In the context of controlling population development in a planned way,China entered an aging society in the early 21 st century.In this context,how to meet the needs of the elderly care and form an effective elderly c...In the context of controlling population development in a planned way,China entered an aging society in the early 21 st century.In this context,how to meet the needs of the elderly care and form an effective elderly care model has become a key problem to be solved urgently by local government departments.With the continuous advancement of the elderly care policy,the community-based elderly care has gradually become the mainstream and is in the stage of vigorous promotion.Taking the Gannan old revolutionary base area in Jiangxi Province as an example,this study puts forward"1+4+X"community-based elderly care model based on the policy system of community-based elderly care,the physical and mental health of the elderly,the material space and the construction of evaluation system,and explores how to promote the application of this community model efficiently in the form of industrialization,so as to drive the economic growth of the Gannan old revolutionary base area,promote the employment development and improve the community-based elderly care service.展开更多
Metabolic reprogramming is a hallmark of cancer,including lung cancer.However,the exact underlying mechanism and therapeutic potential are largely unknown.Here we report that protein arginine methyltransferase 6(PRMT6...Metabolic reprogramming is a hallmark of cancer,including lung cancer.However,the exact underlying mechanism and therapeutic potential are largely unknown.Here we report that protein arginine methyltransferase 6(PRMT6)is highly expressed in lung cancer and is required for cell metabolism,tumorigenicity,and cisplatin response of lung cancer.PRMT6 regulated the oxidative pentose phosphate pathway(PPP)flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phosphogluconate dehydrogenase(6PGD)and a-enolase(ENO1).Furthermore,PRMT6 methylated R324 of 6PGD to enhancing its activity;while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate(2-PG)binding to ENO1,respectively.Lastly,targeting PRMT6 blocked the oxidative PPP flux,glycolysis pathway,and tumor growth,as well as enhanced the antitumor effects of cisplatin in lung cancer.Together,this study demonstrates that PRMT6 acts as a posttranslational modification(PTM)regulator of glucose metabolism,which leads to the pathogenesis of lung cancer.It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.展开更多
Sense mutations in several conserved modifiable sites of histone H3 have been found to be strongly correlated with multiple tissuespecific clinical cancers.These clinical site mutants acquire a distinctively new epige...Sense mutations in several conserved modifiable sites of histone H3 have been found to be strongly correlated with multiple tissuespecific clinical cancers.These clinical site mutants acquire a distinctively new epigenetic role and mediate cancer evolution.In this study,we mimicked histone H3 at the 56th lysine(H3K56)mutant incorporation in mouse embryonic stem cells(mESCs)by lentivirus-mediated ectopic expression and analyzed the effects on replication and epigenetic regulation.The data show that two types of H3K56 mutants,namely H3 lysine 56-to-methionine(H3K56M)and H3 lysine 56-to-alanine(H3K56A),promote replication by recruiting more minichromosome maintenance complex component 3 and checkpoint kinase 1 onto chromatin compared with wild-type histone H3 and other site substitution mutants.Under this condition,the frequency of genomic copy number gain in H3K56M and H3K56A cells globally increases,especially in the Mycl1 region,a known molecular marker frequently occurring in multiple malignant cancers.Additionally,we found the disruption of H3K56 acetylation distribution in the copy-gain regions,which indicates a probable epigenetic mechanism of H3K56M and H3K56A.We then identified that H3K56M and H3K56A can trigger a potential adaptation to transcription;genes involved in the mitogen-activated protein kinase pathway are partially upregulated,whereas genes associated with intrinsic apoptotic function show obvious downregulation.The final outcome of ectopic H3K56M and H3K56A incorporation in mESCs is an enhanced ability to form carcinomas.This work indicates that H3K56 site conservation and proper modification play important roles in harmonizing the function of the replication machinery in mESCs.展开更多
文摘In the context of controlling population development in a planned way,China entered an aging society in the early 21 st century.In this context,how to meet the needs of the elderly care and form an effective elderly care model has become a key problem to be solved urgently by local government departments.With the continuous advancement of the elderly care policy,the community-based elderly care has gradually become the mainstream and is in the stage of vigorous promotion.Taking the Gannan old revolutionary base area in Jiangxi Province as an example,this study puts forward"1+4+X"community-based elderly care model based on the policy system of community-based elderly care,the physical and mental health of the elderly,the material space and the construction of evaluation system,and explores how to promote the application of this community model efficiently in the form of industrialization,so as to drive the economic growth of the Gannan old revolutionary base area,promote the employment development and improve the community-based elderly care service.
