To investigate the progressive fracture processes around a tunnel triggered by static stress and dynamic disturbance,experiments and numerical simulations were performed.The results show that the spatial distributions...To investigate the progressive fracture processes around a tunnel triggered by static stress and dynamic disturbance,experiments and numerical simulations were performed.The results show that the spatial distributions of acoustic emission(AE)events become very different as lateral pressure coefficients change.The combined effect of static stress and dynamic disturbance causes the damage around the tunnel,and initial stress conditions control the damage morphology.The blast disturbance cannot fundamentally change the damaged area but will deepen the extent of damage and accelerate the failure speed.The more significant the difference between the vertical and horizontal stresses is,the higher the impact on the tunnel by the dynamic disturbance is.The AE activity recovers to a relatively stable state within a short time after the blast and conforms to power-law characteristics.展开更多
1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symp...1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].展开更多
Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases,such as cancer,rheumatoid arthritis,and age-related macular degeneration.Recent studies have r...Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases,such as cancer,rheumatoid arthritis,and age-related macular degeneration.Recent studies have revealed that oleanolic acid(OA),a natural pentacyclic triterpenoid,inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs,which may represent an attractive VEGF inhibitor.In this paper,rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential.As a result,a series of novel OA derivatives,possessingα,β-unsat-urated ketone system in ring A and amide functional group at C-28,were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs.The results showed that two promising derivatives,OA-1 and OA-16,exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs,compared with OA.The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VE-GFR2 activation.Furthermore,small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2.Thus,the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors,which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.展开更多
基金Project(2017YFC0602904)supported by the National Key Research and Development Program of ChinaProject(51974059)supported by the National Natural Science Foundation of ChinaProject(N180115010)supported by the Fundamental Research Funds for the Central Universities,China。
文摘To investigate the progressive fracture processes around a tunnel triggered by static stress and dynamic disturbance,experiments and numerical simulations were performed.The results show that the spatial distributions of acoustic emission(AE)events become very different as lateral pressure coefficients change.The combined effect of static stress and dynamic disturbance causes the damage around the tunnel,and initial stress conditions control the damage morphology.The blast disturbance cannot fundamentally change the damaged area but will deepen the extent of damage and accelerate the failure speed.The more significant the difference between the vertical and horizontal stresses is,the higher the impact on the tunnel by the dynamic disturbance is.The AE activity recovers to a relatively stable state within a short time after the blast and conforms to power-law characteristics.
基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(No.2019-I2M-5-023)Hainan Provincial Science and Technology Major Project(No.ZDKJ201804)+2 种基金National Natural Science Foundation of China(No.81871611)National Natural Science Foundation of China(No.81760352)Project of Hainan Provincial Department of Education(No.Hnjg2019ZD-16)
文摘1.Introduction Sudden cardiac death(SCD)refers to sudden death due to a variety of cardiac causes.It is manifested as a sudden loss of consciousness,cardiac arrest,and respiratory arrest and generally shows early symptoms that are atypical and not easily detected[1].According to a recent study,nearly 544000 patients suffer from SCD every year in China[2].
基金supported by the National Natural Science Foundation of China(Nos.21672082 and 31671214)the Natural Science Foundation of Shandong Province(Nos.ZR2019YQ31,ZR2020YQ52,and ZR2020MB103)+1 种基金the Project of Shandong Province Higher Educational Youth Innovation Science and Technology Program(No.2020KJE006)the Science and Technology Project of University of Jinan(No.XKY2004).
文摘Angiogenesis inhibitors targeting the VEGF signaling pathway are developed into drugs for the treatment of vaious diseases,such as cancer,rheumatoid arthritis,and age-related macular degeneration.Recent studies have revealed that oleanolic acid(OA),a natural pentacyclic triterpenoid,inhibited the VEGF/VEGFR2 signaling pathway and angiogenesis in HUVECs,which may represent an attractive VEGF inhibitor.In this paper,rational structural modification towards OA was performed in order to improve its inhibitory effects aganist VEGF and anti-angiogenesis potential.As a result,a series of novel OA derivatives,possessingα,β-unsat-urated ketone system in ring A and amide functional group at C-28,were prepared and evaluated for cytotoxicity and their ability to inhibit VEGF-induced abnormal proliferation of HUVECs.The results showed that two promising derivatives,OA-1 and OA-16,exhibited no in vitro cytotoxicity against HUVECs but showed more potent inhibitory activity against VEGF-induced proliferation and angiogenesis in HUVECs,compared with OA.The results of Western blot indicated that OA-1 and OA-16 inhibited VEGF-induced VE-GFR2 activation.Furthermore,small interfering RNA experiments were performed to confirm that both compounds inhibited VEGF-induced angiogenesis via VEGFR2.Thus,the present study resulted in the discovery of new promising OA-inspired VEGF inhibitors,which can serve as potential lead compounds for the treatment of angiogenesis-related diseases.
