Coxsackievirus A16(CVA16),together with enterovirus type 71(EV71),is responsible for most cases of hand,foot and mouth disease(HFMD) worldwide.Recent findings suggest that the recombination between CVA16 and EV71,and ...Coxsackievirus A16(CVA16),together with enterovirus type 71(EV71),is responsible for most cases of hand,foot and mouth disease(HFMD) worldwide.Recent findings suggest that the recombination between CVA16 and EV71,and the co-circulation of these two viruses may have contributed to the increase of HFMD cases in China over the past few years.It is therefore important to further understand the virology,epidemiology,virus-host interactions and host pathogenesis of CVA16.In this study,we describe the viral kinetics of CVA16 in human rhabdomyosarcoma(RD) cells by analyzing the cytopathic effect(CPE),viral RNA replication,viral protein expression,viral RNA package and viral particle secretion in RD cells.We show that CVA16 appears to first attach,uncoat and enter into the host cell after adsorption for 1 h.Later on,CVA16 undergoes rapid replication from 3 to 6 h at MOI 1 and until 9 h at MOI 0.1.At MOI 0.1,CVA16 initiates a secondary infection as the virions were secreted before 9 h p.i.CPE was observed after 12 h p.i.,and viral antigen was first detected at 6 h p.i.at MOI 1 and at 9 h p.i.at MOI 0.1.Thus,our study provides important information for further investigation of CVA16 in order to better understand and ultimately control infections with this virus.展开更多
Assessing the iron and steel industry's(ISI)impact on climate change and environmental health is vital,particularly in China,where this sector significantly influences air quality and CO_(2)emissions.There is a la...Assessing the iron and steel industry's(ISI)impact on climate change and environmental health is vital,particularly in China,where this sector significantly influences air quality and CO_(2)emissions.There is a lack of comprehensive analyses that consider the environmental and health burdens of manufacturing processes for ISI enterprises.Here,we present an integrated emission inventory that encompasses air pollutants and CO_(2)emissions from 811 ISI enterprises and five key manufacturing processes in 2020.Our analysis shows that sintering is the primary source of air pollution in the ISI.It contributes 71%of SO_(2),73%of NO_(x),and 54%of PM_(2.5)emissions.On the other hand,81%of total CO_(2)emissions come from blast furnaces.Significantly,the contributions of ISI have resulted in an increase of 3.6 mg m^(-3)in national population-weighted PM_(2.5)concentration,causing approximately 59,035 premature deaths in 2020.Emissions from Hebei,Jiangsu,Shandong,Shanxi,and Inner Mongolia provinces contributed to 48%of PM_(2.5)-related deaths in China.Moreover,the transportation of air pollutants across provincial borders highlights a concerning trend of environmental health inequality.Based on the research findings,it is crucial for ISI manufacturers to prioritize the removal of outdated production capacities and adopt energy-efficient and advanced techniques,along with ultra-low emission technologies.This is particularly important for those manufacturers with substantial environmental footprints.These transformative actions are essential in mitigating the environmental and health impacts in the affected regions.展开更多
Black carbon(BC) has importance regarding aerosol composition, radiative balance, and human exposure. This study adopted a backward-trajectory approach to quantify the origins of BC from anthropogenic emissions(BCAn) ...Black carbon(BC) has importance regarding aerosol composition, radiative balance, and human exposure. This study adopted a backward-trajectory approach to quantify the origins of BC from anthropogenic emissions(BCAn) and open biomass burning(BCBB) transported to Xishuangbanna in 2017. Haze months, between haze and clean months, and clean months in Xishuangbanna were defined according to daily PM_(2.5)concentrations of >75, 35–75, and<35 μg/m^(3), respectively. Results showed that the transport efficiency density(TED) of BC transported to Xishuangbanna was controlled by the prevailing winds in different seasons.The yearly contributions to the effective emission