基金supported by grants from the Natural Science Foundation of Tianjin(21JCZDJC00060,China)the National Nature Science Foundation of China(81973356,91957120,81902826,and 81672781)+4 种基金the Fundamental Research Funds for the Central Universities of Nankai University(3206054,91923101,63213082 and 92122017,China)the State Key Laboratory of Drug Research(SIMM2105KF-08,China)the National Key R&D Program of China(No.2018YFC2002000)the Innovative S&T Projects for Young Researchers of Tianjin Academy of Agricultural Science(grant No.201918,China)the Natural Science Foundation of Tianjin(19JCYBJC29600 and 21JCYBJC00180,China)。
文摘Metabolic reprogramming is a hallmark of cancer,including lung cancer.However,the exact underlying mechanism and therapeutic potential are largely unknown.Here we report that protein arginine methyltransferase 6(PRMT6)is highly expressed in lung cancer and is required for cell metabolism,tumorigenicity,and cisplatin response of lung cancer.PRMT6 regulated the oxidative pentose phosphate pathway(PPP)flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phosphogluconate dehydrogenase(6PGD)and a-enolase(ENO1).Furthermore,PRMT6 methylated R324 of 6PGD to enhancing its activity;while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate(2-PG)binding to ENO1,respectively.Lastly,targeting PRMT6 blocked the oxidative PPP flux,glycolysis pathway,and tumor growth,as well as enhanced the antitumor effects of cisplatin in lung cancer.Together,this study demonstrates that PRMT6 acts as a posttranslational modification(PTM)regulator of glucose metabolism,which leads to the pathogenesis of lung cancer.It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.
基金supported by grants from the National Key Research and Development Program of China(2017YFA0103301)the National Natural Science Foundation of China(81972743)China Postdoctoral Science Foundation(2020M671205).
文摘Sense mutations in several conserved modifiable sites of histone H3 have been found to be strongly correlated with multiple tissuespecific clinical cancers.These clinical site mutants acquire a distinctively new epigenetic role and mediate cancer evolution.In this study,we mimicked histone H3 at the 56th lysine(H3K56)mutant incorporation in mouse embryonic stem cells(mESCs)by lentivirus-mediated ectopic expression and analyzed the effects on replication and epigenetic regulation.The data show that two types of H3K56 mutants,namely H3 lysine 56-to-methionine(H3K56M)and H3 lysine 56-to-alanine(H3K56A),promote replication by recruiting more minichromosome maintenance complex component 3 and checkpoint kinase 1 onto chromatin compared with wild-type histone H3 and other site substitution mutants.Under this condition,the frequency of genomic copy number gain in H3K56M and H3K56A cells globally increases,especially in the Mycl1 region,a known molecular marker frequently occurring in multiple malignant cancers.Additionally,we found the disruption of H3K56 acetylation distribution in the copy-gain regions,which indicates a probable epigenetic mechanism of H3K56M and H3K56A.We then identified that H3K56M and H3K56A can trigger a potential adaptation to transcription;genes involved in the mitogen-activated protein kinase pathway are partially upregulated,whereas genes associated with intrinsic apoptotic function show obvious downregulation.The final outcome of ectopic H3K56M and H3K56A incorporation in mESCs is an enhanced ability to form carcinomas.This work indicates that H3K56 site conservation and proper modification play important roles in harmonizing the function of the replication machinery in mESCs.
