BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene ma...BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.展开更多
Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of...Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of the virus in 1994,resulting in a total of 37 equine cases and six human cases. All human cases have been attributed to exposure to infected horses;there is no evidence of bat-to-human or human-to-human transmission. Low infectivity and a high case fatality rate are features of Hendra virus infection in both horses and humans. The temporal pattern of spillover events suggests seasonal factors(plausibly be environmental,biological or ecological) as the proximate triggers for spillover. Minimisation of the future occurrence and impact of Hendra virus infections requires an understanding of the ecology of flying foxes,of virus infection dynamics in flying foxes,and of the factors that promote spillover. Management strategies seek to minimize the opportunity for effective contact between bats and horses,and limit potential horse-to-horse and horse-to-human transmission. Incomplete knowledge of the ecology of the virus,of the proximate factors associated with spillover,and the inherent difficulties of effectively managing wild populations,preclude a management approach targeted at bats.展开更多
Migratory birds are considered natural reservoirs of avian influenza A viruses(AIVs).To further our viral ecology knowledge and understand the subsequent risk posed by wild birds,we conducted a 4-year surveillance stu...Migratory birds are considered natural reservoirs of avian influenza A viruses(AIVs).To further our viral ecology knowledge and understand the subsequent risk posed by wild birds,we conducted a 4-year surveillance study of AIVs in the bird wintering wetlands of the Yangtze River,China.We collected over8000 samples and isolated 122 AIV strains.Analyses were then carried out with 108 novel sequenced genomes and data were deposited in GISAID and other public databases.The results showed that the Yangtze River wintering wetlands functioned as a mixing ground,where various subtypes of AIVs were detected harboring a high diversity of nucleotide sequences;moreover,a portion of AIV gene segments were persistent inter-seasonally.Phylogenetic incongruence presented complex reassortment events and distinct patterns among various subtypes.In addition,we observed that viral gene segments in wintering wetlands were closely related to known North American isolates,indicating that intercontinental gene flow occurred.Notably,highly pathogenic H5 and low pathogenic H9 viruses,which usually circulate in poultry,were found to have crossed the poultry/wild bird interface,with the viruses introduced to wintering birds.Overall,this study represented the largest AIV surveillance effort of wild birds within the Yangtze River wintering wetlands.Surveillance data highlighted the important role of wintering wild birds in the ecology of AIVs and may enable future early warnings of novel AIV emergence.展开更多
Using the viruses to sustainable control forest pest insects were reviewed in this paper. And the status of forest pest insects and bio-control technique in China were introduced. The criterion of stable ecological sy...Using the viruses to sustainable control forest pest insects were reviewed in this paper. And the status of forest pest insects and bio-control technique in China were introduced. The criterion of stable ecological system and the methods of restoration and construction were also analyzed. Meanwhile, the experiment in which 4 species of insect viruses were used and successfully control the forest pest insects persistently indicate that the insect viruses play an important role in restoring and constructing stable forest ecology system.展开更多
Electron microscopy(EM) should be used in the front line for detection of agents in emergencies and bioterrorism,on accounts of its speed and accuracy.However,the number of EM diagnostic laboratories has decreased con...Electron microscopy(EM) should be used in the front line for detection of agents in emergencies and bioterrorism,on accounts of its speed and accuracy.However,the number of EM diagnostic laboratories has decreased considerably and an increasing number of people encounter difficulties with EM results.Therefore,the research on viral structure and morphology has become important in EM diagnostic practice.EM has several technological advantages,and should be a fundamental tool in clinical diagnosis of viruses,particularly when agents are unknown or unsuspected.In this article,we review the historical contribution of EM to virology,and its use in virus differentiation,localization of specific virus antigens,virus-cell interaction,and viral morphogenesis.It is essential that EM investigations are based on clinical and comprehensive pathogenesis data from light or confocal microscopy.Furthermore,avoidance of artifacts or false results is necessary to exploit fully the advantages while minimizing its limitations.展开更多
文摘BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.
