Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induc...Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.展开更多
We previously developed a powered hip prosthetic mechanism with kinematic functions of hip flexion-extension and abduction-adduction,and its theoretical and simulation-based kinematics were verified.Because internal-e...We previously developed a powered hip prosthetic mechanism with kinematic functions of hip flexion-extension and abduction-adduction,and its theoretical and simulation-based kinematics were verified.Because internal-external hip rotation has a positive effect on the movements of human lower limbs according to medical research,we developed a novel hip prosthetic mechanism based on a previous hip prosthesis that possesses motion characteristics similar to those of a human bionic hip,and the motion characteristics of multiple Degrees-of-Freedom(DoFs)were analyzed after kinematic modeling.Then,a walking model of the human‒machine model was established,and the walking stability of an amputee,which reflects the rehabilitation effect,was explored while the hip prosthetic mechanism considered the internal-external rotation of the hip.Finally,a prototype and its verification platform were built,and kinematic validation of the hip prosthetic mechanism was carried out.The results showed that the designed Parallel Mechanism(PM)possesses human-like motion characteristics similar to those of a human bionic hip and can be used as a hip prosthesis.Moreover,the existing motion characteristic of internal-external hip rotation can enhance the walking stability of an amputee via this hip prosthetic mechanism.展开更多
In this paper, the Von Mises stresses and stiffnesses measured by experiments on a human cadaveric tibia and composite ones compared to those predicted by a FE model based on the same bone. Modeling of exact geometric...In this paper, the Von Mises stresses and stiffnesses measured by experiments on a human cadaveric tibia and composite ones compared to those predicted by a FE model based on the same bone. Modeling of exact geometrical tibia including cortical and spongy bone using human bone CT scan images and mechanical validating of obtained model, is the aim of this study .The model produced by the current study supplies a tool for simulating mechanical test conditions on human tibia.展开更多
[目的]运用网络药理学和体外实验探讨玉泉胶囊治疗糖尿病肾病的潜在作用机制。[方法]借助中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)和中医药综合数据...[目的]运用网络药理学和体外实验探讨玉泉胶囊治疗糖尿病肾病的潜在作用机制。[方法]借助中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)和中医药综合数据库(Traditional Chinese Medicine Integrated Database,TCMID)筛选玉泉胶囊有效成分及靶点基因,基因组注释数据平台(Genome Annotation Database Platform,GeneCards)、疾病基因网络(Disease Gene Network,DisGeNET)数据库和治疗靶点数据库(Therapeutic Target Database,TTD)筛选糖尿病肾病的疾病相关基因,STRING 11.5数据库构建蛋白互作(protein-protein interaction,PPI)网络,并利用Cytoscape 3.7.2软件可视化,利用Cytoscape 3.7.2软件的CytoHubba和MCODE插件筛选关键化合物与核心靶点,利用R软件(ClusterProfiler包)进行基因本体(gene ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)信号通路富集分析,利用AutoDock和PyMOL软件进行分子对接验证,最后对网络药理学预测结果进行体外实验验证。[结果]玉泉胶囊抗糖尿病肾病活性成分有177个,活性成分作用靶点共477个,作用于糖尿病肾病的靶点有135个,核心靶点包括丝氨酸/苏氨酸激酶1(serine/threonine kinase 1,AKT1)、白细胞介素-1β(interleukin-1 beta,IL1B)、过氧化氢酶(catalase,CAT)、一氧化氮合酶(nitric oxide synthase 3,NOS3)、瘦素(leptin,LEP)、胰岛素样生长因子1(insulin-like growth factor 1,IGF1)和趋化因子配体2(C-C motif chemokine ligand 2,CCL2);GO富集分析共得到相关条目2557个,其中生物过程1415个、细胞组成657个、分子功能48个;KEGG通路分析结果显示玉泉胶囊作用于糖尿病肾病的靶点富集在66条通路上,其中环磷酸腺苷(cyclic adenosine monophosphate,cAMP)信号通路、高级糖基化终末产物-受体(advanced glycation end products-receptor for advanced glycation end products,AGE-RAGE)信号通路在糖尿病并发症中的作用等可能是玉泉胶囊治疗糖尿病肾病的关键通路。分子对接结果显示核心靶点与关键化合物均能较好地结合。实验验证显示,CCL2蛋白水平呈药物剂量依赖性下降,CAT、内皮型一氧化氮合酶(endothelial nitric oxide synthase,eNOs)蛋白水平呈药物剂量依赖性上升。[结论]玉泉胶囊治疗糖尿病肾病具有多成分、多靶点的特点,其机制可能与下调CCL2、上调CAT、eNOs的蛋白表达,抑制糖尿病肾病的氧化应激,调节关键通路相关。展开更多
This work proposes to study the effective elastic properties(EEP)of a wood-plastic composite(WPC)made from polyethylene terephthalate(PET)and Chilean Radiate pine’s wood our,using nite element simulations of a repres...This work proposes to study the effective elastic properties(EEP)of a wood-plastic composite(WPC)made from polyethylene terephthalate(PET)and Chilean Radiate pine’s wood our,using nite element simulations of a representative volume element(RVE)with periodic boundary conditions.Simulations are validated through a static 3-point bending test,with specimens obtained by extruding and injection.The effect of different weight fractions,space orientations and sizes of particles are here examined.Numerical predictions are empirically conrmed in the sense that composites with more wood our content and bigger size,have higher elastic modulus.However,these results are very sensitive to the orientation of particles.Voigt and Reuss mean-eld homogenisation approaches are also given as upper and lower limits.Experimental tests evidence that exural strengths and ultimate tensile elongations decrease respect to 100%PET,but these properties can be enhanced considering particle-size distributions instead of a xed size of wood our.展开更多
