Implications of inflammatory cell death-related IFNG and co-expressed RNAs (AC006369.1 and CCR7) in breast carcinoma prognosis, and anti-tumor immunity

Objective: Interferon-γ (IFN-γ) encoded by IFNG gene is a pleiotropic molecule linked with inflammatory cell death mechanisms. This work aimed to determine and characterize IFNG and co-expressed genes, and to define their implications in breast carcinoma (BRCA).Methods: Transcriptome profiles of BRCA were retrospectively acquired from public datasets. Combination of differential expression analysis with WGCNA was conducted for selecting IFNG-co-expressed genes. A prognostic signature was generated through Cox regression approaches. The tumor microenvironment populations were inferred utilizing CIBERSORT. Epigenetic and epitranscriptomic mechanisms were also probed.Results: IFNG was overexpressed in BRCA, and connected with prolonged overall survival and recurrence-free survival. Two IFNG-co-expressed RNAs (AC006369.1, and CCR7) constituted a prognostic model that acted as an independent risk factor. The nomogram composed of the model, TNM, stage, and new event owned the satisfying efficacy in BRCA prognostication. IFNG, AC006369.1, and CCR7 were closely linked with the tumor microenvironment components (e.g., macrophages, CD4/CD8 T cells, NK cells), and immune checkpoints (notably PD1/PD-L1). Somatic mutation frequencies were 6%, and 3% for CCR7, and IFNG, and high amplification potentially resulted in their overexpression in BRCA. Hypomethylated cg05224770 and cg07388018 were connected with IFNG and CCR7 upregulation, respectively. Additionally, transcription factors, RNA-binding proteins, and non-coding RNAs possibly regulated IFNG and co-expressed genes at the transcriptional and post-transcriptional levels.Conclusion: Collectively, our work identifies IFNG and co-expressed genes as prognostic markers for BRCA, and as possible therapeutic targets for improving the efficacy of immunotherapy

COMPOSITION AND MICROSTRUCTURE OF MgAl2O4–W COMPOSITE OBTAINED BY ALUMINOTHERMIC REACTION UNDER COKE PROTECTION

MgAl2O4–W composite was synthesized by aluminothermic reducing method using Al, WO3, MgO and corundum as raw materials under coke protection. The effects of temperature, content of corundum on the synthesis of MgAl2O4–W composite and lattice parameter of spinel has been discussed. The differential scanning calorimetry (DSC) and thermogravimetric (TG) analysis indicated that spinel began to form at 1058.2°C without corundum and shifted to 1120.7°C with 0.8 mol of corundum. The XRD analysis confirmed that spinel and tungsten are the main phases under coke protection. Alumina rich spinel with a high solubility of alumina was easily formed because of the high exothermic heats. The solubility limit of Al2O3 in spinel is reached when corundum content is 2.1 mol. Furthermore, the calculated lattice parameter of spinel increases with the increment of added corundum content and rising of temperature. Microstructural observation indicates that cubic tungsten located at grain boundaries of well crystallized spinel. Residual WO3 has needle like morphology

Pluripotent and Metabolic Features of Two Types of Porcine iPSCs Derived from Defined Mouse and Human ES Cell Culture Conditions.

The domestic pig is an excellent animal model for stem cell research and clinical medicine. There is still no suitable culture condition to generate authentic porcine embryonic stem cells (pESCs) and high quality porcine induced pluripotent stem cells (piPSCs). In this study, we found that culture conditions affected pluripotent and metabolic features of piPSCs. Using defined human embryonic stem cell (hESC) and mouse ESC (mESC) culture conditions, we generated two types of piPSCs, one of which was morphologically similar to hESCs (here called hpiPSCs), the other resembled mESCs (here called mpiPSCs). Transcriptome analysis and signaling pathway inhibition results suggested that mpiPSCs shared more of mESC signaling pathways, such as the BMP pathway and JAK/STAT pathway and hpiPSCs shared more hESC signaling pathways, such as the FGF pathway. Importantly, the mpiPSCs performed embryonic chimera incorporation more efficiently than the hpiPSCs did. In addition, the mpiPSCs showed mitochondrial features of naive ESCs and lipid droplets accumulation. These evidences may facilitate understanding of the gene regulation network and metabolism in piPSCs and promote derivation of bona fide pESCs for translational medicine