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
Efficiently enriching low-concentration CH4 is pivotal for enhancing the utilization of unconventional energy sources and mitigating greenhouse gas emissions.This study focuses on modifying the overall performance of ...Efficiently enriching low-concentration CH4 is pivotal for enhancing the utilization of unconventional energy sources and mitigating greenhouse gas emissions.This study focuses on modifying the overall performance of CH_(4)/N_(2)separation membranes.A novel mixed matrix membrane(MMM)with a reinforced substrate structure was developed through a straightforward dip-coating technique.This MMM incorporates a polytetrafluoroethylene(PTFE)porous membrane as the supporting framework,while a composite of block polymer(styrene-butadiene-styrene)and metal-organic framework(Ni-MOF-74)forms the selective separation layer.Comprehensive characterization of Ni-MOF-74 and the fabricatedmembranes was conducted using X-rays diffraction,scanning electron microscope,Brunauer-Emmett-Teller analysis,and gas permeance tests.The findings indicate a robust integration of the PTFE porous support with the membrane layer,enhancing the mechanical stability of theMMM.Under optimal conditions,the mechanical strength of the PM20 membrane(containing 20%Ni-MOF-74)was observed to be 37.7 MPa,representing remarkable increase compared to the non-reinforcedMMM.Additionally,thePM20membrane exhibited an impressive CH4 permeation rate of 92 barrer(1 barrer﹦3.35×10^(-16)mol·m·m^(-2)·s^(-1)·Pa^(-1))alongside a CH_(4)/N_(2)selectivity of 4.18.These results underscore the MMM's substantial performance and its promising potential in methane enrichment applications.展开更多
A novel liquid settling method was investigated and applied to fabricate TC4 spherical particle reinforced AZ91 alloy matrix composites.This method was called liquid state settling technique in which TC4 particles wou...A novel liquid settling method was investigated and applied to fabricate TC4 spherical particle reinforced AZ91 alloy matrix composites.This method was called liquid state settling technique in which TC4 particles would settle down under the force of gravity.High volume fraction(50%)particle reinforced AZ91 composites could be easily obtained via this novel method.This is difficult to achieve for other traditional liquid fabrication methods.In addition,there was a good dispersion of TC4 particles in the AZ91 matrix and no clusters were found,which indicate that this method was feasible.Interfacial reaction occurred and the reaction product was confirmed to be Al2Ti.Three kinds of pre-dispersion technologies were used before the settling process and different interfacial microstructures were found.Theoretical calculation and experimental results both indicated that the interfacial product which was embedded in the matrix strengthened the composites and improved the tensile strength.展开更多
Two-dimension （2D） fused-silica fiber reinforced porous silicon nitride matrix composites were fabricated using slurry impregnation and cyclic infiltration with colloidal silica sol. The microstructure and fracture ...Two-dimension （2D） fused-silica fiber reinforced porous silicon nitride matrix composites were fabricated using slurry impregnation and cyclic infiltration with colloidal silica sol. The microstructure and fracture surface were characterized by SEM, the mechanical behavior was investigated by three-point bending test, and the dielectric constant was also measured by impedance analysis. The microstructure showed that the fiber and the matrix had a physical bonding, forming a clearance interface. The mechanical behavior suggested that the porous matrix acted as crack deflection, and the fracture surface had a lot of fiber pull-out. However, the interlaminar shear strength was not so good. The dielectric constant of the composites at room temperature was about 2.8-3.1. The relatively low dielectric constant and non-catastrophic failure indicated the potential application in the radome materials field. 2008 University of Science and Technology Beijing. All rights reserved.展开更多
