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Myocardial ischemia-reperfusion injury (MIRI) results in increased myocardial infarct size and leads to poor clinical outcomes. Hypoxia-inducible factor 2-alpha (HIF2α) exerts myocardial protective effects during MIRI through as yet unclear mechanisms. Here, we show that knockdown of HIF2α with cardiotropic recombinant adeno-associated virus serotype 9 (rAAV9) in mouse hearts significantly increased the infarct sizes during myocardial ischemia/reperfusion (MI/R). In addition, HIF2α transcriptionally regulated the expression of interleukin 6 (IL-6) in cardiomyocytes to elicit cardioprotection. Likewise, IL-6 deficiency aggravated MIRI, while treatment with recombinant IL-6 had cardioprotective effects and rescued the mice with HIF2α knockdown. Furthermore, IL-6 treatment significantly activated the PI3K/Akt and STAT3 signaling pathways in the myocardium during MI/R, and the specific inhibitors wortmannin (specific phosphoinositide 3-kinase inhibitor) and Stattic (specific STAT3 inhibitor) substantially abolished HIF2α/IL-6-induced cardioprotection. These studies suggest that HIF2α transcription regulates the expression of IL-6 in cardiomyocytes and plays a protective role during MI/R.Alternative splicing (AS), contributing to vast protein diversity from a rather limited number of genes in eukaryotic transcripts, has emerged as an important signature for tumor initiation and progression. However, a systematic understanding of its functional impact and relevance to gastric cancer (GC) tumorigenesis is lacking. Differentially expressed AS (DEAS) was verified among GC-associated AS events based on RNA-seq profiles from the TCGA database. Functional enrichment analysis, unsupervised clustering analysis and prognostic models were used to infer the potential roles of DEAS events and their molecular, clinical and immune features. In total, 12,225 AS events were detected from 5,199 genes, among which 314 AS events were identified as DEAS events in GC. The parental genes of the DEAS events were significantly enriched in the regulation of GC-related processes. The splicing correlation network suggested a significant relationship between DEAS events and splicing factors (SFs). Three clusters of DEAS events were identified to be different in prognosis, cancer-specific signatures and immune features between distinct clusters. Univariate and multivariate analyses regarded 3 DEAS events as independent prognostic indicators. Profiling of the AS landscape in GC elucidated the functional roles of the splicing network in GC and might serve as a novel prognostic indicator and therapeutic target.There are rarely systematic studies to analyze the prognostic factors among non-surgical liver cancer patients. Whether there is a gender difference in the survival of non-surgical liver cancer patients and what may cause this difference is still unclear. A total of 12,312 non-surgical liver cancer patients were enrolled in this study. Age, race, sex, grade, tumor TNM stage, marital status, tumor size, and histological type were independent risk factors in liver cancer and were confirmed in the validation cohort. Before menopause, females demonstrated a better mean survival probability than males (39.4±1.4 vs. 32.7±0.8 months, respectively; p less then 0.001), and continued in post-menopause. The results of differentially expressed genes (DEGs) and KEGG pathway analysis showed that there were significant differences in steroid hormone biosynthesis between male and female liver cancer patients. In vitro experiments revealed that estradiol inhibited the proliferation of hepatocellular cancer cell lines and increased apoptosis, but estrone exerted no effect. In conclusion, gender differences in prognosis among non-surgical liver cancer patients were confirmed and attributable primarily to estradiol.MicroRNA-205 (miR-205) is believed to be related to the progress of tumors. HOXD9 has been proved to be expressed abnormally in several kinds of cancers. However, the role of miR-205 and HOXD9 in breast cancer remains unclear. The biological role of miR-205 in breast cancer cell proliferation and chemoresistance was investigated. The expression of miR-205 in clinical tissues and breast cancer cell lines were analyzed using quantitative real-time PCR test (qRT-PCR). Overexpression and knockdown models of miR-205 were established to study cell proliferation and chemotherapy-resistant. Moreover, the potential relationships between miR-205 and HOXD9/Snail1 were measured using qRT-PCR, western blot, and chemotherapy-resistant study. miR-205 was lowly expressed in breast cancer tissues and cell lines. Namodenoson Overexpression of miR-205 could inhibit cell proliferation and chemotherapy-resistance. Moreover, we proved that miR-205 could target the HOXD9-Snail1 axis to suppress triple negative breast cancer cell proliferation and chemoresistance. The activation of Snail1 gene by HOXD9 was also proved in this study. The present study may provide a novel insight for the therapeutic strategies of breast cancer through targeting miR-205/HOXD9/Snail1.Many studies have reported that estrogen (E2) promotes lung cancer by binding to nuclear estrogen receptors (ER), and altering ER related nuclear protein expressions. With the GEO database analysis, Human centromere protein F (CENPF) is highly expressed in lung adenocarcinoma (LUAD), and the co-expression of CENPF and ERβ was found in the nucleus of LUAD cells through immunofluorescence. We identified the nuclear protein CENPF and explored its relationship with the ER pathway. CENPF and ERβ2/5 were related with T stage and poor prognosis (P less then 0.05). CENPF knockout significantly inhibited LUAD cell growth, the tumor growth of mice and the expression of ERβ2/5 (P less then 0.05). The