Identification of important genes related to HVSMC proliferation and migration in graft restenosis based on WGCNA.

The great saphenous vein is the most commonly used vessel for coronary artery bypass grafting (CABG), but its use has been associated with a high restenosis rate at 10-year follow-up. This study sought to determine the key genes associated with vein graft restenosis that could serve as novel therapeutic targets. A total of 3075 upregulated and 1404 downregulated genes were identified after transcriptome sequencing of three pairs of restenosed vein grafts and intraoperative spare great saphenous veins. Weighted gene co-expression network analysis showed that the floralwhite module had the highest correlation with vein graft restenosis. The intersection of the floralwhite module gene set and the upregulated gene set contained 615 upregulated genes strongly correlated with vein graft restenosis. Protein-protein interaction network analysis identified six hub genes (ITGAM, PTPRC, TLR4, TYROBP, ITGB2 and CD4), which were obtained using the STRING database and CytoHubba. Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses showed that the common hub genes were mainly involved in the composition of the cell membrane; in biological processes such as neutrophil degranulation, receptor binding and intercellular adhesion, innate immune deficiency; and other signaling pathways. Finally, ITGB2 was selected as the target gene, and its expression was verified in tissues. The results showed that ITGB2 was significantly overexpressed in occluded vein grafts. To study the function of ITGB2 in HVSMCs, primary HVSMCs were cultured and successfully identified. EdU incorporation, wound healing and transwell assays showed that ITGB2 silencing significantly inhibited the proliferation and migration of HVSMCs stimulated by PDGF-BB. Overall, our study provides a basis for future studies on preventing restenosis following CABG.

Melatonin alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis in Atherosclerosis progression.

BACKGROUND: Atherosclerosis (AS), a significant contributor to cardiovascular disease (CVD), is steadily rising with the aging of the global population. Pyroptosis and apoptosis, both caspase-mediated cell death mechanisms, play an essential role in the occurrence and progression of AS. The human pineal gland primarily produces melatonin (MT), an indoleamine hormone with powerful anti-oxidative, anti-pyroptotic, and anti-apoptotic properties. This study examined MT's anti-oxidative stress and anti-pyroptotic effects on human THP-1 macrophages treated with nicotine. METHODS: In vitro, THP-1 macrophages were induced by 1 µM nicotine to form a pyroptosis model and performed 30 mM MT for treatment. In vivo, ApoE-/- mice were administered 0.1 mg/mL nicotine solution as drinking water, and 1 mg/mL MT solution was intragastric administrated at 10 mg/kg/day. The changes in pyroptosis, apoptosis, and oxidative stress were detected. RESULTS: MT downregulated pyroptosis, whose changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of sirtuin3 (SIRT3), and Forkhead box O3 (FOXO3α) upregulation. MT also inhibited apoptosis, mainly caused by the interaction of caspase-1 and caspase-3 proteins. Vivo studies confirmed that nicotine could accelerate plaque formation. Moreover, mice treated with MT showed a reduction in AS lesion area. CONCLUSIONS: MT alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis. Importantly, our understanding of the inhibitory pathways for macrophage pyroptosis will allow us to identify other novel therapeutic targets that will help treat, prevent, and reduce AS-associated mortality.

Efficient Total Synthesis and Herbicidal Activity of 3-Acyltetramic Acids: Endogenous Abscisic Acid Synthesis Regulators.

An efficient synthesis method will allow a large number of tetramic acid analogues to be synthesized for property and potency optimization. In this study, a facile and efficient method was described for the synthesis of 3-acyltetramic acids. The synthesis was accomplished mainly via (1) mild intramolecular cyclization and (2) the formation of ß-ketoamides between nucleophiles and acyl Meldrum's acids. 3-Acyltetramic acid exhibited phytotoxicity against Echinochloa crusgalli and Portulaca oleracea. At a dosage of 750 g ha-1, 6k and 6a showed high herbicidal activity against E. crusgalli, Digitaria sanguinalis and P. oleracea, Amaranthus retroflexus, respectively. 6k inhibited the synthesis of endogenous abscisic acid, thus seedling germination and plant growth. The incorporation of various acyl Meldrum's acids and amino acid esters was applicable to the parallel synthesis of 3-acyltetramic acids. The mode of action and herbicidal activity indicate that 3-tetramic acid had good herbicidal performance and was a promising herbicide candidate. This study will provide a reference for novel herbicide development.

