目的探讨肌微管素相关微蛋白7(myotubularin related protein 7,MTMR7)在肺动脉高压中的作用及机制。方法健康♂小鼠、Mtmr7转基因(Mtmr7-Tg)小鼠各20只,分为对照组、Mtmr7-Tg组、野百合碱(monocrotaline,MCT)组、MCT+Mtmr7-Tg组,超声...目的探讨肌微管素相关微蛋白7(myotubularin related protein 7,MTMR7)在肺动脉高压中的作用及机制。方法健康♂小鼠、Mtmr7转基因(Mtmr7-Tg)小鼠各20只,分为对照组、Mtmr7-Tg组、野百合碱(monocrotaline,MCT)组、MCT+Mtmr7-Tg组,超声测量肺动脉血流加速时间(pulmonary artery acceleration time,PAT)和射血时间(pulmonary artery ejection time,PET),取材时分离右心室游离壁,计算右心肥厚指数,免疫染色观察肺小动脉重构。将小鼠肺动脉平滑肌细胞(pulmonary arterial smooth muscle cells,PASMCs)以低氧处理,观察其增殖和迁移情况。结果MTMR7在肺血管中表达,并且MCT处理之后,Mtmr7-Tg小鼠的PAT/PET比值降低(P<0.05),右心肥厚指数升高(P<0.01)。以Mtmr7基因过表达腺病毒转染PASMCs,可以抑制其增殖和迁移。用chemerin-9恢复p-ERK1/2的活性,过表达MTMR7对PASMCs增殖、迁移抑制作用消失。结论过表达MTMR7可减轻低氧诱导的小鼠PASMCs增殖和迁移,从而逆转肺动脉高压,机制与MTMR7降低ERK1/2磷酸化密切相关。展开更多
BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression result...BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCFFBXW7,p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCFFBXW7(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCFFBXW7 and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7,thereby influencing the ubiquitination and degradation of cyclin E1.展开更多
Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report...Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.展开更多
棉田虫害的快速检测与准确识别是预防棉田虫害、提高棉花品质的重要前提。针对真实棉田环境下昆虫相似度高、背景干扰严重的问题,该研究提出一种ECSF-YOLOv7棉田虫害检测模型。首先,采用EfficientFormerV2作为特征提取网络,以加强网络...棉田虫害的快速检测与准确识别是预防棉田虫害、提高棉花品质的重要前提。针对真实棉田环境下昆虫相似度高、背景干扰严重的问题,该研究提出一种ECSF-YOLOv7棉田虫害检测模型。首先,采用EfficientFormerV2作为特征提取网络,以加强网络的特征提取能力并减少模型参数量;同时,将卷积注意力模块(convolution block attention module,CBAM)嵌入到模型的主干输出端,以增强模型对小目标的特征提取能力并削弱背景干扰;其次,使用GSConv卷积搭建Slim-Neck颈部网络结构,在减少模型参数量的同时保持模型的识别精度;最后,采用Focal-EIOU(focal and efficient IOU loss,Focal-EIOU)作为边界框回归损失函数,加速网络收敛并提高模型的检测准确率。结果表明,改进的ECSF-YOLOv7模型在棉田虫害测试集上的平均精度均值(mean average precision,mAP)为95.71%,检测速度为69.47帧/s。与主流的目标检测模型YOLOv7、SSD、YOLOv5l和YOLOX-m相比,ECSF-YOLOv7模型的mAP分别高出1.43、9.08、1.94、1.52个百分点,并且改进模型具有参数量更小、检测速度更快的优势,可为棉田虫害快速准确检测提供技术支持。展开更多
基金Supported by Innovative Practice Platform for Undergraduate Students,School of Public Health Xiamen University,No.2021001.
