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
Acoustic emission(AE)source localization is a fundamental element of rock fracture damage imaging.To improve the efficiency and accuracy of AE source localization,this paper proposes a joint method comprising a three-...Acoustic emission(AE)source localization is a fundamental element of rock fracture damage imaging.To improve the efficiency and accuracy of AE source localization,this paper proposes a joint method comprising a three-dimensional(3D)AE source localization simplex method and grid search scanning.Using the concept of the geometry of simplexes,tetrahedral iterations were first conducted to narrow down the suspected source region.This is followed by a process of meshing the region and node searching to scan for optimal solutions,until the source location is determined.The resulting algorithm was tested using the artificial excitation source localization and uniaxial compression tests,after which the localization results were compared with the simplex and exhaustive methods.The results revealed that the localization obtained using the proposed method is more stable and can be effectively avoided compared with the simplex localization method.Furthermore,compared with the global scanning method,the proposed method is more efficient,with an average time of 10%–20%of the global scanning localization algorithm.Thus,the proposed algorithm is of great significance for laboratory research focused on locating rupture damages sustained by large-sized rock masses or test blocks.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.
基金supported by the Natural Science Foundation of Henan Province(No.222300420596)China Railway Science and Technology Innovation Program Funded Project(CZ02-Special-03)Science and Technology Innovation Project funded by China Railway Tunnel Group(Tunnel Research 2021-03)。
文摘Acoustic emission(AE)source localization is a fundamental element of rock fracture damage imaging.To improve the efficiency and accuracy of AE source localization,this paper proposes a joint method comprising a three-dimensional(3D)AE source localization simplex method and grid search scanning.Using the concept of the geometry of simplexes,tetrahedral iterations were first conducted to narrow down the suspected source region.This is followed by a process of meshing the region and node searching to scan for optimal solutions,until the source location is determined.The resulting algorithm was tested using the artificial excitation source localization and uniaxial compression tests,after which the localization results were compared with the simplex and exhaustive methods.The results revealed that the localization obtained using the proposed method is more stable and can be effectively avoided compared with the simplex localization method.Furthermore,compared with the global scanning method,the proposed method is more efficient,with an average time of 10%–20%of the global scanning localization algorithm.Thus,the proposed algorithm is of great significance for laboratory research focused on locating rupture damages sustained by large-sized rock masses or test blocks.
