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Angiotensin II (Ang-II)-induced fibroblast differentiation plays an important role in the development of atrial fibrosis and atrial fibrillation (AF). Here, we show that the expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2) is increased in atrial muscle and atrial fibroblasts in patients with AF, accompanied by significant atrial fibrosis and atrial fibroblast differentiation. In addition, EZH2 is induced in murine models of atrial fibrosis. Furthermore, either pharmacological GSK126 inhibition or molecular silencing of EZH2 can inhibit the differentiation of atrial fibroblasts and the ability to produce ECM induced by Ang-II. Simultaneously, inhibition of EZH2 can block the Ang-II-induced migration of atrial fibroblasts. We found that EZH2 promotes fibroblast differentiation mainly through the Smad signaling pathway and can form a transcription complex with Smad2 to bind to the promoter region of the ACTA2 gene. Finally, our in vivo experiments demonstrated that the EZH2 inhibitor GSK126 significantly inhibited Ang-II-induced atrial enlargement and fibrosis and reduced AF vulnerability. Our results demonstrate that targeting EZH2 or EZH2-regulated genes might present therapeutic potential in AF. • EZH2 expression was significantly elevated in atrial muscle specimens of patients with atrial fibrillation. • EZH2 regulates the transformation and migration of atrial fibroblasts. • EZH2 regulates fibroblasts transformation mainly through Ang-II-TGF-β-Smads signaling pathway. • EZH2 inhibitor GSK126 significantly inhibits Ang-II-induced atrial enlargement, fibrosis, and reduced AF vulnerability. [ABSTRACT FROM AUTHOR]

Abstract Endothelial-to-mesenchymal transition (EndMT) plays a pivotal role in the development of organ fibrosis and can be induced by TGF-β. It is characterized by the loss of endothelial cell markers and the acquisition of mesenchymal markers. In this study, we found that methyl-CpG binding protein 2 (MeCP2) was increased in TGF-β-induced EndMT, and silencing of MeCP2 inhibited EndMT induction. Viral overexpression of MeCP2 in vitro promoted EndMT and suppressed the expression of bone morphogenic protein-7 (BMP7). The methylation of CpG islands in BMP7 promoter was increased in MeCP2-overexpressing endothelial cells and Chromatin immunoprecipitation assay showed the direct binding of MeCP2 at the BMP7 promoter. In summary, our results suggest that MeCP2 promotes EndMT by epigenetically silencing BMP7 in endothelial cells and MeCP2 may be a target for diseases driven by EndMT. Highlights • MeCP2 may be a target for diseases driven by EndMT. • MeCP2 promotes EndMT by epigenetically silencing BMP7 in endothelial cells. • MeCP2 directly binds to the BMP7 promoter and induces its methylation. [ABSTRACT FROM AUTHOR]

Abstract Cardiac fibrosis (CF), a process characterized by potentiated proliferation of cardiac fibroblasts and excessive secretion and deposition of extracellular matrix (ECM) from the cells, contributes strongly to the pathogenesis of a series of cardiovascular (CV) diseases, including AMI, heart failure and atrial fibrillation. Endothelial-mesenchymal transition (EndMT), one of the sources of transformed cardiac fibroblasts, has been reported as a key factor involved in CF. However, the molecular basis of EndMT has not been thoroughly elucidated to date. At the posttranscriptional level, of the three epigenetic regulators, writer and eraser are reported to be involved in EndMT, but the role of reader in the process is still unknown. In this study, we aimed to explore the role of Bromodomain-containing protein 4 (BRD4), an acetyl-lysine reader protein, in EndMT-induced CF and related mechanisms. We found that BRD4 was upregulated in endothelial cells (ECs) in the pressure-overload mouse heart and that its functional inhibitor JQ1 potently attenuated the TAC-induced CF and preserved cardiac function. In umbilical vein endothelial cells (HUVECs) and mouse aortic endothelial cells (MAECs), bothJQ1 and shRNA-mediated silencing of BRD4 blocked TGF-β-induced EC migration, EndMT and ECM synthesis and preserved the EC sprouting behavior, possibly through the downregulation of a group of transcription factors specific for EndMT (Snail, Twist and Slug), the Smads pathway and TGF-β receptor I. In the absence of TGF-β stimulation, ectopic expression of BRD4 alone could facilitate EndMT, accelerate migration and increase the synthesis of ECM. In vivo, JQ1 also attenuated TAC-induced EndMT and CF, which was consistent with JQ1's intracellular mechanisms of action. Our results showed that BRD4 plays a critical role in EndMT-induced CF and that targeting BRD4 might be a novel therapeutic option for CF. [ABSTRACT FROM AUTHOR]

A new synergistic approach was proposed to reuse waste poplar sawdust. Novel high S-doped amorphous carbon/carbon quantum dots coupled micro-frame (SCMF) were prepared by chemical exfoliation and S/Se-assisted carbonization. Amorphous carbon and carbon quantum dots coexisted at the nanoscale. The CQDs acted as fast electron channels, while amorphous carbon can accommodate more large-size K-ions and mitigate volume expansion, resulting in high-speed and long-lasting potassium storage. Theoretical calculations further demonstrated the important role of S-doped carbon quantum dots for K-ions storage. [Display omitted] Anode materials with excellent rate capability, capacity, and cycle life have been a challenge in obtaining cost-effective K-ion batteries (KIBs). Based on the concept of waste recycling, we prepared the S-doped (21.5%) amorphous carbon/carbon quantum dots coupled micro-frame (SCMF) by combining chemical exfoliation and S/Se-assisted carbonization. SCMF exhibited the advantages of integrating amorphous carbon and carbon quantum dots (CQDs). The CQDs serve as fast electron channels, while amorphous carbon can accommodate more large-size K-ions and mitigate volume expansion. In KIBs, SCMF maintained a high reversible capacity (414.0 mAh g−1, after 100 cycles at 100 mA g−1), a good rate capability (224.0 mAh g−1, 2000 mA g−1), and excellent capacity retention (208.9 mAh g−1, after 2000 cycles at 1000 mA g−1). The molecular dynamic simulation revealed that CQDs provided fast electron transport channels and that C, O and S atoms had suitable interactions with K, facilitating potassium storage. Moreover, the potassium-ion capacitor (PIC) assembled from SCMF and activated carbon exhibited stable electrochemical performance, proving its potential for application. The research provided valuable insights into the reuse of biomass waste in new secondary batteries. [ABSTRACT FROM AUTHOR]

