Both a conventional flow distributer and an improved one with a flow buffer were applied respectively during the high pressure die casting(HPDC)process,and samples of AZ91D magnesium alloy with different microstructur...Both a conventional flow distributer and an improved one with a flow buffer were applied respectively during the high pressure die casting(HPDC)process,and samples of AZ91D magnesium alloy with different microstructure mainly consisting ofα-Mg grains,β-phase and porosities were obtained.According to the grain orientation analysis,the predominant deformation behavior inα-Mg grains was dislocation slip,supplemented by deformation twinning.Dislocation slip was more difficult to occur in the samples with the improved flow distributer on account of the fact that the size ofα-Mg grains in the microstructure was finer and more uniform.During the in situ tensile deformation test,cracks were observed to initiate from gas-shrinkage pore and island-shrinkage,and two main crack propagation mechanisms,porosity growth and coalescence were found accordingly.When the crack was in contact with theβ-phase,it would pass through and fracture the networkβ-phase,whereas bypass the islandβ-phase by detaching it from the surroundingα-Mg grains.Mechanical property tests showed that the samples with relatively more homogeneous microstructure would perform higher mechanical properties,which was the combined effect of matrixα-Mg grains,β-phase,and porosities.展开更多
Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide.Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs.Nevertheless,...Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide.Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs.Nevertheless,the adaptive immune responses of subunit vaccines are still unfavorable,which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design.An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy.In this review,we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration.The engineered subunit vaccines with lymph node and specific cell targeting ability,antigen cross-presentation,T cell activation properties,and tailorable antigen release patterns may achieve effective immune protection with high precision,efficiency,and stability.We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.展开更多
The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictab...The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical translation.Herein,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce self-assembly.Furthermore,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune response.The synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen cross-presentation.In virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and adjuvants.In vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing mice.These results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.展开更多
基金financially the National Natural Science Foundation of China(No.51805389)Natural Science Foundation of Hubei Province of China(No.2018CFB210)111 Project(B17034)。
文摘Both a conventional flow distributer and an improved one with a flow buffer were applied respectively during the high pressure die casting(HPDC)process,and samples of AZ91D magnesium alloy with different microstructure mainly consisting ofα-Mg grains,β-phase and porosities were obtained.According to the grain orientation analysis,the predominant deformation behavior inα-Mg grains was dislocation slip,supplemented by deformation twinning.Dislocation slip was more difficult to occur in the samples with the improved flow distributer on account of the fact that the size ofα-Mg grains in the microstructure was finer and more uniform.During the in situ tensile deformation test,cracks were observed to initiate from gas-shrinkage pore and island-shrinkage,and two main crack propagation mechanisms,porosity growth and coalescence were found accordingly.When the crack was in contact with theβ-phase,it would pass through and fracture the networkβ-phase,whereas bypass the islandβ-phase by detaching it from the surroundingα-Mg grains.Mechanical property tests showed that the samples with relatively more homogeneous microstructure would perform higher mechanical properties,which was the combined effect of matrixα-Mg grains,β-phase,and porosities.
基金supported by the Key Research and Development Program of Science and Technology Department of Sichuan Province(No.2019YFS0514)Young Talents Project of Sichuan Academy of Medical Sciences and Sichuan Provincial People’s Hospital(No.2022QN08)。
文摘Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide.Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs.Nevertheless,the adaptive immune responses of subunit vaccines are still unfavorable,which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design.An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy.In this review,we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration.The engineered subunit vaccines with lymph node and specific cell targeting ability,antigen cross-presentation,T cell activation properties,and tailorable antigen release patterns may achieve effective immune protection with high precision,efficiency,and stability.We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.
基金financially supported by the National Natural Science Foundation of China(81925036&81872814)the Key Research and Development Program of Science and Technology Department of Sichuan Province(2020YFS0570,China)+2 种基金Sichuan Veterinary Medicine and Drug Innovation Group of China Agricultural Research System(CARS-SVDIP)111 project(b18035,China)the Fundamental Research Funds for the Central Universities(China)。
文摘The rise of nanotechnology has opened new horizons for cancer immunotherapy.However,most nano vaccines fabricated with nanomaterials suffer from carrier-related concerns,including low drug loading capacity,unpredictable metabolism,and potential systemic toxicity,which bring obstacles for their clinical translation.Herein,we developed an antigen self-assembled nanovaccine,which was resulted from a simple acryloyl modification of the antigen to induce self-assembly.Furthermore,a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid(Zol)were integrated or absorbed onto the nanoparticles(denoted as MEAO-Z)to intensify the immune response.The synthesized nano vaccine with a diameter of around 70 nm showed successful lymph node transportation,high dendritic cell internalization,promoted costimulatory molecule expression,and preferable antigen cross-presentation.In virtue of the above superiorities,MEAO-Z induced remarkably higher titers of serum antibody,stronger cytotoxic T lymphocyte immune responses and IFN-γsecretion than free antigen and adjuvants.In vivo,MEAO-Z significantly suppressed EG7-OVA tumor groth and prolonged the survival time of tumor-bearing mice.These results indicated the translation promise of our self-assembled nano vaccine for immune potentiation and cancer immunotherapy.