protein expression of CENPF and ERβ2/5 in the CENPF-Knockdown+Fulvestrant group was lower than CENPF- Negative Control +Fulvestrant group (P=0.002, 0.004, 0.001) in A549 cells. The tumor size and weight of the CENPF-Knockdown+Fulvestrant group were significantly lower than CENPF- Negative Control +Fulvestrant group (P=0.001, 0.039) in nude mice. All the results indicated that both CENPF and ERβ2/5 play important roles in the progression of LUAD, and knockdown CENPF can inhibit the progression of LUAD by inhibiting the expression of ER2/5. Thus, the development of inhibitors against ERβ2/5 and CENPF remained more effective in improving the therapeutic effect of LUAD.From the points of view of phenomena and experience, aging and constipation are inextricably correlated. However, experimental support and underlying mechanisms are still lacking. The purpose of this study is to explore the relationships between aging and constipation from the perspectives of fecal metabolites and network pharmacology. The behavioral analyses of aging and constipation were carried out on both aging rats and constipation rats. We found that aging rats exhibited not only significant aging behaviors but also significant constipation behaviors, while constipation rats exhibited both significant constipation and aging behaviors. Additionally, fecal metabolomics was carried out and found that 23 metabolites were aging-related and 22 metabolites were constipation-related. Among them, there were 16 differential metabolites in common with 11 metabolic pathways. Network pharmacology was applied to construct the target-pathway network of aging and constipation, revealing that pathway in cancer was the most associated signaling pathway. The current findings will provide not only a novel perspective for understanding aging and constipation, but a theoretical association and understanding the traditional Chinese medicine theory and the Western medicine theory about aging and constipation, as well as support for the clinical research and development of medicine related to constipation in the elderly.In this study, we performed bioinformatics analyses to identify hub genes that regulate tumor infiltration by immune cells and antitumor immunity in the lung squamous cell carcinoma (LUSC). We identified 1738 robust and stable differentially expressed genes (DEGs) in the LUSC tissues based on robust rank aggregation (RRA) analysis of RNA-sequencing data from 5 GEO-LUSC datasets. We then classified TCGA-LUSC patients based on ssGSEA and ESTIMATE analyses of LUSC tissues into high, medium and low immunity subgroups showing significant differences in tumor purity. Weighted gene co-expression network analysis of the robust DEGs revealed five immunity-related modules, including the brown module with 762 DEGs and 30 hub genes showing the highest correlation with the immunity-related LUSC patient subgroups and their clinicopathological characteristics. We selected four hub genes, LAPTM5, C1QC, CSF1R and SLCO2B1, for validation of the immunity status and prognosis of LUSC patients. High expression of these four genes correlated with increased infiltration of immune cell types, upregulation of the immunosuppressive TOX pathway genes, CD8+ T cell exhaustion, and shorter overall survival of LUSC patients. These findings demonstrate that four hub genes regulate tumor infiltration of immune cells, anti-tumor immunity, and survival outcomes in LUSC patients.Although the emergence of new treatments has improved the prognosis of women with lung adenocarcinoma (LUAD), the emergence of drug resistance limits their clinical efficacy. Therefore, there is an urgent need to identify new targets and develop a risk scoring system to evaluate the prognosis of patients. 6-methyladenine (M6A), as the most common methyl modification in RNA modification, its clinicopathological features, diagnosis and prognostic value in lung cancer, especially in LUAD remain to be discussed. We analyzed the clinical and sequencing data of the female LUAD cohort from The Cancer Genome Atlas (TCGA), evaluated the expression profiles of 16 M6A regulation-related genes in the cohort and the relationships between genetic changes and clinical characteristics, developed an M6A-related risk scoring system using Cox analysis. Finally, the copy number variations (CNVs) of the related genes in the samples were analyzed and verified using the cBioPortal platform. Compared with other clinical factors, this risk scoring system showed a higher predictive sensitivity and specificity. The M6A-related risk scoring system developed in this study may help to improve the screening of female patients at high risk of LUAD and provides important theoretical bioinformatics support for evaluating the prognosis of such patients.The aim of this study was to establish a novel competing endogenous RNA (ceRNA) network able to predict prognosis in patients with triple-negative breast cancer (TNBC). Differential gene expression analysis was performed using the GEO2R tool. Enrichr and STRING were used to conduct protein-protein interaction and pathway enrichment analyses, respectively. Upstream lncRNAs and miRNAs were identified using miRNet and mirTarBase, respectively. Prognostic values, expression, and correlational relationships of mRNAs, lncRNAs, and miRNAs were examined using GEPIA, starBase, and Kaplan-Meier plotter. It total, 860 upregulated and 622 downregulated differentially expressed mRNAs were identified in TNBC. Ten overexpressed and two underexpressed hub genes were screened. Next, 10 key miRNAs upstream of these key hub genes were predicted, of which six upregulated miRNAs were significantly associated with poor prognosis and four downregulated miRNAs were associated with good prognosis in TNBC. NEAT1 and MAL2 were selected as key lncRNAs.