Cardiovascular disease(CVD)remains one of the leading causes of mortality among adults globally,with continuously rising morbidity and mortality rates.Metabolic disorders are closely linked to various cardiovascular d...Cardiovascular disease(CVD)remains one of the leading causes of mortality among adults globally,with continuously rising morbidity and mortality rates.Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression,involving multifaceted mechanisms such as altered substrate utilization,mitochondrial structural and functional dysfunction,and impaired ATP synthesis and transport.In recent years,the potential role of peroxisome proliferator-activated receptors(PPARs)in cardiovascular diseases has garnered significant attention,particularly peroxisome proliferator-activated receptor alpha(PPARα),which is recognized as a highly promising therapeutic target for CVD.PPARαregulates cardiovascular physiological and pathological processes through fatty acid metabolism.As a ligand-activated receptor within the nuclear hormone receptor family,PPARαis highly expressed in multiple organs,including skeletal muscle,liver,intestine,kidney,and heart,where it governs the metabolism of diverse substrates.Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions,PPARαexerts its cardioprotective effects through multiple pathways:modulating lipid metabolism,participating in cardiac energy metabolism,enhancing insulin sensitivity,suppressing inflammatory responses,improving vascular endothelial function,and inhibiting smooth muscle cell proliferation and migration.These mechanisms collectively reduce the risk of cardiovascular disease development.Thus,PPARαplays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation,anti-inflammatory actions,and anti-apoptotic effects.PPARαis activated by binding to natural or synthetic lipophilic ligands,including endogenous fatty acids and their derivatives(e.g.,linoleic acid,oleic acid,and arachidonic acid)as well as synthetic peroxisome proliferators.Upon ligand binding,PPARαactivates the nuclear receptor retinoid X receptor(RXR),forming a PPARα-RXR heterodimer.This heterodimer,in conjunction with coactivators,undergoes further activation and subsequently binds to peroxisome proliferator response elements(PPREs),thereby regulating the transcription of target genes critical for lipid and glucose homeostasis.Key genes include fatty acid translocase(FAT/CD36),diacylglycerol acyltransferase(DGAT),carnitine palmitoyltransferase I(CPT1),and glucose transporter(GLUT),which are primarily involved in fatty acid uptake,storage,oxidation,and glucose utilization processes.Advancing research on PPARαas a therapeutic target for cardiovascular diseases has underscored its growing clinical significance.Currently,PPARαactivators/agonists,such as fibrates(e.g.,fenofibrate and bezafibrate)and thiazolidinediones,have been extensively studied in clinical trials for CVD prevention.Traditional PPARαagonists,including fenofibrate and bezafibrate,are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol(HDL-C)levels.These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα,and their cardioprotective effects have been validated in numerous clinical studies.Recent research highlights that fibrates improve insulin resistance,regulate lipid metabolism,correct energy metabolism imbalances,and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells,thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure.Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications,activating PPARαmay serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy,atherosclerosis,ischemic cardiomyopathy,myocardial infarction,diabetic cardiomyopathy,and heart failure.This review comprehensively examines the regulatory roles of PPARαin cardiovascular diseases and evaluates its clinical application value,aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.展开更多
Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and ...Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and metabolites,although most studies have primarily focused on proteins and RNA.Recently,exosome metabolomics has demonstrated clinical value and potential advantages in disease detection and pathophysiology,despite significant challenges,particularly in exosome isolation and metabolite detection.This review discusses the significant technical challenges in exosome isolation and metabolite detection,highlighting the advancements in these areas that support the clinical application of exosome metabolomics,and illustrates the potential of exosomal metabolites from various body fluids as biomarkers for early disease diagnosis and treatment.展开更多
An iterative direct-forcing immersed boundary method is extended and used to solve convection heat transfer problems.The pressure,momentum source,and heat source at immersed boundary points are calculated simultaneous...An iterative direct-forcing immersed boundary method is extended and used to solve convection heat transfer problems.The pressure,momentum source,and heat source at immersed boundary points are calculated simultaneously to achieve the best coupling.Solutions of convection heat transfer problems with both Dirichlet and Neumann boundary conditions are presented.Two approaches for the implementation of Neumann boundary condition,i.e.direct and indirect methods,are introduced and compared in terms of accuracy and computational efficiency.Validation test cases include forced convection on a heated cylinder in an unbounded flow field and mixed convection around a circular body in a lid-driven cavity.Furthermore,the proposed method is applied to study the mixed convection around a heated rotating cylinder in a square enclosure with both iso-heat flux and iso-thermal boundary conditions.Computational results show that the order of accuracy of the indirect method is less than the direct method.However,the indirect method takes less computational time both in terms of the implementation of the boundary condition and the post processing time required to compute the heat transfer variables such as the Nusselt number.It is concluded that the iterative direct-forcing immersed boundary method is a powerful technique for the solution of convection heat transfer problems with stationary/moving boundaries and various boundary conditions.展开更多
