Integrating the characteristic genes of macrophage pseudotime analysis in single-cell RNA-seq to construct a prediction model of atherosclerosis.

BACKGROUND: Macrophages play an important role in the occurrence and development of atherosclerosis. However, few existing studies have deliberately analyzed the changes in characteristic genes in the process of macrophage phenotype transformation. METHOD: Carotid atherosclerotic plaque single-cell RNA (scRNA) sequencing data were analyzed to define the cells involved and determine their transcriptomic characteristics. KEGG enrichment analysis, CIBERSORT, ESTIMATE, support vector machine (SVM), random forest (RF), and weighted correlation network analysis (WGCNA) were applied to bulk sequencing data. All data were downloaded from Gene Expression Omnibus (GEO). RESULT: Nine cell clusters were identified. M1 macrophages, M2 macrophages, and M2/M1 macrophages were identified as three clusters within the macrophages. According to pseudotime analysis, M2/M1 macrophages and M2 macrophages can be transformed into M1 macrophages. The ROC curve values of the six genes in the test group were statistically significant (AUC (IL1RN): 0.899, 95% CI: 0.764-0.990; AUC (NRP1): 0.817, 95% CI: 0.620-0.971; AUC (TAGLN): 0.846, 95% CI: 0.678-0.971; AUC (SPARCL1): 0.825, 95% CI: 0.620-0.988; AUC (EMP2): 0.808, 95% CI: 0.630-0.947; AUC (ACTA2): 0.784, 95% CI: 0.591-0.938). The atherosclerosis prediction model showed significant statistical significance in both the train group (AUC: 0.909, 95% CI: 0.842-0.967) and the test group (AUC: 0.812, 95% CI: 0.630-0.966). CONCLUSIONS: IL1RNHigh M1, NRP1High M2, ACTA2High M2/M1, EMP2High M1/M1, SPACL1High M2/M1 and TAGLNHigh M2/M1 macrophages play key roles in the occurrence and development of arterial atherosclerosis. These marker genes of macrophage phenotypic transformation can also be used to establish a model to predict the occurrence of atherosclerosis.

Analysis of immunogenic cell death in ascending thoracic aortic aneurysms based on single-cell sequencing data.

Background: At present, research on immunogenic cell death (ICD) is mainly associated with cancer therapy. Little is known about the role of ICD in cardiovascular disease, especially in ascending thoracic aortic aneurysms (ATAA). Method: ATAA single-cell RNA (scRNA) sequencing data were analyzed to identify the involved cell types and determine their transcriptomic characteristics. The chi-square test, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Gene Set Enrichment Analysis (GSEA), and CellChat for cell-to-cell communication analysis from the Gene Expression Omnibus (GEO) database were used. Result: A total of 10 cell types were identified, namely, monocytes, macrophages, CD4 T/NK (CD4+ T cells and natural killer T cells), mast cells, B/Plasma B cells, fibroblasts, endothelial cells, cytotoxic T cells (CD8+ T cells, CTLs), vascular smooth muscle cells (vSMCs), and mature dendritic cells (mDCs). A large number of inflammation-related pathways were present in the GSEA results. A large number of ICD-related pathways were found in the KEGG enrichment analysis of differentially expressed genes in endothelial cells. The number of mDCs and CTLs in the ATAA group was significantly different from that in the control group. A total of 44 pathway networks were obtained, of which 9 were associated with ICD in endothelial cells (CCL, CXCL, ANNEXIN, CD40, IL1, IL6, TNF, IFN-II, GALECTIN). The most important ligand-receptor pair by which endothelial cells act on CD4 T/NK cells, CTLs and mDCs is CXCL12-CXCR4. The most important ligand-receptor pair by which endothelial cells act on monocytes and macrophages is ANXA1-FPR1. The most important ligand-receptor pair by which CD4 T/NK cells and CTLs act on endothelial cells is CCL5-ACKR1. The most important ligand-receptor pair that myeloid cells (macrophages, monocytes and mDCs) act on endothelial cells is CXCL8-ACKR1. Moreover, vSMCs and fibroblasts mainly promote inflammatory responses through the MIF signaling pathway. Conclusion: ICD is present in ATAA and plays an important role in the development of ATAA. The target cells of ICD may be mainly endothelial cells, in which the aortic endothelial cell ACKR1 receptor can not only promote T-cell infiltration through the CCL5 ligand but also promote myeloid cell infiltration through the CXCL8 ligand. ACKR1 and CXCL12 may become target genes for ATAA drug therapy in the future.

