Chongqing Z County E-sports Town was once included in the“first batch of sports and leisure characteristic town pilot project list”issued by the General Administration of Sports of China.After several years of devel...Chongqing Z County E-sports Town was once included in the“first batch of sports and leisure characteristic town pilot project list”issued by the General Administration of Sports of China.After several years of development,the e-sports industry in Z County e-sports town has struggled with issues such as a limited market,low popularity,poor business performance,and a lack of income generation capabilities.These challenges have severely hindered the town’s development,resulting in its exclusion from the recent“Chongqing characteristic town list.”Under the requirements of new policies,it can no longer promote itself,attract investment,or undertake project construction under the name of a“characteristic town”and must undergo redevelopment.This paper employs case analysis and comparative investigation methods to conduct an in-depth empirical study on the development of Z County E-sports Town.It is proposed that under the new policy environment,the town should foster the deep integration of its existing e-sports industry and culture with tourism and agriculture,transforming Z County E-sports Town into a new characteristic tourist destination.The findings of this paper offer a reference for the development of similar towns facing stagnation and provide case support for the construction of tourist destinations featuring e-sports.展开更多
The main urban area of Chongqing is surrounded by two rivers and set against each other.With its unique waterfront landscape,it has the resource conditions to become a leisure tourism destination.Intending to enhance ...The main urban area of Chongqing is surrounded by two rivers and set against each other.With its unique waterfront landscape,it has the resource conditions to become a leisure tourism destination.Intending to enhance people’s happiness,improve city quality,and promote Chongqing’s main urban area to become a tourist destination,this paper finds out the existing problems in the construction of public outdoor leisure and fitness facilities on the two rivers and four banks of Chongqing’s main urban area through investigation and analysis based on relevant experiences at home and abroad,takes the value chain theory as the guidance,and to find solutions to the problem.On this basis,combined with the law of economic operation,this paper puts forward the guiding ideology,principles,development goals,functional orientation,and development path for the improvement of public outdoor leisure and fitness on two rivers and four banks in the main city of Chongqing,and accordingly puts forward the policy system and guarantee measures for its improvement.展开更多
Accurate and seamless auxiliary services in the power market can guarantee smooth and continuous power system operation. China’s new round of power system reform has entered a critical period, and reform implementati...Accurate and seamless auxiliary services in the power market can guarantee smooth and continuous power system operation. China’s new round of power system reform has entered a critical period, and reform implementation requires comprehensive improvements in the maturity of the supporting auxiliary service market. This study reviews the development status and evolution path of the European unified power market and the US regional power market, provides experience for the development of China’s regional power market, then identifies the key influencing factors of auxiliary service trading mechanism design in regional power markets. To analyze the rationality of the auxiliary service trading evaluation index, this paper established an evaluation model for assessing regional power markets. Using combined weight optimization, the gray correlation TOPSIS method was applied to comprehensively evaluate auxiliary service trading in the regional power market. Finally, the application of the proposed evaluation method was briefly analyzed to examine four regional power markets in China and evaluate the effectiveness of current market construction in different regions and provide suggestions for future market construction.展开更多
Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodie...Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodies.This highlights a critical need to discover new therapeutic agents to overcome the variants mutations.Despite the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants infection.Here,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 variants.The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron challenge.Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining normal.Furthermore,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron infection.Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection.展开更多
Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in e...Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.展开更多
Summary What is already known on this topic?Hemorrhagic fever with renal syndrome(HFRS)is endemic in Liaoning Province.Both Seoul and Hantaan virus are circulating in rodents,and epidemic outbreaks and sporadic cases ...Summary What is already known on this topic?Hemorrhagic fever with renal syndrome(HFRS)is endemic in Liaoning Province.Both Seoul and Hantaan virus are circulating in rodents,and epidemic outbreaks and sporadic cases have been recorded every year since the disease was recognized.展开更多
