Background&Objective Knee osteoarthritis(OA)is a degenerative disease,which not only induces superficial cartilage defects and full-thickness cartilage defects,but also exacerbates the microenvironment of the knee...Background&Objective Knee osteoarthritis(OA)is a degenerative disease,which not only induces superficial cartilage defects and full-thickness cartilage defects,but also exacerbates the microenvironment of the knee joint and affects the mechano-chemical responses of the organ.As a growth/repair factor,mechanical growth factor(MGF)has the function of preventing OA,promoting cartilage regeneration and repairing damaged ligaments.activating transcription factor 2(ATF-2),a transcription factor,has the property of binding to cytokines,which makes it involved in the transcriptional regulation of various pathways in response to cellular stress,inflammatory cytokine and growth factors.At present,little is known about the effect of MGF on human osteoarthritis ligament fibroblasts(OA-LFs),and whether the approach can promote OA-LFs timely response to the mechanical injury and initiate signaling pathway for cell survival.Therefore,the purpose of this study is to investigate whether MGF promotes mechanical response to ligament fibroblasts in osteoarthritis knee cavity via ATF-2.Methods OA-LFs were seeded onto six-cell BioFlex plates and suffered from 12%static mechanical stretch[60 cycles/minute(1 Hz)]for 12 hours to mimic mechanical force mediated ligament injury.Meanwhile,OA-LFs were treated with MGF before and during mechanical stretch.Intracellular reactive oxygen species(ROS)and GRP78 mRNA expression were investigated to detect the cellular stress response of OA-LFs.The scratch test was performed to detect the migration ability of cells,gelatin zymography was used to examine the effect of MGF on the activity of matrix metalloproteinase 2(MMP-2)in OA-LFs,and cell deformation was detected by phalloidin-FITC staining after stretching.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to screen the messenger RNA(mRNA)expression of ATF family members after OALFs treatment with MGF.Western blotting further proved that MGF is capable to activate the p-ATF-2.Results OA delays LFs response to mechanical injury,while MGF pretreatment can promote cells timely feedback the mechanically stimuli by inducing cellular stress.MGF treatment can alleviate the decline in cell migration ability caused by mechanical injury and further promote cell migration.In addition,MGF can reduce the activity of MM P-5 and alleviate the stretch-induced deformation of OA-LFs.Furthermore,the mRNA expression of ATF-2 up-regulated in a dose-dependent manner upon MGF treatment compared with control,while the expression of ATF-5 gene was down-regulated in a dose-dependent.Protein levels showed that the expression of p-ATF-2 increased with increasing MGF concentration.Conclusions Our study shows that MGF pretreatment of OA-LFs can respond quickly to mechanical damage and accelerate the ligament injury repair by promoting cell migration,decreasing the MMP-2 activity,and remitting the cell deformation.Therefore,MGF has potential as a therapeutic for OA patients.展开更多
Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, ...Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on agonist-induced vasorelaxation and vasoconstriction using the isolated rat aortic rings in in vitro organ bath system. Treatment with inorganic arsenite (AsⅢ) inhibited acetylcholine-induced relaxation of aortic rings by inhibiting production of nitric oxide in endothelium.展开更多
单级式双有源桥(dual active bridge,DAB)DC/AC变换器控制自由度多,变压器匝比、漏感、开关频率等参数相互耦合,导致变换器效率优化面临多重制约。该文分析变压器匝比、漏感与软开关范围、漏感电流有效值、漏感电流峰值之间的约束关系,...单级式双有源桥(dual active bridge,DAB)DC/AC变换器控制自由度多,变压器匝比、漏感、开关频率等参数相互耦合,导致变换器效率优化面临多重制约。该文分析变压器匝比、漏感与软开关范围、漏感电流有效值、漏感电流峰值之间的约束关系,提出直接表征DAB-DC/AC变换器效率的物理量:效率敏感因子。通过研究效率敏感因子对系统损耗的影响机理,实现变换器效率最优的硬件参数设计,为多参数耦合的单级式DAB-DC/AC变换器效率优化提供理论指导。最后通过一台450 W样机验证所提理论的正确性。展开更多