Improved myocardial performance in infarcted rat heart by injection of disulfide-cross-linked chitosan hydrogels loaded with basic fibroblast growth factor.

Myocardial infarction (MI) has been considered as the leading cause of cardiovascular-related deaths worldwide. Basic fibroblast growth factor (bFGF) is a member of the fibroblast growth factor family that promotes angiogenesis after MI; however, it has poor clinical efficacy due to proteolytic degradation, low drug accumulation, and severe drug-induced side effects. In this study, an injectable disulfide-cross-linked chitosan hydrogel loaded with bFGF was prepared via a thiol-disulfide exchange reaction for MI treatment. The thiol-disulfide exchange reaction between pyridyl disulfide-modified carboxymethyl chitosan (CMCS-S-S-Py) and reduced BSA (rBSA) was carried out under physiological conditions (37 °C and pH 7.4). The mechanical properties of the disulfide-cross-linked chitosan hydrogel were evaluated based on the molar ratio of the pyridyl disulfide groups of CMCS-S-S-Py and the thiol groups of rBSA. The disulfide-cross-linked chitosan hydrogel showed good swelling performance, rapid glutathione-triggered degradation behavior and well-defined cell proliferation towards NIH 3T3 fibroblast cells. In the process of establishing a rat MI model, the squeezing heart method was used to make the operation more accurate and the mortality of rats was decreased by using a ventilator. The disulfide-cross-linked chitosan hydrogel loaded with bFGF (bFGF-hydrogel) was injected into a peri-infarcted area of cardiac tissue immediately following MI. Echocardiography demonstrated that the left ventricular functions were improved by the bFGF-hydrogel after 28 days of treatment. Histological results revealed that the hydrogel significantly reduced the fibrotic area of MI, and this was further improved by the bFGF-hydrogel treatment. TUNEL and immunohistochemical staining results showed that the bFGF-hydrogel had a more synergistic effect on antiapoptosis and proangiogenesis than using either bFGF or the hydrogel alone.

Inhibition of the miR-193b-3p protects against oxidized low-density lipoprotein-induced HUVECs injury by upregulating ALDH2.

Atherosclerosis (AS) is the most dangerous factor for human death, which is a lipid-driven chronic inflammatory disorder of the arteries. Growing evidence has showed that microRNAs play an important role in AS. However, the role of mir-193b-3p in atherosclerosis has been poorly studied to date. Therefore, we focused on the potential role of miR-193b-3p in atherosclerosis. The expressions of miR-193b-3p in the serum of AS patients were detected. We also established an oxidized low density lipoprotein (ox-LDL)-induced human umbilical vein endothelial cells (HUVECs) apoptosis model in vitro. The mRNA and protein levels of target molecules were detected by RT-qPCR and Western blotting. Apoptosis of HUVECs was determined by Annexin V/PI staining on a flow cytometry. The potential molecular targets of miR-193b-3p were investigated by applying such technologies as dual-luciferase reporter and RIP assay. Our study showed that miR-193b-3p expression level was significantly lower in AS patients than controls. ROC curve analysis showed that the areas under the curve (AUC) of plasma miR-193b-3p was 0.859. We also found that miR-193b-3p was decreased in ox-LDL-induced HUVECs and knockdown of miR-193b-3p suppressed ox-LDL-induced HUVECs injury. By using bioinformatics analysis, aldehyde dehydrogenase (ALDH2) was predicted as a downstream target of miR-193b-3p. The ALDH2 gene is also involved in the development of atherosclerosis. Meanwhile, inhibition of miR-193b-3p and ALDH2 protects ox-LDL-induced HUVECs against endoplasmic-reticulum (ER) stress. In conclusion, inhibition of miR-193b-3p was able to suppress ox-LDL-induced injury in AS through targeting ALDH2 and reducing ER stress.

Myricetin ameliorates ox-LDL-induced HUVECs apoptosis and inflammation via lncRNA GAS5 upregulating the expression of miR-29a-3p.

Oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell dysfunction is a significant event in the progression of atherosclerosis. Even Myricetin (Myr) has been exhibited strong antioxidant potency, the effect on atherosclerosis is still elusive. HUVECs were subjected to ox-LDL, before which cells were preconditioned with Myr. Cell Counting Kit-8 assay, flow cytometry, quantitative real-time polymerase chain reaction and Western blot were carried out to assess the impacts of ox-LDL and Myr on HUVECs. The expression of EndMT markers was determined by Western blot analysis and immunocytochemistry. In addition, the relationship of GAS5 and miR-29a-3p was evaluated by RNA Fluorescent in Situ Hybridization and RNA immunoprecipitation assay. Myr preconditioning prevented ox-LDL-induced apoptosis, inflammatory response, and EndMT. GAS5 was upregulated in response to ox-LDL while it was down-regulated by Myr preconditioning. GAS5 over-expression attenuates Myr protective effects against ox-LDL-mediated HUVEC injury. Besides, miR-29a-3p is a target of GAS5 and down-regulated miR-29a-3p could further reduce the effects of GAS5 in ox-LDL-mediated HUVEC. Furthermore, Myr inactivated the TLR4/NF-κB signalling pathway in ox-LDL-treated HUVEC by down-regulating GAS5 or upregulating miR-26a-5p. Myr possessed an anti-inflammatory and anti-EndMT function against ox-LDL-induced HUVEC injury by regulating the GAS5/miR-29a-3p, indicating that Myr may have an important therapeutic function for atherosclerosis.

Short reaction times coupled with alkalization improves the release of phosphorus from Al-waste activated sludge.

In this study, the performance and mechanism of P release from Al-waste activated sludge (WAS) via wet-chemical treatment at different reaction times were investigated. The maximum P release (46% of TP) was achieved at 20 min when the pH was maintained at 2 during acidic treatment. During alkali treatment, the maximum P concentration (363.96 mg/L, 46.07%) was achieved at 10 min when pH was initially adjusted to 12. Acidic treatment took twice as long to achieve the same efficiency of released P as the alkali treatment. Furthermore, P release mainly originated from Al-P and Ca-P during acidic treatment and Al-P dissolution during alkali treatment. The cost of chemical consumption was 483.96 USD/ton TS sludge with acidic treatment, which was 8.49 times higher than that of alkali treatment without pH control. Thus, short reaction times (ca. 10 min) coupled with alkalization provide an effective approach for improving P release from Al-WAS.

Fabrication and assessment of chondroitin sulfate-modified collagen nanofibers for small-diameter vascular tissue engineering applications.

Chondroitin sulfate (ChS) has shown promising results in promoting cell proliferation and antithrombogenic activity. To engineered develop a dual-function vascular scaffold with antithrombosis and endothelialization, ChS was tethered to collagen to accelerate the growth of endothelial cells and prevent platelet activation. First, ChS was used to conjugate with collagen to generate glycosylated products (ChS-COL) via reductive amination. Then, the fabricated ChS-COL conjugates were electrospun into nanofibers and their morphologies and physicochemical characteristics, cell-scaffold responses and platelet behaviors upon ChS-COL nanofibers were comprehensively characterized to evaluate their potential use for small-diameter vascular tissue-engineered scaffolds. The experimental results demonstrated that the ChS modified collagen electrospun nanofibers were stimulatory of endothelial cell behavior, alleviated thrombocyte activation and maintained an antithrombotic effect in vivo in 10-day post-transplantation. The ChS-COL scaffolds encouraged rapid endothelialization, thus probably ensuring the antithrombotic function in long-term implantation, suggesting their promise for small-diameter vascular tissue engineering applications.

Bovine pericardial versus porcine stented replacement mitral valves: early hemodynamic performance and clinical results of a randomized comparison of the Perimount and the Mosaic valves.

