Exceptional Hole-Selective Properties of Ta2O5 Films via Sn4+ Doping for High Performance Silicon Heterojunction Solar Cells.

Carrier-selective passivating contacts using transition metal oxides (TMOs) have attracted great attention for crystalline silicon (c-Si) heterojunction solar cells recently. Among them, tantalum oxide (Ta2O5) exhibits outstanding advantages, such as a wide bandgap, good surface passivation, and a small conduction band offset with c-Si, which is typically used as an electron-selective contact layer. Interestingly, it is first demonstrated that solution-processed Ta2O5 films exhibit a high hole selectivity, which blocks electrons and promotes hole transport simultaneously. Through the ozone pre-treatment of Ta2O5/p-Si interface and optimization of the film thickness (≈9 nm), the interfacial recombination is suppressed and the contact resistivity is reduced from 178.0 to 29.3 mΩ cm2. Moreover, the Sn4+ doping increases both the work function and oxygen vacancies of the film, contributing to the improved hole-selective contact performance. As a result, the photoelectric conversion efficiencies of Ta2O5/p-Si heterojunction solar cells are significantly improved from 14.84% to 18.47%, with a high thermal stability up to 300 °C. The work has provided a feasible strategy to explore new features of TMOs for carrier-selective contact applications, that is, bipolar carrier transport properties.

CuCl2-modified SnO2electron transport layer for high efficiency perovskite solar cells.

SnO2film is one of the most widely used electron transport layers (ETL) in perovskite solar cells (PSCs). However, the inherent surface defect states in SnO2film and mismatch of the energy level alignment with perovskite limit the photovoltaic performance of PSCs. It is of great interesting to modify SnO2ETL with additive, aiming to decrease the surface defect states and obtain well aligned energy level with perovskite. In this paper, anhydrous copper chloride (CuCl2) was employed to modify the SnO2ETL. It is found that the adding of a small amount of CuCl2into the SnO2ETL can improve the proportion of Sn4+in SnO2, passivate oxygen vacancies at the surface of SnO2nanocrystals, improve the hydrophobicity and conductivity of ETL, and obtain a good energy level alignment with perovskite. As a result, both the photoelectric conversion efficiency (PCE) and stability of the PSCs based on SnO2ETLs modified with CuCl2(SnO2-CuCl2) is improved in comparison with that of the PSCs on pristine SnO2ETLs. The optimal PSC based on SnO2-CuCl2ETL exhibits a much higher PCE of 20.31% as compared to the control device (18.15%). The unencapsulated PSCs with CuCl2modification maintain 89.3% of their initial PCE after exposing for 16 d under ambient conditions with a relative humidity of 35%. Cu(NO3)2was also employed to modify the SnO2ETL and achieved a similar effect as that of CuCl2, indicating that the cation Cu2+plays the main role in SnO2ETL modification.

FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE-/- mice atherosclerosis.

Atherosclerosis is a chronic inflammatory vascular disease, and inflammation plays a critical role in its formation and progression. Elevated serum homocysteine (Hcy) is an independent risk factor for atherosclerosis. Previous studies have shown that fatty acid binding protein 4 (FABP4) plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis induced by Hcy. However, the underlying molecular mechanism of FABP4 in Hcy-induced macrophage inflammation remains unknown. In this study, we found that FABP4 activated the Janus kinase 2/signal transducer and activator of transcription 2 (JAK2/STAT2) pathway in macrophage inflammation induced by Hcy. Of note, we further observed that ras-related protein Rap-1a (Rap1a) induced the Tyr416 phosphorylation and membrane translocation of non-receptor tyrosine kinase (c-Src) to activate the JAK2/STAT2 pathway. In addition, the suppressor of cytokine signaling 1 (SOCS1)-a transcriptional target of signal transducer and activator of transcription (STATs) inhibited the JAK2/STAT2 pathway and Rap1a expression via a negative feedback loop. In summary, these results demonstrated that FABP4 promotes c-Src phosphorylation and membrane translocation via Rap1a to activate the JAK2/STAT2 pathway, contributing to Hcy-accelerated macrophage inflammation in ApoE-/- mice.