文摘BACKGROUND Previous cellular studies have demonstrated that elevated expression of Cx43 promotes the degradation of cyclin E1 and inhibits cell proliferation through ubiquitination.Conversely,reduced expression results in a loss of this capacity to facilitate cyclin E degradation.The ubiquitination and degradation of cyclin E1 may be associated with phosphorylation at specific sites on the protein,with Cx43 potentially enhancing this process by facilitating the phosphorylation of these critical residues.AIM To investigate the correlation between expression of Cx43,SKP1/Cullin1/F-box(SCF)FBXW7,p-cyclin E1(ser73,thr77,thr395)and clinicopathological indexes in colon cancer.METHODS Expression levels of Cx43,SCFFBXW7,p-cyclin E1(ser73,thr77,thr395)in 38 clinical colon cancer samples were detected by immunohistochemistry and were analyzed by statistical methods to discuss their correlations.RESULTS Positive rate of Cx43,SCFFBXW7,p-cyclin E1(Ser73),p-cyclin E1(Thr77)and p-cyclin E1(Thr395)in detected samples were 76.32%,76.32%,65.79%,5.26%and 55.26%respectively.Positive expressions of these proteins were not related to the tissue type,degree of tissue differentiation or lymph node metastasis.Cx43 and SCFFBXW7(r=0.749),p-cyclin E1(Ser73)(r=0.667)and p-cyclin E1(Thr395)(r=0.457),SCFFBXW7 and p-cyclin E1(Ser73)(r=0.703)and p-cyclin E1(Thr395)(0.415)were correlated in colon cancer(P<0.05),and expressions of the above proteins were positively correlated in colon cancer.CONCLUSION Cx43 may facilitate the phosphorylation of cyclin E1 at the Ser73 and Thr195 sites through its interaction with SCFFBXW7,thereby influencing the ubiquitination and degradation of cyclin E1.
基金supported by the National Natural Science Foundation of China,Nos.82171429,81771384a grant from Wuxi Municipal Health Commission,No.1286010241190480(all to YS)。
文摘Interferon regulatory factor 7 plays a crucial role in the innate immune response.However,whether interferon regulatory factor 7-mediated signaling contributes to Parkinson's disease remains unknown.Here we report that interferon regulatory factor 7 is markedly up-regulated in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease and co-localizes with microglial cells.Both the selective cyclic guanosine monophosphate adenosine monophosphate synthase inhibitor RU.521 and the stimulator of interferon genes inhibitor H151 effectively suppressed interferon regulatory factor 7 activation in BV2 microglia exposed to 1-methyl-4-phenylpyridinium and inhibited transformation of mouse BV2 microglia into the neurotoxic M1 phenotype.In addition,si RNA-mediated knockdown of interferon regulatory factor 7 expression in BV2 microglia reduced the expression of inducible nitric oxide synthase,tumor necrosis factorα,CD16,CD32,and CD86 and increased the expression of the anti-inflammatory markers ARG1 and YM1.Taken together,our findings indicate that the cyclic guanosine monophosphate adenosine monophosphate synthase-stimulator of interferon genes-interferon regulatory factor 7 pathway plays a crucial role in the pathogenesis of Parkinson's disease.
文摘棉田虫害的快速检测与准确识别是预防棉田虫害、提高棉花品质的重要前提。针对真实棉田环境下昆虫相似度高、背景干扰严重的问题,该研究提出一种ECSF-YOLOv7棉田虫害检测模型。首先,采用EfficientFormerV2作为特征提取网络,以加强网络的特征提取能力并减少模型参数量;同时,将卷积注意力模块(convolution block attention module,CBAM)嵌入到模型的主干输出端,以增强模型对小目标的特征提取能力并削弱背景干扰;其次,使用GSConv卷积搭建Slim-Neck颈部网络结构,在减少模型参数量的同时保持模型的识别精度;最后,采用Focal-EIOU(focal and efficient IOU loss,Focal-EIOU)作为边界框回归损失函数,加速网络收敛并提高模型的检测准确率。结果表明,改进的ECSF-YOLOv7模型在棉田虫害测试集上的平均精度均值(mean average precision,mAP)为95.71%,检测速度为69.47帧/s。与主流的目标检测模型YOLOv7、SSD、YOLOv5l和YOLOX-m相比,ECSF-YOLOv7模型的mAP分别高出1.43、9.08、1.94、1.52个百分点,并且改进模型具有参数量更小、检测速度更快的优势,可为棉田虫害快速准确检测提供技术支持。
