Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia w...Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses,but is very challenging.Herein,an engineered macrophage-biomimetic versatile nanoantidote(OT-Lipo@M)is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression.Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain,but also efficiently reduce neurotoxin levels to prevent them from activating microglia.The loaded oxytocin(OT)can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4(TLR4)on microglia,inhibiting TLR4-mediated pro-inflammatory signalling cascade.Benefiting from this two-pronged immunosuppressive strategy,OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits,inhibiting neuronal apoptosis,and enhancing synaptic plasticity in AD mice,accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging.This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.展开更多
设计并制作了一个发射/接收一体的鸟笼线圈,该线圈采用正交激发/接收,谐振频率可以达到400 MHz,在9.4T成像系统中,可对H原子成像。Workbench测试表明,该线圈Q值较高,两个通道的隔离度达到20 d B。进行了样品测试,结果显示图像均匀、信...设计并制作了一个发射/接收一体的鸟笼线圈,该线圈采用正交激发/接收,谐振频率可以达到400 MHz,在9.4T成像系统中,可对H原子成像。Workbench测试表明,该线圈Q值较高,两个通道的隔离度达到20 d B。进行了样品测试,结果显示图像均匀、信噪比高、对比清晰。该线圈设计工艺简单,成本较低,对于超高场磁共振成像射频线圈的设计与制作具有一定的借鉴意义。展开更多
基金financially supported by the National Natural Science Foundation of China(Grant No.81871431,82171905 and 81801828)the Tianjin Natural Science Foundation(Grant No.21JCQNJC01570 and 22JCYBJC01340)+2 种基金Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-001A)Tianjin Municipal Education Research Project(20140115)Fund for Distinguished Young Scholars of Tianjin Medical University General Hospital(22ZYYJQ03).
文摘Immune recognition of excessive neurotoxins by microglia is a trigger for the onset of neuroinflammation in the brain,leading to neurodegeneration in Alzheimer’s disease(AD).Blocking active recognition of microglia while removing neurotoxins holds promise for fundamentally alleviating neurotoxin-induced immune responses,but is very challenging.Herein,an engineered macrophage-biomimetic versatile nanoantidote(OT-Lipo@M)is developed for inflammation-targeted therapy against AD by neurotoxin neutralization and immune recognition suppression.Coating macrophage membranes can not only endow OT-Lipo@M with anti-phagocytic and inflammation-tropism capabilities to target inflammatory lesions in AD brain,but also efficiently reduce neurotoxin levels to prevent them from activating microglia.The loaded oxytocin(OT)can be slowly released to downregulate the expression of immune recognition site Toll-like receptor 4(TLR4)on microglia,inhibiting TLR4-mediated pro-inflammatory signalling cascade.Benefiting from this two-pronged immunosuppressive strategy,OT-Lipo@M exhibits outstanding therapeutic effects on ameliorating cognitive deficits,inhibiting neuronal apoptosis,and enhancing synaptic plasticity in AD mice,accompanied by the delayed hippocampal atrophy and brain microstructural disruption by in vivo 9.4T MR imaging.This work provides new insights into potential AD therapeutics targeting microglia-mediated neuroinflammation at the source.
文摘设计并制作了一个发射/接收一体的鸟笼线圈,该线圈采用正交激发/接收,谐振频率可以达到400 MHz,在9.4T成像系统中,可对H原子成像。Workbench测试表明,该线圈Q值较高,两个通道的隔离度达到20 d B。进行了样品测试,结果显示图像均匀、信噪比高、对比清晰。该线圈设计工艺简单,成本较低,对于超高场磁共振成像射频线圈的设计与制作具有一定的借鉴意义。