Extracellular-superoxide dismutase DNA methylation promotes oxidative stress in homocysteine-induced atherosclerosis.

In the present study, we investigate the effect of homocysteine (Hcy) on extracellular-superoxide dismutase (EC-SOD) DNA methylation in the aorta of mice, and explore the underlying mechanism in macrophages, trying to identify the key targets of Hcy-induced EC-SOD methylation changes. ApoE -/- mice are fed different diets for 15 weeks, EC-SOD and DNA methyltransferase 1 (DNMT1) expression levels are detected by RT-PCR and western blot analysis. EC-SOD methylation levels are assessed by ntMS-PCR. After EC-SOD overexpression or knockdown in macrophages, following the transfection of macrophages with pEGFP-N1-DNMT1, the methylation levels of EC-SOD are detected. Our data show that the concentrations of Hcy and the area of atherogenic lesions are significantly increased in ApoE -/- mice fed with a high-methionine diet, and have a positive correlation with the levels of superoxide anions, which indicates that Hcy-activated superoxide anions enhance the development of atherogenic lesions. EC-SOD expression is suppressed by Hcy, and the content of superoxide anion is increased when EC-SOD is silenced by RNAi in macrophages, suggesting that EC-SOD plays a major part in oxidative stress induced by Hcy. Furthermore, the promoter activity of EC-SOD is increased following transfection with the -1/-1100 fragment, and EC-SOD methylation level is significantly suppressed by Hcy, and more significantly decreased upon DNMT1 overexpression. In conclusion, Hcy may alter the DNA methylation status and DNMT1 acts as the essential enzyme in the methyl transfer process to disturb the status of EC-SOD DNA methylation, leading to decreased expression of EC-SOD and increased oxidative stress and atherosclerosis.

Antisolvent engineering on low-temperature processed CsPbI3 inorganic perovskites for improved performances of solar cells.

CsPbI3 inorganic perovskites with ideal bandgap and much enhanced thermal stability compared with organic-inorganic hybrid perovskites, have attracted much interest in the field of solar cells. The performances of solar cells highly depend on the quality of perovskite films, yet the research on fabrication methods of inorganic perovskites is far below that of organic-inorganic hybrid counterparts. Antisolvent engineering is a widely used method in controlling the morphology and crystallinity of organic-inorganic hybrid perovskites. Its effect varies with parameters such as the physicochemical properties of antisolvents and the compositions of perovskite precursors. Specially, there lacks a comprehensive study comparing different antisolvents used in low-temperature processed CsPbI3 from dimethylammonium-based precursors. In this work, we used three different antisolvents to control the growth of CsPbI3 films in a low-temperature (<200 °C) processed procedure and systematically compared the properties of resultant films. The green antisolvent ethyl acetate (EA) engineered CsPbI3 films exhibit improved morphology and crystallinity as well as reduced defects, compared with the counterparts processed without antisolvent or those with widely employed toxic antisolvents toluene and chlorobenzene. The EA antisolvent engineering results in efficient CsPbI3 perovskite solar cells with a champion power conversion efficiency of 8.8%. Our work thus provides a green and viable way to prepare high quality CsPbI3 perovskite films for optoelectronic applications.

In-situ growth of high-density ultrafine Ag3PO4 nanoparticles on 3D TiO2 hierarchical spheres for enhanced photocatalytic degradation of organic pollutants.

