He CEL-3是一个高温、高压、高流量的氦气冷却实验回路,主要用于聚变堆包层部件热工水力实验。根据实验回路的系统设计与布局参数,运用APROS软件对回路建模,模拟氦气在不同工况下的温度、压力、流量等重要工艺参数分布与变化,以及重要...He CEL-3是一个高温、高压、高流量的氦气冷却实验回路,主要用于聚变堆包层部件热工水力实验。根据实验回路的系统设计与布局参数,运用APROS软件对回路建模,模拟氦气在不同工况下的温度、压力、流量等重要工艺参数分布与变化,以及重要设备如印刷电路板式换热器(PCHE)和风机等在运行或状态切换过程中的瞬态参数,以获得热工特性曲线。目前He CEL-3实验回路已建设完工,回路已完成部分运行状态的实验研究工作。通过对模拟获取的热工特性与调试实验参数进行对比,以验证APROS模拟方法的有效性与适用性,为未来运用该方法设计和运行聚变堆氦气冷却回路提供参考。展开更多
The non-coding RNAs(ncRNAs)are a family of single-stranded RNAs that have become recognized as crucial gene expression regulators in normal and cancer cell biology.The gut microbiota,which consists of several differen...The non-coding RNAs(ncRNAs)are a family of single-stranded RNAs that have become recognized as crucial gene expression regulators in normal and cancer cell biology.The gut microbiota,which consists of several different bacteria,can actively contribute to the regulation of host metabolism,immunity,and inflammation.Roles of ncRNAs and gut microbiota could significantly interact with each other to regulate the growth of various types of cancer.In particular,a causal relationship among ncRNAs,gut microbiota,and immune cells has been shown for their potential importance in the development of breast cancer.Alteration of ncRNA expression and/or gut microbiota profiles could also influence several intracellular signaling pathways with the function of anti-proliferative(APRO)family proteins associated with the malignancy.Targeting ncRNAs and/or APRO family proteins for the treatment of various cancers has been revealed with novel immune therapies.Here,the most recent studies to underline the key role of ncRNAs,APRO family proteins,and gut microbiota in breast cancer progression have been discussed.For more effective breast cancer therapy,it would be imperative to figure out the collective mechanism of ncRNAs,APRO family proteins,and gut microbiota.展开更多
Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in an...Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a.展开更多
文摘The non-coding RNAs(ncRNAs)are a family of single-stranded RNAs that have become recognized as crucial gene expression regulators in normal and cancer cell biology.The gut microbiota,which consists of several different bacteria,can actively contribute to the regulation of host metabolism,immunity,and inflammation.Roles of ncRNAs and gut microbiota could significantly interact with each other to regulate the growth of various types of cancer.In particular,a causal relationship among ncRNAs,gut microbiota,and immune cells has been shown for their potential importance in the development of breast cancer.Alteration of ncRNA expression and/or gut microbiota profiles could also influence several intracellular signaling pathways with the function of anti-proliferative(APRO)family proteins associated with the malignancy.Targeting ncRNAs and/or APRO family proteins for the treatment of various cancers has been revealed with novel immune therapies.Here,the most recent studies to underline the key role of ncRNAs,APRO family proteins,and gut microbiota in breast cancer progression have been discussed.For more effective breast cancer therapy,it would be imperative to figure out the collective mechanism of ncRNAs,APRO family proteins,and gut microbiota.
基金grants from Beijing Natural Science Foundation(No.19G10290)National Natural Science Foundation of China(No.81772184).
文摘Enterovirus A71(EV-A71) is the major pathogen responsible for the severe hand, foot and mouth disease worldwide, for which few effective antiviral drugs are presently available. Interferon-a(IFN-a) has been used in antiviral therapy for decades;it has been reported that EV-A71 antagonizes the antiviral activity of IFN-a based on viral 2 Apro-mediated reduction of the interferon-alpha receptor 1(IFNAR1);however, the mechanism remains unknown. Here, we showed a significant increase in IFNAR1 protein induced by IFN-a in RD cells, whereas EV-A71 infection caused obvious downregulation of the IFNAR1 protein and blockage of IFN-a signaling. Subsequently, we observed that EV-A71 2 Apro inhibited IFNAR1 translation by cleavage of the eukaryotic initiation factor 4 GI(eIF4GI), without affecting IFNAR1 m RNA levels induced by IFN-a. The inhibition of IFNAR1 translation also occurred in puromycin-induced apoptotic cells when caspase-3 cleaved e IF4 GI. Importantly, we verified that 2 Aprocould activate cellular caspase-3, which was subsequently involved in e IF4 GI cleavage mediated by 2 Apro. Furthermore, inhibition of caspase-3 activation resulted in the partial restoration of IFNAR1 in cells transfected with 2 A or infected with EV-A71, suggesting the pivotal role of both viral 2 Aproand caspase-3 activation in the disturbance of IFN-a signaling. Collectively, we elucidate a novel mechanism by which cellular caspase-3 contributes to viral 2 Apro-mediated down-regulation of IFNAR1 at the translation level during EV-A71 infection, indicating that caspase-3 inhibition could be a potential complementary strategy to improve clinical anti-EV-A71 therapy with IFN-a.
