A combined analysis of bulk RNA-seq and scRNA-seq was performed to investigate the molecular mechanisms associated with the occurrence of myocardial infarction.

BACKGROUND: Myocardial infarction (MI) induces complex transcriptional changes across diverse cardiac cell types. Single-cell RNA sequencing (scRNA-seq) provides an unparalleled ability to discern cellular diversity during infarction, yet the veracity of these discoveries necessitates confirmation. This investigation sought to elucidate MI mechanisms by integrating scRNA-seq and bulk RNA-seq data. METHODS: Publicly available scRNA-seq (GSE136088) and bulk RNA-seq (GSE153485) data from mice MI models were analyzed. Cell types were annotated, and differential expression analysis conducted. Bulk RNA-seq underwent quality control, principal component analysis, and differential expression analysis. RESULTS: In scRNA-seq data, the comparison between MI and sham groups unveiled a reduction in endothelial cell populations, but macrophages and monocytes increased. Within fibroblast subgroups, three distinct categories were discerned, with two exhibiting upregulation in MI. Notably, endothelial cells exhibited an elevated expression of genes associated with apoptosis and ferroptosis. In bulk RNA-seq analysis, distinct patterns emerged when comparing MI and sham groups. Specifically, six genes linked to endothelial ferroptosis exhibited heightened expression in MI group, thereby corroborating the scRNA-seq findings. Moreover, the examination of isolated cardiac macrophages from mice MI model revealed increased expression of Spp1, Col1a2, Col3a1, Ctsd, and Lgals3 compared to sham group, thus substantiating the dysregulation of macrophage apoptosis-related proteins following MI. CONCLUSION: MI altered the transcriptomic landscapes of cardiac cells with increased expression of apoptotic genes. Moreover, the upregulation of macrophage apoptosis marker was confirmed within MI models. The presence of endothelial cell depletion and ferroptosis in MI has been demonstrated.

Deciphering heart failure: an integrated proteomic and transcriptomic approach with experimental validation.

This study analyzed transcriptomic and proteomic data to identify molecular changes during heart failure (HF). Additionally,we embarked on an exploration of the prospect of therapeutic intervention through the manipulation of proteins implicated in ferroptosis. Three publicly available microarray datasets (GSE135055, GSE147236, GSE161472) profiling left ventricular samples from HF patients and healthy controls were obtained. Differentially expressed genes were identified in each dataset and cross-analyzed to determine shared gene signatures. Enrichment analysis of Gene Ontology (GO) terms, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and gene set enrichment analysis were performed. Differentially expressed proteins were obtained from published proteomic studies and integrated with the transcriptomic results. To validate findings, a HF mouse model was generated and ferroptosis-related proteins were evaluated. Additionally, the effect of suppression of ferroptosis on hypoxia-induced ischemia model in HL-1 cardiomyocytes was assessed by knocking down Acyl-CoA synthetase long-chain family member 4 (ACSL4) using small interfering RNA (siRNA).Cross-analysis of differentially expressed genes (DEGs) in the GSE135055, GSE147236 and GSE161472 datasets revealed 224 up-regulated and 187 down-regulated potential genes which showed high enrichment in immune, inflammatory and metabolic pathways. Notably, four proteins, among them ACSL4, displayed consistent alterations at both the transcriptional and protein levels. In the HF mouse model, ACSL4 exhibited an elevation, whereas negative regulators of ferroptosis witnessed a decrement. Subsequently, knockdown of ACSL4 in a hypoxia-induced ischemic HL-1 cardiomyocyte cell model upregulated the expression of ferroptosis inhibitory protein and decreased the levels of reactive oxygen species (ROS), malondialdehyde (MDA)., and free iron and increased cell viability. Comprehensive multi-omics analysis revealed that the expression of the molecular target ACSL4 was increased in HF. Targeting ACSL4 to inhibit ferroptosis may represent a novel therapeutic strategy for HF treatment.

lncRNA H19 facilitates vascular neointima formation by targeting miR-125a-3p/FLT1 axis.

