Identification of Key Genes Mediated by N6-Methyladenosine Methyltransferase METTL3 in Ischemic Stroke via Bioinformatics Analysis and Experiments.

The N6-methyladenosine (m6A) methyltransferase METTL3 has been demonstrated to function in mediating m6A modification, but its role in ischemic stroke (IS) has not been fully elucidated. This study aimed to explore the downstream mechanism of METTL3-mediated m6A modification in IS. GSE16561 and GSE22255 were downloaded from the Gene Expression Omnibus database for analysis of differentially expressed genes (DEGs), and it was found that METTL3 mRNA was downregulated in IS. Then quantitative real-time polymerase chain reaction was used to verify the downregulation of METTL3 mRNA in the peripheral blood of IS patients and the cortexes of transient middle cerebral artery occlusion mice. By combining DEGs with the m6A-downregulated genes in GSE142386 which performed methylated RNA immunoprecipitation sequencing (MeRIP-seq) on METTL3-deficient and control endothelial cells, a total of 131 genes were identified as the METTL3-mediated m6A-modified genes in IS. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the genes were mainly involved in cytokine-cytokine receptor interaction, MAPK signaling pathway and NF-kappa B signaling pathway. CTSS and SBK1 were further screened as the key METTL3-mediated m6A-modified genes by random forest model and PCR validation. The ROC curve analysis showed that the combination with CTSS and SBK1 was of good diagnostic value for IS, with the AUC of 0.810, sensitivity of 0.780, and specificity of 0.773. Overall, we found that METTL3-mediated m6A modification may influence the occurrence and development of IS by participating in inflammation-related biological processes, and two key m6A-modified genes mediated by METTL3 (CTSS and SBK1) can be used as diagnostic biomarkers for IS.

Age at smoking initiation and smoking cessation influence the incidence of stroke in China: a 10-year follow-up study.

Our study aimed to explore the correlation between age at smoking initiation and smoking cessation for the risk for stroke in China. We investigated 50,174 participants from one of the urban areas of China Kadoorie Biobank (CKB) Study. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for association between smoking and incidence of stroke were estimated using Cox regression model. During a median of 10.7 years of follow-up, 4370 total stroke cases were documented. Among men, comparing current smokers to never smokers, the HR of total stroke for current smokers was 1.279 (95% CI, 1.134-1.443) for total stroke. The HRs of total stroke were 1.344 (1.151-1.570) for those started smoking at age less than 20 years, 1.254 (1.090-1.443) for those started smoking at age 20-30 years, and 1.205 (1.012-1.435) for those started smoking at age 30 year and above, with a dose-response relation (P for trend, 0.004). Comparing former smokers to current smokers, in the low pack-year group, those stopped smoking at age less than 65 years had a 18.2% decreased risk for total stroke (0.818; 0.673-0.994). The decreased risk was not found in those stopped smoking at age 65 years and above. Similar results were observed in the high pack-year group. In conclusion, we found that current smokers had a higher stroke risk than never smokers, and the risk increased with a younger age at smoking initiation. Smoking cessation can reduce the risk for stroke, especially could benefit from cessation at a younger age.

Bioinformatics analysis based on high-throughput sequencing data to identify hub genes related to different clinical types of COVID-19.

This article aims to explore hub genes related to different clinical types of cases with COVID-19 and predict the therapeutic drugs related to severe cases. The expression profile of GSE166424 was divided into four data sets according to different clinical types of COVID-19 and then calculated the differential expression genes (DEGs). The specific genes of four clinical types of COVID-19 were obtained by Venn diagram and conducted enrichment analysis, protein-protein interaction (PPI) networks analysis, screening hub genes, and ROC curve analysis. The hub genes related to severe cases were verified in GSE171110, their RNA-specific expression tissues were obtained from the HPA database, and potential therapeutic drugs were predicted through the DGIdb database. There were 536, 266, 944, and 506 specific genes related to asymptomatic infections, mild, moderate, and severe cases, respectively. The hub genes of severe specific genes were AURKB, BRCA1, BUB1, CCNB1, CCNB2, CDC20, CDC6, KIF11, TOP2A, UBE2C, and RPL11, and also differentially expressed in GSE171110 (P < 0.05), and their AUC values were greater than 0.955. The RNA tissue specificity of AURKB, CDC6, KIF11, UBE2C, CCNB2, CDC20, TOP2A, BUB1, and CCNB1 specifically enhanced on lymphoid tissue; CCNB2, CDC20, TOP2A, and BUB1 specifically expressed on the testis. Finally, 55 drugs related to severe COVID-19 were obtained from the DGIdb database. Summary, AURKB, BRCA1, BUB1, CCNB1, CCNB2, CDC20, CDC6, KIF11, TOP2A, UBE2C, and RPL11 may be potential diagnostic biomarkers for severe COVID-19, which may affect immune and male reproductive systems. 55 drugs may be potential therapeutic drugs for severe COVID-19.

Comprehensive Analysis of Blood-Based m6A Methylation in Human Ischemic Stroke.

