The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tum...The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.展开更多
Rip currents are a significant threat to swimmers worldwide,responsible for numerous drowning incidents each year.In Vietnam,Bai Dai Beach in Cam Ranh Bay,Khanh Hoa Province,has experienced an increase in drowning eve...Rip currents are a significant threat to swimmers worldwide,responsible for numerous drowning incidents each year.In Vietnam,Bai Dai Beach in Cam Ranh Bay,Khanh Hoa Province,has experienced an increase in drowning events due to rip currents in recent years.To address this issue,a comprehensive study was conducted based on developing a depth-averaged 2D hydrodynamic model to simulate rip currents in the Bai Dai-Cam Ranh coast.The HYDIST-2D numerical model was applied to simulate the rip current evolution in space and time for the study area.The results showed that the HYDIST-2D numerical model can accurately predict the location,magnitude,and microstructure of rip currents,including rip current speed,width,and length.The simulation results revealed that the rip current speed is greater during the low tide phase,with an average speed of 0.5 m s^(-1),while during high tide,the rip current speed is lower,around 0.1–0.8 m s^(-1).The width and length of the rip current also vary with the tide phase,with a wider and longer rip current observed during the low tide phase.The results also showed that the rip current speed and microstructure are influenced by the wave features,tide current,and bathymetry of the study area.The present study provides valuable insights into the dynamics of rip currents in the Bai Dai-Cam Ranh coast.The findings can be used to support the management of bathing activities and provide early warnings for potential risks associated with rip currents.展开更多
路由信息协议(Routing Information Protocol,RIP)是中小型计算机网络常用的路由协议,也是一种重要的基于距离矢量(Distance-Vector)算法的路由协议。本文利用华三HCL(H3C Cloud Lab)网络仿真软件,设计环状拓扑结构实验网络,配置网络路...路由信息协议(Routing Information Protocol,RIP)是中小型计算机网络常用的路由协议,也是一种重要的基于距离矢量(Distance-Vector)算法的路由协议。本文利用华三HCL(H3C Cloud Lab)网络仿真软件,设计环状拓扑结构实验网络,配置网络路由协议RIP,抓取RIP数据报文,跟踪分析网络路由环路生成。通过实验及协议数据报分析,观察路由环路动态变化,有助于深入理解RIP防止路由环路机制,提高路由故障排查能力。展开更多
文摘The incidence and mortality rate of lung cancer rank among the highest worldwide,severely endangering human health and life.Metformin,an anti-diabetes drug,has been shown to elicit anticancer activities in various tumors.However,its underlying mechanisms remain elusive.In this work,we explore the role of receptor-interacting protein 1(RIP1)which plays a crucial role in the process of cell death,in metformin-induced anticancer activities in lung cancer.Metformin inhibits lung cancer cell proliferation in a dose-dependent manner and promotes apoptotic cell death,as evidenced by metformin-induced PARP and caspase cleavage.Furthermore,the pan-caspase inhibitor z-VAD-fmk reverses metformin-induced cell death.Western blot and qPCR results suggest that metformin markedly downregulates RIP1 expression without affecting its mRNA and ubiquitination levels(0 vs 80 mmol/L,100%vs 20%,100%vs 15%).Additionally,co-immunoprecipitation and immunofluorescence results reveal that metformin may suppress RIP1 expression in an Hsp70-dependent manner,as metformin promotes Hsp70 degradation,and Hsp70 endogenously interacts with RIP1.Subsequent CCK-8,flow cytometry,and Western blot analyses suggest that metformin decreases Hsp70/RIP1 expression through AMPK/PKA/GSK-3βaxis.Consistently,results from a subcutaneous transplant tumor model indicate that metformin retards tumor growth without affecting mouse body weight.Collectively,these data highlight the part of RIP1 in metformin-induced anticancer activities in lung cancer in vitro and in vivo,providing novel strategy for lung cancer administration.
文摘Rip currents are a significant threat to swimmers worldwide,responsible for numerous drowning incidents each year.In Vietnam,Bai Dai Beach in Cam Ranh Bay,Khanh Hoa Province,has experienced an increase in drowning events due to rip currents in recent years.To address this issue,a comprehensive study was conducted based on developing a depth-averaged 2D hydrodynamic model to simulate rip currents in the Bai Dai-Cam Ranh coast.The HYDIST-2D numerical model was applied to simulate the rip current evolution in space and time for the study area.The results showed that the HYDIST-2D numerical model can accurately predict the location,magnitude,and microstructure of rip currents,including rip current speed,width,and length.The simulation results revealed that the rip current speed is greater during the low tide phase,with an average speed of 0.5 m s^(-1),while during high tide,the rip current speed is lower,around 0.1–0.8 m s^(-1).The width and length of the rip current also vary with the tide phase,with a wider and longer rip current observed during the low tide phase.The results also showed that the rip current speed and microstructure are influenced by the wave features,tide current,and bathymetry of the study area.The present study provides valuable insights into the dynamics of rip currents in the Bai Dai-Cam Ranh coast.The findings can be used to support the management of bathing activities and provide early warnings for potential risks associated with rip currents.
文摘路由信息协议(Routing Information Protocol,RIP)是中小型计算机网络常用的路由协议,也是一种重要的基于距离矢量(Distance-Vector)算法的路由协议。本文利用华三HCL(H3C Cloud Lab)网络仿真软件,设计环状拓扑结构实验网络,配置网络路由协议RIP,抓取RIP数据报文,跟踪分析网络路由环路生成。通过实验及协议数据报分析,观察路由环路动态变化,有助于深入理解RIP防止路由环路机制,提高路由故障排查能力。