The aberrant proliferation and migration of vascular smooth muscle cells (VSMCs) contribute to the development of neointima formation in vascular restenosis. This study aims to explore the function of the long noncoding RNA H19 in neointima formation. A mouse carotid ligation model was established, and human vascular smooth muscle cells (VSMCs) were used as a cell model. lncRNA H19 overexpression promoted VSMC proliferation and migration. Moreover, miR-125a-3p potentially bound to lncRNA H19, and Fms-like tyrosine kinase-1 (FLT1) might be a direct target of miR-125a-3p in VSMCs. Upregulation of miR-125a-3p alleviated lncRNA H19-enhanced VSMC proliferation and migration. Furthermore, rescue experiments showed that enhanced expression of miR-125a-3p attenuated lncRNA H19-induced FLT1 expression in VSMCs. In addition, the overexpression of lncRNA H19 significantly exacerbated neointima formation in a mouse carotid ligation model. In summary, lncRNA H19 stimulates VSMC proliferation and migration by acting as a competing endogenous RNA (ceRNA) of miR-125a-3p. lncRNA H19 may be a therapeutic target for restenosis.

The Long non-coding RNA MALAT1 functions as a competing endogenous RNA to regulate vascular remodeling by sponging miR-145-5p/HK2 in hypertension.

Long non-coding RNAs (LncRNAs) have been found to play a regulatory role in the pathophysiology of vascular remodeling-associated illnesses through the lncRNA-microRNA (miRNA) regulation axis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is thought to be involved in proliferation, migration, apoptosis, and calcification of vascular smooth muscle cells (VSMCs). The purpose of this study was to investigate the regulatory role of MALAT1 on vascular remodeling in hypertension. Our data indicate that the expression of MALAT1 is significantly upregulated in hypertensive aortic smooth muscle. Knockdown of MALAT1 inhibited the proliferation, migration, and phenotypic transition of VSMCs induced by Ang II. Bioinformatics analysis was used to predict the complementary binding of miR-145-5p to the 3'-untranslated region of MALAT1. Besides, the expressions of MALAT1 and miR-145-5p were negatively correlated, while luciferase reporter assays and RNA immunoprecipitation assay validated the interaction between miR-145-5p and MALAT1. The proliferation, migration and phenotypic transformation of VSMCs induced by overexpression of MALAT1 were reversed in the presence of miR-145-5p. Furthermore, we verified that miR-145-5p could directly target and bind to hexokinase 2 (HK2) mRNA, and that HK2 expression was negatively correlated with miR-145-5p in VSMCs. Knockdown of HK2 significantly inhibited the effects of overexpression of MALAT1 on Ang II-induced VSMCs proliferation, migration and phenotypic transformation. Taken together, the MALAT1/miR-145-5p/HK2 axis may play a critical regulatory role in the vascular remodeling of VSMCs in hypertension.

Spatiotemporal variability and predictability of Normalized Difference Vegetation Index (NDVI) in Alberta, Canada.

As one of the most popular vegetation indices to monitor terrestrial vegetation productivity, Normalized Difference Vegetation Index (NDVI) has been widely used to study the plant growth and vegetation productivity around the world, especially the dynamic response of vegetation to climate change in terms of precipitation and temperature. Alberta is the most important agricultural and forestry province and with the best climatic observation systems in Canada. However, few studies pertaining to climate change and vegetation productivity are found. The objectives of this paper therefore were to better understand impacts of climate change on vegetation productivity in Alberta using the NDVI and provide reference for policy makers and stakeholders. We investigated the following: (1) the variations of Alberta's smoothed NDVI (sNDVI, eliminated noise compared to NDVI) and two climatic variables (precipitation and temperature) using non-parametric Mann-Kendall monotonic test and Thiel-Sen's slope; (2) the relationships between sNDVI and climatic variables, and the potential predictability of sNDVI using climatic variables as predictors based on two predicted models; and (3) the use of a linear regression model and an artificial neural network calibrated by the genetic algorithm (ANN-GA) to estimate Alberta's sNDVI using precipitation and temperature as predictors. The results showed that (1) the monthly sNDVI has increased during the past 30 years and a lengthened growing season was detected; (2) vegetation productivity in northern Alberta was mainly temperature driven and the vegetation in southern Alberta was predominantly precipitation driven for the period of 1982-2011; and (3) better performances of the sNDVI-climate relationships were obtained by nonlinear model (ANN-GA) than using linear (regression) model. Similar results detected in both monthly and summer sNDVI prediction using climatic variables as predictors revealed the applicability of two models for different period of year ecologists might focus on.

