Higher vocational colleges pay more attention to the establishment and improvement of the internal quality assurance system. An objective and reasonable evaluation system was established by analyzing the law of the de...Higher vocational colleges pay more attention to the establishment and improvement of the internal quality assurance system. An objective and reasonable evaluation system was established by analyzing the law of the development of higher education and vocational education in the world. Through the integration of the evaluation system and the information platform, it showed the advantages of the efficient flat structure of the information platform and the zero-distance advantages of the participants. And teachers and students were served efficiently. By analyzing all kinds of data in real time, the problems were discovered in each link in time. A normal diagnosis and improvement working mechanism were gradually formed, and internal quality assurance system of sustainable development was constructed for school governance services based on objective data, realizing the continuous improvement of the quality of higher vocational talents training.展开更多
Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal ceils...Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal ceils in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.展开更多
Based on the lung adenocarcinoma(LUAD)gene expression data from the cancer genome atlas(TCGA)database,the Stromal score,Immune score and Estimate score in tumor microenvironment(TME)were computed by the Estimation of ...Based on the lung adenocarcinoma(LUAD)gene expression data from the cancer genome atlas(TCGA)database,the Stromal score,Immune score and Estimate score in tumor microenvironment(TME)were computed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data(ESTIMATE)algorithm.And gene modules significantly related to the three scores were identified by weighted gene coexpression network analysis(WGCNA).Based on the correlation coefficients and P values,899 key genes affecting tumor microenvironment were obtained by selecting the two most correlated modules.It was suggested through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis that these key genes were significantly involved in immune-related or cancer-related terms.Through univariate cox regression and elastic network analysis,genes associated with prognosis of the LUAD patients were screened out and their prognostic values were further verified by the survival analysis and the University of ALabama at Birmingham CANcer(UALCAN)database.The results indicated that eight genes were significantly related to the overall survival of LUAD.Among them,six genes were found differentially expressed between tumor and control samples.And immune infiltration analysis further verified that all the six genes were significantly related to tumor purity and immune cells.Therefore,these genes were used eventually for constructing a Naive Bayes projection model of LUAD.The model was verified by the receiver operating characteristic(ROC)curve where the area under curve(AUC)reached 92.03%,which suggested that the model could discriminate the tumor samples from the normal accurately.Our study provided an effective model for LUAD projection which improved the clinical diagnosis and cure of LUAD.The result also confirmed that the six genes in the model construction could be the potential prognostic biomarkers of LUAD.展开更多
文摘Higher vocational colleges pay more attention to the establishment and improvement of the internal quality assurance system. An objective and reasonable evaluation system was established by analyzing the law of the development of higher education and vocational education in the world. Through the integration of the evaluation system and the information platform, it showed the advantages of the efficient flat structure of the information platform and the zero-distance advantages of the participants. And teachers and students were served efficiently. By analyzing all kinds of data in real time, the problems were discovered in each link in time. A normal diagnosis and improvement working mechanism were gradually formed, and internal quality assurance system of sustainable development was constructed for school governance services based on objective data, realizing the continuous improvement of the quality of higher vocational talents training.
基金We are grateful to Drs. Ted Dawson and Jian Feng for generously providing the plasmids. We are also grateful to Professor Mark Bartlam from Nankai University, Tianjin, China for a critical reading of the manuscript. The research was supported by the National Basic Research Program (973 Program) (No. 2011 CB910903) from MOST and project (Grant Nos. 81130045, 31471300, 31271529, 301520103904) from the National Natural Science Foundation of China.
文摘Mutations or inactivation of parkin, an E3 ubiquitin ligase, are associated with familial form or sporadic Parkinson's disease (PD), respectively, which manifested with the selective vulnerability of neuronal ceils in substantia nigra (SN) and striatum (STR) regions. However, the underlying molecular mechanism linking parkin with the etiology of PD remains elusive. Here we report that p62, a critical regulator for protein quality control, inclusion body formation, selective autophagy and diverse signaling pathways, is a new substrate of parkin. P62 levels were increased in the SN and STR regions, but not in other brain regions in parkin knockout mice. Parkin directly interacts with and ubiquitinates p62 at the K13 to promote proteasomal degradation of p62 even in the absence of ATG5. Pathogenic mutations, knockdown of parkin or mutation of p62 at K13 prevented the degradation of p62. We further showed that parkin deficiency mice have pronounced loss of tyrosine hydroxylase positive neurons and have worse performance in motor test when treated with 6-hydroxydopamine hydrochloride in aged mice. These results suggest that, in addition to their critical role in regulating autophagy, p62 are subjected to parkin mediated proteasomal degradation and implicate that the dysregulation of parkin/p62 axis may involve in the selective vulnerability of neuronal cells during the onset of PD pathogenesis.
基金Our deepest gratitude goes to the editors and anonymous reviewers for their careful work and thoughtful suggestions that have helped to improve this paper substantially.The workwas supported by the National Natural Science Foundation of China(No.12071382)the Bowang scholar youth talent program(Zhiqiang Ye)of Chongqing Normal University,the Natural Science and Engineering Research Council of Canada,and the Canada Research Chair Program(JWu).
文摘Based on the lung adenocarcinoma(LUAD)gene expression data from the cancer genome atlas(TCGA)database,the Stromal score,Immune score and Estimate score in tumor microenvironment(TME)were computed by the Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data(ESTIMATE)algorithm.And gene modules significantly related to the three scores were identified by weighted gene coexpression network analysis(WGCNA).Based on the correlation coefficients and P values,899 key genes affecting tumor microenvironment were obtained by selecting the two most correlated modules.It was suggested through Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis that these key genes were significantly involved in immune-related or cancer-related terms.Through univariate cox regression and elastic network analysis,genes associated with prognosis of the LUAD patients were screened out and their prognostic values were further verified by the survival analysis and the University of ALabama at Birmingham CANcer(UALCAN)database.The results indicated that eight genes were significantly related to the overall survival of LUAD.Among them,six genes were found differentially expressed between tumor and control samples.And immune infiltration analysis further verified that all the six genes were significantly related to tumor purity and immune cells.Therefore,these genes were used eventually for constructing a Naive Bayes projection model of LUAD.The model was verified by the receiver operating characteristic(ROC)curve where the area under curve(AUC)reached 92.03%,which suggested that the model could discriminate the tumor samples from the normal accurately.Our study provided an effective model for LUAD projection which improved the clinical diagnosis and cure of LUAD.The result also confirmed that the six genes in the model construction could be the potential prognostic biomarkers of LUAD.