Two-dimensional(2D)Stiefel-Whitney insulator(SWI),which is characterized by the second Stiefel-Whitney class,is a class of topological phases with zero Berry curvature.As an intriguing topological state,it has been we...Two-dimensional(2D)Stiefel-Whitney insulator(SWI),which is characterized by the second Stiefel-Whitney class,is a class of topological phases with zero Berry curvature.As an intriguing topological state,it has been well studied in theory but seldom realized in realistic materials.Here we propose that a large class of liganded Xenes,i.e.,hydrogenated and halogenated 2D group-IV honeycomb lattices,are 2D SWIs.The nontrivial topology of liganded Xenes is identified by the bulk topological invariant and the existence of protected corner states.Moreover,the large and tunable bandgap(up to 3.5 eV)of liganded Xenes will facilitate the experimental characterization of the 2D SWI phase.Our findings not only provide abundant realistic material candidates that are experimentally feasible but also draw more fundamental research interest towards the topological physics associated with Stiefel-Whitney class in the absence of Berry curvature.展开更多
SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in China.SFTS wa...SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in China.SFTS was subsequently identified in South Korea and Japan in 2012.To explore themolecular evolution and genetic characteristics of this newly identified pathogen,we reported 72 whole genome sequences of SFTSV,and built a dataset of SFTSV genome sequences containing 292 L-segment,302 M-segment and 502 S-segment.We clearly divided SFTSV into six genotypes,Genotype A-F.It was found that genotype F was the dominant epidemic genotype of Japan,South Korea,and Zhejiang province of China.The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province,and Genotype F was the most primitive one.Henan,Hubei,and Anhui provinces which are located in Dabie Mountain area weremainly epidemic of Genotype A,which emerged relatively late but distributed widely.A total of 37 recombination events were identified,making SFTSV with a high recombination frequency(L segment 5.1%,Msegment 3.6%,S segment 0.8%)among negative-strand segmented RNA viruses.It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms.The reassortment virus and recombination in tick were both found for the first time.We also found many of genotype-specific mutation sites,7 of which could be considered as potential molecular marker for genotype classification.This study promoted a more comprehensive understanding of the phylogeny and origin,and the genetic diversity of SFTSV,and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.展开更多
Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular m...Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular mechanisms and host cellular factors required for SFTSV infection remain uncharacterized.Using a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV infection.An SNX11-KO HeLa cell line was established,and SFTSV replication was significantly reduced.The glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi apparatus.pH values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO cells.Overall,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11.Our study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery.展开更多
This study aimed to investigate the serological characteristics of Ebola virus(EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus di...This study aimed to investigate the serological characteristics of Ebola virus(EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease(EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction(RT-PCR) for viral RNA and enzyme-linked immunosorbent assay(ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1%(18/31) and 93.5%(29/31) of the confirmed EVD patients and in 3.8%(25/663) and 17.8%(118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV infection.The present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations.展开更多
Severe fever with thrombocytopenia syndrome(SFTS),caused by a novel identified bunyavirus SFTS virus(SFTSV),was an emerging viral infectious disease that was firstly reported in China.There are no licensed vaccines an...Severe fever with thrombocytopenia syndrome(SFTS),caused by a novel identified bunyavirus SFTS virus(SFTSV),was an emerging viral infectious disease that was firstly reported in China.There are no licensed vaccines and therapeutics against SFTSV currently.B‐Propiolactone(BPL)inactivated whole virions of SFTSV strain AH12 were prepared as experimental vaccine in different antigen dose with or without Al(OH)3 adjuvant.The experimental SFTS vaccine was a satisfying immunogen,which could efficiently trigger the development of high levels of SFTSV NP‐specific IgG antibodies and neutralizing antibodies against SFTSV Strain HB29 in BALB/c and C57/BL6 mice,and could induce SFTS virus‐specific cellular immune responses to a certain extent.A single dose of vaccine was immunogenically insufficient in BALB/c mice;the second and third dose resulted in significant boost in antibody response.The use of Al(OH)3 adjuvant resulted in higher antibody titers.The mediate‐dose of vaccine could induce as high and equivalent level of antibody titer as that of high‐dose.The experimental SFTS vaccine in mediate‐and high antigen dose with adjuvant resulted in solid protection of C57/BL6 mice against wild‐type SFTSV challenge with markedly accelerated virus clearance from blood and spleen compared with controls.The experimental SFTS vaccine prepared in this study could efficiently elicit virus specific humoral and cellular immune responses in both BALB/c and C57/BL6 mice,and could protect C57/BL6 mice against SFTS virus challenge.These results supplied evidence that inactivated vaccine was a promising vaccine candidate for the prevention of SFTSV infection.展开更多