intensity of BCAnand BCBBtransported to Xishuangbanna were 52% and 48%, respectively. However, when haze occurred in Xishuangbanna, the average BCAnand BCBBcontributions were 23% and 77%, respectively. This suggests that open biomass burning(BB) becomes the dominant source in haze months. Myanmar, India, and Laos were the dominant source regions of BC transported to Xishuangbanna during haze months, accounting for 59%, 18%, and 13% of the total, respectively. Furthermore, India was identified as the most important source regions of BCAntransported to Xishuangbanna in haze months, accounting for 14%. The two countries making the greatest contributions to BCBBtransported to Xishuangbanna were Myanmar and Laos in haze months, accounting for 55% and 13%, respectively. BC emissions from Xishuangbanna had minimal effects on the results of the present study. It is suggested that open BB in Myanmar and Laos, and anthropogenic emissions in India were responsible for poor air quality in Xishuangbanna.展开更多
Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral...Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated.In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrep^(TM) density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27 a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies.展开更多
The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate thi...The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate this issue,we developed a myristoylation-deficient virus and reporter(luciferase)pseudovirus with a Gly-to-Ala mutation(G2A)on EV71 VP4.When transfecting the EV71-G2 A genome encoding plasmid in cells,the loss of myristoylation on VP4 did not affect the expression of viral proteins and the virus morphology,however,it did significantly influence viral infectivity.Further,in myristoylation-deficient reporter pseudovirus-infected cells,the luciferase activity and viral genome RNA decreased significantly as compared to that of wild type virus;however,cytopathic effect and viral capsid proteins were not detected in myristoylation-deficient virus-infected cells.Also,although myristoylation-deficient viral RNA and proteins were detected in the second blind passage of infection,they were much fewer in number compared to that of the wild type virus.The replication of genomic RNA and negative-strand viral RNA were both blocked in myristoylation-deficient viruses,suggesting that myristoylation affects viral genome RNA release from capsid to cytoplasm.Besides,loss of myristoylation on VP4 altered the distribution of VP4-green fluorescent protein protein,which disappeared from the membrane structure fraction.Finally,a liposome leakage assay showed that EV71 myristoylation mediates the permeability of the model membrane.Hence,the amino-terminal myristoylation of VP4 is pivotal to EV71 infection and capsidmembrane structure interaction.This study provides novel molecular mechanisms regarding EV71 infection and potential molecular targets for antiviral drug design.展开更多
Based on the activity level and technical information of coal-fired power-generating units(CFPGU)obtained in China from 2011 to 2015,we,1)analyzed the time and spatial distribution of SO_(2) and NOx emission performan...Based on the activity level and technical information of coal-fired power-generating units(CFPGU)obtained in China from 2011 to 2015,we,1)analyzed the time and spatial distribution of SO_(2) and NOx emission performance of CFPGUs in China;2)studied the impact of installed capacity,sulfur content of coal combustion,and unit operation starting time on CFPGUs’pollutant emission performance;and 3)proposed the SO_(2) and NOx emission performance standards for coal-fired power plants based on the best available control technology.Our results show that:1)the larger the capacity of a CFPGU,the higher the control level and the faster the improvement;2)the CFPGUs in the developed eastern regions had significantly lower SO_(2) and NOx emission performance values than those in other provinces due to better economic and technological development and higher environmental management levels;3)the SO_(2) and NOx emission performance of the Chinese thermal power industry was significantly affected by the single-unit capacity,coal sulfur content,and unit operation starting time;and 4)based on the achievability analysis of best available pollution control technology,we believe that the CFPGUs’SO_(2) emission performance reference values should be 0.34 g/kWh for active units in general areas,0.8 g/kWh for active units in high-sulfur coal areas,and 0.13 g/kWh for newly built units and active units in key areas.In addition,the NOx emission performance reference values should be 0.35 g/kWh for active units in general areas and 0.175 g/kWh for new units and active units in key areas.展开更多
