Efficient in vivo delivery of anti-inflammatory proteins to modulate the microenvironment of an injured spinal cord and promote neuroprotection and functional recovery is a great challenge.Nucleoside-modified messenge...Efficient in vivo delivery of anti-inflammatory proteins to modulate the microenvironment of an injured spinal cord and promote neuroprotection and functional recovery is a great challenge.Nucleoside-modified messenger RNA(mRNA)has become a promising new modality that can be utilized for the safe and efficient delivery of therapeutic proteins.Here,we used lipid nanoparticle(LNP)-encapsulated human interleukin-10(hIL-10)-encoding nucleoside-modified mRNA to induce neuroprotection and functional recovery following rat spinal cord contusion injury.Intralesional administration of hIL-10 mRNA-LNP to rats led to a remarkable reduction of the microglia/macrophage reaction in the injured spinal segment and induced significant functional recovery compared to controls.Furthermore,hIL-10 mRNA treatment induced increased expression in tissue inhibitor of matrix metalloproteinase 1 and ciliary neurotrophic factor levels in the affected spinal segment indicating a time-delayed secondary effect of IL-105 d after injection.Our results suggest that treatment with nucleoside-modified mRNAs encoding neuroprotective factors is an effective strategy for spinal cord injury repair.展开更多
Research on the last 30 years of architectural heritage conservation in Shanghai would highlight the establishment of both a preliminary system for heritage classification and gradation,as well as an authorised herita...Research on the last 30 years of architectural heritage conservation in Shanghai would highlight the establishment of both a preliminary system for heritage classification and gradation,as well as an authorised heritage institution framework.During the course of this process,different conservation methodologies and models(restorations,additions,relocations,extensions and reconstructions)have been put into practice according to the actual situation of the historic architecture of Shanghai.An overall view shows how architectural heritage conservation in Shanghai has undergone three different phases-initial;experimental;and the deepening conservation phase,on which a fundamental step was given in 2002,when the Shanghai Municipal Government issued the‘Legislation for the Conservation of Historical Areas and Heritage Architecture in Shanghai’,creating a conservation system that is participated by the authorities,academic institutions,design institutions and construction companies.The article also stresses the need to provide for a special system of architectural heritage conservation in Shanghai,acknowledging the specificity of its cultural heritage,administrative system,legislation,codes,building technologies and materials;as well as its particular historical situation.展开更多
基金N.P.was supported by NIH R01-AI153064.C.V.and A.M.received generous support from the following grants:2020-1.1.6-JÖVŐ2021-00012 and 2022-2.1.1-NL-2022-00008 for the National Biotechnology Laboratory.A.N.was supported by the NKFIH KLINO-117031 grant.
文摘Efficient in vivo delivery of anti-inflammatory proteins to modulate the microenvironment of an injured spinal cord and promote neuroprotection and functional recovery is a great challenge.Nucleoside-modified messenger RNA(mRNA)has become a promising new modality that can be utilized for the safe and efficient delivery of therapeutic proteins.Here,we used lipid nanoparticle(LNP)-encapsulated human interleukin-10(hIL-10)-encoding nucleoside-modified mRNA to induce neuroprotection and functional recovery following rat spinal cord contusion injury.Intralesional administration of hIL-10 mRNA-LNP to rats led to a remarkable reduction of the microglia/macrophage reaction in the injured spinal segment and induced significant functional recovery compared to controls.Furthermore,hIL-10 mRNA treatment induced increased expression in tissue inhibitor of matrix metalloproteinase 1 and ciliary neurotrophic factor levels in the affected spinal segment indicating a time-delayed secondary effect of IL-105 d after injection.Our results suggest that treatment with nucleoside-modified mRNAs encoding neuroprotective factors is an effective strategy for spinal cord injury repair.
文摘Research on the last 30 years of architectural heritage conservation in Shanghai would highlight the establishment of both a preliminary system for heritage classification and gradation,as well as an authorised heritage institution framework.During the course of this process,different conservation methodologies and models(restorations,additions,relocations,extensions and reconstructions)have been put into practice according to the actual situation of the historic architecture of Shanghai.An overall view shows how architectural heritage conservation in Shanghai has undergone three different phases-initial;experimental;and the deepening conservation phase,on which a fundamental step was given in 2002,when the Shanghai Municipal Government issued the‘Legislation for the Conservation of Historical Areas and Heritage Architecture in Shanghai’,creating a conservation system that is participated by the authorities,academic institutions,design institutions and construction companies.The article also stresses the need to provide for a special system of architectural heritage conservation in Shanghai,acknowledging the specificity of its cultural heritage,administrative system,legislation,codes,building technologies and materials;as well as its particular historical situation.