Silver phosphate (Ag3PO4, APO) has attracted intense attention as a visible-light-driven photocatalyst, but its large-scale application is limited by severe charge recombination and inevitable photo-corrosion. Various rational APO-based heterostructures composed of APO nanoparticles (NPs) and band-matched semiconductor support are designed to address the above issues. Nevertheless, the size, density, stability, and dispersion of APO NPs are critical challenges for the photocatalytic performance of APO-based photocatalysts. Here, three-dimensional (3D) self-assembled TiO2 hierarchical spheres (THS) prepared by a simple one-step hydrothermal method are employed as innovative support, and ultrafine high-density APO NPs with an average size of about 3 nm are successfully deposited and uniformly dispersed throughout THS to form hierarchical THS/APO composites. The novel THS/APO microstructure provides abundant reactive sites for photocatalytic reactions and promotes the photogenerated charge separation and transfer due to the ultrafine size of APO NPs and the TiO2/APO Type-II heterojunction. As a result, the THS/APO composites show significant improvement in photocatalytic activity and stability in methylene blue (MB) degradation. The reaction constant of THS/APO composites far exceeds that of either THS or APO, roughly 16 and 7 times higher than that of THS and APO under full-spectrum light, and 41 and 4 times higher under visible light. Our results strongly suggest new insights into the low-cost, large-scale application of high-efficiency APO-based photocatalyst.

DNA Hypomethylation of miR-30a Mediated the Protection of Hypoxia Postconditioning Against Aged Cardiomyocytes Hypoxia/Reoxygenation Injury Through Inhibiting Autophagy.

BACKGROUND: Ischemic postconditioning (IPostC) is an endogenous protective mechanism to reduce ischemia-reperfusion (I/R) injury. However, whether IPostC protects aged cardiomyocytes against I/R injury is not fully understood. Considering the protective function of microRNA 30a (miR-30a) against ischemia-induced injury in H9C2 cells, its role in the protective effects of IPostC on I/R injury of aged cardiomyocytes was investigated further.Methods and Results:To mimic I/R and IPostC in vitro, the aged cardiomyocyte model for hypoxia postconditioning (HPostC) treatment was established by 9 days of incubation with 8 mg/mL D-galactose and then followed by exposure to hypoxic environment. HPostC significantly alleviated hypoxia/reoxygenation (H/R) injury and reduced autophagy of aged cardiomyocytes, as evidenced by decreased LC3B-II expression and increased p62 by Western blot. Quantified by quantitative real-time polymerase chain reaction (qRT-PCR), miR-30a was increased in aged cardiomyocytes treated with HPostC compared with I/R injury group. Overexpression of miR-30a by LV3-rno-miR-30a mimic promoted cardioprotective effect of HPostC in aged cardiomyocytes by suppressing BECN1-mediated autophagy, all of which was abrogated by knockdown of miR-30a expression. Epigenetic analyses demonstrated that HPostC reduced DNA methyltransferase 3b-mediated DNA hypomethylation levels at miR-30a promoter, leading to upregulation of miR-30a. CONCLUSIONS: HPostC protected aged cardiomyocytes survival against H/R injury via DNMT3b-dependent activation of miR-30a. miR-30a could be a potential therapeutic target for ischemic myocardial infarction.

Aberrant MFN2 transcription facilitates homocysteine-induced VSMCs proliferation via the increased binding of c-Myc to DNMT1 in atherosclerosis.