The information integration method of semantic web based on agent ontology(SWAO method) was put forward aiming at the problems in current network environment,which integrates,analyzes and processes enormous web inform...The information integration method of semantic web based on agent ontology(SWAO method) was put forward aiming at the problems in current network environment,which integrates,analyzes and processes enormous web information and extracts answers on the basis of semantics. With SWAO method as the clue,the following technologies were studied:the method of concept extraction based on semantic term mining,agent ontology construction method on account of multi-points and the answer extraction in view of semantic inference. Meanwhile,the structural model of the question answering system applying ontology was presented,which adopts OWL language to describe domain knowledge from where QA system infers and extracts answers by Jena inference engine. In the system testing,the precision rate reaches 86%,and the recalling rate is 93%. The experimental results prove that it is feasible to use the method to develop a question answering system,which is valuable for further study in more depth.展开更多
The factor of safety of mechanically stabilized earth(MSE) structures can be analyzed either using limit equilibrium method(LEM) or strength reduction method(SRM) in finite element/difference method. In LEM, the stren...The factor of safety of mechanically stabilized earth(MSE) structures can be analyzed either using limit equilibrium method(LEM) or strength reduction method(SRM) in finite element/difference method. In LEM, the strengths of the reinforcement members and soils are reduced with the same factor. While using the SRM, only soil strength is reduced during the calculation of the factor of safety. This causes inconsistence in calculating the factor of safety of the MSE structures. To overcome this, an iteration method is proposed to consider the strength reduction of the reinforcements in SRM. The method is demonstrated by using PLAXIS, a finite element software. The results show that the factor of safety converges after a few iterations. The reduction of strength has different effects on the factor of safety depending on the properties of the reinforcements and the soil, and failure modes.展开更多
An object segment similarity function is taken into account from the continuous media frames to measure the individual streaming profit of certain segment versions of a media object.Therefore,a new segment version-bas...An object segment similarity function is taken into account from the continuous media frames to measure the individual streaming profit of certain segment versions of a media object.Therefore,a new segment version-based transcoding(SVT)mechanism is derived for a quality of service(QoS)of client-centric media streaming in wireless mobile networks.The derived function utilizes the fuzzy similarity of certain segment versions of an object.This mechanism provides the effectiveness of reduction of the stream startup latency among segment versions,and the average access of each version.Thus,the proposed segment version transcoding mechanism reduces packet loss which in turn increases streaming performance and throughput.The performance of the partitioned segment versions is simulated and some segment versions are completed.The simulation results show that the proposed mechanism outperforms the other mechanisms in average cache hit ratio and in average startup latency ratio.展开更多
Utilizing mine solid waste as a partial cement substitute(CS)to develop new cementitious materials is a significant technological innovation that will decrease the expenses associated with filling mining.To realize th...Utilizing mine solid waste as a partial cement substitute(CS)to develop new cementitious materials is a significant technological innovation that will decrease the expenses associated with filling mining.To realize the resource utilization of magnesium slag(MS)and blast furnace slag(BFS),the effects of different contents of MS and BFS as partial CSs on the deformation and energy characteristics of cemented tailings backfill on different curing ages(3,7,and 28 d)were discussed.Meanwhile,the destabilization failure energy criterion of the backfill was established from the direction of energy change.The results show that the strength of all backfills increased with increasing curing age,and the strengths of the backfills exceeded 1.342 MPa on day 28.The backfill with 50%BFS+50%cement has the best performance in mechanical properties(the maximum strength can reach 6.129 MPa)and is the best choice among these CS combinations.The trend in peak strain and elastic modulus of the backfill with increasing curing age may vary depending on the CS combination.The energy index at peak stress of the backfill with BFS as a partial CS was significantly higher than that of the backfill under other CS combinations.In contrast,the enhancement of the energy index when MS was used as a partial CS was not as significant as BFS.Sharp changes in the energy consumption ratio after continuous smooth changes can be used as a criterion for destabilization and failure of the backfill.The research results can provide guidance for the application of MS and BFS as partial CSs in mine filling.展开更多