The selection of milling tools for Si C14Cu4Mg0.5Si based on Aluminium matrix 2A14 was analyzed, and the factors that affect the efficiency of the milling were discussed. The Si C14Cu4Mg0.5Si was designed for use on t...The selection of milling tools for Si C14Cu4Mg0.5Si based on Aluminium matrix 2A14 was analyzed, and the factors that affect the efficiency of the milling were discussed. The Si C14Cu4Mg0.5Si was designed for use on the moon landing vehicle or missile wings, but the hardness of aluminium-silicon carbide composite material was very high, much higher than the general hardness of cemented carbide, which will bring many difficulties in the aluminium-silicon carbide composite material processing. The chemical compositions of Si C14Cu4Mg0.5Si were analyzed. A new selected indexable cutter was designed to mill Si C14Cu4Mg0.5Si. The structure design of milling cutter was different from the conventional milling cutter, breaking the previous limitations to a certain extent, pioneering the idea. The tool material wear was detected by experiments. The mechanical and physical properties of Si C14Cu4Mg0.5Si were also tested. Si C14Cu4Mg0.5Si exhibited different surface quality characteristics under different milling tools.展开更多
In SiC（f）/Ti-6Al-4V composites, the microstructure of the matrix close to the fiber was different from that of the fiber-less material. Microstructure observations show that a layer of fine grains was located adjace...In SiC（f）/Ti-6Al-4V composites, the microstructure of the matrix close to the fiber was different from that of the fiber-less material. Microstructure observations show that a layer of fine grains was located adjacent to the fiber, and more dislocations and faults were found in this region. Higher recrystallization nucleation rate due to the undeformed SiC fiber and thermal residual stress induced during cooling from the fabrication temperature caused the microstructural changes of the matrix. Hardness measurement indicates that the matrix in the fiber neighborhood was strengthened, and the strengthening effect decreased with distance away from the fiber.展开更多
A sophisticated stir casting route to fabricate large scale AA6061-31%B4C composite was developed. Key process parameters were studied, microstructure and mechanical properties of the composite were investigated. The ...A sophisticated stir casting route to fabricate large scale AA6061-31%B4C composite was developed. Key process parameters were studied, microstructure and mechanical properties of the composite were investigated. The results indicated that vacuum stirring/casting, B4C/Mg feeding and ingots cooling were essential to the successful fabrication of AA6061-31%B4C composite. Chemical erosion examination verified the designed B4 C content; X-ray fluorescence spectrometer（XFS） showed the chemical composition of Mg and Si in the matrix conformed to industry standards; scanning electronic microscope（SEM） and X-ray diffraction（XRD） revealed that B4 C particles were evenly distributed in the composites with well dispersed Mg2Si precipitates. Tensile testing results showed that the AA6061-31%B4C composite had a tensile strength of 340 MPa, improved by 112.5% compared with AA1100-31%B4C composite, which is attributed to the enhanced strength of the matrix alloy.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financial support from the National Natural Science Foundation of China(52174229 and 52174230)the Natural Science Foundation of Liaoning Province(2022-KF-13-05)+1 种基金Fushun Revitalization Talents Program(FSYC202107010)the program funded by Liaoning Province Education Administration(LJKZ0411).
文摘Efficiently enriching low-concentration CH4 is pivotal for enhancing the utilization of unconventional energy sources and mitigating greenhouse gas emissions.This study focuses on modifying the overall performance of CH_(4)/N_(2)separation membranes.A novel mixed matrix membrane(MMM)with a reinforced substrate structure was developed through a straightforward dip-coating technique.This MMM incorporates a polytetrafluoroethylene(PTFE)porous membrane as the supporting framework,while a composite of block polymer(styrene-butadiene-styrene)and metal-organic framework(Ni-MOF-74)forms the selective separation layer.Comprehensive characterization of Ni-MOF-74 and the fabricatedmembranes was conducted using X-rays diffraction,scanning electron microscope,Brunauer-Emmett-Teller analysis,and gas permeance tests.The findings indicate a robust integration of the PTFE porous support with the membrane layer,enhancing the mechanical stability of theMMM.Under optimal conditions,the mechanical strength of the PM20 membrane(containing 20%Ni-MOF-74)was observed to be 37.7 MPa,representing remarkable increase compared to the non-reinforcedMMM.Additionally,thePM20membrane exhibited an impressive CH4 permeation rate of 92 barrer(1 barrer﹦3.35×10^(-16)mol·m·m^(-2)·s^(-1)·Pa^(-1))alongside a CH_(4)/N_(2)selectivity of 4.18.These results underscore the MMM's substantial performance and its promising potential in methane enrichment applications.
基金the National Natural Science Foundation of China(Grant No.51471059).