It is well-established that homocysteine (Hcy) is an independent risk factor for atherosclerosis. Hcy can promote vascular smooth muscle cell (VSMC) proliferation, it plays a key role in neointimal formation and thus contribute to arteriosclerosis. However, the molecular mechanism on VSMCs proliferation underlying atherosclerosis is not well elucidated. Mitofusin-2 (MFN2) is an important transmembrane GTPase in the mitochondrial outer membrane and it can block cells in the G0/G1 stage of the cell cycle. To investigate the contribution of aberrant MFN2 transcription in Hcy-induced VSMCs proliferation and the underlying mechanisms. Cell cycle analysis revealed a decreased proportion of VSMCs in G0/G1 and an increased proportion in S phase in atherosclerotic plaque of APOE-/- mice with hyperhomocystinaemia (HHcy) as well as in VSMCs exposed to Hcy in vitro. The DNA methylation level of MFN2 promoter was obviously increased in VSMCs treated with Hcy, leading to suppressed promoter activity and low expression of MFN2. In addition, we found that the expression of c-Myc was increased in atherosclerotic plaque and VSMCs treated with Hcy. Further study showed that c-Myc indirectly regulates MFN2 expression is duo to the binding of c-Myc to DNMT1 promoter up-regulates DNMT1 expression leading to DNA hypermethylation of MFN2 promoter, thereby inhibits MFN2 expression in VSMCs treated with Hcy. In conclusion, our study demonstrated that Hcy-induced hypermethylation of MFN2 promoter inhibits the transcription of MFN2, leading to VSMCs proliferation in plaque formation, and the increased binding of c-Myc to DNMT1 promoter is a new and relevant molecular mechanism.

CsPbBr3 quantum dots assisted crystallization of solution-processed perovskite films with preferential orientation for high performance perovskite solar cells.

The performance of hybrid perovskite solar cells (PSCs) is significantly influenced by the crystallization and morphology of perovskite films. Herein, a novel method of CsPbBr3 quantum dots (QDs) assisted nucleation is applied to prepare high quality solution-processed methylammonium lead iodide (MAPbI3) films by employing CsPbBr3 QDs as an additive into diethyl ether anti-solvent. The appropriate amount of CsPbBr3 QDs can act as effective heterogeneous nucleation centers, leading to the formation of smooth and pinhole-free perovskite films with increased grain size. Furthermore, the growth direction of MAPbI3 grains is regulated by CsPbBr3 QDs, exhibiting preferential orientation of (110) plane. Therefore, the MAPbI3 films with CsPbBr3 QDs modification show reduced defects and increased carrier lifetime. As a result, the champion PSC with a maximum power conversion efficiency (PCE) up to 20.17% is achieved and 85% of its initial PCE is maintained after aging 1000 h at room temperature under a relative humidity of 50%. This work demonstrates a feasible way to prepare high quality perovskite films for optoelectronic applications.

Effects of n-butyl amine incorporation on the performance of perovskite light emitting diodes.

The efficiency of perovskite light emitting diodes (PeLEDs) is crucially limited by leakage current and nonradiative recombination. Here we introduce n-butyl amine (BA) to modulate the growth of perovskite films as well as improve the performance of PeLEDs, and investigate in detail the effects of BA incorporation on the structural, optical, and electrical characteristics of perovskite films. The results indicate that BA would terminate the grain surface and inhibit crystal growth, leading to increased radiative recombination. However, BA overload would make the films loose and recreate shunt paths. The electrical detriment of BA overload outweighs its optical benefit. As a result, optimal PeLEDs can be obtained only with moderate BA incorporation.

Amine treatment induced perovskite nanowire network in perovskite solar cells: efficient surface passivation and carrier transport.

In the fabrication of high efficiency organic-inorganic metal halide perovskite solar cells (PSCs), an additional interface modifier is usually applied for enhancing the interface passivation and carrier transport. In this paper, we develop an innovative method with in-situ growth of one-dimensional perovskite nanowire (1D PNW) network triggered by Lewis amine over the perovskite films. To our knowledge, this is the first time to fabricate PSCs with shape-controlled perovskite surface morphology, which improved power conversion efficiency (PCE) from 14.32% to 16.66% with negligible hysteresis. The amine molecule can passivate the trap states on the polycrystalline perovskite surface to reduce trap-state density. Meanwhile, as a fast channel, the 1D PNWs would promote carrier transport from the bulk perovskite film to the electron transport layer. The PSCs with 1D PNW modification not only exhibit excellent photovoltaic performances, but also show good stability with only 4% PCE loss within 30 days in the ambient air without encapsulation. Our results strongly suggest that in-situ grown 1D PNW network provides a feasible and effective strategy for nanostructured optoelectronic devices such as PSCs to achieve superior performances.

miR-34a Targets HDAC1-Regulated H3K9 Acetylation on Lipid Accumulation Induced by Homocysteine in Foam Cells.

