Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival.Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment(TME)....Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival.Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment(TME).Pore-forming gasdermins(GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME,however,the expressions and relationships of GSDMs with osteosarcoma remain unclear.Herein,gasdermin E(GSDME)expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients,and low GSDME expression was observed.A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction.Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction.The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction.The pyroptosis further initiated proinflammatory cytokines release,increased immune cell infiltration,activated adaptive immune responses and create a favorable immunogenic hot TME.The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma,but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.展开更多
The modernization of Shanghai has experienced two boosting periods.The first appeared in the 1930s,when it formed the civil society of Shanghai and initially facilitated the trade port into an international metropolis...The modernization of Shanghai has experienced two boosting periods.The first appeared in the 1930s,when it formed the civil society of Shanghai and initially facilitated the trade port into an international metropolis.The second started after the nation’s reform and opening-up,which attempted to promote the city into a global metropolis in the 2010s.In order to evaluate the socio-spatial transitions of communities in Shanghai during the process,Lilong historical neighborhoods in the 1930s and 2010s are successively chosen as research objects.Meanwhile,three specific neighborhoods in each period are selected for case study,so as to depict different symbiosis patterns of the socio-spatial structures under different spatiotemporal conditions by means of a cross-sectional analysis of the consumption level.By pointing out Shanghai in the 1930s was marked with social integration and local-based consumption,while it was inundated with administration tendency and global-oriented consumption in the 2010s,the article believes the dual integration of local-based and global-oriented consumptions is an alternative solution for Shanghai.Finally,the article proposes that Shanghai’s current urban regeneration should rely on the multi-centered symbiotic structure to create a compound network,during which territorial socio-spatial structures and basic living needs of the plebeian can be simultaneously preserved.展开更多
The provision of open space is seen as a feasible solution in mitigating the challenges of urbanization,which accomm odates the daily leisure activities of residents and contributes to sustainable developm ent.This st...The provision of open space is seen as a feasible solution in mitigating the challenges of urbanization,which accomm odates the daily leisure activities of residents and contributes to sustainable developm ent.This study aims at understanding how users perceive open space in 29-3 Park in Da Nang,Vietnam.This understanding may help to adopt a better approach to development and improvements.More specifically,it focuses on identifying roles and attributes of the space and determ ining those elements which affect how users of the space gather,based on their perspective.Residents,behaviour param eters were identified and classified based on activities that occurred in this space,and were collected using a behavioural mapping survey method.The analysis of 20 in-depth interviews,and 287 question naires,show existing problems that need to be improved and detail 11 physical factors that have potential to impact on users'satisfaction.These results may have the potential to play an im portant role in assisting designers and administrators to create successful open space in urban areas of Vietnam or other developing countries in the future.展开更多
基金supported in part by National Key Research and Development Program of China(2021YFC2400500)National Natural Science Foundation of China(52273121,52373128)+3 种基金Beijing Natural Science Foundation(7222011)Beijing Hospitals Authority Youth Programme(QML20210402)the Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(BMHC-2021-6,JYY2023-11,JYY2023-8,BJRITO-RDP-2024)Beijing Jishuitan Hospital Program(JSTYC202206,XKXX202114,XKXX202115).The authors also gratefully acknowledge the support of Prof.Fu-Jian Xu and Prof.Bingran Yu from Beijing University of Chemical Technology,China in the preparation of LPAD polymers,and Dr.Jing Li from Jining Medical University,China in the molecule dynamic simulation.
文摘Osteosarcoma is the most common malignant bone tumor without efficient management for improving 5-year event-free survival.Immunotherapy is also limited due to its highly immunosuppressive tumor microenvironment(TME).Pore-forming gasdermins(GSDMs)-mediated pyroptosis has gained increasing concern in reshaping TME,however,the expressions and relationships of GSDMs with osteosarcoma remain unclear.Herein,gasdermin E(GSDME)expression is found to be positively correlated with the prognosis and immune infiltration of osteosarcoma patients,and low GSDME expression was observed.A vector termed as LPAD contains abundant hydroxyl groups for hydrating layer formation was then prepared to deliver the GSDME gene to upregulate protein expression in osteosarcoma for efficient TME reshaping via enhanced pyroptosis induction.Atomistic molecular dynamics simulations analysis proved that the hydroxyl groups increased LPAD hydration abilities by enhancing coulombic interaction.The upregulated GSDME expression together with cleaved caspase-3 provided impressive pyroptosis induction.The pyroptosis further initiated proinflammatory cytokines release,increased immune cell infiltration,activated adaptive immune responses and create a favorable immunogenic hot TME.The study not only confirms the role of GSDME in the immune infiltration and prognosis of osteosarcoma,but also provides a promising strategy for the inhibition of osteosarcoma by pore-forming GSDME gene delivery induced enhanced pyroptosis to reshape the TME of osteosarcoma.
文摘The modernization of Shanghai has experienced two boosting periods.The first appeared in the 1930s,when it formed the civil society of Shanghai and initially facilitated the trade port into an international metropolis.The second started after the nation’s reform and opening-up,which attempted to promote the city into a global metropolis in the 2010s.In order to evaluate the socio-spatial transitions of communities in Shanghai during the process,Lilong historical neighborhoods in the 1930s and 2010s are successively chosen as research objects.Meanwhile,three specific neighborhoods in each period are selected for case study,so as to depict different symbiosis patterns of the socio-spatial structures under different spatiotemporal conditions by means of a cross-sectional analysis of the consumption level.By pointing out Shanghai in the 1930s was marked with social integration and local-based consumption,while it was inundated with administration tendency and global-oriented consumption in the 2010s,the article believes the dual integration of local-based and global-oriented consumptions is an alternative solution for Shanghai.Finally,the article proposes that Shanghai’s current urban regeneration should rely on the multi-centered symbiotic structure to create a compound network,during which territorial socio-spatial structures and basic living needs of the plebeian can be simultaneously preserved.
文摘The provision of open space is seen as a feasible solution in mitigating the challenges of urbanization,which accomm odates the daily leisure activities of residents and contributes to sustainable developm ent.This study aims at understanding how users perceive open space in 29-3 Park in Da Nang,Vietnam.This understanding may help to adopt a better approach to development and improvements.More specifically,it focuses on identifying roles and attributes of the space and determ ining those elements which affect how users of the space gather,based on their perspective.Residents,behaviour param eters were identified and classified based on activities that occurred in this space,and were collected using a behavioural mapping survey method.The analysis of 20 in-depth interviews,and 287 question naires,show existing problems that need to be improved and detail 11 physical factors that have potential to impact on users'satisfaction.These results may have the potential to play an im portant role in assisting designers and administrators to create successful open space in urban areas of Vietnam or other developing countries in the future.
