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Blood reflux and metabolic regulation play important roles in chronic venous disease (CVD) development. Histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) serve as repressors that inhibit metabolic signaling, which is induced by proatherogenic flow to promote aortic endothelial cell (EC) dysfunction and atherosclerosis. The aim of this study was to elucidate the relationship between blood reflux and epigenetic factors HDACs and DNMTs in CVD. Human varicose veins with different levels of blood reflux versus normal veins with normal venous flow were examined. The results show that HDAC-1, -2, -3, -5, and -7 are overexpressed in the endothelium of varicose veins with blood reflux. Blood reflux-induced HDACs are enhanced in the varicose veins with a longer duration time of blood reflux. In contrast, these HDACs are rarely expressed in the endothelium of the normal vein with normal venous flow. Similar results are obtained for DNMT1 and DNMT3a. Our findings suggest that the epigenetic factors, HDACs and DNMTs, are induced in venous ECs in response to blood reflux but are inhibited in response to normal venous flow. Blood reflux-induced HDACs and DNMTs could inhibit metabolic regulation and promote venous EC dysfunction, which is highly correlated with CVD pathogenesis.
Assuntos
Histona Desacetilases , Varizes , Humanos , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Metilases de Modificação do DNA/genética , Varizes/genética , Epigênese Genética , DNA , Doença CrônicaRESUMO
BACKGROUND: MicroRNA-10a (miR-10a) inhibits transcriptional factor GATA6 to repress inflammatory GATA6/VCAM-1 signaling, which is regulated by blood flow to affect endothelial function/dysfunction. This study aimed to identify the expression patterns of miR-10a/GATA6/VCAM-1 in vivo and study their implications in the pathophysiology of human coronary artery disease (CAD), i.e., atherosclerosis. METHODS: Human atherosclerotic coronary arteries and nondiseased arteries were used to detect the expressions of miR-10a/GATA6/VCAM-1 in pathogenic vs. normal conditions. In addition, sera from CAD patients and healthy subjects were collected to detect the level of circulating miR-10a. RESULTS: The comparison of human atherosclerotic coronary arteries with nondiseased arteries demonstrated that lower levels of endothelial miR-10a are related to human atherogenesis. Moreover, GATA6/VCAM-1 (a downstream target of miR-10a) was highly expressed in the endothelium, accompanied by the reduced levels of miR-10a during the development of human atherosclerosis. In addition, CAD patients had a significantly lower concentration of miR-10a in their serum compared to healthy subjects. CONCLUSIONS: Our findings suggest that low miR-10a and high GATA6/VCAM-1 in the cardiovascular endothelium correlates to the development of human atherosclerotic lesions, suggesting that miR-10a signaling has the potential to be developed as a biomarker for human atherosclerosis.
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Using first-principles calculations based on density functional theory, we systematically investigated the electronic properties and charge transfer of topological insulator Bi2Te3-xSex thin films under an external electric field. As the selenium content in Bi2Te3-xSex thin films increases, the band gap is gradually opened, with changes in the charge distribution. In addition, the experimentally stable Bi2Te2Se and Bi2Se2Te thin films are extremely robust under vertical electric fields up to 0.2 V Å-1. The electronic structures of Bi2Te2Se and Bi2Se2Te thin films are insensitive to the electric fields and exhibit only a Rashba-like splitting pattern near the Fermi level. Remarkably, the charge transfer in Bi2Te2Se and Bi2Se2Te thin films under an external electric field is suppressed. We found that the robustness characteristic is inextricably linked to the strong covalent bonding of tellurium and bismuth atoms. These results indicated that Bi2Te2Se and Bi2Se2Te thin films are robust to the internal electrical field during growth on the substrate, which is beneficial for experimental studies as well as for the potential applications of spintronic devices.
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Magnetic doping in topological insulator Sb2Te3 can produce very novel physical phenomena such as quantum anomalous Hall effect (QAHE). However, experimental observations of QAHE in the magnetic atoms doped Sb2Te3 have encountered significant challenges due to the complexity of the electronic structure and the relatively small band gap. Generally, mechanical strain can effectively modulate the band structure, thus we theoretically investigate the electronic structures of Cr-doped Sb2Te3 under mechanical strain using first-principles calculations within density functional theory. The band gap of Cr-doped Sb2Te3 is 0.031 eV. When the compressive strain η becomes as -2%, the band gap will be further enlarged to 0.045 eV, which is 45% larger than that of the unstrained material. However, as the compressive strain η exceed -2%, strong hybridization between Cr and Te atoms will cause the overlap of bands, which leads to the closure of band gap. In addition, when tensile strain is applied to Cr-doped Sb2Te3, the decrease in the spacing between quintuple layers can enhance the coupling between Te and Sb atoms, which can also result in the closing of the band gap. Finally, we used HSE06 to calculated the band gaps. The band gaps may be underestimated, but HSE06 and GGA have the same band structures evolution tendency under mechanical strain. Our calculated results provide a guideline for the modulation of band structure by mechanical strain, which pave the way for the observation of QAHE in Cr-doped Sb2Te3.
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GeSe is considered as a potential absorber material for thin film solar cells owing to its ideal band gap, strong light absorption, remarkable air durability, Earth-abundance and non-toxic constituents. However, the high vapor pressure of GeSe at a temperature below its melting point makes it difficult to synthesize a high-quality GeSe film. To alleviate this limitation, in this work, a thermal evaporation combining a novel sandwiching post-annealing method was introduced to deposit high quality GeSe thin films with (100)-orientation. The self-assembling mechanism of the highly oriented GeSe film was carefully investigated by the systematic experiments and confirmed by the lowest total energy of the (100) crystal plane. Finally, the fully-inorganic, low-cost and non-toxic planar device with the superstrate configuration of FTO/TiO2/GeSe/carbon/Ag was also successfully fabricated. Notably, as a result, an impressive open circuit voltage (VOC) of 340 mV (maximum: 456 mV) was achieved, which is the highest VOC of GeSe solar cells reported so far. Furthermore, through current-voltage, capacitance-voltage profiling and drive level capacitance profiling measurements, it was demonstrated that the limiting factors of the GeSe solar cell performance were the narrow depletion width (138 nm) and the drastic recombination at the TiO2/GeSe interface.
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Heteroatom-doping is a promising strategy to tuning the microstructure of carbon material toward improved electrochemical storage performance. However, it is a big challenge to control the doping sites for heteroatom-doping and the rational design of doping is urgently needed. Herein, S doping sites and the influence of interlayer spacing for two kinds of hard carbon, perfect structure and vacancy defect structure, are explored by the first-principles method. S prefers doping in the interlayer for the former with interlayer distance of 3.997 Å, while S is doped on the carbon layer for the latter with interlayer distance of 3.695 Å. More importantly, one step molten salts method is developed as a universal synthetic strategy to fabricate hard carbon with tunable microstructure. It is demonstrated by the experimental results that S-doping hard carbon with fewer pores exhibits a larger interlayer spacing than that of porous carbon, agreeing well with the theoretical prediction. Furthermore, the S-doping carbon with larger interlayer distance and fewer pores exhibits remarkably large reversible capacity, excellent rate performance, and long-term cycling stability for Na-ion storage. A stable and reversible capacity of ≈200 mAh g-1 is steadily kept even after 4000 cycles at 1 A g-1 .