What is already known about this topic?Severe fever with thrombocytopenia syndrome(SFTS)is a serious tick-borne disease in East Asia with high mortality,particularly affecting the elderly.Since its discovery in 2010,i...What is already known about this topic?Severe fever with thrombocytopenia syndrome(SFTS)is a serious tick-borne disease in East Asia with high mortality,particularly affecting the elderly.Since its discovery in 2010,inconsistencies in small-scale studies and the lack of decade-long research on antibody levels in large population samples after natural infection,along with the absence of an effective vaccine,highlight the need for large-scale,long-term data in highincidence regions of China.What is added by this report?This study of 1,410 serum samples from SFTS patients in high-incidence regions of China reveals that immunoglobulin M(IgM)levels peak at 8–14 days post-infection,declining to nearly undetectable levels by 180 days.Immunoglobulin G(IgG)and neutralizing antibodies(NAb)levels peak at 22–180 days,persisting up to 10 years.IgM levels correlate with viral load and various immune and coagulation parameters,with lower levels observed in fatal cases.During convalescence,elderly patients have lower IgG levels,whereas females exhibit higher IgG levels compared with males.What are the implications for public health practice?The study’s findings on long-term antibody dynamics in SFTS patients can significantly improve vaccine development,optimize therapy scheduling,inform public health policies,and enhance diagnostic tools,leading to better disease management and prevention in high-incidence areas.展开更多
基金Humanities and Social Sciences Research Planning Fund of the Ministry of Education of the People’s Republic of China“Research on the Application and Improvement of the PPP Model for the Construction of Sports and Leisure Characteristic Towns Based on Value Chain Theory”(Project No.18XJA890002)。
文摘Chongqing Z County E-sports Town was once included in the“first batch of sports and leisure characteristic town pilot project list”issued by the General Administration of Sports of China.After several years of development,the e-sports industry in Z County e-sports town has struggled with issues such as a limited market,low popularity,poor business performance,and a lack of income generation capabilities.These challenges have severely hindered the town’s development,resulting in its exclusion from the recent“Chongqing characteristic town list.”Under the requirements of new policies,it can no longer promote itself,attract investment,or undertake project construction under the name of a“characteristic town”and must undergo redevelopment.This paper employs case analysis and comparative investigation methods to conduct an in-depth empirical study on the development of Z County E-sports Town.It is proposed that under the new policy environment,the town should foster the deep integration of its existing e-sports industry and culture with tourism and agriculture,transforming Z County E-sports Town into a new characteristic tourist destination.The findings of this paper offer a reference for the development of similar towns facing stagnation and provide case support for the construction of tourist destinations featuring e-sports.
基金funded by the Humanities and Social Sciences Research Planning Fund of the Ministry of Education of the People’s Republic of China,entitled“Research on the Application and Improvement of PPP Model for the Construction of Sports and Leisure Characteristic Towns Based on Value Chain Theory”(Project No.18XJA890002).
文摘The main urban area of Chongqing is surrounded by two rivers and set against each other.With its unique waterfront landscape,it has the resource conditions to become a leisure tourism destination.Intending to enhance people’s happiness,improve city quality,and promote Chongqing’s main urban area to become a tourist destination,this paper finds out the existing problems in the construction of public outdoor leisure and fitness facilities on the two rivers and four banks of Chongqing’s main urban area through investigation and analysis based on relevant experiences at home and abroad,takes the value chain theory as the guidance,and to find solutions to the problem.On this basis,combined with the law of economic operation,this paper puts forward the guiding ideology,principles,development goals,functional orientation,and development path for the improvement of public outdoor leisure and fitness on two rivers and four banks in the main city of Chongqing,and accordingly puts forward the policy system and guarantee measures for its improvement.
