In recent years,high-tech development zones(hi-tech zones)have always occupied a very important position in the strategy of promoting China's innovative development.The combination of the"four-transform and t...In recent years,high-tech development zones(hi-tech zones)have always occupied a very important position in the strategy of promoting China's innovative development.The combination of the"four-transform and three-famous"coordinated economic development strategy pioneered by Zhejiang Province in 2015 and the coordinated economic development of high-tech zones is particularly important for modern China at a critical time for innovative economic development.In this article,based on the research on the coordination mechanism of economic activities and development of Nanchang High-tech Zone,the development course of high-tech zones in China is elaborated,the early economic models in high-tech zones of Nanchang and China are analyzed,the existing problems in the structure of economic development of high-tech zones are analyzed in depth,the main driving factors for promoting the economic development of high-tech zones are studied from the aspects of capital,space,industry,economic model,etc.,and corresponding development strategies for high-tech development zones in China are proposed.展开更多
Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption.Dysregulation of this process leads to multiple diseases,including osteoporosis.However,the underlying...Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption.Dysregulation of this process leads to multiple diseases,including osteoporosis.However,the underlying molecular mechanisms are not fully understood.Here,we show that the global and conditional osteoblast knockout of a deubiquitinase Otub1 result in low bone mass and poor bone strength due to defects in osteogenic differentiation and mineralization.Mechanistically,the stability of FGFR2,a crucial regulator of osteogenesis,is maintained by OTUB1.OTUB1 attenuates the E3 ligase SMURF1-mediated FGFR2 ubiquitination by inhibiting SMURF1’s E2 binding.In the absence of OTUB1,FGFR2 is ubiquitinated excessively by SMURF1,followed by lysosomal degradation.Consistently,adeno-associated virus serotype 9(AAV9)-delivered FGFR2 in knee joints rescued the bone mass loss in osteoblast-specific Otub1-deleted mice.Moreover,Otub1 mRNA level was significantly downregulated in bones from osteoporotic mice,and restoring OTUB1 levels through an AAV9-delivered system in ovariectomy-induced osteoporotic mice attenuated osteopenia.Taken together,our results suggest that OTUB1 positively regulates osteogenic differentiation and mineralization in bone homeostasis by controlling FGFR2 stability,which provides an optical therapeutic strategy to alleviate osteoporosis.展开更多
文摘In recent years,high-tech development zones(hi-tech zones)have always occupied a very important position in the strategy of promoting China's innovative development.The combination of the"four-transform and three-famous"coordinated economic development strategy pioneered by Zhejiang Province in 2015 and the coordinated economic development of high-tech zones is particularly important for modern China at a critical time for innovative economic development.In this article,based on the research on the coordination mechanism of economic activities and development of Nanchang High-tech Zone,the development course of high-tech zones in China is elaborated,the early economic models in high-tech zones of Nanchang and China are analyzed,the existing problems in the structure of economic development of high-tech zones are analyzed in depth,the main driving factors for promoting the economic development of high-tech zones are studied from the aspects of capital,space,industry,economic model,etc.,and corresponding development strategies for high-tech development zones in China are proposed.
基金supported by the National Key Research and Development Project of China (2021YFA1300200)China Postdoctoral Science Foundation (2021T140797)+2 种基金the National Natural Science Foundation of China (82192881,81825014,31830003,32201023,81900765)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29020000)the State Key Laboratory of Proteomics (SKLP-K202001).
文摘Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption.Dysregulation of this process leads to multiple diseases,including osteoporosis.However,the underlying molecular mechanisms are not fully understood.Here,we show that the global and conditional osteoblast knockout of a deubiquitinase Otub1 result in low bone mass and poor bone strength due to defects in osteogenic differentiation and mineralization.Mechanistically,the stability of FGFR2,a crucial regulator of osteogenesis,is maintained by OTUB1.OTUB1 attenuates the E3 ligase SMURF1-mediated FGFR2 ubiquitination by inhibiting SMURF1’s E2 binding.In the absence of OTUB1,FGFR2 is ubiquitinated excessively by SMURF1,followed by lysosomal degradation.Consistently,adeno-associated virus serotype 9(AAV9)-delivered FGFR2 in knee joints rescued the bone mass loss in osteoblast-specific Otub1-deleted mice.Moreover,Otub1 mRNA level was significantly downregulated in bones from osteoporotic mice,and restoring OTUB1 levels through an AAV9-delivered system in ovariectomy-induced osteoporotic mice attenuated osteopenia.Taken together,our results suggest that OTUB1 positively regulates osteogenic differentiation and mineralization in bone homeostasis by controlling FGFR2 stability,which provides an optical therapeutic strategy to alleviate osteoporosis.