Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea...Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.展开更多
本研究旨在探索DHRS7C基因外显子多态性及其与阳原驴体尺性状的相关性。基于课题组前期阳原驴的体尺性状全基因组关联分析(Genome-wide Association Study,GWAS)结果,选择DHRS7C(Dehydrogenase/Reductase Member 7C)为候选基因,通过PCR...本研究旨在探索DHRS7C基因外显子多态性及其与阳原驴体尺性状的相关性。基于课题组前期阳原驴的体尺性状全基因组关联分析(Genome-wide Association Study,GWAS)结果,选择DHRS7C(Dehydrogenase/Reductase Member 7C)为候选基因,通过PCR扩增其外显子区域、Sanger测序、基因分型以及关联分析等方法,寻找与阳原驴体尺性状显著相关的SNP位点。对显著位点突变前后的mRNA二级结构,蛋白质二、三级结构进行预测比对。结果表明:阳原驴DHRS7C基因外显子区域内存在g.12389830 G>A突变,产生GG、GA 2种基因型,不同基因型个体之间的体长、胸围、管围差异不显著,体高差异显著,GA基因型个体体高显著高于GG基因型;该突变造成蛋白质第63位精氨酸变为赖氨酸,形成错义突变,通过在线网站结构预测,突变前后mRNA二级结构,蛋白质二、三级结构均无明显变化;同时,研究发现该基因还存在g.12397240 G>A、g.12397287 G>A、g.12398389 G>A、g.12398466 G>A 4个突变,但在本研究驴群中尚未发现它们与体尺性状存在显著相关性。综上所述,DHRS7C基因外显子3区域中的SNP(g.12389830 G>A)位点可作为阳原驴体高性状的潜在分子标记。展开更多
特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability metho...特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability method,CP)和界面流法(Interface Current method,IC)等。本文从方法理论以及数值计算两方面将MOC、CP和IC进行比较分析,评估其在pin-by-pin计算中的能力。同时在MOC计算中,不同的参数选择会对计算成本和计算精度产生影响,因此有必要进行敏感性分析以寻求最佳参数。本文首先将三种计算方法从原理上进行比较分析,再基于2D C5G7-MOX基准题完成了数值计算及MOC参数敏感性初步分析。计算结果表明:MOC在计算精度、计算效率和内存开销上均优于CP和IC。MOC的计算耗时和内存开销分别为23.9 min和37.5 MB,与参考解的相对误差仅为6.04×10^(-4)。而CP和IC的计算耗时分别为MOC的56.7倍和15.6倍,内存开销分别为MOC的407.7倍和32.8倍。进一步通过参数敏感性分析发现:网格划分对计算内存开销以及计算时间的影响最大,而极角的选择对计算精度的影响最大,并且给出一组综合优化建议参数:网格划分6×6,极角为GAUS且数目为2,方位角个数为30。该组参数的计算耗时为45.4 min,内存开销为264.7 MB,相对误差为5.9×10^(-5),归一化后的栅元均方根误差为0.002 55。展开更多
基金supported by National Natural Science Foundation of China,No.32102745(to XL).
文摘Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.
文摘特征线方法(Method of Characteristics,MOC)因其具备强大的几何处理能力,且在计算过程中亦能兼顾计算成本和计算精度,被广泛应用于高保真数值模拟计算中。常见的中子输运计算方法除MOC外,还包括碰撞概率法(Collision Probability method,CP)和界面流法(Interface Current method,IC)等。本文从方法理论以及数值计算两方面将MOC、CP和IC进行比较分析,评估其在pin-by-pin计算中的能力。同时在MOC计算中,不同的参数选择会对计算成本和计算精度产生影响,因此有必要进行敏感性分析以寻求最佳参数。本文首先将三种计算方法从原理上进行比较分析,再基于2D C5G7-MOX基准题完成了数值计算及MOC参数敏感性初步分析。计算结果表明:MOC在计算精度、计算效率和内存开销上均优于CP和IC。MOC的计算耗时和内存开销分别为23.9 min和37.5 MB,与参考解的相对误差仅为6.04×10^(-4)。而CP和IC的计算耗时分别为MOC的56.7倍和15.6倍,内存开销分别为MOC的407.7倍和32.8倍。进一步通过参数敏感性分析发现:网格划分对计算内存开销以及计算时间的影响最大,而极角的选择对计算精度的影响最大,并且给出一组综合优化建议参数:网格划分6×6,极角为GAUS且数目为2,方位角个数为30。该组参数的计算耗时为45.4 min,内存开销为264.7 MB,相对误差为5.9×10^(-5),归一化后的栅元均方根误差为0.002 55。