基金supported by the Beijing Power Exchange Center (Study on the Medium and Long Term Time Division Transaction Mode and Balance Mechanism of Electric Power)supported by the National Natural Science Foundation of China(No. 72171082)。
文摘Accurate and seamless auxiliary services in the power market can guarantee smooth and continuous power system operation. China’s new round of power system reform has entered a critical period, and reform implementation requires comprehensive improvements in the maturity of the supporting auxiliary service market. This study reviews the development status and evolution path of the European unified power market and the US regional power market, provides experience for the development of China’s regional power market, then identifies the key influencing factors of auxiliary service trading mechanism design in regional power markets. To analyze the rationality of the auxiliary service trading evaluation index, this paper established an evaluation model for assessing regional power markets. Using combined weight optimization, the gray correlation TOPSIS method was applied to comprehensively evaluate auxiliary service trading in the regional power market. Finally, the application of the proposed evaluation method was briefly analyzed to examine four regional power markets in China and evaluate the effectiveness of current market construction in different regions and provide suggestions for future market construction.
基金supported by National Key Research and Development Program of China(2021YFC2600200,2017YFA0205100)。
文摘Multiple new variants of severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)have constantly emerged,as the delta and omicron variants,which have developed resistance to currently gained neutralizing antibodies.This highlights a critical need to discover new therapeutic agents to overcome the variants mutations.Despite the availability of vaccines against coronavirus disease 2019(COVID-19),the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-Co V-2 variants infection.Here,we show that the nasal delivery of two previously characterized broadly neutralizing antibodies(F61 and H121)protected K18-h ACE2 mice against lethal challenge with SARS-Co V-2 variants.The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain(WIV04)and multiple variants,including beta(B.1.351),delta(B.1.617.2),and omicron(B.1.1.529)at 200or 1000 TCID_(50),and the minimum antibody administration doses(5-1.25 mg/kg body weight)were also evaluated with delta and omicron challenge.Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 mg/kg body weight,and corresponding mice lung viral RNA showed negative,with almost all alveolar septa and cavities remaining normal.Furthermore,low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants,whereas the F61/H121 combination showed excellent results against omicron infection.Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-Co V-2 variants infection.
基金supported by the National Science and Technology Major Project(2018ZX10711-001)(2017YFA0205100)。
文摘Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2)has precipitated multiple variants resistant to therapeutic antibodies.In this study,12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries.Of them,two RBD-binding antibodies(F61 and H121)showed high-affinity neutralization against SARS-Co V-2,whereas three S2-target antibodies failed to neutralize SARS-Co V-2.Following structure analysis,F61 identified a linear epitope located in residues G446–S494,which overlapped with angiotensinconverting enzyme 2(ACE2)binding sites,while H121 recognized a conformational epitope located on the side face of RBD,outside from ACE2 binding domain.Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-Co V-2.Importantly,these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351,and reacted with mutations of N501 Y,E484 K,and L452 R,indicated that it may also neutralize the recent India endemic strain B.1.617.The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants,which mitigated the risk of viral escape.Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-Co V-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-Co V-2 variants.
基金This work was supported by National Mega-Projects for Infectious Disease(2016ZX 10004222-002,2018ZX10711001)National Key Research and Development Program of China(2016YFD0500303).
文摘Summary What is already known on this topic?Hemorrhagic fever with renal syndrome(HFRS)is endemic in Liaoning Province.Both Seoul and Hantaan virus are circulating in rodents,and epidemic outbreaks and sporadic cases have been recorded every year since the disease was recognized.
基金the National Natural Science Foundation of China(Grant No.12074006)the National Key Research and Development Program of China(No.2021YFA1401600)the start-up fund from Peking University.
