PC-3 ***,phagocy tosis may mainly contribute to the de-pletion kinetic *** developed methods elaborated here would be useful to study the relationship between macr ophages and tumor metastasis in small animal cancer models.

关键词： Prostate cancer macrophages liposome-encapsulated clodronate in vrivo flow cytometer circulating tumor cells

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Modeling and Experimental Analysis of Roughness Effect on Ultrasonic Nondestructive Evaluation of Micro-crack

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Chinese Journal of Mechanical Engineering 2021年第6期34卷 126-137页

作者： Zhe Wang zhichao fan Xuedong Chen Yihua Kang Jingwei Cheng Wei Chen National Safety Engineering Technology Research Center for Pressure Vessels and Pipeline Hefei General Machinery Research Institute Co.LtdHefei230031China State Key Lab of Digital Manufacturing Equipment&Technology Huazhong University of Science and TechnologyWuhan430074China

A high-precision evaluation of ultrasonic detection sensitivity for a micro-crack can be restricted by a corroded rough surface when the surface microtopography is of the same order of magnitude as the crack *** this study,a back-surface micro-crack is considered as a research target.A roughness-modified ultrasonic testing model for micro-cracks is established based on a multi-Gaussian beam model and the principle of phase-screen *** echo signals of micro-cracks and noises corresponding to different rough front surfaces and rough back surfaces are obtained based on a reference reflector signal acquired from a two-dimensional simulation *** compari-son between the analytical and numerical models shows that the responses of micro-cracks under the effects of dif-ferent corroded rough surfaces can be accurately *** numerical and analytical results show that the echo signal amplitude of the micro-crack decreases significantly with an increase in roughness,whereas the noise ampli-tude slightly ***,the effect of the rough front surface on the echo signal of the micro-crack is greater than that of the rough back *** the root-mean-square(RMS)height of the surface microtopography is less than 15μm,the two rough surfaces have less influence on the echo signals detected by a focused transducer with a frequency of 5 MHz and diameter of 6 mm.A method for predicting and evaluating the detection accuracy of micro-cracks under different rough surfaces is proposed by combining the theoretical model and a finite element ***,a series of rough surface samples containing different micro-cracks are fabricated to experimentally validate the evaluation method.

关键词： Surface roughness Micro-crack Ultrasonic testing model Detection accuracy Evaluation method

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Visualization of integrin molecules by fluorescence imaging and techniques

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BIOCELL 2021年第2期45卷 229-257页

作者： CHEN CAI HAO SUN LIANG HU zhichao fan Department of Immunology School of MedicineUConn HealthFarmington06030USA Department of Medicine University of CaliforniaSan DiegoLa Jolla92093USA Cardiovascular Institute of Zhengzhou University Department of CardiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450051China

Integrin molecules are transmembraneαβheterodimers involved in cell adhesion,trafficking,and *** activation,integrins undergo dynamic conformational changes that regulate their affinity to *** physiological functions and activation mechanisms of integrins have been heavily discussed in previous studies and reviews,but the fluorescence imaging techniques-which are powerful tools for biological studies-have *** we review the fluorescence labeling methods,imaging techniques,as well as Förster resonance energy transfer assays used to study integrin expression,localization,activation,and functions.

关键词： Integrins Fluorescence imaging Fluorescence labeling Live-cell imaging Super-resolution imaging Intravital imaging FRET

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The pitch-catch nonlinear ultrasonic imaging techniques for structural health monitoring

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Science China(Technological Sciences) 2021年第12期64卷 2608-2617页

作者： CHENG JingWei DRINKWATER Bruce W. CHEN XueDong fan zhichao CHEN Wei WANG Zhe National Safety Engineering Technology Research Centre for Pressure Vessels and Pipelines Hefei General Machinery Research Institute Co.Ltd.Hefei 230031China Department of Mechanical Engineering University of BristolBristol BS81TRUnited Kingdom

Nonlinear ultrasonic imaging techniques in pulse-echo configuration have recently shown their potential to allow the effective separation of nonlinear and linear features in a nonlinear *** this study,two ultrasonic phased arrays are implemented to produce an image of elastic nonlinearity through the parallel-sequential subtraction of the coherently scattered components in the through-transmission acoustic field at the transmission or subharmonic *** parallel mode,a physical focus at each pixel is achieved by firing the transmitters with a predefined delay *** sequential mode,each transmitter is fired in sequence and all the receivers are employed to capture the data *** full matrix captured data can be post-processed and focused synthetically at the target *** images of parallel focusing and sequential focusing are expected to be linearly identical and hence any differences remained on the subtracted image can be related to the nonlinearities arising from the ***,the imaging metric here is defined as the difference between parallel and sequentially focused amplitudes obtained from forward coherently scattered fields at each target ***,the negative influences due to the instrumentation nonlinearities are investigated by studying the remaining relative phase and amplitude at undamaged pixels.A compensation method is implemented to suppress these noises,significantly enhancing the selectivity of nonlinear scattering *** proposed techniques are then implemented to monitor fatigue crack growth in order to explore the capability of these methods as measures of elastic nonlinearity induced by different sizes of small closed *** promising results suggest that nonlinear imaging can be used to monitor crack growth and improve the detectability at early stages.

关键词： pitch-catch coherent measurement nonlinear imaging fatigue crack monitoring ultrasonic phased array nonlinearities decoupling

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