IEEE 1012 [1] describes the SDLC phase activities for software independent verification and validation (IV & V) for nuclear power plant in truly general and conceptual manner, which requires the upward and/or down...IEEE 1012 [1] describes the SDLC phase activities for software independent verification and validation (IV & V) for nuclear power plant in truly general and conceptual manner, which requires the upward and/or downward tailoring on its interpretation for practical IV & V. It contains crucial and encompassing check points and guidelines to analyze the design integrity, without addressing the formalized and the specific criteria for IV & V activities confirming the technical integrity. It is necessary to list up the inspection viewpoint via interpretation of the standard that is practical review points checking design consistency. For fruitful IV & V of Control Element Driving Mechanism Control System (CEDMCS) software for Yonggwang Nuclear Power Plant unit 3 & 4, the specific viewpoints and approach are necessary based on the guidelines of IEEE 1012 to enhance the system quality by considering the level of implementation of the theoretical and the practical IV & V. Additionally IV & V guideline of IEEE 1012 does not specifically provide the concrete measure considering the system characteristics of CEDMCS. This paper provides the seven (7) characteristic criteria for CEDMCS IV & V, and by applying these viewpoints, the design analysis such as function, performance, interface and exception, backward and forward requirement traceability analysis has been conducted. The requirement, design, implementation, and test phase were only considered for IV & V in this project. This article also provides the translation of code to map theoretical verification and validation into practical verification and validation. This paper emphasizes the necessity of the intensive design inspection and walkthrough for requirement phase to resolve the design faults because the IV & V of early phase of SDLC obviously contributes to find out most of critical design inconsistency. Especially for test phase IV & V, it is strongly recommended to prepare the test plan document which is going to be the basis for the test coverage selection and test strategy. This test plan document should be based on the critical characteristics of function and performance of CEDMCS. Also to guarantee the independency of V & V organization participating in this project, and to acquire the full package of design details for IV & V, the systematic approach and efforts with an aspect of management is highlighted among the participants.展开更多
文摘Objective:EpimediiFolium(EF),a traditional Chinese medicinal material,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism.However,its clinical applications are limited by its drug-induced liver injury(DILI)effects and the underlying mechanisms have not been elucidated.Methods:Active EF compounds were obtained from the TCMSP database and their targets predicted in Targetnet.Next,DILI-targets were obtained from CTD,Genecards and Digsee databases.Protein-protein interactions of EF DILI-targets were determined using STRING and hub targets identified via topological analyses.Then,hub targets were subjected to GO and KEGG pathway enrichment analyses.Finally,HepaRG cells were used for further validation of molecular mechanisms.Results:Fifty seven active compounds and 164 targets that interacted with these active compounds were identified with Sagittatoside A,icariside I,and Icariin being the best active compounds.Enrichment analysis revealed the PI3K/Akt and NF-kB signaling pathways to be markedly enriched.Molecular docking revealed that Sagittatoside A,icariside I and Icariin had good binding activities to RAC1,PTGS2,and NOS3.Validation analysis in HepaRG cells revealed that Epimedium flavonoids upregulated RAC1,PTGS2 and NOS3 levels.Conclusion:Our findings show that EF induces oxidative stress,inflammation,and apoptosis via PI3K/Akt and NF-kB signaling pathways,and provides a basis for more in-depth studies on EF-induced DILI.
