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The expression dysregulation of microRNAs (miRNA) has been widely reported during cancer development, however, the underling mechanism remains largely unanswered. In the present work, we performed a systematic integrative study for genome-wide DNA methylation, copy number variation and miRNA expression data to identify mechanisms underlying miRNA dysregulation in lower grade glioma. We identify 719 miRNAs whose expression was associated with alterations of copy number variation or promoter methylation. Integrative multi-omics analysis revealed four subtypes with differing prognoses. These glioma subtypes exhibited distinct immune-related characteristics as well as clinical and genetic features. By construction of a miRNA regulatory network, we identified candidate miRNAs associated with immune evasion and response to immunotherapy. Finally, eight prognosis related miRNAs were validated to promote cell migration, invasion and proliferation through in vitro experiments. Our study reveals the crosstalk among DNA methylation, copy number variation and miRNA expression for immune regulation in glioma, and could have important implications for patient stratification and development of biomarkers for immunotherapy approaches. A miRNA multi-omics study reveals not only mechanisms for miRNA dysregulation, but also the tumor heterogeneity and immunological diversity within low grade glioma, and presents better prognostic value than traditional molecular markers. [ABSTRACT FROM AUTHOR]

During the mining process of coal mines, coal pillars are often formed in the goaf on three sides, and the stress behavior of coal seams has a significant impact on the safety of coal mines. The upper part of panel 3104 of Xinwang Coal Mine is the room-pillar goaf of the 2# coal seam, and the lower part is the goaf of the 7# coal seam. The same coal seam is adjacent to the goaf of panel 3102. Therefore, there are hidden dangers for safe mining in panel 3104 affected by the goaf on three sides. Through FLAC3D numerical simulation, on-site Pasat-M detection, microseismic monitoring, and support resistance measurement, the stress distribution law of surrounding rock in the working face is analyzed. The following conclusions are obtained. There are several high wave velocity stress concentration areas in the coal body of 3104 working face. During the mining of the working face, the mining influence 90m in front of the working face began to spread to the area of the left coal pillar, and the vertical stress at the left coal pillar began to increase. Stress concentration appears in 0–20m strata at the top of 3# coal seams. At the top of a 3# coal seam, the vertical stress concentration coefficient can reach 2 in the range of 4–12m. The influence range of 3104 working face mining advance can reach 200m. Under the influence of mining, a large number of microseismic events occurred at 160m above and 150m below 3# coal seam. This law has reference value for the mining strata behaviors of coal seams under similar conditions.

Background: Extrachromosomal circular DNAs (eccDNAs) exist in human blood and somatic cells, and are essential for oncogene plasticity and drug resistance. However, the presence and impact of eccDNAs in type 2 diabetes mellitus (T2DM) remains inadequately understood. Methods: We purified and sequenced the serum eccDNAs obtained from newly diagnosed T2DM patients and normal control (NC) subjects using Circle-sequencing. We validated the level of a novel circulating eccDNA named sorbin and SH3‐domain‐ containing‐1circle97206791–97208025 (SORBS1circle) in 106 newly diagnosed T2DM patients. The relationship between eccDNA SORBS1circle and clinical data was analyzed. Furthermore, we explored the source and expression level of eccDNA SORBS1circle in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Results: A total of 22,543 and 19,195 eccDNAs were found in serum samples obtained from newly diagnosed T2DM patients and NC subjects, respectively. The T2DM patients had a greater distribution of eccDNA on chromosomes 1, 14, 16, 17, 18, 19, 20 and X. Additionally, 598 serum eccDNAs were found to be upregulated, while 856 eccDNAs were downregulated in T2DM patients compared with NC subjects. KEGG analysis demonstrated that the genes carried by eccDNAs were mainly associated with insulin resistance. Moreover, it was validated that the eccDNA SORBS1circle was significantly increased in serum of newly diagnosed T2DM patients (106 T2DM patients vs. 40 NC subjects). The serum eccDNA SORBS1circle content was positively correlated with the levels of glycosylated hemoglobin A1C (HbA1C) and homeostasis model assessment of insulin resistance (HOMA-IR) in T2DM patients. Intracellular eccDNA SORBS1circle expression was significantly enhanced in the high glucose and palmitate (HG/PA)-induced hepatocyte (HepG2 cell) insulin resistance model. Moreover, the upregulation of eccDNA SORBS1circle in the HG/PA-treated HepG2 cells was dependent on generation of apoptotic DNA fragmentation. Conclusions: These results provide a preliminary understanding of the circulating eccDNA patterns at the early stage of T2DM and suggest that eccDNA SORBS1circle may be involved in the development of insulin resistance. [ABSTRACT FROM AUTHOR]