Analysis of immunogenic cell death in atherosclerosis based on scRNA-seq and bulk RNA-seq data.

BACKGROUND: Regulated cell death plays a very important role in atherosclerosis (AS). Despite a large number of studies, there is a lack of literature on immunogenic cell death (ICD) in AS. METHOD: Carotid atherosclerotic plaque single-cell RNA (scRNA) sequencing data were analyzed to define involved cells and determine their transcriptomic characteristics. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, CIBERSORT, ESTIMATE and ssGSEA (Gene Set Enrichment Analysis), consensus clustering analysis, random forest (RF), Decision Curve Analysis (DCA), and the Drug-Gene Interaction and DrugBank databases were applied for bulk sequencing data. All data were downloaded from Gene Expression Omnibus (GEO). RESULT: mDCs and CTLs correlated obviously with AS occurrence and development (k2(mDCs) = 48.333, P < 0.001; k2(CTL) = 130.56, P < 0.001). In total, 21 differentially expressed genes were obtained for the bulk transcriptome; KEGG enrichment analysis results were similar to those for differentially expressed genes in endothelial cells. Eleven genes with a gene importance score > 1.5 were obtained in the training set and validated in the test set, resulting in 8 differentially expressed genes for ICD. A model to predict occurrence of AS and 56 drugs that may be used to treat AS were obtained with these 8 genes. CONCLUSION: Immunogenic cell death occurs mainly in endothelial cells in AS. ICD maintains chronic inflammation in AS and plays a crucial role in its occurrence and development. ICD related genes may become drug-targeted genes for AS treatment.

Examining the antecedents and consequences of mobile travel app engagement.

How and why customers engage with mobile travel apps is vital to mobile marketing of travel-related companies. This paper discusses the antecedents and consequences of mobile travel app engagement. Specifically, this study aims to understand how travel app attributes stimulate mobile travel app engagement and lead to purchase intention. A research model is established based on the Stimulus-Organism-Response (S-O-R) model and the model is tested by Partial Least Squares Path Modeling (PLS-PM). The results show that ease of use, compatibility, and UI attractiveness positively influence mobile travel app engagement, and in turn, affect purchase intention. Furthermore, a multi-group analysis shows that the attributes affecting mobile travel app engagement differ across different customer groups. This paper discusses some theoretical and practical implications.

Emotional arousal modifies auditory steady state response in the auditory cortex and prefrontal cortex of rats.

Emotional state has been shown to influence cognitive performance. However, the influence of mood on auditory processing is not fully understood. The auditory steady state response (ASSR) is the entrainment of neural activities elicited by periodic auditory stimulation, which is commonly used to evaluate the sensory and cognitive functions of brain. It has been shown that ASSR at 40 Hz is impaired at some psychotic disorders, such as schizophrenia and bipolar disorder. The primary goal of this study is to investigate the effect of emotional arousal on ASSR. To this end, we performed simultaneous recordings of local field potential (LFP) in response to 40 Hz click-train stimuli in the primary auditory cortex (A1) and medial prefront cortex (mPFC) of rats. During the electrophysiological recording, a negative mood was induced by means of the foot shocks occurred randomly in the inter-stimulus intervals. We found that both the power and phase-locking of ASSR in A1 were significantly increased under arousal condition, and phase-locking of ASSR in mPFC was also increased. The enhanced ASSRs were accompanied by an increase in coherence between A1 and mPFC. Our results suggest that A1-to-mPFC information transfer is enhanced under arousal state and the functional connectivity between mPFC and A1 may contribute to the emotional modulation of auditory process.