C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma.However,the function of ceramide synthase 1,a key enzyme in C18 ceramide synthesis,in oral squamous cell carcinoma...C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma.However,the function of ceramide synthase 1,a key enzyme in C18 ceramide synthesis,in oral squamous cell carcinoma is still unclear.The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer.In this study,we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines.In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide,ceramide synthase 1 knockout was associated with the severity of oral malignant transformation.Immunohistochemical studies showed significant upregulation of PCNA,MMP2,MMP9,and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area.In addition,ceramide synthase 1 knockdown promoted cell proliferation,migration,and invasion in vitro.Overexpression of CERS1 obtained the opposite effect.Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation.Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation.In addition,mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance.Taken together,our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.展开更多
The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to t...The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.展开更多
The development of overseas education in the new era of China can be divided into four stages,each of which has different characteristics.The achievements of the development of China’s overseas education are as follo...The development of overseas education in the new era of China can be divided into four stages,each of which has different characteristics.The achievements of the development of China’s overseas education are as following:first,persisting in the overall idea of“supporting study abroad,encouraging return home and freedom of coming and going”;second,the number of students of overseas education keeps rising;third,the selection of overseas education is gradually diversified.The future development trend of overseas education is shown as:the return boom is in the ascendant;the“domestic overseas education”is gradually developing;and China’s international education ushers in the climax.展开更多
Jean Anyon(1941-2013)is a critical pedagogical researcher and social activist in the United States.All her life,she devoted herself to taking education as a breakthrough,exposing the ugliness of capitalist countries a...Jean Anyon(1941-2013)is a critical pedagogical researcher and social activist in the United States.All her life,she devoted herself to taking education as a breakthrough,exposing the ugliness of capitalist countries and promoting the equality of society and education.She uses Marxist theory to analyze the relationship between social class and school knowledge,hidden curriculum;education and mainstream ideology;and conflicts and resistances in education,emphasizing the theoretical and practical significance of Marxism in today’s education.In order to find the deepest problem of education,Jean Anyon demonstrates the relationship between school education and macroeconomic policy from the perspective of political economics;the dialectical relationship between education reform and economic reform;and explains the reasons for education failure by quoting David Harvey’s concept of“deprivation accumulation”.Facing the cruel situation,Jean Anyon did not lose confidence,but found the“radical possibility”and put forward the concept of social change centered on education reform.展开更多
The study of Marx and Engels'educational thought has experienced different stages in China,different stages show different characteristics,and has made some progress in the aspects of“human nature”,“all-round d...The study of Marx and Engels'educational thought has experienced different stages in China,different stages show different characteristics,and has made some progress in the aspects of“human nature”,“all-round development of human beings”,“the combination of education and productive labor”,“the relationship between education and various social phenomena”,and“the thought of moral education”.Looking forward to the future,the study of Marx and Engels'educational thought in China should be further carried out:the depth of text research,the strengthening of academic research,the emphasis of method research and the deepening of cross-research.展开更多
基金supported by National Natural Science Foundation of China[81972538].
文摘C18 ceramide plays an important role in the occurrence and development of oral squamous cell carcinoma.However,the function of ceramide synthase 1,a key enzyme in C18 ceramide synthesis,in oral squamous cell carcinoma is still unclear.The aim of our study was to investigate the relationship between ceramide synthase 1 and oral cancer.In this study,we found that the expression of ceramide synthase 1 was downregulated in oral cancer tissues and cell lines.In a mouse oral squamous cell carcinoma model induced by 4-nitroquinolin-1-oxide,ceramide synthase 1 knockout was associated with the severity of oral malignant transformation.Immunohistochemical studies showed significant upregulation of PCNA,MMP2,MMP9,and BCL2 expression and downregulation of BAX expression in the pathological hyperplastic area.In addition,ceramide synthase 1 knockdown promoted cell proliferation,migration,and invasion in vitro.Overexpression of CERS1 obtained the opposite effect.Ceramide synthase 1 knockdown caused endoplasmic reticulum stress and induced the VEGFA upregulation.Activating transcription factor 4 is responsible for ceramide synthase 1 knockdown caused VEGFA transcriptional upregulation.In addition,mild endoplasmic reticulum stress caused by ceramide synthase 1 knockdown could induce cisplatin resistance.Taken together,our study suggests that ceramide synthase 1 is downregulated in oral cancer and promotes the aggressiveness of oral squamous cell carcinoma and chemotherapeutic drug resistance.
