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Obstructive sleep apnea (OSA) is a worldwide health issue that affects more than 400 million people. Given the limitations inherent in the current conventional diagnosis of OSA based on symptoms report, novel diagnostic approaches are required to complement existing techniques. Recent advances in gene sequencing technology have made it possible to identify a greater number of genes linked to OSA. We identified key genes in OSA and CPAP treatment by screening differentially expressed genes (DEGs) using the Gene Expression Omnibus (GEO) database and employing machine learning algorithms. None of these genes had previously been implicated in OSA. Moreover, a new diagnostic model of OSA was developed, and its diagnostic accuracy was verified in independent datasets. By performing Single Sample Gene Set Enrichment Analysis (ssGSEA) and Counting Relative Subsets of RNA Transcripts (CIBERSORT), we identified possible immunologic mechanisms, which led us to conclude that patients with high OSA risk tend to have elevated inflammation levels that can be brought down by CPAP treatment.

Suberoylanilide hydroxamic acid (SAHA), a famous histone deacetylase (HDAC) inhibitor, has been utilized in clinical treatment for cutaneous T-cell lymphoma. Previously, the mechanisms underlying SAHA anti-tumor activity mainly focused on acetylome. However, the characteristics of SAHA in terms of other protein posttranslational modifications (PTMs) and the crosstalk between various modifications are poorly understood. Our previous work revealed that SAHA had anti-tumor activity in nasopharyngeal carcinoma (NPC) cells as well. Here, we reported the profiles of global proteome, acetylome, and phosphoproteome of 5–8 F cells upon SAHA induction and the crosstalk between these data sets. Overall, we detected and quantified 6,491 proteins, 2,456 phosphorylated proteins, and 228 acetylated proteins in response to SAHA treatment in 5–8 F cells. In addition, we identified 46 proteins exhibiting both acetylation and phosphorylation, such as WSTF and LMNA. With the aid of intensive bioinformatics analyses, multiple cellular processes and signaling pathways involved in tumorigenesis were clustered, including glycolysis, EGFR signaling, and Myc signaling pathways. Taken together, this study highlighted the interconnectivity of acetylation and phosphorylation signaling networks and suggested that SAHA-mediated HDAC inhibition may alter both acetylation and phosphorylation of viral proteins. Subsequently, cellular signaling pathways were reprogrammed and contributed to anti-tumor effects of SAHA in NPC cells.

Objective: This study aims to characterize the abnormal changes in placental DNA methylation associated with conotruncal heart defects (CTDs) and the level of methylation as epigenetic biomarkers for CTDs detection.Methods: This was a prospective study involving 28 fetuses diagnosed with CTDs in the second trimester at Beijing Anzhen Hospital between September 2020 and June 2021. These cases were classified into four groups based on their subtypes. 12 normal fetuses were used as controls. Placental tissue was obtained after inducing labor in fetuses. To identify differential methylation sites (DMSs) and regions (DMRs) in cases vs. controls, an Infinium Human Methylation 850 k bead chip was used. Differential methylation was assessed by comparing the β-values for individual CpG loci. Based on the p-value (0.9 in cases compared with controls. HOXD9, CNN1, NOTCH1, and ECE1 were identified as CTDs-detection candidate genes.Conclusion Our study established the abnormal changes in placental methylation associated with CTDs and potential epigenetic biomarkers for CTDs detection.

Objectives: Some genetic causes of heterotaxy have been identified in a small number of heterotaxy familial cases or animal models. However, knowledge on the genetic causes of heterotaxy in the fetal population remains scarce. Here, we aimed to investigate the clinical characteristics and genetic spectrum of a fetal cohort with heterotaxy.Methods: We retrospectively investigated all fetuses with a prenatal diagnosis of heterotaxy at a single center between October 2015 and November 2020. These cases were studied using the genetic testing data acquired from a combination of copy number variation sequencing (CNV-seq) and whole-exome sequencing (WES), and their clinical phenotypes were also reviewed.Result: A total of 72 fetuses diagnosed with heterotaxy and complete clinical and genetic results were enrolled in our research. Of the 72 fetuses, 18 (25%) and 54 (75%) had left and right isomerism, respectively. Consistent with the results of a previous study, intracardiac anomalies were more severe in patients with right atrial isomerism than in those with left atrial isomerism (LAI) and mainly manifested as atrial situs inversus, bilateral right atrial appendages, abnormal pulmonary venous connection, single ventricles or single atria, and pulmonary stenosis or atresia. In 18 fetuses diagnosed with LAI, the main intracardiac anomalies were bilateral left atrial appendages. Of the 72 fetuses that underwent CNV-seq and WES, 11 (15.3%) had positive genetic results, eight had definitive pathogenic variants, and three had likely pathogenic variants. The diagnostic genetic variant rate identified using WES was 11.1% (8/72), in which primary ciliary dyskinesia (PCD)-associated gene mutations (CCDC40, CCDC114, DNAH5, DNAH11, and ARMC4) accounted for the vast majority (n = 5). Other diagnostic genetic variants, such as KMT2D and FOXC1, have been rarely reported in heterotaxy cases, although they have been verified to play roles in congenital heart disease.Conclusion: Thus, diagnostic genetic variants contributed to a substantial fraction in the etiology of fetal heterotaxy. PCD mutations accounted for approximately 6.9% of heterotaxy cases in our fetal cohort. WES was identified as an effective tool to detect genetic causes prenatally in heterotaxy patients.