Background: Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or...Background: Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated.Methods: Immunoblotting, real-time polymerase chain reaction,in vivo/in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4^(+) T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data).Results: The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression (r= 0.5110) and CD4^(+) T-cell counts (r= 0.5083) in HIV-1-infected patients.Conclusions: USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.展开更多
基金Partly supported by the National Natural Science Foundation of China (No. 20872048)
文摘Coxsackievirus A16(CVA16),together with enterovirus type 71(EV71),is responsible for most cases of hand,foot and mouth disease(HFMD) worldwide.Recent findings suggest that the recombination between CVA16 and EV71,and the co-circulation of these two viruses may have contributed to the increase of HFMD cases in China over the past few years.It is therefore important to further understand the virology,epidemiology,virus-host interactions and host pathogenesis of CVA16.In this study,we describe the viral kinetics of CVA16 in human rhabdomyosarcoma(RD) cells by analyzing the cytopathic effect(CPE),viral RNA replication,viral protein expression,viral RNA package and viral particle secretion in RD cells.We show that CVA16 appears to first attach,uncoat and enter into the host cell after adsorption for 1 h.Later on,CVA16 undergoes rapid replication from 3 to 6 h at MOI 1 and until 9 h at MOI 0.1.At MOI 0.1,CVA16 initiates a secondary infection as the virions were secreted before 9 h p.i.CPE was observed after 12 h p.i.,and viral antigen was first detected at 6 h p.i.at MOI 1 and at 9 h p.i.at MOI 0.1.Thus,our study provides important information for further investigation of CVA16 in order to better understand and ultimately control infections with this virus.
基金supported by the National Natural Science Foundation of China[Grant No.72174126,72243008].
文摘Assessing the iron and steel industry's(ISI)impact on climate change and environmental health is vital,particularly in China,where this sector significantly influences air quality and CO_(2)emissions.There is a lack of comprehensive analyses that consider the environmental and health burdens of manufacturing processes for ISI enterprises.Here,we present an integrated emission inventory that encompasses air pollutants and CO_(2)emissions from 811 ISI enterprises and five key manufacturing processes in 2020.Our analysis shows that sintering is the primary source of air pollution in the ISI.It contributes 71%of SO_(2),73%of NO_(x),and 54%of PM_(2.5)emissions.On the other hand,81%of total CO_(2)emissions come from blast furnaces.Significantly,the contributions of ISI have resulted in an increase of 3.6 mg m^(-3)in national population-weighted PM_(2.5)concentration,causing approximately 59,035 premature deaths in 2020.Emissions from Hebei,Jiangsu,Shandong,Shanxi,and Inner Mongolia provinces contributed to 48%of PM_(2.5)-related deaths in China.Moreover,the transportation of air pollutants across provincial borders highlights a concerning trend of environmental health inequality.Based on the research findings,it is crucial for ISI manufacturers to prioritize the removal of outdated production capacities and adopt energy-efficient and advanced techniques,along with ultra-low emission technologies.This is particularly important for those manufacturers with substantial environmental footprints.These transformative actions are essential in mitigating the environmental and health impacts in the affected regions.