文摘A novel liquid settling method was investigated and applied to fabricate TC4 spherical particle reinforced AZ91 alloy matrix composites.This method was called liquid state settling technique in which TC4 particles would settle down under the force of gravity.High volume fraction(50%)particle reinforced AZ91 composites could be easily obtained via this novel method.This is difficult to achieve for other traditional liquid fabrication methods.In addition,there was a good dispersion of TC4 particles in the AZ91 matrix and no clusters were found,which indicate that this method was feasible.Interfacial reaction occurred and the reaction product was confirmed to be Al2Ti.Three kinds of pre-dispersion technologies were used before the settling process and different interfacial microstructures were found.Theoretical calculation and experimental results both indicated that the interfacial product which was embedded in the matrix strengthened the composites and improved the tensile strength.
基金the National Natural Science Foundation of China(No.90405015)the National Young Elitist Foundation(No.50425208).
文摘Two-dimension （2D） fused-silica fiber reinforced porous silicon nitride matrix composites were fabricated using slurry impregnation and cyclic infiltration with colloidal silica sol. The microstructure and fracture surface were characterized by SEM, the mechanical behavior was investigated by three-point bending test, and the dielectric constant was also measured by impedance analysis. The microstructure showed that the fiber and the matrix had a physical bonding, forming a clearance interface. The mechanical behavior suggested that the porous matrix acted as crack deflection, and the fracture surface had a lot of fiber pull-out. However, the interlaminar shear strength was not so good. The dielectric constant of the composites at room temperature was about 2.8-3.1. The relatively low dielectric constant and non-catastrophic failure indicated the potential application in the radome materials field. 2008 University of Science and Technology Beijing. All rights reserved.
基金Funded by the National Natural Science Foundation of China(Nos.51275490,and 51475346)Specialized Research Fund for the Doctoral Program of Higher Education of China(20131420120002)Shanxi Province Science Foundation(2013011025-1)
文摘The selection of milling tools for Si C14Cu4Mg0.5Si based on Aluminium matrix 2A14 was analyzed, and the factors that affect the efficiency of the milling were discussed. The Si C14Cu4Mg0.5Si was designed for use on the moon landing vehicle or missile wings, but the hardness of aluminium-silicon carbide composite material was very high, much higher than the general hardness of cemented carbide, which will bring many difficulties in the aluminium-silicon carbide composite material processing. The chemical compositions of Si C14Cu4Mg0.5Si were analyzed. A new selected indexable cutter was designed to mill Si C14Cu4Mg0.5Si. The structure design of milling cutter was different from the conventional milling cutter, breaking the previous limitations to a certain extent, pioneering the idea. The tool material wear was detected by experiments. The mechanical and physical properties of Si C14Cu4Mg0.5Si were also tested. Si C14Cu4Mg0.5Si exhibited different surface quality characteristics under different milling tools.
文摘In SiC（f）/Ti-6Al-4V composites, the microstructure of the matrix close to the fiber was different from that of the fiber-less material. Microstructure observations show that a layer of fine grains was located adjacent to the fiber, and more dislocations and faults were found in this region. Higher recrystallization nucleation rate due to the undeformed SiC fiber and thermal residual stress induced during cooling from the fabrication temperature caused the microstructural changes of the matrix. Hardness measurement indicates that the matrix in the fiber neighborhood was strengthened, and the strengthening effect decreased with distance away from the fiber.
基金founded by Joint Laboratory of Nuclear Materials and Service Safety (2013966003),China
文摘A sophisticated stir casting route to fabricate large scale AA6061-31%B4C composite was developed. Key process parameters were studied, microstructure and mechanical properties of the composite were investigated. The results indicated that vacuum stirring/casting, B4C/Mg feeding and ingots cooling were essential to the successful fabrication of AA6061-31%B4C composite. Chemical erosion examination verified the designed B4 C content; X-ray fluorescence spectrometer（XFS） showed the chemical composition of Mg and Si in the matrix conformed to industry standards; scanning electronic microscope（SEM） and X-ray diffraction（XRD） revealed that B4 C particles were evenly distributed in the composites with well dispersed Mg2Si precipitates. Tensile testing results showed that the AA6061-31%B4C composite had a tensile strength of 340 MPa, improved by 112.5% compared with AA1100-31%B4C composite, which is attributed to the enhanced strength of the matrix alloy.