文摘Hendra virus,a novel member of the family Paramyxovirus that has emerged from bats in Australia,causes fatal disease in livestock and humans. Eleven spillover events have been identified since the first description of the virus in 1994,resulting in a total of 37 equine cases and six human cases. All human cases have been attributed to exposure to infected horses;there is no evidence of bat-to-human or human-to-human transmission. Low infectivity and a high case fatality rate are features of Hendra virus infection in both horses and humans. The temporal pattern of spillover events suggests seasonal factors(plausibly be environmental,biological or ecological) as the proximate triggers for spillover. Minimisation of the future occurrence and impact of Hendra virus infections requires an understanding of the ecology of flying foxes,of virus infection dynamics in flying foxes,and of the factors that promote spillover. Management strategies seek to minimize the opportunity for effective contact between bats and horses,and limit potential horse-to-horse and horse-to-human transmission. Incomplete knowledge of the ecology of the virus,of the proximate factors associated with spillover,and the inherent difficulties of effectively managing wild populations,preclude a management approach targeted at bats.
基金supported by the National Natural Science Foundation of China(81961138013,31570026,31970174,31970548,and 32061123001)the National Mega Project on Major Infectious Disease Prevention(2017ZX10103005-005)+1 种基金the Special Project of Ministry of Science and Technology(2013FY113500)the Russian Foundation for Basic Research—National Natural Science Foundation of China Collaboration Fund(19-54-55004)。
文摘Migratory birds are considered natural reservoirs of avian influenza A viruses(AIVs).To further our viral ecology knowledge and understand the subsequent risk posed by wild birds,we conducted a 4-year surveillance study of AIVs in the bird wintering wetlands of the Yangtze River,China.We collected over8000 samples and isolated 122 AIV strains.Analyses were then carried out with 108 novel sequenced genomes and data were deposited in GISAID and other public databases.The results showed that the Yangtze River wintering wetlands functioned as a mixing ground,where various subtypes of AIVs were detected harboring a high diversity of nucleotide sequences;moreover,a portion of AIV gene segments were persistent inter-seasonally.Phylogenetic incongruence presented complex reassortment events and distinct patterns among various subtypes.In addition,we observed that viral gene segments in wintering wetlands were closely related to known North American isolates,indicating that intercontinental gene flow occurred.Notably,highly pathogenic H5 and low pathogenic H9 viruses,which usually circulate in poultry,were found to have crossed the poultry/wild bird interface,with the viruses introduced to wintering birds.Overall,this study represented the largest AIV surveillance effort of wild birds within the Yangtze River wintering wetlands.Surveillance data highlighted the important role of wintering wild birds in the ecology of AIVs and may enable future early warnings of novel AIV emergence.
基金National Natural Sciences Fund Project (30671688)
文摘Using the viruses to sustainable control forest pest insects were reviewed in this paper. And the status of forest pest insects and bio-control technique in China were introduced. The criterion of stable ecological system and the methods of restoration and construction were also analyzed. Meanwhile, the experiment in which 4 species of insect viruses were used and successfully control the forest pest insects persistently indicate that the insect viruses play an important role in restoring and constructing stable forest ecology system.
基金supported by the Major Scientific and Technological Special Project of China(2009ZX10004-216)the National Natural Science Foundation of China(81100809,81271417)Fundamental Research Funds for the Central University of China(2011JBM124)
文摘Electron microscopy(EM) should be used in the front line for detection of agents in emergencies and bioterrorism,on accounts of its speed and accuracy.However,the number of EM diagnostic laboratories has decreased considerably and an increasing number of people encounter difficulties with EM results.Therefore,the research on viral structure and morphology has become important in EM diagnostic practice.EM has several technological advantages,and should be a fundamental tool in clinical diagnosis of viruses,particularly when agents are unknown or unsuspected.In this article,we review the historical contribution of EM to virology,and its use in virus differentiation,localization of specific virus antigens,virus-cell interaction,and viral morphogenesis.It is essential that EM investigations are based on clinical and comprehensive pathogenesis data from light or confocal microscopy.Furthermore,avoidance of artifacts or false results is necessary to exploit fully the advantages while minimizing its limitations.