Hyperhomocysteinemia (HHcy) promotes atherogenesis by modification of histone acetylation patterns and regulation of miRNA expression while the underlying molecular mechanisms are not well known. In this study, we investigated the effects of homocysteine (Hcy) on the expression of histone deacetylase 1 (HDAC1) and tested our hypothesis that Hcy-induced atherosclerosis is mediated by increased HDAC1 expression, which is regulated by miR-34a. The expression of HDAC1 increased and acetylation of histone H3 at lysine 9 (H3K9ac) decreased in the aorta of ApoE-/- mice fed with high methionine diet, whereas miR-34a expression was inhibited. Over-expression of HDAC1 inhibited H3K9ac level and promoted the accumulation of total cholesterol, free cholesterol, and triglycerides in the foam cells. Furthermore, up-regulation of miR-34a reduced HDAC1 expression and inhibited the accumulation of total cholesterol (TC), free cholesterol (FC), and triglycerides (TG) in the foam cells. These data suggest that HDAC1-related H3K9ac plays a key role in Hcy-mediated lipid metabolism disorders, and that miR-34a may be a novel therapeutic target in Hcy-related atherosclerosis. J. Cell. Biochem. 118: 4617-4627, 2017. © 2017 Wiley Periodicals, Inc.

Enhanced optoelectronic quality of perovskite films with excess CH3NH3I for high-efficiency solar cells in ambient air.

Solution-processed polycrystalline perovskite films contribute critically to the high photovoltaic performance of perovskite-based solar cells (PSCs). The inevitable electronic trap states at grain boundaries and intrinsic defects such as metallic lead (Pb0) and halide vacancies in perovskite films cause serious carrier recombination loss. Furthermore, the film can easily decompose into PbI2 in a moist atmosphere. Here, we introduce a simple strategy, through a small increase in methylammonium iodide (CH3NH3I, MAI), molar proportion (5%), for perovskite fabrication in ambient air with ∼50% relative humidity. Analysis of the morphology and crystallography demonstrates that excess MAI significantly promotes grain growth without decomposition. X-ray photoemission spectroscopy shows that no metallic Pb0 exists in the perovskite film and the I/Pb ratio is improved. A time-resolved photoluminescence measurement indicates efficient suppression of non-radiative recombination in the perovskite layer. As a result, the device yields improved power conversion efficiency from 14.06% to 18.26% with reduced hysteresis and higher stability under AM1.5G illumination (100 mW cm-2). This work strongly provides a feasible and low-cost way to develop highly efficient PSCs in ambient air.

Roles of NlAKTIP in the Growth and Eclosion of the Rice Brown Planthopper, Nilaparvata lugens Stål, as Revealed by RNA Interference.

AKT-interacting protein (AKTIP) interacts with serine/threonine protein kinase B (PKB)/AKT. AKTIP modulates AKT's activity by enhancing the phosphorylation of the regulatory site and plays a crucial role in multiple biological processes. In this study, the full length cDNA of NlAKTIP, a novel AKTIP gene in the brown planthopper (BPH) Nilaparvata lugens, was cloned. The reverse transcription quantitive PCR (RT-qPCR) results showed that the NlAKTIP gene was strongly expressed in gravid female adults, but was relatively weakly expressed in nymphs and male adult BPH. In female BPH, treatment with dsAKTIP resulted in the efficient silencing of NlAKTIP, leading to a significant reduction of mRNA levels, about 50% of those of the untreated control group at day 7 of the study. BPH fed with dsAKTIP had reduced growth with lower body weights and smaller sizes, and the body weight of BPH treated with dsAKTIP at day 7 decreased to about 30% of that of the untreated control. Treatment of dsAKTIP significantly delayed the eclosion for over 7 days relative to the control group and restricted ovarian development to Grade I (transparent stage), whereas the controls developed to Grade IV (matured stage). These results indicated that NlAKTIP is crucial to the growth and development of female BPH. This study provided a valuable clue of a potential target NlAKTIP for inhibiting the BPH, and also provided a new point of view on the interaction between BPH and resistant rice.