基金supported by the National Natural Science Foundation of China (Nos. 41705109 and 41805098)State Environmental Protection Key Laboratory of Sources and Control of Air Pollution Complex (No. SCAPC_(2)02001)+1 种基金State Key Laboratory of Severe Weather & Key Laboratory for Atmospheric Chemistry (No. 2018B04)Tsinghua National Laboratory for Information Science and Technology。
文摘Black carbon(BC) has importance regarding aerosol composition, radiative balance, and human exposure. This study adopted a backward-trajectory approach to quantify the origins of BC from anthropogenic emissions(BCAn) and open biomass burning(BCBB) transported to Xishuangbanna in 2017. Haze months, between haze and clean months, and clean months in Xishuangbanna were defined according to daily PM_(2.5)concentrations of >75, 35–75, and<35 μg/m^(3), respectively. Results showed that the transport efficiency density(TED) of BC transported to Xishuangbanna was controlled by the prevailing winds in different seasons.The yearly contributions to the effective emission intensity of BCAnand BCBBtransported to Xishuangbanna were 52% and 48%, respectively. However, when haze occurred in Xishuangbanna, the average BCAnand BCBBcontributions were 23% and 77%, respectively. This suggests that open biomass burning(BB) becomes the dominant source in haze months. Myanmar, India, and Laos were the dominant source regions of BC transported to Xishuangbanna during haze months, accounting for 59%, 18%, and 13% of the total, respectively. Furthermore, India was identified as the most important source regions of BCAntransported to Xishuangbanna in haze months, accounting for 14%. The two countries making the greatest contributions to BCBBtransported to Xishuangbanna were Myanmar and Laos in haze months, accounting for 55% and 13%, respectively. BC emissions from Xishuangbanna had minimal effects on the results of the present study. It is suggested that open BB in Myanmar and Laos, and anthropogenic emissions in India were responsible for poor air quality in Xishuangbanna.
基金supported by the National Natural Science Foundation of China (Grant No. 31770184)Construction Project of Provincial-School of Jilin Province (No. 440050316A28)
文摘Exosomes are cell-derived vesicles that are secreted by many eukaryotic cells. It has recently attracted attention as vehicles of intercellular communication. Virus-infected cells release exosomes, which contain viral proteins, RNA, and pathogenic molecules. However, the role of exosomes in virus infection process remains unclear and needs to be further investigated.In this study, we aimed to evaluate the effects of exosomes on rabies virus infection. OptiPrep^(TM) density gradient centrifugation was used to isolate exosomes from rabies virus-infected cell culture supernatants. A rabies virus G protein enzyme-linked immunosorbent assay and acetylcholinesterase activity assays were performed to verify the centrifugation fractions. Exosomes were then characterized using transmission electron microscopy and Western blotting. Our results showed that rabies virus infection increased the release of exosomes. Treatment with GW4869 and si-Rab27 a, two exosomal secretion inhibitors, inhibited exosome release. Furthermore, the inhibitors reduced the levels of extracellular and intracellular viral RNA. These data indicated that exosomes may participate in the viral infection process. Moreover, our results establish a basis for future research into the roles of exosomes in rabies virus infection and as potential targets for developing new antiviral strategies.
基金supported by the National Natural Science Foundation of China(Grant No.31770184)
文摘The Enterovirus 71(EV71)VP4 is co-translationally linked to myristic acid at its amino-terminal glycine residue.However,the role of this myristoylation in the EV71 life cycle remains largely unknown.To investigate this issue,we developed a myristoylation-deficient virus and reporter(luciferase)pseudovirus with a Gly-to-Ala mutation(G2A)on EV71 VP4.When transfecting the EV71-G2 A genome encoding plasmid in cells,the loss of myristoylation on VP4 did not affect the expression of viral proteins and the virus morphology,however,it did significantly influence viral infectivity.Further,in myristoylation-deficient reporter pseudovirus-infected cells,the luciferase activity and viral genome RNA decreased significantly as compared to that of wild type virus;however,cytopathic effect and viral capsid proteins were not detected in myristoylation-deficient virus-infected cells.Also,although myristoylation-deficient viral RNA and proteins were detected in the second blind passage of infection,they were much fewer in number compared to that of the wild type virus.The replication of genomic RNA and negative-strand viral RNA were both blocked in myristoylation-deficient viruses,suggesting that myristoylation affects viral genome RNA release from capsid to cytoplasm.Besides,loss of myristoylation on VP4 altered the distribution of VP4-green fluorescent protein protein,which disappeared from the membrane structure fraction.Finally,a liposome leakage assay showed that EV71 myristoylation mediates the permeability of the model membrane.Hence,the amino-terminal myristoylation of VP4 is pivotal to EV71 infection and capsidmembrane structure interaction.This study provides novel molecular mechanisms regarding EV71 infection and potential molecular targets for antiviral drug design.
