The Electro-Fenton(EF)process is one of the promising advanced oxidation processes(AOPs)for environmental remediation.The H_(2)O_(2) yield of EF process largely determines its performance on organic pollutants degrada...The Electro-Fenton(EF)process is one of the promising advanced oxidation processes(AOPs)for environmental remediation.The H_(2)O_(2) yield of EF process largely determines its performance on organic pollutants degradation.Conventional Pd-catalytic EF process generates H_(2)O_(2) via the combination reaction of anodic O_(2) and cathodic H;.However,the relatively expensive catalyst limits its application.Herein,a hybrid Pd/activated carbon(Pd/AC)-stainless steel mesh(SS)cathode(PACSS)was proposed,which enables more efficie nt H_(2)O_(2)generation.It utilizes AC,the support of Pd catalyst,as part of cathode for H_(2)O_(2) generation via 2-electron anodic O_(2) reduction,and SS serve as a current distributor.Moreover,H_(2)O_(2) could be catalytically decomposed upon AC to generate highly reactive·OH,which avoids the use of Fe;.Compared with conventional Pd catalyst,H_(2)O_(2) concentration obtained by PACSS cathode is248.2%higher,the O_(2)utilization efficiency was also increased from 3.2%to 10.8%.Within 50 min,26.3%,72.5%,and 94.0%H_(2)O_(2) was decomposed by Pd,AC,and Pd/AC.Fluorescence detection results implied that Pd/AC is effective upon H_(2)O_(2) activation for·OH generation.Finally,iron-free EF process enabled by PACSS cathode was examined to be effective for reactive blue 19(RB19)degradation.After continuous running for 10 cycles(500 min),the PACSS cathode was still stable for H_(2)O_(2)generation,H_(2)O_(2)activation,and RB19 degradation,showing its potential application for organic pollutants degradation without increase in the running cost.展开更多
The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm.However,the specific mechanisms triggering virus replication and cytokine storm are s...The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm.However,the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated.Here,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells.Specifically,HIF-1αprotein expression is upregulated after H1N1 infection.Deficiency of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in vivo.In addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in vitro.Mechanistically,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and lactate.Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses.Further analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/βproduction.In conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.展开更多
Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus(H1N1), a single-stranded, negative-se...Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus(H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial(A549) cells. In detail, the expression of hexokinase 2(HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells,and the expression of pyruvate kinase M2(PKM2) and pyruvate dehydrogenase kinase 3(PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1(HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.展开更多
基金financially supported by the National Natural Science Foundation of China(Nos.52006049,51776055)the China Postdoctoral Science Foundation(Nos.2019M661293,2020T130149)。
文摘The Electro-Fenton(EF)process is one of the promising advanced oxidation processes(AOPs)for environmental remediation.The H_(2)O_(2) yield of EF process largely determines its performance on organic pollutants degradation.Conventional Pd-catalytic EF process generates H_(2)O_(2) via the combination reaction of anodic O_(2) and cathodic H;.However,the relatively expensive catalyst limits its application.Herein,a hybrid Pd/activated carbon(Pd/AC)-stainless steel mesh(SS)cathode(PACSS)was proposed,which enables more efficie nt H_(2)O_(2)generation.It utilizes AC,the support of Pd catalyst,as part of cathode for H_(2)O_(2) generation via 2-electron anodic O_(2) reduction,and SS serve as a current distributor.Moreover,H_(2)O_(2) could be catalytically decomposed upon AC to generate highly reactive·OH,which avoids the use of Fe;.Compared with conventional Pd catalyst,H_(2)O_(2) concentration obtained by PACSS cathode is248.2%higher,the O_(2)utilization efficiency was also increased from 3.2%to 10.8%.Within 50 min,26.3%,72.5%,and 94.0%H_(2)O_(2) was decomposed by Pd,AC,and Pd/AC.Fluorescence detection results implied that Pd/AC is effective upon H_(2)O_(2) activation for·OH generation.Finally,iron-free EF process enabled by PACSS cathode was examined to be effective for reactive blue 19(RB19)degradation.After continuous running for 10 cycles(500 min),the PACSS cathode was still stable for H_(2)O_(2)generation,H_(2)O_(2)activation,and RB19 degradation,showing its potential application for organic pollutants degradation without increase in the running cost.
基金supported by a grant from the National Natural Science Foundation of China(No.82072210)the Shanghai Municipal Science and Technology Commission,China(No.20ZR1445200)+1 种基金the Chinese Federation of Public Health Foundation(GWLM202001)the Three-Year Initiative Plan for Strengthening Public Health System Construction in Shanghai(No.GWV-10.1-XK25).
文摘The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm.However,the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated.Here,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells.Specifically,HIF-1αprotein expression is upregulated after H1N1 infection.Deficiency of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in vivo.In addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in vitro.Mechanistically,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and lactate.Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses.Further analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/βproduction.In conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.
基金This work was supported by the National Natural Science Funds of China under Grant 81471891 and 82000022Key and Weak Subject Construction Project of Shanghai Health and Family Planning System under Grant 2016ZB0205Natural Science Foundation of Shanghai under Grant 18ZR1431900。
文摘Viruses depend on host cellular metabolism to provide the energy and biosynthetic building blocks required for their replication. In this study, we observed that influenza A virus(H1N1), a single-stranded, negative-sense RNA virus with an eight-segmented genome, enhanced glycolysis both in mouse lung tissues and in human lung epithelial(A549) cells. In detail, the expression of hexokinase 2(HK2), the first enzyme in glycolysis, was upregulated in H1N1-infected A549 cells,and the expression of pyruvate kinase M2(PKM2) and pyruvate dehydrogenase kinase 3(PDK3) was upregulated in H1N1-infected mouse lung tissues. Pharmacologically inhibiting the glycolytic pathway or targeting hypoxia-inducible factor 1(HIF-1), the central transcriptional factor critical for glycolysis, significantly reduced H1N1 replication, revealing a requirement for glycolysis during H1N1 infection. In addition, pharmacologically enhancing the glycolytic pathway further promoted H1N1 replication. Furthermore, the change of H1N1 replication upon glycolysis inhibition or enhancement was independent of interferon signaling. Taken together, these findings suggest that influenza A virus induces the glycolytic pathway and thus facilitates efficient viral replication. This study raises the possibility that metabolic inhibitors, such as those that target glycolysis, could be used to treat influenza A virus infection in the future.