基金supported by the National Natural Science Foundation of China ( 11532004,31270990, 31600762)Innovation and Attracting Talents Program for College and University( “111”Project) ( B06023)
文摘Background&Objective Knee osteoarthritis(OA)is a degenerative disease,which not only induces superficial cartilage defects and full-thickness cartilage defects,but also exacerbates the microenvironment of the knee joint and affects the mechano-chemical responses of the organ.As a growth/repair factor,mechanical growth factor(MGF)has the function of preventing OA,promoting cartilage regeneration and repairing damaged ligaments.activating transcription factor 2(ATF-2),a transcription factor,has the property of binding to cytokines,which makes it involved in the transcriptional regulation of various pathways in response to cellular stress,inflammatory cytokine and growth factors.At present,little is known about the effect of MGF on human osteoarthritis ligament fibroblasts(OA-LFs),and whether the approach can promote OA-LFs timely response to the mechanical injury and initiate signaling pathway for cell survival.Therefore,the purpose of this study is to investigate whether MGF promotes mechanical response to ligament fibroblasts in osteoarthritis knee cavity via ATF-2.Methods OA-LFs were seeded onto six-cell BioFlex plates and suffered from 12%static mechanical stretch[60 cycles/minute(1 Hz)]for 12 hours to mimic mechanical force mediated ligament injury.Meanwhile,OA-LFs were treated with MGF before and during mechanical stretch.Intracellular reactive oxygen species(ROS)and GRP78 mRNA expression were investigated to detect the cellular stress response of OA-LFs.The scratch test was performed to detect the migration ability of cells,gelatin zymography was used to examine the effect of MGF on the activity of matrix metalloproteinase 2(MMP-2)in OA-LFs,and cell deformation was detected by phalloidin-FITC staining after stretching.Quantitative real-time polymerase chain reaction(qRT-PCR)was used to screen the messenger RNA(mRNA)expression of ATF family members after OALFs treatment with MGF.Western blotting further proved that MGF is capable to activate the p-ATF-2.Results OA delays LFs response to mechanical injury,while MGF pretreatment can promote cells timely feedback the mechanically stimuli by inducing cellular stress.MGF treatment can alleviate the decline in cell migration ability caused by mechanical injury and further promote cell migration.In addition,MGF can reduce the activity of MM P-5 and alleviate the stretch-induced deformation of OA-LFs.Furthermore,the mRNA expression of ATF-2 up-regulated in a dose-dependent manner upon MGF treatment compared with control,while the expression of ATF-5 gene was down-regulated in a dose-dependent.Protein levels showed that the expression of p-ATF-2 increased with increasing MGF concentration.Conclusions Our study shows that MGF pretreatment of OA-LFs can respond quickly to mechanical damage and accelerate the ligament injury repair by promoting cell migration,decreasing the MMP-2 activity,and remitting the cell deformation.Therefore,MGF has potential as a therapeutic for OA patients.
文摘Arsenic in drinking water is a worldwide health problem that is associated with cardiovascular disease, but the cause is currently unknown. In order to examine whether arsenic affects vasomotor tone in blood vessels, we investigated the effect of arsenic on agonist-induced vasorelaxation and vasoconstriction using the isolated rat aortic rings in in vitro organ bath system. Treatment with inorganic arsenite (AsⅢ) inhibited acetylcholine-induced relaxation of aortic rings by inhibiting production of nitric oxide in endothelium.
文摘单级式双有源桥(dual active bridge,DAB)DC/AC变换器控制自由度多,变压器匝比、漏感、开关频率等参数相互耦合,导致变换器效率优化面临多重制约。该文分析变压器匝比、漏感与软开关范围、漏感电流有效值、漏感电流峰值之间的约束关系,提出直接表征DAB-DC/AC变换器效率的物理量:效率敏感因子。通过研究效率敏感因子对系统损耗的影响机理,实现变换器效率最优的硬件参数设计,为多参数耦合的单级式DAB-DC/AC变换器效率优化提供理论指导。最后通过一台450 W样机验证所提理论的正确性。