文摘Cardiovascular disease(CVD)remains one of the leading causes of mortality among adults globally,with continuously rising morbidity and mortality rates.Metabolic disorders are closely linked to various cardiovascular diseases and play a critical role in their pathogenesis and progression,involving multifaceted mechanisms such as altered substrate utilization,mitochondrial structural and functional dysfunction,and impaired ATP synthesis and transport.In recent years,the potential role of peroxisome proliferator-activated receptors(PPARs)in cardiovascular diseases has garnered significant attention,particularly peroxisome proliferator-activated receptor alpha(PPARα),which is recognized as a highly promising therapeutic target for CVD.PPARαregulates cardiovascular physiological and pathological processes through fatty acid metabolism.As a ligand-activated receptor within the nuclear hormone receptor family,PPARαis highly expressed in multiple organs,including skeletal muscle,liver,intestine,kidney,and heart,where it governs the metabolism of diverse substrates.Functioning as a key transcription factor in maintaining metabolic homeostasis and catalyzing or regulating biochemical reactions,PPARαexerts its cardioprotective effects through multiple pathways:modulating lipid metabolism,participating in cardiac energy metabolism,enhancing insulin sensitivity,suppressing inflammatory responses,improving vascular endothelial function,and inhibiting smooth muscle cell proliferation and migration.These mechanisms collectively reduce the risk of cardiovascular disease development.Thus,PPARαplays a pivotal role in various pathological processes via mechanisms such as lipid metabolism regulation,anti-inflammatory actions,and anti-apoptotic effects.PPARαis activated by binding to natural or synthetic lipophilic ligands,including endogenous fatty acids and their derivatives(e.g.,linoleic acid,oleic acid,and arachidonic acid)as well as synthetic peroxisome proliferators.Upon ligand binding,PPARαactivates the nuclear receptor retinoid X receptor(RXR),forming a PPARα-RXR heterodimer.This heterodimer,in conjunction with coactivators,undergoes further activation and subsequently binds to peroxisome proliferator response elements(PPREs),thereby regulating the transcription of target genes critical for lipid and glucose homeostasis.Key genes include fatty acid translocase(FAT/CD36),diacylglycerol acyltransferase(DGAT),carnitine palmitoyltransferase I(CPT1),and glucose transporter(GLUT),which are primarily involved in fatty acid uptake,storage,oxidation,and glucose utilization processes.Advancing research on PPARαas a therapeutic target for cardiovascular diseases has underscored its growing clinical significance.Currently,PPARαactivators/agonists,such as fibrates(e.g.,fenofibrate and bezafibrate)and thiazolidinediones,have been extensively studied in clinical trials for CVD prevention.Traditional PPARαagonists,including fenofibrate and bezafibrate,are widely used in clinical practice to treat hypertriglyceridemia and low high-density lipoprotein cholesterol(HDL-C)levels.These fibrates enhance fatty acid metabolism in the liver and skeletal muscle by activating PPARα,and their cardioprotective effects have been validated in numerous clinical studies.Recent research highlights that fibrates improve insulin resistance,regulate lipid metabolism,correct energy metabolism imbalances,and inhibit the proliferation and migration of vascular smooth muscle and endothelial cells,thereby ameliorating pathological remodeling of the cardiovascular system and reducing blood pressure.Given the substantial attention to PPARα-targeted interventions in both basic research and clinical applications,activating PPARαmay serve as a key therapeutic strategy for managing cardiovascular conditions such as myocardial hypertrophy,atherosclerosis,ischemic cardiomyopathy,myocardial infarction,diabetic cardiomyopathy,and heart failure.This review comprehensively examines the regulatory roles of PPARαin cardiovascular diseases and evaluates its clinical application value,aiming to provide a theoretical foundation for further development and utilization of PPARα-related therapies in CVD treatment.
文摘Exosomes,ubiquitously present in body fluids,serve as non-invasive biomarkers for disease diagnosis,monitoring,and treatment.As intercellular messengers,exosomes encapsulate a rich array of proteins,nucleic acids,and metabolites,although most studies have primarily focused on proteins and RNA.Recently,exosome metabolomics has demonstrated clinical value and potential advantages in disease detection and pathophysiology,despite significant challenges,particularly in exosome isolation and metabolite detection.This review discusses the significant technical challenges in exosome isolation and metabolite detection,highlighting the advancements in these areas that support the clinical application of exosome metabolomics,and illustrates the potential of exosomal metabolites from various body fluids as biomarkers for early disease diagnosis and treatment.