文摘Two-dimensional(2D)Stiefel-Whitney insulator(SWI),which is characterized by the second Stiefel-Whitney class,is a class of topological phases with zero Berry curvature.As an intriguing topological state,it has been well studied in theory but seldom realized in realistic materials.Here we propose that a large class of liganded Xenes,i.e.,hydrogenated and halogenated 2D group-IV honeycomb lattices,are 2D SWIs.The nontrivial topology of liganded Xenes is identified by the bulk topological invariant and the existence of protected corner states.Moreover,the large and tunable bandgap(up to 3.5 eV)of liganded Xenes will facilitate the experimental characterization of the 2D SWI phase.Our findings not only provide abundant realistic material candidates that are experimentally feasible but also draw more fundamental research interest towards the topological physics associated with Stiefel-Whitney class in the absence of Berry curvature.
基金supported by the National Major Science and Technol-ogy Project of China(2018ZX10711001,2016ZX10004222-002)。
文摘SFTS virus(SFTSV)is a novel bunyavirus,which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome(SFTS)in China in 2009,and was now prevalent in at least 25 provinces in China.SFTS was subsequently identified in South Korea and Japan in 2012.To explore themolecular evolution and genetic characteristics of this newly identified pathogen,we reported 72 whole genome sequences of SFTSV,and built a dataset of SFTSV genome sequences containing 292 L-segment,302 M-segment and 502 S-segment.We clearly divided SFTSV into six genotypes,Genotype A-F.It was found that genotype F was the dominant epidemic genotype of Japan,South Korea,and Zhejiang province of China.The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province,and Genotype F was the most primitive one.Henan,Hubei,and Anhui provinces which are located in Dabie Mountain area weremainly epidemic of Genotype A,which emerged relatively late but distributed widely.A total of 37 recombination events were identified,making SFTSV with a high recombination frequency(L segment 5.1%,Msegment 3.6%,S segment 0.8%)among negative-strand segmented RNA viruses.It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms.The reassortment virus and recombination in tick were both found for the first time.We also found many of genotype-specific mutation sites,7 of which could be considered as potential molecular marker for genotype classification.This study promoted a more comprehensive understanding of the phylogeny and origin,and the genetic diversity of SFTSV,and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.
基金supported by the National Key Project for Infectious Disease from the Ministry of Science and Technology (Grant No. 2018ZX10711-001)
文摘Severe fever with thrombocytopenia syndrome virus(SFTSV)is a highly pathogenic tick-borne bunyavirus that causes lethal infectious disease and severe fever with thrombocytopenia syndrome(SFTS)in humans.The molecular mechanisms and host cellular factors required for SFTSV infection remain uncharacterized.Using a genome-wide CRISPR-based screening strategy,we identified a host cellular protein,sorting nexin 11(SNX11)which is involved in the intracellular endosomal trafficking pathway,as an essential cell factor for SFTSV infection.An SNX11-KO HeLa cell line was established,and SFTSV replication was significantly reduced.The glycoproteins of SFTSV were detected and remained in later endosomal compartments but were not detectable in the endoplasmic reticulum(ER)or Golgi apparatus.pH values in the endosomal compartments of the SNX11-KO cells increased compared with the pH of normal HeLa cells,and lysosomal-associated membrane protein 1(LAMP1)expression was significantly elevated in the SNX11-KO cells.Overall,these results indicated that penetration of SFTSV from the endolysosomes into the cytoplasm of host cells was blocked in the cells lacking SNX11.Our study for the first time provides insight into the important role of the SNX11 as an essential host factor in the intracellular trafficking and penetrating process of SFTSV infection via potential regulation of viral protein sorting,membrane fusion,and other endocytic machinery.