Monocyte/lymphocyte ratio as a risk factor of cardiovascular and all-cause mortality in coronary artery disease with low-density lipoprotein cholesterol levels below 1.4 mmol/L: A large longitudinal multicenter study.

BACKGROUND AND AIMS: The monocyte/lymphocyte ratio (MLR), an inflammatory marker, has an unclear relationship with the risk of residual inflammation in patients with coronary artery disease (CAD) and low-density lipoprotein cholesterol (LDL-C) below 1.4 mmol/L. This study aimed to assess the association between the MLR and cardiovascular and all-cause mortalities in these patients. METHODS: A total of 2747 patients diagnosed with CAD via coronary angiography (CAG) and presenting with LDL-C levels < 1.4 mmol/L were enrolled in this observational study conducted from January 2007 to December 2020. Patients were categorized into four groups based on the MLR quartiles. We used Kaplan-Meier analysis and Cox regression models to evaluate the relationship between baseline MLR and cardiovascular and all-cause mortalities. RESULTS: Among the 2747 participants followed up for a median duration of 6 years, there were 184 cardiovascular and 462 all-cause deaths. Elevated MLR levels were found to be associated with an increased risk of both cardiovascular and all-cause mortalities according to the Kaplan-Meier analysis. Multivariate Cox regression analysis demonstrated a significant association between higher MLR and an elevated risk of cardiovascular and all-cause mortality. Compared to the older group, with an increase in MLR levels, the younger group showed a higher hazard ratio for cardiovascular death. Similar results were obtained in the single-vessel disease group. CONCLUSIONS: In patients with CAD and LDL-C levels < 1.4 mmol/L, MLR can serve as a risk factor for both cardiovascular and all-cause mortalities owing to the risk of residual inflammation.

Urban rainstorm and waterlogging scenario simulation based on SWMM under changing environment.

Urban rainstorm and waterlogging occurred more frequently in recent years, causing huge economic losses and serious social harms. Accurate rainstorm and waterlogging simulation is of significant value for disaster prevention and mitigation. This paper proposed a numerical model for urban rainstorm and waterlogging based on the Storm Water Management Model (SWMM) and Geographic Information System (GIS), and the model was applied in Lianhu district of Xi'an city of China. Furthermore, the effects of rainfall characteristics, pipe network implementation level and urbanization level on waterlogging were explored from the perspectives of spatial distribution of waterlogging points, drainage capacity of pipe network and surface runoff generation and confluence. The results show that: (1) with the increase of rainfall recurrence period, the peak of total water accumulating volume, the average decline rate of water accumulating volume and the number of waterlogging nodes increase; (2) optimizing the pipe diameter can shorten the average overload time of the pipe network from the entire pipe network, but for a single pipe, optimizing the pipe diameter may lead to overloading of unoptimized downstream pipeline; (3) the lower the imperviousness, the less the number of waterlogging nodes and average time of water accumulating, and (4) the west, northwest and southwest areas are relatively affected by the imperviousness, only improving the underlying surface conditions has limited influence on waterlogging in the study area. This study can provide reference for urban waterlogging prevention and reduction and pipe network reconstruction.

Application of edge computing and GIS in ecological water requirement prediction and optimal allocation of water resources in irrigation area.

The purposes are to use water resources efficiently and ensure the sustainable development of social water resources. The edge computing technology and GIS (Geographic Information Science) image data are combined from the perspective of sustainable development. A prediction model for the water resources in the irrigation area is constructed. With the goal of maximizing comprehensive benefits, the optimal allocation of water quality and quantity of water resources is determined. Finally, the actual effect of the model is verified through specific instance data in a province. Results demonstrate that the proposed irrigation area ecological prediction model based on edge computing and GIS images can provide better performance than other state of the art models on water resources prediction. Specifically, the accuracy can remain above 90%. The proposed model for ecological water demand prediction in the irrigation area and optimal allocation of water resources is based on the principle of quality water supply. The optimal allocation of water resources reveals the sustainable development ideas and the requirements of the optimal allocation model, which is very reasonable. The improvement of the system is effective and feasible, and the optimal allocation results are reasonable. This allocation model aims at the water quality and quantity conditions, water conservancy project conditions, and specific water demand requirements in the study area. The calculation results have great practicability and a strong guiding significance for the sustainable utilization and management of the irrigation area.

