We took the iron-efficient and iron-inefficient soybean varieties with significant differences in iron efficiency as the test materials,in order to ascertain the relationship between the low iron stress and the iron e...We took the iron-efficient and iron-inefficient soybean varieties with significant differences in iron efficiency as the test materials,in order to ascertain the relationship between the low iron stress and the iron efficiency of soybean varieties.The results showed that through the principal component analysis,it was found that the contribution rate of the shoot light energy absorption factor and root morphological factor was the highest,reaching 41.0% and 67.2%,respectively.According to the eigenvector with high absolute value for the two factors,it was found that improving photosynthesis and root surface area could help to improve the ability of soybean to resist low iron.From the dynamic simulation results of Logistic equation,both V and Vmof the shoot and root of iron-efficient varieties were higher than those of iron-inefficient varieties;the low iron treatment postponed the time of the root of iron-inefficient varieties to reach Vm,while the iron-efficient varieties were resistant to the damage caused by the low iron to growth by improving root V.However,when the iron concentration was 0 mM,regardless of iron-efficient varieties or iron-inefficient varieties,the shoot V,Vmand △t were all low,indicating that the division of different iron efficiency varieties was relative,not absolute,and the ability of plant to resist stress was not only determined by its own characteristics,but also closely related to the degree of stress.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
Coxsackievirus A10(CVA10)is one of the major etiological agents of hand,foot,and mouth disease.There are no vaccine and antiviral drugs for controlling CVA10 infection.Reverse genetic tools for CVA10 will benefit its ...Coxsackievirus A10(CVA10)is one of the major etiological agents of hand,foot,and mouth disease.There are no vaccine and antiviral drugs for controlling CVA10 infection.Reverse genetic tools for CVA10 will benefit its mechanistic study and development of vaccines and antivirals.Here,two infectious clones for the prototype and a Myc-tagged CVA10 were constructed.Viable CVA10 viruses were harvested by transfecting the viral m RNA into human rhabdomyosarcoma(RD)cells.Rescued CVA10 was further confirmed by next generation sequencing and characterized experimentally.We also constructed the vectors for CVA10 subgenomic replicon with luciferase reporter and viral capsid with EGFP reporter,respectively.Co-transfection of the viral replicon RNA and capsid expresser in human embryonic kidney 293 T(HEK293 T)cells led to the production of single round infectious particles(SRIPs).Based on CVA10 replicon RNA,SRIPs with either the enterovirus A71(EVA71)capsid or the CVA10 capsid were generated.Infection by EVA71 SRIPs required SCARB2,while CVA10 SRIPs did not.Finally,we showed great improvement of the replicon activity and SRIPs production by insertion of a cis-active hammerhead ribozyme(HHRib)before the 50-untranslated region(UTR).In summary,reverse genetic tools for prototype strain of CVA10,including both the infectious clone and the SRIPs system,were successfully established.These tools will facilitate the basic and translational study of CVA10.展开更多
The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop r...The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop resistance are in urgent need.Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture,there are few confirmed antiviral candidates in vivo.In this study,94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs.Among them,24 compounds with low cytotoxicity were selected,and of these,17 compounds also effectively suppressed SARS-CoV-2 infection in He La cells transduced with human ACE2.Six compounds disturb multiple processes of the SARSCoV-2 life cycle.Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2infection.Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant.Except for cisatracurium,six compounds reduced hamster pulmonary viral load,and IL-6 and TNF-αm RNAwhen assayed at 4 d postinfection.In particular,sertraline,salinomycin,and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro,suggesting promising application for COVID-19 treatment.展开更多
Carbonyl sulfide (COS) and dimethyl sulfide (DMS) fluxes from as urban Cynodon dactylon lawn and adjacent bare soil were measured during April-July 2005 in Guangzhou, China. Both the lawn and bare soil acted as si...Carbonyl sulfide (COS) and dimethyl sulfide (DMS) fluxes from as urban Cynodon dactylon lawn and adjacent bare soil were measured during April-July 2005 in Guangzhou, China. Both the lawn and bare soil acted as sinks for COS and sources for DMS. The mean fluxes of COS and DMS in the lawn (-19.27 and 18.16 pmol/(m^2.sec), respectively) were significantly higher than those in the bare soil (-9.89 and 9.35 pmol/(m^A2.sec), respectively). Fluxes of COS and DMS in mowed lawn were also higher than those in bare soils. Both COS and DMS fluxes showed diurnal variation with detectable but much lower values in the nighttime than in the daytime. COS fluxes were related significantly to temperature and the optimal temperature for COS uptake was 29℃. While positive linear correlations were found between DMS fluxes and temperature. COS fluxes increased linearly with ambient COS mixing ratios, and had a compensation point of 336 ppt.展开更多
