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
Epigenetic factors, including altered microRNA （miRNA） expression, may contribute to aberrant immune cell function in systemic lupus erythematosus （SLE）. MiRNA-let-7a （let-7a） has been shown to directly alter ce...Epigenetic factors, including altered microRNA （miRNA） expression, may contribute to aberrant immune cell function in systemic lupus erythematosus （SLE）. MiRNA-let-7a （let-7a） has been shown to directly alter cell cycle progression and proinflammatory cytokine production. Due to the crucial role of let-7a in cell division and inflammation, we investigated let-7a-mediated proliferation and NFKB translocation in J774A. 1 macrophages and MES 13 mesangial cells in vitro. In immune-stimulated cells transfected with let-7a, cell proliferation was significantly increased over time. There was a significant increase in the number of immune-stimulated cells in S and G2 phases. Immune-stimulated cells overexpressing let-7a had increased nuclear translocation of NFKB. Bioinformatical analysis revealed that the E2F family, critical regulators of the G1-S transition, has potential binding sites for let-7a in their mRNA transcripts. Let-7a overexpression significantly increased the expression of the cell cycle activator E2F2 and increased retinoblastoma protein （Rb） phosphorylation in immune-stimulated cells. The cell cycle inhibitor E2F5 was significantly decreased in let-7a-transfected cells that were immune-stimulated. Bioinformatical analysis revealed E2F2 and NFKB are transcription factors predicted to regulate the let-7a promoter. We analyzed transcriptional regulation of let-7a by real-time RT-PCR using chromatin immunoprecipitation with E2F2 and NFKB antibodies. There was an increase in E2F2 and NFKB binding in DNA enriched for the let-7a promoter in immune-stimulated cells. Silencing E2F2 or NFKB significantly decreased let-7a expression and IL-6 production in immune-stimulated cells. Taken together, our results suggest that overexpression of let-7a may contribute to hyperplasia and the proinflammatory response in SLE.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Epigenetic factors, including altered microRNA （miRNA） expression, may contribute to aberrant immune cell function in systemic lupus erythematosus （SLE）. MiRNA-let-7a （let-7a） has been shown to directly alter cell cycle progression and proinflammatory cytokine production. Due to the crucial role of let-7a in cell division and inflammation, we investigated let-7a-mediated proliferation and NFKB translocation in J774A. 1 macrophages and MES 13 mesangial cells in vitro. In immune-stimulated cells transfected with let-7a, cell proliferation was significantly increased over time. There was a significant increase in the number of immune-stimulated cells in S and G2 phases. Immune-stimulated cells overexpressing let-7a had increased nuclear translocation of NFKB. Bioinformatical analysis revealed that the E2F family, critical regulators of the G1-S transition, has potential binding sites for let-7a in their mRNA transcripts. Let-7a overexpression significantly increased the expression of the cell cycle activator E2F2 and increased retinoblastoma protein （Rb） phosphorylation in immune-stimulated cells. The cell cycle inhibitor E2F5 was significantly decreased in let-7a-transfected cells that were immune-stimulated. Bioinformatical analysis revealed E2F2 and NFKB are transcription factors predicted to regulate the let-7a promoter. We analyzed transcriptional regulation of let-7a by real-time RT-PCR using chromatin immunoprecipitation with E2F2 and NFKB antibodies. There was an increase in E2F2 and NFKB binding in DNA enriched for the let-7a promoter in immune-stimulated cells. Silencing E2F2 or NFKB significantly decreased let-7a expression and IL-6 production in immune-stimulated cells. Taken together, our results suggest that overexpression of let-7a may contribute to hyperplasia and the proinflammatory response in SLE.
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。
