The specific pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)is still not fully understood,and there is currently no effective early cure.Understanding the role and mechanism of long noncoding ...The specific pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)is still not fully understood,and there is currently no effective early cure.Understanding the role and mechanism of long noncoding RNAs(lnc RNAs)in the pathogenesis of SONFH will help reveal the pathogenesis of SONFH and provide new targets for its early prevention and treatment.In this study,we first confirmed that glucocorticoid(GC)-induced apoptosis of bone microvascular endothelial cells(BMECs)is a pre-event in the pathogenesis and progression of SONFH.Then,we identified a new lnc RNA in BMECs via lnc RNA/m RNA microarray,termed Fosassociated linc RNA ENSRNOT00000088059.1(FAR591).FAR591 is highly expressed during GC-induced BMEC apoptosis and femoral head necrosis.Knockout of FAR591 effectively blocked the GC-induced apoptosis of BMECs,which then alleviated the damage of GCs to the femoral head microcirculation and inhibited the pathogenesis and progression of SONFH.In contrast,overexpression of FAR591 significantly promoted the GC-induced apoptosis of BMECs,which then aggravated the damage of GCs to the femoral head microcirculation and promoted the pathogenesis and progression of SONFH.Mechanistically,GCs activate the glucocorticoid receptor,which translocates to the nucleus and directly acts on the FAR591 gene promoter to induce FAR591 gene overexpression.Subsequently,FAR591 binds to the Fos gene promoter(–245–51)to form a stable RNA:DNA triplet structure and then recruits TATA-box binding protein associated factor 15 and RNA polymerase II to promote Fos expression through transcriptional activation.Fos activates the mitochondrial apoptotic pathway by regulating the expression of Bcl-2 interacting mediator of cell death(Bim)and P53 upregulated modulator of apoptosis(Puma)to mediate GC-induced apoptosis of BMECs,which leads to femoral head microcirculation dysfunction and femoral head necrosis.In conclusion,these results confirm the mechanistic link between lnc RNAs and the pathogenesis of SONFH,which helps reveal the pathogenesis of SONFH and provides a new target for the early prevention and treatment of SONFH.展开更多
The evolution of the microstructure,microchemistry and magnetic properties of the Sm(CobalFe_(0.28)-CuyZrx)_(7.6)magnets with different Zr and Cu contents was investigated.It is found that the coercivity of the Sm(Co,...The evolution of the microstructure,microchemistry and magnetic properties of the Sm(CobalFe_(0.28)-CuyZrx)_(7.6)magnets with different Zr and Cu contents was investigated.It is found that the coercivity of the Sm(Co,Fe,Cu,Zr)_(z)magnets is sensitive to Zr content.The deficiency of Zr content causes heterogeneity of Cu and Fe distributions,while an excessive Zr content leads to the formation of a SmCoZr impurity phase.The cellular structure and distribution of Cu concentration.gradient between the cell boundary phase and cell pha se are destroyed by inappropriate Zr content,which results in a reduction of coercivity.The Cu concentration difference between the cell boundary phase and cell phase increases with increasing Cu content.The coercivity of the Sm(CobalFe_(0.28)CuyZ_(r0.02))_(7.6)magnets increases from 10.4 to 25.4 kOe for y=0.05 and y=0.07.However,the excess of Cu element destroys the cell boundary phase and enlarges the cell size,resulting in a significant decrease of squareness and energy density.The optimum performance(remanence of 11.4 kG,coercivity of 25.4 kOe,maximum magnetic ene rgy product of 30.4 MGOe)was obtained for the Sm(Co_(0.63)Fe_(0.28)Cu_(0.07)Zr_(0.02))_(7.6)magnet.展开更多
Microstructure and magnetic properties were studied for the commercial Sm(Co FeCuZr)_(z) magnets before and after post annealing treatment.The results show that the phases composition and orientation of the magnet do ...Microstructure and magnetic properties were studied for the commercial Sm(Co FeCuZr)_(z) magnets before and after post annealing treatment.The results show that the phases composition and orientation of the magnet do not change after post annealing treatment,but the substantial redistribution of Cu element within multiscale(the microscale crystal grain and the nanoscale cellular structure) is observed simultaneously.In detail,along with the Cu redistribution,the thickness of the Cu-rich Sm(Co,Cu)_(5) cell boundary becomes thinner,and the Cu concentration in the boundary increases sharply.The pinning field of domain walls and corresponding coercivity increase remarkably with slight remanence and maximum energy product loss,and the overall magnetic performance of(BH)_(max)(MGOe)+H_(Cj)(kOe)increases by 54.3% as a result.Moreover,the thermal stability of the magnet improves as well.On the other hand,Cu-lean phenomenon was observed along the grain boundary region,triggering to magnetic domain reversal process and slightly undermining the squareness of the demagnetization curve of the magnet.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.:82260429,82060397,82260434)the Guizhou Provincial Natural Science Foundation(Grant Nos.:Qiankehebasis[2020]1Y311,Qiankehebasis-ZK[2022]general 399,Qiankehebasis-ZK[2022]general 447)+3 种基金the Science and Technology Foundation of Guizhou Provincial Health Committee(Grant Nos.:gzwkj2021-232,gzwjkj2020-1-130,and gzwkj2021-234)the Start-up Fund for Doctoral Research at the Affiliated Hospital of Guizhou Medical University(gyfybsky-2022-14)the NSFC Cultivation Project of Guizhou Medical University(21NSFCP08)the Discipline Outstanding Reserve Talent Program of Affiliated Hospital of Guizhou Medical University。