文摘An iterative direct-forcing immersed boundary method is extended and used to solve convection heat transfer problems.The pressure,momentum source,and heat source at immersed boundary points are calculated simultaneously to achieve the best coupling.Solutions of convection heat transfer problems with both Dirichlet and Neumann boundary conditions are presented.Two approaches for the implementation of Neumann boundary condition,i.e.direct and indirect methods,are introduced and compared in terms of accuracy and computational efficiency.Validation test cases include forced convection on a heated cylinder in an unbounded flow field and mixed convection around a circular body in a lid-driven cavity.Furthermore,the proposed method is applied to study the mixed convection around a heated rotating cylinder in a square enclosure with both iso-heat flux and iso-thermal boundary conditions.Computational results show that the order of accuracy of the indirect method is less than the direct method.However,the indirect method takes less computational time both in terms of the implementation of the boundary condition and the post processing time required to compute the heat transfer variables such as the Nusselt number.It is concluded that the iterative direct-forcing immersed boundary method is a powerful technique for the solution of convection heat transfer problems with stationary/moving boundaries and various boundary conditions.
基金Projects(60773462, 60672171) supported by the National Natural Science Foundation of ChinaProjects(2009AA12143, 2009AA012136) supported by the National High-Tech Research and Development Program of ChinaProject(20080430250) supported by the Foundation of Post-Doctor in China
文摘The information integration method of semantic web based on agent ontology(SWAO method) was put forward aiming at the problems in current network environment,which integrates,analyzes and processes enormous web information and extracts answers on the basis of semantics. With SWAO method as the clue,the following technologies were studied:the method of concept extraction based on semantic term mining,agent ontology construction method on account of multi-points and the answer extraction in view of semantic inference. Meanwhile,the structural model of the question answering system applying ontology was presented,which adopts OWL language to describe domain knowledge from where QA system infers and extracts answers by Jena inference engine. In the system testing,the precision rate reaches 86%,and the recalling rate is 93%. The experimental results prove that it is feasible to use the method to develop a question answering system,which is valuable for further study in more depth.
基金Project(41072200)supported by the National Natural Science Foundation of ChinaProject(14PJD032)supported by the Shanghai Pujiang Program,China
文摘The factor of safety of mechanically stabilized earth(MSE) structures can be analyzed either using limit equilibrium method(LEM) or strength reduction method(SRM) in finite element/difference method. In LEM, the strengths of the reinforcement members and soils are reduced with the same factor. While using the SRM, only soil strength is reduced during the calculation of the factor of safety. This causes inconsistence in calculating the factor of safety of the MSE structures. To overcome this, an iteration method is proposed to consider the strength reduction of the reinforcements in SRM. The method is demonstrated by using PLAXIS, a finite element software. The results show that the factor of safety converges after a few iterations. The reduction of strength has different effects on the factor of safety depending on the properties of the reinforcements and the soil, and failure modes.
基金Project(2011)financially supported by Research Funds of Chonbuk National University,Korea
文摘An object segment similarity function is taken into account from the continuous media frames to measure the individual streaming profit of certain segment versions of a media object.Therefore,a new segment version-based transcoding(SVT)mechanism is derived for a quality of service(QoS)of client-centric media streaming in wireless mobile networks.The derived function utilizes the fuzzy similarity of certain segment versions of an object.This mechanism provides the effectiveness of reduction of the stream startup latency among segment versions,and the average access of each version.Thus,the proposed segment version transcoding mechanism reduces packet loss which in turn increases streaming performance and throughput.The performance of the partitioned segment versions is simulated and some segment versions are completed.The simulation results show that the proposed mechanism outperforms the other mechanisms in average cache hit ratio and in average startup latency ratio.
基金Projects(52274108,U2341265)supported by the National Natural Science Foundation of ChinaProject(2022YFC2904103)supported by the National Key Research and Development Program of China。
文摘Utilizing mine solid waste as a partial cement substitute(CS)to develop new cementitious materials is a significant technological innovation that will decrease the expenses associated with filling mining.To realize the resource utilization of magnesium slag(MS)and blast furnace slag(BFS),the effects of different contents of MS and BFS as partial CSs on the deformation and energy characteristics of cemented tailings backfill on different curing ages(3,7,and 28 d)were discussed.Meanwhile,the destabilization failure energy criterion of the backfill was established from the direction of energy change.The results show that the strength of all backfills increased with increasing curing age,and the strengths of the backfills exceeded 1.342 MPa on day 28.The backfill with 50%BFS+50%cement has the best performance in mechanical properties(the maximum strength can reach 6.129 MPa)and is the best choice among these CS combinations.The trend in peak strain and elastic modulus of the backfill with increasing curing age may vary depending on the CS combination.The energy index at peak stress of the backfill with BFS as a partial CS was significantly higher than that of the backfill under other CS combinations.In contrast,the enhancement of the energy index when MS was used as a partial CS was not as significant as BFS.Sharp changes in the energy consumption ratio after continuous smooth changes can be used as a criterion for destabilization and failure of the backfill.The research results can provide guidance for the application of MS and BFS as partial CSs in mine filling.