基金supported by the National Key Research and Development Plan(No.2016YFC0208400).
文摘Based on the activity level and technical information of coal-fired power-generating units(CFPGU)obtained in China from 2011 to 2015,we,1)analyzed the time and spatial distribution of SO_(2) and NOx emission performance of CFPGUs in China;2)studied the impact of installed capacity,sulfur content of coal combustion,and unit operation starting time on CFPGUs’pollutant emission performance;and 3)proposed the SO_(2) and NOx emission performance standards for coal-fired power plants based on the best available control technology.Our results show that:1)the larger the capacity of a CFPGU,the higher the control level and the faster the improvement;2)the CFPGUs in the developed eastern regions had significantly lower SO_(2) and NOx emission performance values than those in other provinces due to better economic and technological development and higher environmental management levels;3)the SO_(2) and NOx emission performance of the Chinese thermal power industry was significantly affected by the single-unit capacity,coal sulfur content,and unit operation starting time;and 4)based on the achievability analysis of best available pollution control technology,we believe that the CFPGUs’SO_(2) emission performance reference values should be 0.34 g/kWh for active units in general areas,0.8 g/kWh for active units in high-sulfur coal areas,and 0.13 g/kWh for newly built units and active units in key areas.In addition,the NOx emission performance reference values should be 0.35 g/kWh for active units in general areas and 0.175 g/kWh for new units and active units in key areas.
基金This work was supported in part by,grants from the National Key R&D Program of China(Nos.2021YFC2301900 and 2301904)the National Natural Science Foundation of China(Nos.81930062,81672004 to ZWY,and 31900457,82272304 to GWY)+2 种基金the Science and Technology Department,of Jilin_Province,(Nos.20190101003JH,20200201422JC,20190201272JC,YDZJ202201ZYTS671,and YDZJ202201ZYTS590)Program of Jilin Finance Department(No.2019SRCJ017)the Key Laboratory of Molecular Virology,Jilin Province(No.20102209).
文摘Background: Ubiquitination plays an essential role in many biological processes, including viral infection, and can be reversed by deubiquitinating enzymes (DUBs). Although some studies discovered that DUBs inhibit or enhance viral infection by various mechanisms, there is lack of information on the role of DUBs in virus regulation, which needs to be further investigated.Methods: Immunoblotting, real-time polymerase chain reaction,in vivo/in vitro deubiquitination, protein immunoprecipitation, immunofluorescence, and co-localization biological techniques were employed to examine the effect of ubiquitin-specific protease 3 (USP3) on APOBEC3G (A3G) stability and human immunodeficiency virus (HIV) replication. To analyse the relationship between USP3 and HIV disease progression, we recruited 20 HIV-infected patients to detect the levels of USP3 and A3G in peripheral blood and analysed their correlation with CD4^(+) T-cell counts. Correlation was estimated by Pearson correlation coefficients (for parametric data).Results: The results demonstrated that USP3 specifically inhibits HIV-1 replication in an A3G-dependent manner. Further investigation found that USP3 stabilized 90% to 95% of A3G expression by deubiquitinating Vif-mediated polyubiquitination and blocking its degradation in an enzyme-dependent manner. It also enhances the A3G messenger RNA (mRNA) level by binding to A3G mRNA and stabilizing it in an enzyme-independent manner. Moreover, USP3 expression was positively correlated with A3G expression (r= 0.5110) and CD4^(+) T-cell counts (r= 0.5083) in HIV-1-infected patients.Conclusions: USP3 restricts HIV-1 viral infections by increasing the expression of the antiviral factor A3G. Therefore, USP3 may be an important target for drug development and serve as a novel therapeutic strategy against viral infections.