基金the financial support provided by the Key Research and Development Program of Zhejiang Province under Grant 2021C03050in part by the Scientific Research Project of Agriculture and Social Development of Hangzhou under Grant 2020ZDSJ0881+1 种基金in part by the National Natural Science Foundation of China under Grant 52275004in part by the State Key Program of National Natural Science Foundation of China under Grant 62333023.
文摘We previously developed a powered hip prosthetic mechanism with kinematic functions of hip flexion-extension and abduction-adduction,and its theoretical and simulation-based kinematics were verified.Because internal-external hip rotation has a positive effect on the movements of human lower limbs according to medical research,we developed a novel hip prosthetic mechanism based on a previous hip prosthesis that possesses motion characteristics similar to those of a human bionic hip,and the motion characteristics of multiple Degrees-of-Freedom(DoFs)were analyzed after kinematic modeling.Then,a walking model of the human‒machine model was established,and the walking stability of an amputee,which reflects the rehabilitation effect,was explored while the hip prosthetic mechanism considered the internal-external rotation of the hip.Finally,a prototype and its verification platform were built,and kinematic validation of the hip prosthetic mechanism was carried out.The results showed that the designed Parallel Mechanism(PM)possesses human-like motion characteristics similar to those of a human bionic hip and can be used as a hip prosthesis.Moreover,the existing motion characteristic of internal-external hip rotation can enhance the walking stability of an amputee via this hip prosthetic mechanism.
文摘In this paper, the Von Mises stresses and stiffnesses measured by experiments on a human cadaveric tibia and composite ones compared to those predicted by a FE model based on the same bone. Modeling of exact geometrical tibia including cortical and spongy bone using human bone CT scan images and mechanical validating of obtained model, is the aim of this study .The model produced by the current study supplies a tool for simulating mechanical test conditions on human tibia.
基金support from the Chilean Regional Government of Maule through the FIC-R project“Valorization of recycled waste through the creation of new materials for the manufacture of marketable products”,code BIP 30.481.945。
文摘This work proposes to study the effective elastic properties(EEP)of a wood-plastic composite(WPC)made from polyethylene terephthalate(PET)and Chilean Radiate pine’s wood our,using nite element simulations of a representative volume element(RVE)with periodic boundary conditions.Simulations are validated through a static 3-point bending test,with specimens obtained by extruding and injection.The effect of different weight fractions,space orientations and sizes of particles are here examined.Numerical predictions are empirically conrmed in the sense that composites with more wood our content and bigger size,have higher elastic modulus.However,these results are very sensitive to the orientation of particles.Voigt and Reuss mean-eld homogenisation approaches are also given as upper and lower limits.Experimental tests evidence that exural strengths and ultimate tensile elongations decrease respect to 100%PET,but these properties can be enhanced considering particle-size distributions instead of a xed size of wood our.
文摘IEEE 1012 [1] describes the SDLC phase activities for software independent verification and validation (IV & V) for nuclear power plant in truly general and conceptual manner, which requires the upward and/or downward tailoring on its interpretation for practical IV & V. It contains crucial and encompassing check points and guidelines to analyze the design integrity, without addressing the formalized and the specific criteria for IV & V activities confirming the technical integrity. It is necessary to list up the inspection viewpoint via interpretation of the standard that is practical review points checking design consistency. For fruitful IV & V of Control Element Driving Mechanism Control System (CEDMCS) software for Yonggwang Nuclear Power Plant unit 3 & 4, the specific viewpoints and approach are necessary based on the guidelines of IEEE 1012 to enhance the system quality by considering the level of implementation of the theoretical and the practical IV & V. Additionally IV & V guideline of IEEE 1012 does not specifically provide the concrete measure considering the system characteristics of CEDMCS. This paper provides the seven (7) characteristic criteria for CEDMCS IV & V, and by applying these viewpoints, the design analysis such as function, performance, interface and exception, backward and forward requirement traceability analysis has been conducted. The requirement, design, implementation, and test phase were only considered for IV & V in this project. This article also provides the translation of code to map theoretical verification and validation into practical verification and validation. This paper emphasizes the necessity of the intensive design inspection and walkthrough for requirement phase to resolve the design faults because the IV & V of early phase of SDLC obviously contributes to find out most of critical design inconsistency. Especially for test phase IV & V, it is strongly recommended to prepare the test plan document which is going to be the basis for the test coverage selection and test strategy. This test plan document should be based on the critical characteristics of function and performance of CEDMCS. Also to guarantee the independency of V & V organization participating in this project, and to acquire the full package of design details for IV & V, the systematic approach and efforts with an aspect of management is highlighted among the participants.