Sensitization of Er3+ ions in silicon rich oxynitride films: effect of thermal treatments.

The optical properties of reactive co-sputtered erbium doped silicon rich oxynitride (Er:SRON) films are studied as a function of annealing temperatures (Ta). The sensitization mechanism of Er3+ is found to evolve with Ta: excess Si related localized states play the essential role in samples when Ta is below 700 °C, while silicon nanoclusters (Si-NCs) become the dominate sensitizers when Ta exceeds 800 °C. Our results show that higher density of sensitized Er3+ could be acquired via energy transfer from localized states, and thus provide an alternative way for the engineering of light sources based on Er:SRON.

Strain Regulation and Defect Passivation of FA-Based Perovskite Materials for Highly Efficient Solar Cells.

Formamidine lead triiodide (FAPbI3 ) perovskites have attracted increasing interest for photovoltaics attributed to the optimal bandgap, high thermal stability, and the record power conversion efficiency (PCE). However, the materials still face several key challenges, such as phase transition, lattice defects, and ion migration. Therefore, external ions (e.g., cesium ions (Cs+ )) are usually introduced to promote the crystallization and enhance the phase stability. Nevertheless, the doping of Cs+ into the A-site easily leads to lattice compressive strain and the formation of pinholes. Herein, trioctylphosphine oxide (TOPO) is introduced into the precursor to provide tensile strain outside the perovskite lattice through intermolecular forces. The special strain compensation strategy further improves the crystallization of perovskite and inhibits the ion migration. Moreover, the TOPO molecule significantly passivates grain boundaries and undercoordinated Pb2+ defects via the forming of P═O─Pb bond. As a result, the target solar cell devices with the synergistic effect of Cs+ and TOPO additives have achieved a significantly improved PCE of 22.71% and a high open-circuit voltage of 1.16 V (voltage deficit of 0.36 V), with superior stability under light exposure, heat, or humidity conditions.

Hypermethylation of the CTRP9 promoter region promotes Hcy induced VSMC lipid deposition and foam cell formation via negatively regulating ER stress.