基金funded by the National Natural Science Foundation of China,Nos.82171363(to PL),82171321(to XL),82171458(to XJ)the Youth Nova Program of Shaanxi,No.2021KJXX-19(to PL)。
文摘The cumulative damage caused by repetitive mild traumatic brain injury can cause long-term neurodegeneration leading to cognitive impairment.This cognitive impairment is thought to result specifically from damage to the hippocampus.In this study,we detected cognitive impairment in mice 6 weeks after repetitive mild traumatic brain injury using the novel object recognition test and the Morris water maze test.Immunofluorescence staining showed that p-tau expression was increased in the hippocampus after repetitive mild traumatic brain injury.Golgi staining showed a significant decrease in the total density of neuronal dendritic spines in the hippocampus,as well as in the density of mature dendritic spines.To investigate the specific molecular mechanisms underlying cognitive impairment due to hippocampal damage,we performed proteomic and phosphoproteomic analyses of the hippocampus with and without repetitive mild traumatic brain injury.The differentially expressed proteins were mainly enriched in inflammation,immunity,and coagulation,suggesting that non-neuronal cells are involved in the pathological changes that occur in the hippocampus in the chronic stage after repetitive mild traumatic brain injury.In contrast,differentially expressed phosphorylated proteins were mainly enriched in pathways related to neuronal function and structure,which is more consistent with neurodegeneration.We identified N-methyl-D-aspartate receptor 1 as a hub molecule involved in the response to repetitive mild traumatic brain injury,and western blotting showed that,while N-methyl-D-aspartate receptor 1 expression was not altered in the hippocampus after repetitive mild traumatic brain injury,its phosphorylation level was significantly increased,which is consistent with the omics results.Administration of GRP78608,an N-methyl-D-aspartate receptor 1 antagonist,to the hippocampus markedly improved repetitive mild traumatic brain injury-induced cognitive impairment.In conclusion,our findings suggest that N-methyl-D-aspartate receptor 1 signaling in the hippocampus is involved in cognitive impairment in the chronic stage after repetitive mild traumatic brain injury and may be a potential target for intervention and treatment.
文摘The development of overseas education in the new era of China can be divided into four stages,each of which has different characteristics.The achievements of the development of China’s overseas education are as following:first,persisting in the overall idea of“supporting study abroad,encouraging return home and freedom of coming and going”;second,the number of students of overseas education keeps rising;third,the selection of overseas education is gradually diversified.The future development trend of overseas education is shown as:the return boom is in the ascendant;the“domestic overseas education”is gradually developing;and China’s international education ushers in the climax.
文摘Jean Anyon(1941-2013)is a critical pedagogical researcher and social activist in the United States.All her life,she devoted herself to taking education as a breakthrough,exposing the ugliness of capitalist countries and promoting the equality of society and education.She uses Marxist theory to analyze the relationship between social class and school knowledge,hidden curriculum;education and mainstream ideology;and conflicts and resistances in education,emphasizing the theoretical and practical significance of Marxism in today’s education.In order to find the deepest problem of education,Jean Anyon demonstrates the relationship between school education and macroeconomic policy from the perspective of political economics;the dialectical relationship between education reform and economic reform;and explains the reasons for education failure by quoting David Harvey’s concept of“deprivation accumulation”.Facing the cruel situation,Jean Anyon did not lose confidence,but found the“radical possibility”and put forward the concept of social change centered on education reform.
文摘The study of Marx and Engels'educational thought has experienced different stages in China,different stages show different characteristics,and has made some progress in the aspects of“human nature”,“all-round development of human beings”,“the combination of education and productive labor”,“the relationship between education and various social phenomena”,and“the thought of moral education”.Looking forward to the future,the study of Marx and Engels'educational thought in China should be further carried out:the depth of text research,the strengthening of academic research,the emphasis of method research and the deepening of cross-research.