文摘The specific pathogenesis of steroid-induced osteonecrosis of the femoral head(SONFH)is still not fully understood,and there is currently no effective early cure.Understanding the role and mechanism of long noncoding RNAs(lnc RNAs)in the pathogenesis of SONFH will help reveal the pathogenesis of SONFH and provide new targets for its early prevention and treatment.In this study,we first confirmed that glucocorticoid(GC)-induced apoptosis of bone microvascular endothelial cells(BMECs)is a pre-event in the pathogenesis and progression of SONFH.Then,we identified a new lnc RNA in BMECs via lnc RNA/m RNA microarray,termed Fosassociated linc RNA ENSRNOT00000088059.1(FAR591).FAR591 is highly expressed during GC-induced BMEC apoptosis and femoral head necrosis.Knockout of FAR591 effectively blocked the GC-induced apoptosis of BMECs,which then alleviated the damage of GCs to the femoral head microcirculation and inhibited the pathogenesis and progression of SONFH.In contrast,overexpression of FAR591 significantly promoted the GC-induced apoptosis of BMECs,which then aggravated the damage of GCs to the femoral head microcirculation and promoted the pathogenesis and progression of SONFH.Mechanistically,GCs activate the glucocorticoid receptor,which translocates to the nucleus and directly acts on the FAR591 gene promoter to induce FAR591 gene overexpression.Subsequently,FAR591 binds to the Fos gene promoter(–245–51)to form a stable RNA:DNA triplet structure and then recruits TATA-box binding protein associated factor 15 and RNA polymerase II to promote Fos expression through transcriptional activation.Fos activates the mitochondrial apoptotic pathway by regulating the expression of Bcl-2 interacting mediator of cell death(Bim)and P53 upregulated modulator of apoptosis(Puma)to mediate GC-induced apoptosis of BMECs,which leads to femoral head microcirculation dysfunction and femoral head necrosis.In conclusion,these results confirm the mechanistic link between lnc RNAs and the pathogenesis of SONFH,which helps reveal the pathogenesis of SONFH and provides a new target for the early prevention and treatment of SONFH.
基金the National Natural Science Foundation of China(51871005,51931007)the International S&T Cooperation Program of China(2015DFG52020)。
文摘The evolution of the microstructure,microchemistry and magnetic properties of the Sm(CobalFe_(0.28)-CuyZrx)_(7.6)magnets with different Zr and Cu contents was investigated.It is found that the coercivity of the Sm(Co,Fe,Cu,Zr)_(z)magnets is sensitive to Zr content.The deficiency of Zr content causes heterogeneity of Cu and Fe distributions,while an excessive Zr content leads to the formation of a SmCoZr impurity phase.The cellular structure and distribution of Cu concentration.gradient between the cell boundary phase and cell pha se are destroyed by inappropriate Zr content,which results in a reduction of coercivity.The Cu concentration difference between the cell boundary phase and cell phase increases with increasing Cu content.The coercivity of the Sm(CobalFe_(0.28)CuyZ_(r0.02))_(7.6)magnets increases from 10.4 to 25.4 kOe for y=0.05 and y=0.07.However,the excess of Cu element destroys the cell boundary phase and enlarges the cell size,resulting in a significant decrease of squareness and energy density.The optimum performance(remanence of 11.4 kG,coercivity of 25.4 kOe,maximum magnetic ene rgy product of 30.4 MGOe)was obtained for the Sm(Co_(0.63)Fe_(0.28)Cu_(0.07)Zr_(0.02))_(7.6)magnet.
基金Supported by the National Natural Science Foundation of China(31570063,31870020)the Shandong Key Research and Development Program(2017GSF17129)+1 种基金the Shandong Key Scientific and Technological Innovation Program(2017CXGC0303)the Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences(+CXGC2016B10)~~
基金Project supported by the National Natural Science Foundation of China(51871005,51931007)the Key Program of Science and Technology Development Project of Beijing Municipal Education Commission of China(KZ202010005009)。
文摘Microstructure and magnetic properties were studied for the commercial Sm(Co FeCuZr)_(z) magnets before and after post annealing treatment.The results show that the phases composition and orientation of the magnet do not change after post annealing treatment,but the substantial redistribution of Cu element within multiscale(the microscale crystal grain and the nanoscale cellular structure) is observed simultaneously.In detail,along with the Cu redistribution,the thickness of the Cu-rich Sm(Co,Cu)_(5) cell boundary becomes thinner,and the Cu concentration in the boundary increases sharply.The pinning field of domain walls and corresponding coercivity increase remarkably with slight remanence and maximum energy product loss,and the overall magnetic performance of(BH)_(max)(MGOe)+H_(Cj)(kOe)increases by 54.3% as a result.Moreover,the thermal stability of the magnet improves as well.On the other hand,Cu-lean phenomenon was observed along the grain boundary region,triggering to magnetic domain reversal process and slightly undermining the squareness of the demagnetization curve of the magnet.