Monoterpenes(MTs)play crucial roles not only in atmospheric chemistry and global climate change but also in soil processes and soil ecology.Elevated nitrogen(N)deposition can influence soil microbial community and lit...Monoterpenes(MTs)play crucial roles not only in atmospheric chemistry and global climate change but also in soil processes and soil ecology.Elevated nitrogen(N)deposition can influence soil microbial community and litter decomposition,and consequently alters MT fluxes from forest floors and litter.Yet,the responses of soil and litter MT to increased N deposition remain poorly understood and the influences of N addition are sometimes contradictory.In the present study,static chambers were placed in masson pine forest(PF)and in monsoon evergreen broad-leaf forest(BF)at Dinghushan,subtropical China.The preconcentrator-GC–MS was used to analyze the effect of N addition on MT fluxes from the forest floors and litter.The results showed that under control treatment(without N addition),the total MT emission rates were 279.90±137.17 and 102.70±45.36 pmol m^(–2)s^(–1) in the PF and BF floors,respectively,withα-pinene being the largest MT species in the PF and limonene in the BF.α-pinene andβ-pinene emission rates decreased significantly in both forest floors after N addition,whereas a diverse trend was found for limonene and camphene in the PF floor.Furthermore,some MT fluxes showed significant negative correlations with soil respiration and soil temperature.Litter was important in MT fluxes from forest floors and its emission rates were enhanced by N addition.Moreover,different MT response to elevated N was found between the forest floor and litter.This study indicated that the elevated N deposition in the future would inhibit the MT emissions from the subtropical forest floor.展开更多
Hepatitis C virus(HCV)causes chronic infection in over 75%of the HCV-infected individuals,resulting in liver cancer in substantial patients.Since its discovery in 1989,HCV experiences a journey from discovery to cure,...Hepatitis C virus(HCV)causes chronic infection in over 75%of the HCV-infected individuals,resulting in liver cancer in substantial patients.Since its discovery in 1989,HCV experiences a journey from discovery to cure,largely due to the virology studies and success of direct antiviral agent(DAA)development.We reviewed the HCV research journey,from the discovery of this virus to the development of DAAs for cure.Learning the methodology used in HCV studies and the knowledge of developing DAAs against HCV may inspire the studies of other difficult-to-culture viruses,such as hepatitis E virus and norovirus,as well as the development of DAAs for other single-stranded positive-sense RNA viruses,including the pandemic-causing SARS-CoV-2 virus,which shares the common replication strategy of forming a membrane-bound viral replicase.展开更多
基金Supported by National Natural Science Foundation(31271647,31601245)Jilin Natural Science Foundation(20150101100JC)+1 种基金Key Scientific Achievement Conversion Project of Jilin Provincial Department of Science and Technology(20150307026NY)Key National Research and Development Program(2017YFD0201804-9)
文摘We took the iron-efficient and iron-inefficient soybean varieties with significant differences in iron efficiency as the test materials,in order to ascertain the relationship between the low iron stress and the iron efficiency of soybean varieties.The results showed that through the principal component analysis,it was found that the contribution rate of the shoot light energy absorption factor and root morphological factor was the highest,reaching 41.0% and 67.2%,respectively.According to the eigenvector with high absolute value for the two factors,it was found that improving photosynthesis and root surface area could help to improve the ability of soybean to resist low iron.From the dynamic simulation results of Logistic equation,both V and Vmof the shoot and root of iron-efficient varieties were higher than those of iron-inefficient varieties;the low iron treatment postponed the time of the root of iron-inefficient varieties to reach Vm,while the iron-efficient varieties were resistant to the damage caused by the low iron to growth by improving root V.However,when the iron concentration was 0 mM,regardless of iron-efficient varieties or iron-inefficient varieties,the shoot V,Vmand △t were all low,indicating that the division of different iron efficiency varieties was relative,not absolute,and the ability of plant to resist stress was not only determined by its own characteristics,but also closely related to the degree of stress.
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.
基金supported by the Shanghai Public Health Clinical Center(KY-GW2018-17)Shanghai Municipal Commission of Health and Family Planning(20174Y0099)。
文摘Coxsackievirus A10(CVA10)is one of the major etiological agents of hand,foot,and mouth disease.There are no vaccine and antiviral drugs for controlling CVA10 infection.Reverse genetic tools for CVA10 will benefit its mechanistic study and development of vaccines and antivirals.Here,two infectious clones for the prototype and a Myc-tagged CVA10 were constructed.Viable CVA10 viruses were harvested by transfecting the viral m RNA into human rhabdomyosarcoma(RD)cells.Rescued CVA10 was further confirmed by next generation sequencing and characterized experimentally.We also constructed the vectors for CVA10 subgenomic replicon with luciferase reporter and viral capsid with EGFP reporter,respectively.Co-transfection of the viral replicon RNA and capsid expresser in human embryonic kidney 293 T(HEK293 T)cells led to the production of single round infectious particles(SRIPs).Based on CVA10 replicon RNA,SRIPs with either the enterovirus A71(EVA71)capsid or the CVA10 capsid were generated.Infection by EVA71 SRIPs required SCARB2,while CVA10 SRIPs did not.Finally,we showed great improvement of the replicon activity and SRIPs production by insertion of a cis-active hammerhead ribozyme(HHRib)before the 50-untranslated region(UTR).In summary,reverse genetic tools for prototype strain of CVA10,including both the infectious clone and the SRIPs system,were successfully established.These tools will facilitate the basic and translational study of CVA10.
