After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astr...After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.展开更多
提高蛇形机器人的三维运动控制能力是提高蛇形机器人环境适应能力的关键之一.虽然联结中枢模式生成器(Connectionist central pattern generator,CCPG)模型具有复杂度小、适合硬件实现等优点,但是目前的CCPG模型难以生成相位协调的多自...提高蛇形机器人的三维运动控制能力是提高蛇形机器人环境适应能力的关键之一.虽然联结中枢模式生成器(Connectionist central pattern generator,CCPG)模型具有复杂度小、适合硬件实现等优点,但是目前的CCPG模型难以生成相位协调的多自由度运动的控制信号,从而限制了它的三维步态控制能力.本文根据生物CPG机制的分层结构和运动神经元的功能,提出一个有层次化结构的CCPG(Hierarchical CCPG,HCCPG)模型.HCCPG模型由基本节律信号生成层、模式形成层、运动信号调整层这三个部分组成.运动信号调整层的运动神经元能够独立地对模式形成层的输出信号的幅值、相位等进行调整,从而较好地解决了CCPG模型难以生成相位协调的多自由度运动控制信号的问题.HCCPG模型具有步态控制能力强、复杂度小、有良好的扩展性等优点,从而适合用于控制三维步态.在HCCPG模型的基础上提出一个三维步态控制方法.仿真验证了这个控制方法的有效性.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82101455(to RYY),31872773(to GC),82001168(to JYP)the Key Research and Development Program(Social Development)of Jiangsu Province,No.BE2020667(to GC)+3 种基金the Foundation of Jiangsu Province,333 Project High-level Talents",No.BRA2020076(to GC)the Nantong Civic Science and Technology Project of China,No.JC2020028(to RYY)the Natural Science Research of Jiangsu Higher Education Institutions of China,No.19KJB310012(to RYY)Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘After spinal cord injury(SCI),a fibroblast-and microglia-mediated fibrotic scar is formed in the lesion core,and a glial scar is formed around the fibrotic scar as a res ult of the activation and proliferation of astrocytes.Simultaneously,a large number of neuro ns are lost in the injured area.Regulating the dense glial scar and re plenishing neurons in the injured area are essential for SCI repair.Polypyrimidine tra ct binding protein(PTB),known as an RNA-binding protein,plays a key role in neurogenesis.Here,we utilized short hairpin RNAs(shRNAs)and antisense oligonucleotides(ASOs)to knock down PTB expression.We found that reactive spinal astrocytes from mice were directly reprogrammed into motoneuron-like cells by PTB downregulation in vitro.In a mouse model of compressioninduced SCI,adeno-associated viral shRNA-mediated PTB knockdown replenished motoneuron-like cells around the injured area.Basso Mouse Scale scores and forced swim,inclined plate,cold allodynia,and hot plate tests showed that PTB knockdown promoted motor function recovery in mice but did not improve sensory perception after SCI.Furthermore,ASO-mediated PTB knockdown improved motor function resto ration by not only replenishing motoneuron-like cells around the injured area but also by modestly reducing the density of the glial scar without disrupting its overall structure.Together,these findings suggest that PTB knockdown may be a promising therapeutic strategy to promote motor function recovery during spinal cord repair.
文摘提高蛇形机器人的三维运动控制能力是提高蛇形机器人环境适应能力的关键之一.虽然联结中枢模式生成器(Connectionist central pattern generator,CCPG)模型具有复杂度小、适合硬件实现等优点,但是目前的CCPG模型难以生成相位协调的多自由度运动的控制信号,从而限制了它的三维步态控制能力.本文根据生物CPG机制的分层结构和运动神经元的功能,提出一个有层次化结构的CCPG(Hierarchical CCPG,HCCPG)模型.HCCPG模型由基本节律信号生成层、模式形成层、运动信号调整层这三个部分组成.运动信号调整层的运动神经元能够独立地对模式形成层的输出信号的幅值、相位等进行调整,从而较好地解决了CCPG模型难以生成相位协调的多自由度运动控制信号的问题.HCCPG模型具有步态控制能力强、复杂度小、有良好的扩展性等优点,从而适合用于控制三维步态.在HCCPG模型的基础上提出一个三维步态控制方法.仿真验证了这个控制方法的有效性.
