目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制...目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制。方法:本研究将从天然药物琐琐葡萄中提取活性成分总黄酮VTF,作用于APP/PS-1小鼠,VTF灌胃8周,通过Morris水迷宫实验评估小鼠空间学习能力;ELISA检测小鼠脑组织中IL-1β、IL-6、TNF-α因子,血清中5-HT、GABA因子的含量;苏木精-伊红(Hematoxylin and eosin staining,HE)染色法观察结肠组织形态,免疫组化法检测Occludin、Claudin、Zo-1、NLRP3蛋白表达;高通量测序检测小鼠粪便肠道菌群;结果:1)水迷宫实验结果显示:VTF低剂量组平均逃逸潜伏期缩短(P<0.05);VTF低、中剂量组有效区域运动距离,运动时间以及进入次数显著增多(P<0.01);2)结肠组织HE染色结果显示;AD模型小鼠肠粘膜膜层萎缩,隐窝丢失和绒毛断裂,而VTF干预之后小鼠上述情况均有所减轻;3)结肠组织免疫组化结果显示:VTF干预可以上调Occludin、Claudin、Zo-1等紧密连接蛋白阳性表达(P<0.01),减少NLRP3炎症相关蛋白的表达(P<0.01);4)ELISA结果:VTF各剂量组小鼠脑组织中IL-1β、IL-6、TNFα等炎症因子水平降低(P<0.01);VTF各剂量组中5-HT和GABA的含量增多(P<0.01);5)肠道菌群检测结果显示:VTF高剂量干预后的AD小鼠厚壁菌门相对丰度增多(P<0.05),与模型组小鼠相比,VTF中、高剂量组中乳杆菌科(Lactobacillaceae)相对丰度增多,VTF低剂量组中Muribaculaceae相对丰度增多,多奈哌齐组,VTF各剂量组中丹毒科(Erysipelotrichaceae)、瘤胃球菌科(Ruminococcaceae)相对丰度增多;而VTF各剂量组中毛螺菌科(Lachnospiraceae)、螺杆菌科(Helicobacteraceae),脱铁杆菌科(Deferribacteraceae)相对丰度减少。结论:这些结果表明,VTF调节肠道菌群可能具有治疗衰老过程中微生物导致脑轴和认知功能缺陷的潜力,其机制可能与改变肠道菌群组成,修复受损的肠道屏障,炎症反应和神经递质有关。因此,调节肠道微生物群可能是治疗AD相关神经疾病的一种潜在策略。展开更多
This paper addresses weak target detection problem for bistatic radar via a pseudo-spectrum(PS)based track-before-detect(TBD).Generally,PS-TBD estimates target position and velocity by means of pseudo-spectrum constru...This paper addresses weak target detection problem for bistatic radar via a pseudo-spectrum(PS)based track-before-detect(TBD).Generally,PS-TBD estimates target position and velocity by means of pseudo-spectrum construction in the discrete measurement space and accurate energy accumulation in mixed coordinates.However,the grids within the polar sensing region of the receivers in the bistatic radar are not aligned.Traditional PS-TBD can not directly process these measurements.In this paper,a PS-TBD method for bistatic radar is proposed to overcome this problem.Each cell in the measurement space of the receivers is mapped to the aligned Cartesian coordinates and predicted to the integration frame according to the assumed filter velocity.A PS is formulated centered on the predicted Cartesian position.Then the samples of the pseudo-spectra are accumulated to the nearest cell around the predicted Cartesian position.The procedure of the energy integration is derived in detail.Simulation results validate the efficacy of the proposed method in terms of detection accuracy and parameter estimation.展开更多
文摘目的:在前期发现琐琐葡萄总黄酮(Flavones from Vitis vinifera L,VTF)可改善APP/PS-1双转基因(Alzheimer's disease,AD)小鼠认知功能的基础上,进一步验证“VTF是否通过重塑肠道菌群-肠-脑轴而发挥神经保护作用”,并阐明其潜在机制。方法:本研究将从天然药物琐琐葡萄中提取活性成分总黄酮VTF,作用于APP/PS-1小鼠,VTF灌胃8周,通过Morris水迷宫实验评估小鼠空间学习能力;ELISA检测小鼠脑组织中IL-1β、IL-6、TNF-α因子,血清中5-HT、GABA因子的含量;苏木精-伊红(Hematoxylin and eosin staining,HE)染色法观察结肠组织形态,免疫组化法检测Occludin、Claudin、Zo-1、NLRP3蛋白表达;高通量测序检测小鼠粪便肠道菌群;结果:1)水迷宫实验结果显示:VTF低剂量组平均逃逸潜伏期缩短(P<0.05);VTF低、中剂量组有效区域运动距离,运动时间以及进入次数显著增多(P<0.01);2)结肠组织HE染色结果显示;AD模型小鼠肠粘膜膜层萎缩,隐窝丢失和绒毛断裂,而VTF干预之后小鼠上述情况均有所减轻;3)结肠组织免疫组化结果显示:VTF干预可以上调Occludin、Claudin、Zo-1等紧密连接蛋白阳性表达(P<0.01),减少NLRP3炎症相关蛋白的表达(P<0.01);4)ELISA结果:VTF各剂量组小鼠脑组织中IL-1β、IL-6、TNFα等炎症因子水平降低(P<0.01);VTF各剂量组中5-HT和GABA的含量增多(P<0.01);5)肠道菌群检测结果显示:VTF高剂量干预后的AD小鼠厚壁菌门相对丰度增多(P<0.05),与模型组小鼠相比,VTF中、高剂量组中乳杆菌科(Lactobacillaceae)相对丰度增多,VTF低剂量组中Muribaculaceae相对丰度增多,多奈哌齐组,VTF各剂量组中丹毒科(Erysipelotrichaceae)、瘤胃球菌科(Ruminococcaceae)相对丰度增多;而VTF各剂量组中毛螺菌科(Lachnospiraceae)、螺杆菌科(Helicobacteraceae),脱铁杆菌科(Deferribacteraceae)相对丰度减少。结论:这些结果表明,VTF调节肠道菌群可能具有治疗衰老过程中微生物导致脑轴和认知功能缺陷的潜力,其机制可能与改变肠道菌群组成,修复受损的肠道屏障,炎症反应和神经递质有关。因此,调节肠道微生物群可能是治疗AD相关神经疾病的一种潜在策略。
基金supported by the National Natural Science Foundation of China(62371155)the Heilongjiang Outstanding Youth Science Fund(JQ2022F002)。
文摘This paper addresses weak target detection problem for bistatic radar via a pseudo-spectrum(PS)based track-before-detect(TBD).Generally,PS-TBD estimates target position and velocity by means of pseudo-spectrum construction in the discrete measurement space and accurate energy accumulation in mixed coordinates.However,the grids within the polar sensing region of the receivers in the bistatic radar are not aligned.Traditional PS-TBD can not directly process these measurements.In this paper,a PS-TBD method for bistatic radar is proposed to overcome this problem.Each cell in the measurement space of the receivers is mapped to the aligned Cartesian coordinates and predicted to the integration frame according to the assumed filter velocity.A PS is formulated centered on the predicted Cartesian position.Then the samples of the pseudo-spectra are accumulated to the nearest cell around the predicted Cartesian position.The procedure of the energy integration is derived in detail.Simulation results validate the efficacy of the proposed method in terms of detection accuracy and parameter estimation.