To provide a theoretical basis for the prevention and treatment of atherosclerosis (As), the current study aimed to investigate the mechanism underlying the effect of homocysteine (Hcy) on inducing the lipid deposition and foam cell formation of the vascular smooth muscle cell (VSMC) via C1q/Tumor necrosis factor-related protein9 (CTRP9) promoter region Hypermethylation negative regulating endoplasmic reticulum stress (ERs). Therefore, apolipoprotein E deficient (ApoE-/-) mice were randomly divided into the control [ApoE-/- + normal diet (NC)] and high methionine [ApoE-/- + (normal diet supplemented with 1.7% methionine (HMD)] groups (n = 6 mice/group). Following feeding for 15 weeks, the serum levels of Homocysteine (Hcy), total cholesterol (TC), and triglyceride (TG) were measured using an automatic biochemical analyzer. HE and oil red O staining were performed on the aorta roots to observe the pathological changes. Additionally, immunofluorescence staining was performed to detect the protein expression levels of CTRP9, glucose-regulated protein 78 kD (GRP78), phosphorylated protein kinase RNA-like ER kinase (p-PERK), activating transcription factor 6a (ATF6a), phosphorylated inositol-requiring enzyme-1α (p-IRE1α), sterol regulatory element binding proteins-1c (SREBP1c) and sterol regulatory element binding proteins-2 (SREBP2) in VSMC derived from murine aortic roots. In vitro, VSMC was stimulated with 100 µmol/l Hcy. After transfection of plasmids with overexpression and interference of CTRP9, ERs agonist (TM) and inhibitor (4-PBA) were given to stimulate VSMC cells. HE staining and oil red O staining were used to observe the effect of Hcy stimulation on lipid deposition in VSMC. Additionally, The mRNA and protein expression levels of CTRP9, GRP78, PERK, ATF6a, IRE1α, SREBP1c, and SREBP2 in VSMC were detected by RT-qPCR and western blot analysis, respectively. Finally, The methylation modification of the CTRP9 promoter region has been studied. The NCBI database was used to search the promoter region of the CTRP9 gene, and CpG Island was used to predict the methylation site. After Hcy stimulation of VSMC, overexpression of DNMT1, and intervention with 5-Azc, assess the methylation level of the CTRP9 promoter through bisulfite sequencing PCR (BSP). The results showed that the serum levels of Hcy, TC, and TG in the ApoE-/- + HMD group were significantly increased compared with the ApoE-/- + NC group. In addition, HE staining and oil red O staining showed obvious AS plaque formation in the vessel wall, and a large amount of fat deposition in VSMC, thus indicating that the hyperhomocysteinemia As an animal model was successfully established. Furthermore, CTRP9 were downregulated, while GRP78, p-PERK, ATF6a, p-IRE1α, SREBP1c, SREBP2 was upregulated in aortic VSMC in the ApoE-/- + HMD group. Consistent with the in vivo results, Hcy can inhibit the expression of CTRP9 in VSMC and induce ERs and lipid deposition in VSMC. Meanwhile, the increased expression of CTRP9 can reduce ERs and protect the lipid deposition in Hcy induced VSMC. Furthermore, ERs can promote Hcy induced VSMC lipid deposition, inhibition of ERs can reduce Hcy induced VSMC lipid deposition, and CTRP9 may play a protective role in Hcy induced VSMC lipid deposition and foam cell transformation through negative regulation of ERs. In addition, The CTRP9 promoter in the Hcy group showed hypermethylation. At the same time as Hcy intervention, overexpression of DNMT1 increases the methylation level of the CTRP9 promoter, while 5-Azc can reduce the methylation level of the CTRP9 promoter. Finally, Hcy can up-regulate the expression of DNMT1 and down-regulate the expression of CTRP9. After overexpression of DNMT1, the expression of CTRP9 is further decreased. After 5-Azc inhibition of DNMT1, the expression of DNMT1 decreases, while the expression of CTRP9 increases. It is suggested that the molecular mechanism of Hcy inhibiting the expression of CTRP9 is related to the hypermethylation of the CTRP9 promoter induced by Hcy and regulated by DNMT1. 5-Azc can inhibit the expression of DNMT1 and reverse the regulatory effect of DNMT1 on CTRP9. Overall, the results of the present study suggested that Hcy induces DNA hypermethylation in the CTRP9 promoter region by up-regulating DNMT1 expression, and negatively regulates ERs mediated VSMC lipid deposition and foam cell formation. CTRP9 may potentially be a therapeutic target in the treatment of hyperhomocysteinemia and As.

Identification and Validation of Immune-Related Genes Diagnostic for Progression of Atherosclerosis and Diabetes.

Background: Atherosclerosis and type 2 diabetes mellitus contribute to a large part of cardiovascular events, but the underlying mechanism remains unclear. In this study, we focused on identifying the linking genes of the diagnostic biomarkers and effective therapeutic targets associated with these two diseases. Methods: The transcriptomic datasets of atherosclerosis and type 2 diabetes mellitus were obtained from the GEO database. Differentially expressed genes analysis was performed by R studio software, and differential analysis including functional enrichment, therapeutic small molecular agents prediction, and protein-protein interaction analysis were applied to the common shared differentially expressed genes. Hub genes were identified and further validated using an independent dataset and clinical samples. Furthermore, we measured the expression correlations, immune cell infiltration, and diagnostic capability of the three key genes. Results: We screened out 28 up-regulated and six down-regulated common shared differentially expressed genes. Functional enrichment analysis showed that cytokines and immune activation were involved in the development of these two diseases. Six small molecules with the highest absolute enrichment value were identified. Three critical genes (CD4, PLEK, and THY1) were further validated both in validation sets and clinical samples. The gene correlation analysis showed that CD4 was strongly positively correlated with PLEK, and ROC curves confirmed the good discriminatory capacity of CD4 and PLEK in two diseases.We have established the co-expression network between atherosclerosis lesions progressions and type 2 diabetes mellitus, and identified CD4 and PLEK as key genes in the two diseases, which may facilitate both development of diagnosis and therapeutic strategies.

