Ischemic stroke (IS) is a fatal neurological disease that occurs when the blood flow to the brain is disrupted, leading to brain tissue damage and functional impairment. Cellular senescence, a vital characteristic of aging, is associated with a poor prognosis for IS. This study explores the potential role of cellular senescence in the pathological process following IS by analyzing transcriptome data from multiple datasets (GSE163654, GSE16561, GSE119121, and GSE174574). By using bioinformatics methods, we identified hub-senescence-related genes such as ANGPTL4, CCL3, CCL7, CXCL16, and TNF and verified them using quantitative reverse transcription polymerase chain reaction. Further analysis of single-cell RNA sequencing data suggests that MG4 microglial is highly correlated with cellular senescence in MCAO, and might play a crucial role in the pathological process after IS. Additionally, we identified retinoic acid as a potential drug for improving the prognosis of IS. This comprehensive investigation of cellular senescence in various brain tissues and peripheral blood cell types provides valuable insights into the underlying mechanisms of the pathology of IS and identifies potential therapeutic targets for improving patient outcomes.

Particulate matter (PM) degrades air quality and negatively impacts human health. The spatial–temporal heterogeneity of PM (PM2.5 and PM10) concentration in Heilongjiang Province during 2014–2018 and the key impacting factors were investigated based on principal component analysis-based ordinary least square regression (PCA-OLS), PCA-based geographically weighted regression (PCA-GWR), PCA-based temporally weighted regression (PCA-TWR), and PCA-based geographically and temporally weighted regression (PCA-GTWR). Results showed that six principal components represented the temperature, wind speed, air pressure, atmospheric pollution, humidity, and vegetation cover factor, respectively, contributing 87% of original variables. All the local models (PCA-GWR, PCA-TWR, and PCA-GTWR) were superior to the global model (PCA-OLS), and PCA-GTWR has the best performance. PM had greater temporal than spatial heterogeneity due to seasonal periodicity. Air pollutants (i.e., SO2, NO2, and CO) and pressure were promoted whereas temperature, wind speed, and vegetation cover inhibited the PM concentration. The downward trend of annual PM concentration is obvious, especially after 2017, and the hot spot gradually changed from southwestern to southeastern cities. This study laid the foundation for precise local government prevention and control by addressing both excessive effect factors (i.e., meteorological factors, air pollutants, vegetation cover) and spatial-temporal heterogeneity of PM.

Background: Low grade gliomas(LGGs) present vexatious management issues for neurosurgeons. Chromatin regulators (CRs) are emerging as a focus of tumor research due to their pivotal role in tumorigenesis and progression. Hence, the goal of the current work was to unveil the function and value of CRs in patients with LGGs.Methods: RNA-Sequencing and corresponding clinical data were extracted from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) database. A single-cell RNA-seq dataset was sourced from the Gene Expression Omnibus (GEO) database. Altogether 870 CRs were retrieved from the published articles in top academic journals. The least absolute shrinkage and selection operator (LASSO) algorithm and Cox regression analysis were applied to construct the prognostic risk model. Patients were then assigned into high- and low-risk groups based on the median risk score. The Kaplan–Meier (K-M) survival curve and receiver operating characteristic curve (ROC) were performed to assess the prognostic value. Sequentially, functional enrichment, tumor immune microenvironment, tumor mutation burden, drug prediction, single cell analysis and so on were analyzed to further explore the value of CR-based signature. Finally, the expression of signature genes were validated by immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR).Results: We successfully constructed and validated a 14 CRs-based model for predicting the prognosis of patients with LGGs. Moreover, we also found 14 CRs-based model was an independent prognostic factor. Functional analysis revealed that the differentially expressed genes were mainly enriched in tumor and immune related pathways. Subsequently, our research uncovered that LGGs patients with higher risk scores exhibited a higher TMB and were less likely to be responsive to immunotherapy. Meanwhile, the results of drug analysis offered several potential drug candidates. Furthermore, tSNE plots highlighting the magnitude of expression of the genes of interest in the cells from the scRNA-seq assay. Ultimately, transcription expression of six representative signature genes at the mRNA level was consistent with their protein expression changes.Conclusion: Our findings provided a reliable biomarker for predicting the prognosis, which is expected to offer new insight into LGGs management and would hopefully become a promising target for future research.

Background Cerebral ischemia-reperfusion injury (CIRI) can cause hippocampal inflammation and apoptosis, resulting in anxiety and cognitive dysfunction. Compound porcine cerebroside and ganglioside injections (CPCGI) are used to treat encephalopathy, but its therapeutic effects and mechanism require further exploration. Methods We screened key genes associated with the ischemic stroke (IS) and predicted their binding sites with CPCGI. We subsequently injected CPCGI into a middle cerebral artery occlusion (MCAO) rat model. 2,3,5-triphenyl tetrazolium chloride (TTC) staining and behavioral testing were performed. Hippocampal neuronal apoptosis was assessed by immunofluorescence. IL-1β, TNF-α, and NF-κB pathway were detected by Western blotting. Oxygen-glucose deprivation/reoxygenation (OGD/R)-HT-22 cells were treated CPCGI for 72 h. Cell viability and NF-κB were also evaluated. Results H2AC20, RPL3, RPL13A, RPL9, RPS23, and RPLP0 were identified as key IS genes. CPCGI was confirmed to interact with these proteins via molecular docking. Functional enrichment reflected the critical role of the NF-κB pathway in CIRI. Infarct volume and behavioral impairments in MCAO rats, especially anxiety and cognitive dysfunction, were improved by CPCGI in a dose-dependent manner. Immunofluorescence confirmed that hippocampal neuronal apoptosis was rescued by the CPCGI. Western blotting revealed that inflammation and NF-κB phosphorylation were inhibited. In vitro experiments showed that CPCGI increased the survival of OGD/R-HT-22 cells and inhibited phosphorylation of the NF-κB signaling pathway. Conclusion CPCGI can alleviate anxiety and cognitive dysfunction in CIRI and thus improve psychoneurological symptoms in patients with IS. We confirmed that CPCGI alleviate inflammation and apoptosis in the hippocampus by inhibiting the NF-κB signaling pathway.