受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、...受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。展开更多
目的:探究PET材料人工韧带表面羟基磷灰石(HAp)/明胶(Gel)涂层对移植物-宿主骨愈合的影响。方法:按PET材料人工韧带表面涂层情况分为2组:PET组和PET/HAp/Gel涂层组。用扫描电镜分别观察两种材料表面涂层情况。对48只雄性新西兰大白兔行...目的:探究PET材料人工韧带表面羟基磷灰石(HAp)/明胶(Gel)涂层对移植物-宿主骨愈合的影响。方法:按PET材料人工韧带表面涂层情况分为2组:PET组和PET/HAp/Gel涂层组。用扫描电镜分别观察两种材料表面涂层情况。对48只雄性新西兰大白兔行前交叉韧带重建术,将两种材料分别植入,并于术后4周、8周处死取材,进行组织学HE染色观察和生物力学检测。结果:扫描电镜观察显示涂层覆载成功。组织学HE染色观察显示,术后4周移植物-宿主骨界面形成较厚的纤维结缔组织,术后8周两组界面宽度均缩小,PET/HAp/Gel涂层组界面宽度缩小幅度较大,且于术后8周发现PET/HAp/Gel涂层组界面中有新生骨形成。生物力学检测显示,术后8周时,PET组与PET/HAp/Gel涂层组的断裂载荷(46.16±2.88 N vs 71.32±3.92 N)之间有显著统计学差异(P=0.0021);术后4周和8周,PET组与PET/HAp/Gel涂层组的刚度之间均有显著的统计学差异(11.06±1.14 N/mm vs 16.20±1.17 N/mm,P=0.0199;14.37±0.88 N/mm vs 24.35±1.35 N/mm,P=0.0008)。结论:HAp/Gel涂层材料能提升PET人工韧带的骨诱导性,促进移植物-宿主骨界面新生骨的形成,加强移植物-宿主骨愈合。展开更多
Based on electromagnetic radiation characteristics, the present research studied the damage evolution of rock under uniaxial compression. Besides, this research built the coal-rock damage evolution model considered re...Based on electromagnetic radiation characteristics, the present research studied the damage evolution of rock under uniaxial compression. Besides, this research built the coal-rock damage evolution model considered residual strength. The applicability and accuracy of the model were verified through experiments. The results show that coal-rock damage evolution consists of four periods. The first period is from the beginning of compression to nearly 20% of the stress peak value, during which the damage variable changes stably about 0.1, and accordingly a few of electromagnetic radiation signals emerge. The second period is from about 20% to 70% of the stress peak value. The damage has stable development, and the parameter of electromagnetic radiation characteristics turns larger continuously with the increase of stress. The third period is when the damage has accelerated development, the coal-rock was broken which result from sharp increasing of the damage variable, meanwhile a great quantity of electromagnetic radiation signals emerge. The fourth period is after the coal-rock fracture, during which the damage variable corresponding to the parameter of electromagnetic radiation characteristics has a stable development. This research has great academic and realistic significance for further studies the electromagnetic radiation characteristics of coal-rock under loading and damage and the forecasting of coal-rock dynamic disasters.展开更多
文摘受体相互作用蛋白激酶1(receptor-interacting protein kinase 1,RIPK1)是一种多结构域丝氨酸/苏氨酸蛋白激酶。它通过磷酸化特定的蛋白质,引起下游的信号转导和生物效应。近年来,随着对RIPK1的深入研究,学者发现其在自身免疫性疾病、神经退行性疾病,以及多种实体瘤和血液肿瘤中具有重要意义。一方面,RIPK1通过激活特定通路如核因子-κB(nuclear factor-κB,NF-κB)和丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等促进细胞存活及炎症反应。另一方面,RIPK1通过与胱天蛋白酶-8(cysteinyl aspartate specific proteinase-8,caspase-8)作用促进凋亡,或与RIPK3和混合谱系激酶结构域样假激酶(mixed lineage kinase domain-like protein,MLKL)作用促进坏死性凋亡的发生。RIPK1作为上游信号在不同肿瘤患者中表达水平不同。其支架功能和激酶活性可以调节癌症进展,也可以启动机体适应性免疫,抑制肿瘤进展;此外,还能产生免疫抑制性肿瘤微环境而促进肿瘤的发展。其双重作用在调节癌症的发生、发展及机体免疫反应方面都有所展现,可以作为新的治疗靶点控制癌症进展。该文从RIPK1的结构入手,深入探讨其功能,特别是其在调节癌症进展和免疫反应方面的功能,为癌症靶向药物的开发提供新的思路。
文摘目的:探究PET材料人工韧带表面羟基磷灰石(HAp)/明胶(Gel)涂层对移植物-宿主骨愈合的影响。方法:按PET材料人工韧带表面涂层情况分为2组:PET组和PET/HAp/Gel涂层组。用扫描电镜分别观察两种材料表面涂层情况。对48只雄性新西兰大白兔行前交叉韧带重建术,将两种材料分别植入,并于术后4周、8周处死取材,进行组织学HE染色观察和生物力学检测。结果:扫描电镜观察显示涂层覆载成功。组织学HE染色观察显示,术后4周移植物-宿主骨界面形成较厚的纤维结缔组织,术后8周两组界面宽度均缩小,PET/HAp/Gel涂层组界面宽度缩小幅度较大,且于术后8周发现PET/HAp/Gel涂层组界面中有新生骨形成。生物力学检测显示,术后8周时,PET组与PET/HAp/Gel涂层组的断裂载荷(46.16±2.88 N vs 71.32±3.92 N)之间有显著统计学差异(P=0.0021);术后4周和8周,PET组与PET/HAp/Gel涂层组的刚度之间均有显著的统计学差异(11.06±1.14 N/mm vs 16.20±1.17 N/mm,P=0.0199;14.37±0.88 N/mm vs 24.35±1.35 N/mm,P=0.0008)。结论:HAp/Gel涂层材料能提升PET人工韧带的骨诱导性,促进移植物-宿主骨界面新生骨的形成,加强移植物-宿主骨愈合。
基金provided by the National Key Technology R&D Program of China (No. 2012BAK09B01)the National Natural Science Foundation of China (Nos. 50904067 and 51104156)+1 种基金the Program for the New Century Excellent Talents in University of China (No. NCET-10-0768)the Jiangsu Planned Projects for Postdoctoral Research Funds of China (No. 1102085C)
文摘Based on electromagnetic radiation characteristics, the present research studied the damage evolution of rock under uniaxial compression. Besides, this research built the coal-rock damage evolution model considered residual strength. The applicability and accuracy of the model were verified through experiments. The results show that coal-rock damage evolution consists of four periods. The first period is from the beginning of compression to nearly 20% of the stress peak value, during which the damage variable changes stably about 0.1, and accordingly a few of electromagnetic radiation signals emerge. The second period is from about 20% to 70% of the stress peak value. The damage has stable development, and the parameter of electromagnetic radiation characteristics turns larger continuously with the increase of stress. The third period is when the damage has accelerated development, the coal-rock was broken which result from sharp increasing of the damage variable, meanwhile a great quantity of electromagnetic radiation signals emerge. The fourth period is after the coal-rock fracture, during which the damage variable corresponding to the parameter of electromagnetic radiation characteristics has a stable development. This research has great academic and realistic significance for further studies the electromagnetic radiation characteristics of coal-rock under loading and damage and the forecasting of coal-rock dynamic disasters.