Developing a Novel Immune-Related Seven-Gene Signature and Immune Infiltration Pattern in Patients with COVID-19 and Cardiovascular Disease.

BACKGROUND: patients with pre-existence of cardiovascular disease (CVD) are vulnerable to coronavirus disease 2019 (COVID-19), and COVID-19 will cause long-term burden of CVD. However, the common pathogenic mechanisms are not fully elucidated. More detailed knowledge of linking biological molecules and the role of immune signature would allow more valuable and specific clinical management. METHODS: the gene expression profiles of CVD and COVID-19 were retrieved from the GEO database. Common differentially expressed genes (DEGs) were screened with the Limma R package and the WGCNA algorithm, and then functional enrichment analysis, protein-protein interaction network, hub genes, and small therapeutic molecules analyses were performed. The hub immune-related genes (HIRGs) were intersected, and their associations with immune cells, expressional correlation, evaluated performance, and potential signal pathways were further investigated. RESULTS: In total, 57 common DEGs were identified as a shared transcriptional signature between CVD and COVID-19, and 12 hub genes were screened using five topological algorithms. There are common altered immune responses in the response of these two diseases, and seven HIRGs, including C5AR1, MMP9, CYBB, FPR2, CSF1R, TLR2, and TLR4, were identified, with positive correlation to altered macrophages and neutrophils. Nine small molecular agents (SMAs) were detected as promising therapeutic drugs. These seven HIRGs mainly participated in the inflammatory immune response through activation of Il2 stat5 signaling and Tnfa signaling via nfκb pathways, and ROC curves confirmed their good discriminatory capacity in the two diseases. CONCLUSIONS: this study established the co-expression network and identified a new immune-related seven-gene signature as therapeutic targets, which may provide new insights into pathogenic mechanisms and novel clinical management strategies.

Ischemic Postconditioning Protects against Aged Myocardial Ischemia/Reperfusion Injury by Transcriptional and Epigenetic Regulation of miR-181a-2-3p.

Ischemic postconditioning (IPostC) has been proposed as a strategy to mitigate the risk of ischemia/reperfusion (I/R) injury, and autophagy is involved in I/R-induced aged myocardial injury, while the underlying mechanism of IPostC-regulated autophagy is unknown. Here, we implemented miRNA sequencing analysis in aged cardiomyocytes to identify a novel miR-181a-2-3p after HPostC, which inhibits autophagy by targeting AMBRA1 in aged myocardium to protect I/R-induced aged myocardial injury. Mechanistically, we identified that IPostC can induce DNA hypomethylation and H3K14 hyperacetylation of miR-181a-2-3p promoter due to the decreased binding of DNMT3b and HDAC2 at its promoter, which contributes to enhancing the expression of miR-181a-2-3p. More importantly, cooperation of DNMT3b and HDAC2 inhibits the binding of c-Myc at the miR-181a-2-3p promoter in aged cardiomyocytes. In summary, IPostC attenuates I/R-induced aged myocardial injury through upregulating miR-181a-2-3p expression, which is an attribute to transcriptional and epigenetic regulation of its promoter. Our data indicate that miR-181a-2-3p may be a potential therapeutic target against I/R injury in aged myocardium.