基金supported by National Mega project for Infectious Disease,Ministry of Science and technology(Grant Nos.2016ZX10004222-002,2016ZX10004222-003)National Natural Science Foundation of China(Grant Nos.81373141 and 81401312)National key project of Ebola research,National Natural Science Foundation of China(NSFC,Grant No.81590763)
文摘This study aimed to investigate the serological characteristics of Ebola virus(EBOV) infection during the late phase of the Ebola outbreak in Sierra Leone. In total, 877 blood samples from 694 suspected Ebola virus disease(EVD) cases assessed from March to December 2015, were analyzed via real-time reverse transcription polymerase chain reaction(RT-PCR) for viral RNA and enzyme-linked immunosorbent assay(ELISA) and Luminex to detect antibodies against EBOV. Viral load and EBOV-specific IgM/IgG titers displayed a declining trend during March to December 2015. Viral RNA load decreased rapidly at earlier stages after disease onset, while EBOV-specific IgM and IgG still persisted in 58.1%(18/31) and 93.5%(29/31) of the confirmed EVD patients and in 3.8%(25/663) and 17.8%(118/663) of the RNA-negative suspected patients in the later phase, respectively. Dynamic analysis of longitudinally collected samples from eight EVD patients revealed typically reversed trends of declining viral load and increasing IgM and/or IgG titers in response to the EBOV infection.The present results indicate that certain populations of Sierra Leone developed immunity to an EBOV infection in the late phase of the outbreak, providing novel insights into the risk assessment of EBOV infections among human populations.
基金This study was supported by the National Major Science and Technology Project of China(2018ZX10711001 and 2013ZX09102029)The funders had no role in study design,data collection and analysis,decision to publish,or preparation of the manuscript.
文摘Severe fever with thrombocytopenia syndrome(SFTS),caused by a novel identified bunyavirus SFTS virus(SFTSV),was an emerging viral infectious disease that was firstly reported in China.There are no licensed vaccines and therapeutics against SFTSV currently.B‐Propiolactone(BPL)inactivated whole virions of SFTSV strain AH12 were prepared as experimental vaccine in different antigen dose with or without Al(OH)3 adjuvant.The experimental SFTS vaccine was a satisfying immunogen,which could efficiently trigger the development of high levels of SFTSV NP‐specific IgG antibodies and neutralizing antibodies against SFTSV Strain HB29 in BALB/c and C57/BL6 mice,and could induce SFTS virus‐specific cellular immune responses to a certain extent.A single dose of vaccine was immunogenically insufficient in BALB/c mice;the second and third dose resulted in significant boost in antibody response.The use of Al(OH)3 adjuvant resulted in higher antibody titers.The mediate‐dose of vaccine could induce as high and equivalent level of antibody titer as that of high‐dose.The experimental SFTS vaccine in mediate‐and high antigen dose with adjuvant resulted in solid protection of C57/BL6 mice against wild‐type SFTSV challenge with markedly accelerated virus clearance from blood and spleen compared with controls.The experimental SFTS vaccine prepared in this study could efficiently elicit virus specific humoral and cellular immune responses in both BALB/c and C57/BL6 mice,and could protect C57/BL6 mice against SFTS virus challenge.These results supplied evidence that inactivated vaccine was a promising vaccine candidate for the prevention of SFTSV infection.
基金Supported by the National Key R&D Program of China(ZDYF-2022YFC2303402)the Young Scientists Fund of China CDC(CCDC-2022A104)the National Major Science and Technology Project of China(2018ZX10711001).
文摘What is already known about this topic?Severe fever with thrombocytopenia syndrome(SFTS)is a serious tick-borne disease in East Asia with high mortality,particularly affecting the elderly.Since its discovery in 2010,inconsistencies in small-scale studies and the lack of decade-long research on antibody levels in large population samples after natural infection,along with the absence of an effective vaccine,highlight the need for large-scale,long-term data in highincidence regions of China.What is added by this report?This study of 1,410 serum samples from SFTS patients in high-incidence regions of China reveals that immunoglobulin M(IgM)levels peak at 8–14 days post-infection,declining to nearly undetectable levels by 180 days.Immunoglobulin G(IgG)and neutralizing antibodies(NAb)levels peak at 22–180 days,persisting up to 10 years.IgM levels correlate with viral load and various immune and coagulation parameters,with lower levels observed in fatal cases.During convalescence,elderly patients have lower IgG levels,whereas females exhibit higher IgG levels compared with males.What are the implications for public health practice?The study’s findings on long-term antibody dynamics in SFTS patients can significantly improve vaccine development,optimize therapy scheduling,inform public health policies,and enhance diagnostic tools,leading to better disease management and prevention in high-incidence areas.