Assessment of vegetation growth and drought conditions using satellite-based vegetation health indices in Jing-Jin-Ji region of China.

Terrestrial vegetation growth activity plays pivotal roles on regional development, which has attracted wide attention especially in water resources shortage areas. The paper investigated the spatiotemporal change characteristics of vegetation growth activity using satellite-based Vegetation Health Indices (VHIs) including smoothed Normalized Difference Vegetation Index (SMN), smoothed Brightness Temperature (SMT), Vegetation Condition Index (VCI), Temperature Condition Index (TCI) and VHI, based on 7-day composite temporal resolution and 16 km spatial resolution gridded data, and also estimated the drought conditions for the period of 1982-2016 in Jing-Jin-Ji region of China. The Niño 3.4 was used as a substitution of El Niño Southern Oscillation (ENSO) to reveal vegetation sensitivity to ENSO using correlation and wavelet analysis. Results indicated that monthly SMN has increased throughout the year especially during growing season, starts at approximate April and ends at about October. The correlation analysis between SMN and SMT, SMN and precipitation indicated that the vegetation growth was affected by joint effects of temperature and precipitation. The VCI during growing season was positive trends dominated and vice versa for TCI. The relationships between VHIs and drought make it possible to identify and quantify drought intensity, duration and affected area using different ranges of VHIs. Generally, the intensity and affected area of drought had mainly decreased, but the trends varied for different drought intensities, regions and time periods. Large-scale global climate anomalies such as Niño 3.4 exerted obvious impacts on the VHIs. The Niño 3.4 was mainly negatively correlated to VCI and positively correlated to TCI, and the spatial distributions of areas with positive (negative) correlation coefficients were mainly opposite. The linear relationships between Niño 3.4 and VHIs were in accordance with results of nonlinear relationships revealed using wavelet analysis. The results are of great importance to assess the vegetation growth activity, to monitor and quantify drought using satellite-based VHIs in Jing-Jin-Ji region.

Oxidized high-density lipoprotein induces the proliferation and migration of vascular smooth muscle cells by promoting the production of ROS.

AIM: As the major atheroprotective particle in plasma, high-density lipoprotein(HDL) is oxidized during atherosclerotic processes. Oxidized HDL(ox-HDL) may lose its cardioprotective properties and develop a proinflammatory and proatherogenic phenotype. The proliferation and migration of vascular smooth muscle cells(VSMCs) play a crucial role in atherogenesis. However, the influence of ox-HDL on VSMC proliferation and migration remains poorly understood. METHODS: VSMCs were treated with native HDL(N-HDL) or ox-HDL at varying concentrations for different time intervals and used in several analyses. The degree of cell proliferation was assayed using CCK-8 kits. The level of cell migration was determined using a Transwell chamber and scratch-wound assay. The presence of intracellular reactive oxygen species(ROS) was detected based on ROS-mediated 2',7'-dichlorofluorescein fluorescence. The activation of NADPH oxidase was measured in terms of the Rac1 activity and NADP(＋)/NADPH ratio. RESULTS: Compared to N-HDL, ox-HDL significantly promoted VSMC proliferation and migration in a dose-dependent manner. In addition, ox-HDL remarkably activated NADPH oxidase and enhanced ROS generation in the VSMCs. Diphenyleneiodonium chloride, an inhibitor of NADPH oxidase, and N-acetylcysteine, a ROS scavenger, efficiently inhibited the ROS production triggered by ox-HDL and subsequently blocked the proliferating and migrating effects of ox-HDL in the VSMCs. CONCLUSIONS: Ox-HDL significantly induces VSMC proliferation and migration by promoting NADPH oxidase activation and ROS production. Furthermore, the inhibition of NADPH oxidase and ROS generation blocks the proliferation and migration of VSMCs induced by ox-HDL. These proliferating and migrating effects of ox-HDL are closely related to its proinflammatory and proatherogenic roles.