Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral inf...Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y13 and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y13, as a typical interferon-stimulated gene, is induced together with extracellular ADP during viral infection. Most importantly, extracellular ADP restricts the replication of different kinds of viruses, including vesicular stomatitis virus, Newcastle disease virus, herpes simplex virus 1, and murine leukemia virus. This kind of protection is dependent on P2Y13 but not P2Y1 or P2Y12, which are also considered as receptors for ADP. Furthermore, cyclic adenosine monophosphate and EPAC1 are downregu-lated by extracellular ADP through the P2Y13-coupled Gi alpha subunit. Accordingly, inhibition or deletion of EPAC1 significantly eliminates ADP/P2Y13-mediated antiviral activities. Taken together, our results show that P2Y13 and ADP play pivotal roles in the clearance of invaded virus and have the potential as antiviral targets.展开更多
Thermal compression testing was investigated using the Gleeble 3800 thermal simulator,and thermal deformation behavior of particle-reinforced titanium matrix composites(TMCs)was studied under deformation temperatures ...Thermal compression testing was investigated using the Gleeble 3800 thermal simulator,and thermal deformation behavior of particle-reinforced titanium matrix composites(TMCs)was studied under deformation temperatures of 750-900°C,strain rates of 0.001-1 s^(-1),and experimental deformation of 60%.According to obtained flow stress curves,the hot deformation characteristics were analyzed.Based on the Arrhenius hyperbolic sinusoidal model,the constitutive equation at high temperature was established.Based on the theory of dynamic material models,a hot processing map of TMCs at high temperature was established,and the peak region of power dissipation rate and the instability region in the hot processing map were both determined.At the same time,the corresponding microstructures in the peak power dissipation rate and rheological instability regions were observed.The results showed that flow stress decreased with increasing deformation temperature and increased with increasing strain rate.The thermal deformation activation energy of titanium matrix composites was 301.8 kJ/mol.The Ti-6Al-4V/(TiB+TiC)composites possessed only one instability zone under high-temperature compression at a strain of 0.5,with corresponding temperatures at 750-840°C and strain rates at 0.1-1 s^(-1).The optimal thermal deformation parameters included corresponding temperatures of 830-880°C and strain rates of 0.001-0.05 s^(-1).The microstructures corresponding to optimal hot working parameters in processing maps were more homogeneous than the microstructures in the instability zone,including the distribution uniformity of reinforcement and the degree of dynamic recrystallization,and no instability phenomena including abnormal grain growth,microcracks or intensive fracture of reinforcements were found,indicating that the hot processing map had a positive guiding effect on the option of desirable material thermal-working parameters.展开更多
基金the National Key R&D Program of China (2018YFA0507000 to B.D.)the National Natural Science Foundation of China (31570896 and 31770969 to B.D., 81672811 to M.Q.)+2 种基金Joint Research Institute for Science and Society (JoRISS)(14JORISS01 to B.D.)Science and Technology Commission of Shanghai Municipality (15JC14O15OO to B.D.)Innovation Program of Shanghai Municipal Educati on Commissi on (2017-01- 07-00-05-E00011 to A/LL.).
文摘Among the most important sensors of extracellular danger signals, purinergic receptors have been demonstrated to play crucial roles in host defense against infection. However, the function of P2 receptors in viral infection has been little explored. Here we demonstrated that P2Y13 and its ligand ADP play an important role in protecting hosts from viral infections. First, we demonstrate that P2Y13, as a typical interferon-stimulated gene, is induced together with extracellular ADP during viral infection. Most importantly, extracellular ADP restricts the replication of different kinds of viruses, including vesicular stomatitis virus, Newcastle disease virus, herpes simplex virus 1, and murine leukemia virus. This kind of protection is dependent on P2Y13 but not P2Y1 or P2Y12, which are also considered as receptors for ADP. Furthermore, cyclic adenosine monophosphate and EPAC1 are downregu-lated by extracellular ADP through the P2Y13-coupled Gi alpha subunit. Accordingly, inhibition or deletion of EPAC1 significantly eliminates ADP/P2Y13-mediated antiviral activities. Taken together, our results show that P2Y13 and ADP play pivotal roles in the clearance of invaded virus and have the potential as antiviral targets.
基金This work was financially supported by the General project of Education Department of Liaoning Province(No.LQGD2019001)the Natural Science Foundation of China(No.51805335)。
文摘Thermal compression testing was investigated using the Gleeble 3800 thermal simulator,and thermal deformation behavior of particle-reinforced titanium matrix composites(TMCs)was studied under deformation temperatures of 750-900°C,strain rates of 0.001-1 s^(-1),and experimental deformation of 60%.According to obtained flow stress curves,the hot deformation characteristics were analyzed.Based on the Arrhenius hyperbolic sinusoidal model,the constitutive equation at high temperature was established.Based on the theory of dynamic material models,a hot processing map of TMCs at high temperature was established,and the peak region of power dissipation rate and the instability region in the hot processing map were both determined.At the same time,the corresponding microstructures in the peak power dissipation rate and rheological instability regions were observed.The results showed that flow stress decreased with increasing deformation temperature and increased with increasing strain rate.The thermal deformation activation energy of titanium matrix composites was 301.8 kJ/mol.The Ti-6Al-4V/(TiB+TiC)composites possessed only one instability zone under high-temperature compression at a strain of 0.5,with corresponding temperatures at 750-840°C and strain rates at 0.1-1 s^(-1).The optimal thermal deformation parameters included corresponding temperatures of 830-880°C and strain rates of 0.001-0.05 s^(-1).The microstructures corresponding to optimal hot working parameters in processing maps were more homogeneous than the microstructures in the instability zone,including the distribution uniformity of reinforcement and the degree of dynamic recrystallization,and no instability phenomena including abnormal grain growth,microcracks or intensive fracture of reinforcements were found,indicating that the hot processing map had a positive guiding effect on the option of desirable material thermal-working parameters.