The endothelial-mesenchymal transition (EndMT) plays a key role in the development of cardiac fibrosis (CF) after acute myocardial infarction (AMI). The results of our previous study showed that amphiregulin (AR) expression was enhanced after MI. However, the role of AR on EndMT post MI remains unknown. This study aimed to elucidate the impact of AR on EndMT post MI and the associated molecular mechanisms. AR expression was markedly enhanced in infarct border area post MI, and endothelial cells were one of the primary cell sources of AR secretion. Stimulation with AR promoted endothelial cell proliferation, invasion, migration, collagen synthesis and EndMT. In addition, EGFR and downstream gene expression was significantly enhanced. In vivo, EndMT was significantly inhibited after lentivirus-AR-shRNA was delivered to the myocardium post MI. In addition, silencing AR ameliorated cardiac function by decreasing the extent of CF. Furthermore, the levels of EGFR pathway components in endothelial cells extracted from infarct border myocardium were all significantly decreased in lentivirus-AR-shRNA-treated MI mice. Our results demonstrate that AR induces CF post MI by enhancing EndMT in endothelial cells. Thus, targeting the regulation of AR may provide a potentially novel therapeutic option for CF after MI. [ABSTRACT FROM AUTHOR]

The quantitative study of urban-rural gradients for persistent organic pollutants (POPs) is extremely important to understand the behavior of POPs as well as for ecological risk assessment and management. In this study, a practical urban-rural gradient model (URGM) was developed using atmospheric point source diffusion combined with a fugacity approach to test potential mathematical relationships among urban and rural soils. The mean value of polycyclic aromatic hydrocarbons (PAHs) for urban soils (0–2-km sites) was 570.80 ng/g, and was approximately 3.5 times higher than rural soils (30–50 km sites). Significant linear correlations were found between the amounts of PAHs in the surface soil and the city population and between the soil concentration and artificial surface area. Urban-rural PAH concentrations were simulated by the URGM and calibrated by city population and land-cover data, with average relative errors of 12.84%. The results showed that the URGM was suitable for simulating urban-rural PAH concentrations at a regional scale. The combustion of fossil fuels, biomass, and coal was the main source of soil PAHs in the study area, and the characteristic ratios of PAHs indicated a transition trend from pyrogenic to petrogenic sources along the urban-rural transects. This study thus provides a combined method for quantifying urban-rural gradients of PAHs and can thereby promote quantitative research on coupling among land cover, socio-economic data, and POP concentrations. Image 1 • Urban-rural gradients were quantitatively described through theoretical deduction. • The URGM model was found suitable for describing urban-rural PAH gradients. • The slopes for urban-rural gradients between soil and air were similar. • A new method for simulating urban-rural gradients for PAHs in soil was developed. [ABSTRACT FROM AUTHOR]

Water quality safety has attracted global attention and is closely related to the development of the social economy and human health. It is widely recognized that climate change and human activities significantly affect water quality changes. Therefore, quantifying the contributions of factors that drive long-term water quality changes is crucial for effective water quality management. Here, we built a climate-water quality assessment framework (CWQAF) based on climate-water quality response coefficients and trend analysis methods, to achieve this goal. Our results showed that the water quality improved significantly by 4.45%–20.54% from 2011 to 2020 in the Minjiang River basin (MRB). Human activities (including the construction of ecological projects, stricter discharge measures, etc.) were the main driving factors contributing 65%–77% of the improvement effect. Notably, there were differences in the contributions of human activities to water quality parameter changes, such as DO (increase (I): 0.12 mg/L, human contribution (HC): 66.8%), COD Mn (decrease (D): 0.71 mg/L, HC: 67.2%), BOD 5 (D: 1.10 mg/L, HC: 77.7%), COD Cr (D: 4.20 mg/L, HC: 81.2%), TP (D: 0.13 mg/L,HC: 72.8%) and NH 3 –N (D: 0.40 mg/L, HC: 63.0%). Climate change explained 23%–35% of the variation in water quality. The water quality response to climate change was relatively significant with precipitation. For example, the downstream region was more susceptible to climate change than was the upstream region, as the downstream movement of precipitation centers strengthened the process of climatic factors affecting water quality changes in the MRB. Generally, although human activities were the main driving factor of water quality changes at the basin scale, the contribution of climate change could not be ignored. This study provided a manageable framework for the quantitative analysis of the influence of human activities and climate change on water quality to enable more precise and effective water quality management. [Display omitted] • A quantitative framework (CWQAF) was developed to analyse water quality changes. • CWQAF coupled climate-water quality response coefficients and trend analysis methods. • Human activities were the main driver of water quality improvement. • Shifting precipitation centers increased the contribution to changes in water quality. • Spatially differentiated management of climate change impacts needed to be addressed. [ABSTRACT FROM AUTHOR]