The iron oxide nanoparticles(IONPs)that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications.However,the effect of magnetic stimulation in...The iron oxide nanoparticles(IONPs)that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications.However,the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear.Here,we have constructed a series of IONPs with different magneto-thermal conversion abilities,and systematically study the effect of magnetic field stimulation on the peroxidase(POD)activity of IONPs.The results show that POD activity is effectively amplified via an in situ alternating magnetic field(AMF)stimulation with no solution temperature rise,and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs,confirming the origin of activity enhancement arises from the local magnetothermal effect.As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate(SAR),this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.展开更多
Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymp...Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.展开更多
基金supported by the National Natural Science Foundation of China(81771981,82072063,and 31400663)the National Natural Science Foundation for Young Scholars of China(31901003)+2 种基金Shaanxi Province Funds for Distinguished Young Scholars(202031900097)Shaanxi Science and Technology Department(2019KW-078)the Postdoctoral Science Foundation of China(2020M673631XB)。
文摘The iron oxide nanoparticles(IONPs)that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications.However,the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear.Here,we have constructed a series of IONPs with different magneto-thermal conversion abilities,and systematically study the effect of magnetic field stimulation on the peroxidase(POD)activity of IONPs.The results show that POD activity is effectively amplified via an in situ alternating magnetic field(AMF)stimulation with no solution temperature rise,and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs,confirming the origin of activity enhancement arises from the local magnetothermal effect.As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate(SAR),this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.
基金supported by the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(Grant Nos.2016ZX310182-2 and 2016ZX310176-6 to NY)the Medical Epigenetics Research Center,Chinese Academy of Medical Sciences(Grant Nos.2017PT31035 and 2018PT31035 to NY)the National Natural Science Foundation of China(Grant No.81773163 to JF)
文摘Although DNA 5-hydroxymethylcytosine(5 hmC)is recognized as an important epigenetic mark in cancer,its precise role in lymph node metastasis remains elusive.In this study,we investigated how 5 hmC associates with lymph node metastasis in breast cancer.Accompanying with high expression of TET1 and TET2 proteins,large numbers of genes in the metastasis-positive primary tumors exhibit higher 5 hmC levels than those in the metastasis-negative primary tumors.In contrast,the TET protein expression and DNA 5 hmC decrease significantly within the metastatic lesions in the lymph nodes compared to those in their matched primary tumors.Through genomewide analysis of 8 sets of primary tumors,we identified 100 high-confidence metastasis-associated5 hmC signatures,and it is found that increased levels of DNA 5 hmC and gene expression of MAP7 D1 associate with high risk of lymph node metastasis.Furthermore,we demonstrate that MAP7 D1,regulated by TET1,promotes tumor growth and metastasis.In conclusion,the dynamic5 hmC profiles during lymph node metastasis suggest a link between DNA 5 hmC and lymph node metastasis.Meanwhile,the role of MAP7 D1 in breast cancer progression suggests that the metastasis-associated 5 hmC signatures are potential biomarkers to predict the risk for lymph node metastasis,which may serve as diagnostic and therapeutic targets for metastatic breast cancer.