As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systemati...As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systematically expounds the coordinated mechanism of the dual axes of succinate/H3K9ac andα-ketoglutarate(α-KG)/TET enzymes:Succinate activates regeneration-related genes by regulating histone acetylation(H3K9ac),whileα-KG relieves the epigenetic repression of the Wnt pathway through TET-mediated DNA demethylation.The dynamic balance between the two maintains epigenetic plasticity.Multi-omics integration strategies(such as Gaussian graphical models and deep learning frameworks)and single-cell epigenetic tracking technologies(such as spatial metabolomics)have revealed the regulation of metabolite gradients on cellular heterogeneity and the immune microenvironment.The coordinated application of metabolite precursor supplementation(such as NAD precursors)and dynamic monitoring systems(such as isotope tracing and artifi cial intelligence models)has promoted the shift of metabolic medicine from the“static replacement”paradigm to the“dynamic reshaping”paradigm.However,technical bottlenecks(such as insuffi cient multimodal integration)and clinical translation pitfalls(such as challenges in standardized production)still need to be overcome.In the future,through the development of“metabolism-immunity”co-regulatory strategies and intelligent closed-loop systems,it is expected to achieve precise interventions for kidney regeneration and disease treatment.展开更多
The absorption coefficient of water is an important bio-optical parameter for water optics and water color remote sensing. However, scattering correction is essential to obtain accurate absorption coefficient values i...The absorption coefficient of water is an important bio-optical parameter for water optics and water color remote sensing. However, scattering correction is essential to obtain accurate absorption coefficient values in situ using the nine-wavelength absorption and attenuation meter AC9. Establishing the correction always fails in Case 2 water when the correction assumes zero absorption in the near-infrared(NIR) region and underestimates the absorption coefficient in the red region, which affect processes such as semi-analytical remote sensing inversion. In this study, the scattering contribution was evaluated by an exponential fitting approach using AC9 measurements at seven wavelengths(412, 440, 488, 510, 532, 555, and 715 nm) and by applying scattering correction. The correction was applied to representative in situ data of moderately turbid coastal water, highly turbid coastal water, eutrophic inland water, and turbid inland water. The results suggest that the absorption levels in the red and NIR regions are significantly higher than those obtained using standard scattering error correction procedures. Knowledge of the deviation between this method and the commonly used scattering correction methods will facilitate the evaluation of the effect on satellite remote sensing of water constituents and general optical research using different scatteringcorrection methods.展开更多
GATA4 is a particularly important cardiogenic transcription factor and serves as a potent driver of cardiogenesis.Recent progress in the field has made it clear that histone acetylation can influence gene expression t...GATA4 is a particularly important cardiogenic transcription factor and serves as a potent driver of cardiogenesis.Recent progress in the field has made it clear that histone acetylation can influence gene expression through changing the structure of chromatin.Our previous research had revealed that hypo-acetylation could repress gata4 expression in cardiocytes,however the underlying mechanism by which this occurred was still unclear.To reveal the mechanism of histone acetylation involved in the regulation of gata4 transcription,we concentrated on P300,one of the important histone acetyltransferase associated with cardiogenesis.We found that P300 participated in gata4 expression through regulating histone acetylation in embryonic mouse hearts.RNAi-mediated downregulation of P300 modulated the global acetylation of H3 and the acetylation of H3K4,H3K9,and H3K27 in gata4 and Tbx5 promoters.Interestingly,there was an obvious inhibition of gata4 transcription,whereas Tbx5 was not influenced.Furthermore,SGC-CBP30,the selective inhibitor of the bromodomain in CBP/P300,downregulated gata4 transcription by repressing the acetylation of H3K4,H3K9,and H3K27 in the gata4 promoters.Taken together,our results identified that acetylation of H3K4,H3K9,and H3K27 mediated by P300 plays an important role in regulation of gata4 expression in cardiogenesis.展开更多
基金funded by Medical Science Research Project of Hebei(No.20220364).