BACKGROUND: To compare the hemodynamic and clinical outcomes following mitral valve replacement with the Perimount valve with those of the Mosaic valve. METHODS: A total of 145 consecutive patients with rheumatic heart valve disease who underwent single bioprosthetic mitral valve replacement were randomized to receive either the Perimount (n=72) valve or the Mosaic bioprosthesis (n=73). The mean age of patients was 72.1 years (range, 58-89 years) with a sex distribution of 55.2% female and 44.8% male. Patients underwent follow up transthoracic echocardiography at 3 months and 1 year postoperatively. We compared demographics, preoperative clinical data, operative data, hemodynamic profiles, and clinical outcomes. RESULTS: The cross-clamp time was similar, with 50.7±15.3 minutes for the Perimount and 50.7±21.8 minutes for the Mosaic bioprosthesis. The total bypass time was also similar, with 91.3±25.7 minutes for the Perimount and 87.8±25.6 minutes for the Mosaic valve. The peak and mean pressure gradients were lower in the Perimount group for all valve sizes and the difference was statistically significant at 1 year. The effective orifice area (EOA) was slightly larger in the Perimount valve (1.98±0.21 vs. 1.89±0.71 cm2, P=0.538) postoperatively, but there was no significant difference at 1 year. There were no differences in preoperative or postoperative left atrium diameter (LAD), left ventricular diastolic diameter (LVDD), left ventricular systolic diameter (LVSD), left ventricular ejection fraction (LVEF), pulmonary artery pressure (PAP). The mortality and major complications rate were similar between the two groups. CONCLUSIONS: The Perimount prostheses is superior to the Mosaic prostheses after mitral valve replacement, achieving statistically significant lower gradients and larger EOA when compared on the basis of manufacturer-labeled valve sizes. Both valves appear to provide satisfactory clinical results.

BPI and KIR6.1 as significant hub genes for vein graft restenosis.

BACKGROUND: Vein graft restenosis (VGR), which appears to be caused by dyslipidemia following vascular transplantation, seriously affects the prognosis and long-term quality of life of patients. METHODS: This study analyzed the genetic data of restenosis (VGR group) and non-stenosis (control group) vessels from patients with coronary heart disease post-vascular transplantation and identified hub genes that might be responsible for its occurrence. GSE110398 was downloaded from the Gene Expression Omnibus database. A repeatability test for the GSE110398 dataset was performed using R language. This included the identification of differentially expressed genes (DEGs), enrichment analysis via Metascape software, pathway enrichment analysis, and construction of a protein-protein interaction network and a hub gene network. RESULTS: Twenty-four DEGs were identified between VGR and control groups. The four most important hub genes (KIR6.1, PCLP1, EDNRB, and BPI) were identified, and Pearson's correlation coefficient showed that KIR6.1 and BPI were significantly correlated with VGR. KIR6.1 could also sensitively predict VGR (0.9 < area under the curve ≤1). CONCLUSION: BPI and KIR6.1 were differentially expressed in vessels with and without stenosis after vascular transplantation, suggesting that these genes or their encoded proteins may be involved in the occurrence of VGR.

First-principles calculations of mechanical and thermodynamic properties of tetragonal Be12Ti.

The elastic and thermodynamic properties of tetragonal Be12Ti under high temperature and pressure are investigated by first-principles calculations based on pseudopotential plane-wave density functional theory (DFT) within the generalized gradient approximation (GGA) and quasi-harmonic approximation (QHA). The calculated lattice parameters and bulk modulus are in good agreement with the available experimental data. The calculated elastic constants of Be12Ti increase monotonously with increasing pressure, and the elastic stability criterion and the phonon dispersion calculation show that the Be12Ti crystal satisfies the mechanical and dynamic stability under applied pressure (0-100 GPa). The related mechanical properties such as bulk modulus (B), shear modulus (G), Young's modulus (E), and Poisson's ratio (ν) are also studied for polycrystalline of Be12Ti; the calculated B/G value shows that Be12Ti behaves in a brittle manner, and higher pressure can significantly improve the brittleness of Be12Ti. The elastic anisotropy is demonstrated by the elastic anisotropy factors. The direction-dependent Young's modulus and bulk modulus of Be12Ti are dealt with in detail under pressure from 0 GPa to 100 GPa. The pressure and temperature dependencies of the relative volume, the bulk modulus, the elastic constants, the heat capacity and the thermal expansion coefficient, as well as the entropy are obtained and discussed using the quasi-harmonic approximation in the ranges of temperature 0-1600 K and pressure 0-100 GPa.