Atherosclerosis is a common and deadly cardiovascular disease with extremely high prevalence. Areas of the vasculature exposed to oscillatory shear stress (OSS) or disturbed blood flow are particularly prone to the development of atherosclerotic lesions. In part, various mechanosensitive receptors on the surface of endothelial cells play a role in regulating the ability of the vasculature to cope with variations in blood flow patterns. However, the exact mechanisms behind flow-mediated endothelial responses remain poorly understood. Along with the development of highly specific receptor agonists, the class of G coupled-protein receptors has been receiving increasing attention as potential therapeutic targets. G coupled-protein receptor 81 (GPR81), also known as hydroxycarboxylic acid receptor 1 (HCA 1 ), is activated by lactate, its endogenous ligand. In the present study, we show for the first time that expression of GPR81 is significantly downregulated in response to OSS in endothelial cells and that activation of GPR81 using physiologically relevant doses of lactate can rescue OSS-induced reduced GPR81 expression. Importantly, our findings demonstrate that activation of GPR81 can exert valuable atheroprotective effects in endothelial cells exposed to OSS by reducing oxidative stress and significantly downregulating the expression of inflammatory cytokines including interleukin (IL)-6, IL-8, monocyte chemoattractant protein (MCP)-1, and high mobility group box 1 (HMGB1). We also show that activation of GPR81 can potentially prevent the attachment of monocytes to the endothelium by suppressing OSS-induced secretion of vascular cellular adhesion molecule (VCAM)-1 and endothelial-selectin (E-selectin). Finally, we show that activation of GPR81 can rescue OSS-induced reduced expression of the key atheroprotective transcription factor Kruppel-like factor 2 (KLF2), which is mediated through the extracellularregulated kinase 5 (ERK5) pathway. These findings demonstrate a potential Abbreviations: ECL, electrochemiluminescence; E-selectin, endothelial-selectin; ELISA, Enzyme-linked immunosorbent assay; ERK5, extracellularregulated kinase 5; FBS, fetal bovine serum; GPR81, G coupled-protein receptor 81; GPCRs, G protein-coupled receptors; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; HMGB1, high mobility group box 1; HSS, high shear stress; HUVECs, human umbilical vascular endothelial cells; HCA 1 , hydroxycarboxylic acid receptor 1; IL-6, interleukin; KLF2, Kruppel-like factor 2; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemoattractant protein; OSS, oscillatory shear stress; PAK1, p21-activated kinase 1; PVDF, polyvinylidene fluoride; ROS, reactive oxygen species; RT-PCR, reverse transcription PCR; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; VCAM-1, vascular cellular adhesion molecule.
Based on the three-dimensional (3D) ecological footprint model, this paper has provided the measurements of the dynamic changes of the 3D ecological footprint of Shenyang from 2005 to 2016, and the analysis of the driving factors behind such footprint through the partial least-squares regression. Our research findings reveal that: The overall per capita 3D ecological footprint of the Shenyang City went upward from 2005 to 2016, with an average annual growth rate of 16.5%; at the meantime, the per capita ecological carrying capacity showed a year-on-year downward trend at an average annual rate of 0.79%. The analysis of partial least squares regression indicates that urban ecological construction and environmental pollution constitute the significant factors that lead to the increase of the ecological footprint year by year in Shenyang. On the contrary, the exchange and trade, the environmental governance and the structure of land use are conducive to relieving the pressure on the ecological expansion. Our analysis of the importance of variable projections demonstrates that per capita public green area and the emission indicators of the industrial waste have imposed a greater influence on the index of ecological footprint of Shenyang and are relatively consistent with the comprehensive evaluation results of the regression analysis. In the future, we shall enhance the efficiency of urban ecological construction by optimizing industrial structure, using clean energy, actively developing foreign trade and exchanges, and rationally planning urban land use.
The analytic hierarchy process is used to construct the health evaluation index system and grading standard of small- and medium-sized rivers in the region. Based on the principles of RBF and GRNN neural network algorithms, the river health evaluation models of radial basis function neural network (RBF) and general regression neural network (GRNN) algorithms are constructed, respectively. The network training samples are constructed by the interpolation method. The standard value of river health classification evaluation is taken as the “prediction” sample to “predict”. Then the results are applied as the division basis of the river health classification evaluation, which is to evaluate and analyze the health status of small and medium rivers in Suzhou Prefecture. The results indicate that: (1) the RBF and GRNN neural network models have exactly the same results in evaluating the health of small and medium rivers in the region, and are basically the same as the back propagation (BP) neural network evaluation results. RBF and GRNN neural network models have the advantages of fast convergence speed, high prediction accuracy, harder to fall into local minima, less adjustment parameters, and only one spread parameter, which can predict and evaluate the network faster, which is a large calculation advantage. (2) The health evaluation level of the main rivers in Suzhou Prefecture is from grades II to III, that is, between healthy and sub-healthy. This grade objectively reflects the health status of small- and medium-sized rivers in the region, which can provide a reference for the sustainable management of regional rivers and ecological environment construction.
Objective To investigate the efficacy and safety of percutaneous closure of ventricular septal rupture (VSR) after acute myocardial infarction (AMI). Methods This retrospective study included 81 patients who underwent transcatheter closure for postinfarction VSR. We analyzed clinical data from hospitalization and the 30‐day follow‐up, compared clinical data from the survival and death groups, and explored the best closure time and the safety and efficacy of occlusion. The risk factors for death at 30 days were analyzed by logistic regression. Results C‐reactive protein (CRP), white blood cell counts, N‐terminal pro brain natriuretic peptide (NT‐ProBNP), and aspartate aminotransferase were higher in the death group than in the survival group (p < .01), with a higher rate of application of vasoactive drugs, and a shorter time from AMI to operation (p < .05). At 30 days postocclusion, 19 patients (23.5%) had died. The mortality rate was significantly lower for operation performed 3 weeks after AMI than for operation performed within 3 weeks of AMI (12.5% vs. 48%, p < .001). Devices were successfully implanted in 76 patients, with 16 (21.1%) operation‐related complications and 12 (15.8%) valve injuries. Cardiac function improved significantly (p < .001) at discharge (N = 66) and 30 days after procedure (N = 62). Qp/Qs and pulmonary artery systolic pressure decreased significantly, while aortic systolic pressure increased significantly (p < .001). Additionally, EF and LVDd improved (p < .05) after occlusion. Increases in CRP and NT‐ProBNP were risk factors for death at 30 days after closure (p < .05). Conclusion Percutaneous VSR closure can be a valuable treatment option for suitable patients with VSR.
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