Alterations of N6-methyladenosine (m6A) methylation have been reported in the cerebral cortices of mouse and rat models of ischemic stroke (IS). However, the role of m6A methylation in human IS is still unknown. We assessed m6A levels in peripheral blood from patients with IS and healthy controls. A transient middle cerebral artery occlusion and reperfusion (tMCAO/R) mouse model, and an oxygen-glucose deprivation/reperfusion (OGD/R) model in A172 cells were established to further assess m6A levels. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing were performed in the peripheral blood of patients with IS and healthy controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were used to identify underlying biological processes. In this study, we found that global m6A levels were elevated in the peripheral blood of patients with IS, in the cerebral cortex of mice after tMCAO/R treatment and in A172 cells after OGD/R treatment. MeRIP-seq analysis identified 2115 altered m6A peaks in patients with IS, 1052 upregulated and 1063 downregulated. Downregulated methylated mRNAs were enriched in Hippo signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, etc. Upregulated methylated mRNAs were enriched in calcium signaling pathways, Hedgehog signaling pathway, MAPK signaling pathway, etc. Moreover, a total of 84 differentially expressed mRNAs with altered m6A peaks were identified and enriched in EGFR tyrosine kinase inhibitor, Hematopoietic cell lineage, and cytokine-cytokine receptor interactions. This study is the first to profile the transcriptome-wide m6A methylome of peripheral blood in human IS and uncover increased global m6A levels in the peripheral blood of patients with IS.

Exploring biomarkers for ischemic stroke through integrated microarray data analysis.

Stroke is the third leading cause of disability-adjusted life years worldwide, and drugs available for its treatment are limited. This study aimed to explore high-confidence candidate genes associated with ischemic stroke (IS) through bioinformatics analysis and identify potential diagnostic biomarkers and gene-drug interactions. Weighted gene coexpression network analysis (WGCNA) and differentially expressed genes (DEGs) were integrated to identify overlapping genes. Then, high-confidence candidate genes were screened by least absolute shrinkage and selection operator (LASSO) regression. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of high-confidence candidate genes as biomarkers for IS. The NetworkAnalyst database was used to construct the TF-gene network and miRNA-TF regulatory network of the high-confidence candidate genes. The DGIdb database was used to identified gene-drug interactions. Through the comprehensive analysis of GSE58294 and GSE16561, 10 high-confidence candidate genes were identified by LASSO regression: ARG1, LY96, ABCA1, SLC22A4, CD163, TPM2, SLC25A42, ID3, FAM102A and CD79B. FAM102A had the highest diagnostic value, and the area under curve (AUC), sensitivity and specificity values were 0.974, 0.919 and 0.936, respectively. The HPA database demonstrated that 10 high-confidence candidate genes were expressed in the brain and blood in normal humans. Finally, DGIdb database analysis identified 8 gene-drug interactions. We identified IS-related diagnostic biomarkers and gene-drug interactions that potentially provide new insights into the diagnosis and treatment of IS.

Spectral polarization camera based on ghost imaging via sparsity constraints.

A spectral polarization camera based on ghost imaging via sparsity constraints (GISC) is presented. The proposed imager modulates three-dimensional spatial and spectral information of the target into two-dimensional speckle patterns using a spatial random phase modulator and then acquires the speckle patterns at four linear polarization channels through a polarized CCD. The experimental results verify the feasibility of the system structure and reconstruction algorithm. The GISC spectral polarization camera, which has a simple structure and achieves compressive sampling during the imaging acquisition process, provides a simple scheme for obtaining multi-dimensional information of the light field.

Polarization-multiplexed Huygens metasurface holography.

Huygens metasurface, as a subcategory of metamaterials, shows great potential in the capacity and efficiency of electromagnetic wave manipulation within a subwavelength scale. Here, the transmission-type Huygens metasurface is demonstrated for complete and independent control of orthogonally polarized transmitted waves by constructing pairs of crossed electric and magnetic resonances in three-sheet meta-atoms as the building blocks for holographic imaging. Under incoherent horizontally and vertically polarized illuminations, two designated holographic images with negligible mutual interferences are accomplished with at least 62.95% measured imaging efficiency and 63.53 signal-to-noise ratio, respectively. This work addresses several major issues in traditional polarization-multiplexed holography with regard to transmission-coefficient manipulation capacity, image fidelity, and simple fabrication technique, empowering advanced research and applications in polarization-selective microwave devices and information processing.

Hyperspectral ghost imaging camera based on a flat-field grating.

A spectral camera based on ghost imaging via sparsity constraints (GISC) acquires a three-dimensional (3D) spatial-spectral data cube of the target through a two-dimensional (2D) detector in a single snapshot. However, the spectral and spatial resolution are interrelated because both of them are modulated by the same spatial random phase modulator. In this paper, we theoretically and experimentally demonstrate a system by equipping the GISC spectral camera with a flat-field grating to disperse the light fields before the spatial random phase modulator, hence consequently decoupling the spatial and spectral resolution. By theoretical derivation of the imaging process we obtain the spectral resolution 1nm and spatial resolution 50µm about the new system which are verified by the experiment. The new system can not only modulate the spatial and spectral resolution separately, but also provide a possibility of optimizing the light field fluctuations of different wavelengths according to the imaging scene.