文摘As the“fourth messenger”of epigenetic regulation,metabolites playa spatiotemporally specific regulatory role in kidney regeneration by dynamically reshaping the state of chromatin modifications.This review systematically expounds the coordinated mechanism of the dual axes of succinate/H3K9ac andα-ketoglutarate(α-KG)/TET enzymes:Succinate activates regeneration-related genes by regulating histone acetylation(H3K9ac),whileα-KG relieves the epigenetic repression of the Wnt pathway through TET-mediated DNA demethylation.The dynamic balance between the two maintains epigenetic plasticity.Multi-omics integration strategies(such as Gaussian graphical models and deep learning frameworks)and single-cell epigenetic tracking technologies(such as spatial metabolomics)have revealed the regulation of metabolite gradients on cellular heterogeneity and the immune microenvironment.The coordinated application of metabolite precursor supplementation(such as NAD precursors)and dynamic monitoring systems(such as isotope tracing and artifi cial intelligence models)has promoted the shift of metabolic medicine from the“static replacement”paradigm to the“dynamic reshaping”paradigm.However,technical bottlenecks(such as insuffi cient multimodal integration)and clinical translation pitfalls(such as challenges in standardized production)still need to be overcome.In the future,through the development of“metabolism-immunity”co-regulatory strategies and intelligent closed-loop systems,it is expected to achieve precise interventions for kidney regeneration and disease treatment.
基金Supported by the National Key Research and Development Program of China(Nos.2016YFB0501502,2016YFC1400903,2016YFB0500304)the National Natural Science Foundation of China(Nos.91638201,41276184,41325004,41471308,41571361)+1 种基金the High Resolution Earth Observation Systems of National Science and Technology Major Projects(No.41-Y20A31-9003-15/17)the Director Foundation of Institute of Remote Sensing and Digital Earth,Chinese Academy of Sciences(No.Y6SJ2100CX)
文摘The absorption coefficient of water is an important bio-optical parameter for water optics and water color remote sensing. However, scattering correction is essential to obtain accurate absorption coefficient values in situ using the nine-wavelength absorption and attenuation meter AC9. Establishing the correction always fails in Case 2 water when the correction assumes zero absorption in the near-infrared(NIR) region and underestimates the absorption coefficient in the red region, which affect processes such as semi-analytical remote sensing inversion. In this study, the scattering contribution was evaluated by an exponential fitting approach using AC9 measurements at seven wavelengths(412, 440, 488, 510, 532, 555, and 715 nm) and by applying scattering correction. The correction was applied to representative in situ data of moderately turbid coastal water, highly turbid coastal water, eutrophic inland water, and turbid inland water. The results suggest that the absorption levels in the red and NIR regions are significantly higher than those obtained using standard scattering error correction procedures. Knowledge of the deviation between this method and the commonly used scattering correction methods will facilitate the evaluation of the effect on satellite remote sensing of water constituents and general optical research using different scatteringcorrection methods.
基金The study was supported by research grants from the National Natural Science Foundation of China(Grant Number:81300129).
文摘GATA4 is a particularly important cardiogenic transcription factor and serves as a potent driver of cardiogenesis.Recent progress in the field has made it clear that histone acetylation can influence gene expression through changing the structure of chromatin.Our previous research had revealed that hypo-acetylation could repress gata4 expression in cardiocytes,however the underlying mechanism by which this occurred was still unclear.To reveal the mechanism of histone acetylation involved in the regulation of gata4 transcription,we concentrated on P300,one of the important histone acetyltransferase associated with cardiogenesis.We found that P300 participated in gata4 expression through regulating histone acetylation in embryonic mouse hearts.RNAi-mediated downregulation of P300 modulated the global acetylation of H3 and the acetylation of H3K4,H3K9,and H3K27 in gata4 and Tbx5 promoters.Interestingly,there was an obvious inhibition of gata4 transcription,whereas Tbx5 was not influenced.Furthermore,SGC-CBP30,the selective inhibitor of the bromodomain in CBP/P300,downregulated gata4 transcription by repressing the acetylation of H3K4,H3K9,and H3K27 in the gata4 promoters.Taken together,our results identified that acetylation of H3K4,H3K9,and H3K27 mediated by P300 plays an important role in regulation of gata4 expression in cardiogenesis.