基金supported by the National Natural Science Foundation of China(31570170)the National Key Research and Development Program of China(2016YFC1200401)。
文摘The coronavirus disease 2019(COVID-19)pandemic caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2)is a global crisis.Clinical candidates with high efficacy,ready availability,and that do not develop resistance are in urgent need.Despite that screening to repurpose clinically approved drugs has provided a variety of hits shown to be effective against SARS-CoV-2 infection in cell culture,there are few confirmed antiviral candidates in vivo.In this study,94 compounds showing high antiviral activity against SARS-CoV-2 in Vero E6 cells were identified from 2,580 FDA-approved small-molecule drugs.Among them,24 compounds with low cytotoxicity were selected,and of these,17 compounds also effectively suppressed SARS-CoV-2 infection in He La cells transduced with human ACE2.Six compounds disturb multiple processes of the SARSCoV-2 life cycle.Their prophylactic efficacies were determined in vivo using Syrian hamsters challenged with SARS-CoV-2infection.Seven compounds reduced weight loss and promoted weight regain of hamsters infected not only with the original strain but also the D614G variant.Except for cisatracurium,six compounds reduced hamster pulmonary viral load,and IL-6 and TNF-αm RNAwhen assayed at 4 d postinfection.In particular,sertraline,salinomycin,and gilteritinib showed similar protective effects as remdesivir in vivo and did not induce antiviral drug resistance after 10 serial passages of SARS-CoV-2 in vitro,suggesting promising application for COVID-19 treatment.
基金supported by the National Natural Science Foundation of China (No. 40821003, 40971260)the Foundation for University by the Fujian Provincial Department of Science and Technology (No. 2008F5013)
文摘Carbonyl sulfide (COS) and dimethyl sulfide (DMS) fluxes from as urban Cynodon dactylon lawn and adjacent bare soil were measured during April-July 2005 in Guangzhou, China. Both the lawn and bare soil acted as sinks for COS and sources for DMS. The mean fluxes of COS and DMS in the lawn (-19.27 and 18.16 pmol/(m^2.sec), respectively) were significantly higher than those in the bare soil (-9.89 and 9.35 pmol/(m^A2.sec), respectively). Fluxes of COS and DMS in mowed lawn were also higher than those in bare soils. Both COS and DMS fluxes showed diurnal variation with detectable but much lower values in the nighttime than in the daytime. COS fluxes were related significantly to temperature and the optimal temperature for COS uptake was 29℃. While positive linear correlations were found between DMS fluxes and temperature. COS fluxes increased linearly with ambient COS mixing ratios, and had a compensation point of 336 ppt.
基金the National Natural Science Foundation of China(Grant Nos.41877326 and 41473083)。
文摘Monoterpenes(MTs)play crucial roles not only in atmospheric chemistry and global climate change but also in soil processes and soil ecology.Elevated nitrogen(N)deposition can influence soil microbial community and litter decomposition,and consequently alters MT fluxes from forest floors and litter.Yet,the responses of soil and litter MT to increased N deposition remain poorly understood and the influences of N addition are sometimes contradictory.In the present study,static chambers were placed in masson pine forest(PF)and in monsoon evergreen broad-leaf forest(BF)at Dinghushan,subtropical China.The preconcentrator-GC–MS was used to analyze the effect of N addition on MT fluxes from the forest floors and litter.The results showed that under control treatment(without N addition),the total MT emission rates were 279.90±137.17 and 102.70±45.36 pmol m^(–2)s^(–1) in the PF and BF floors,respectively,withα-pinene being the largest MT species in the PF and limonene in the BF.α-pinene andβ-pinene emission rates decreased significantly in both forest floors after N addition,whereas a diverse trend was found for limonene and camphene in the PF floor.Furthermore,some MT fluxes showed significant negative correlations with soil respiration and soil temperature.Litter was important in MT fluxes from forest floors and its emission rates were enhanced by N addition.Moreover,different MT response to elevated N was found between the forest floor and litter.This study indicated that the elevated N deposition in the future would inhibit the MT emissions from the subtropical forest floor.
基金This study is supported in part by the National Natural Science Foundation of China(No.81772181,No.81971926).
文摘Hepatitis C virus(HCV)causes chronic infection in over 75%of the HCV-infected individuals,resulting in liver cancer in substantial patients.Since its discovery in 1989,HCV experiences a journey from discovery to cure,largely due to the virology studies and success of direct antiviral agent(DAA)development.We reviewed the HCV research journey,from the discovery of this virus to the development of DAAs for cure.Learning the methodology used in HCV studies and the knowledge of developing DAAs against HCV may inspire the studies of other difficult-to-culture viruses,such as hepatitis E virus and norovirus,as well as the development of DAAs for other single-stranded positive-sense RNA viruses,including the pandemic-causing SARS-CoV-2 virus,which shares the common replication strategy of forming a membrane-bound viral replicase.