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Lung adenocarcinoma (LUAD) remains one of the most lethal malignancies worldwide, with a high mortality rate and unfavorable prognosis. Endoplasmic reticulum (ER) stress is a key regulator of tumour growth, metastasis, and the response to chemotherapy, targeted therapies and immune response. It acts via responding to misfolded proteins and triggering abnormal activation of ER stress sensors and downstream signalling pathways. Notably, the expression patterns of ER-stress-related-genes (ERSRGs) are indicative of survival outcomes, especially in the context of immune infiltration. Through consensus clustering of prognosis-associated ERSRGs, we delineated two distinct LUAD subtypes: Cluster 1 and Cluster 2. Comprehensive analyses revealed significant disparities between these subtypes in terms of prognosis, immune cell infiltration, and tumor progression. Leveraging the robustness of LASSO regression and Multivariate stepwise regression, we constructed and validated an ER Stress-associated risk signature for LUAD. This signature underwent assessments for its prognostic value, correlation with clinical attributes, and interaction within the tumour immune microenvironment. By integrating this signature with multivariate cox analysis of distinct pathological stages, we devised an enhanced nomogram, validated through various statistical metrics, with an area under the curve for overall survival at 1, 3, and 5 years post-diagnosis being 0.79, 0.80, and 0.81, respectively. In conclusion, our findings introduce a composite signature of 11 pivotal ERSRGs, holding promise as a potent prognostic tool for LUAD, and offering insights for immunotherapeutic and targeted intervention strategies. [ABSTRACT FROM AUTHOR]

Selective oxidation is one of the most important and challenging transformations in both academic research and chemical industry. Recently, a highly selective and efficient way to synthesize biologically active γ-hydroxy-α,β-unsaturated molecules from Cu-catalyzed vinylogous aerobic oxidation of α,β- and β,γ-unsaturated compounds has been developed. However, the detailed reaction mechanism remains elusive. Herein, we report a density functional theory study on this Cu-catalyzed vinylogous aerobic oxidation of γ,γ-disubstituted α,β- and β,γ-unsaturated isomers. Our computational study unveils detailed mechanism for each elementary step, i.e. deprotonation, O2 activation, and reduction. Besides, the origin of regioselectivity, divergent reactivities of substrates as well as reducing agents, and the byproduct generation have also been investigated. Notably, the copper catalyst retains the + 2 oxidation state through the whole catalytic cycle and plays essential roles in multiple steps. These findings would provide hints on mechanistic studies and future development of transition metal-catalyzed aerobic oxidation reactions. [ABSTRACT FROM AUTHOR]

Previous work from our laboratory demonstrated the existence of miRNAs in human follicular fluid. In the current study, we have sought to identify miRNAs that might affect oocyte/embryo quality in patients undergoing intracytoplasmic sperm injection and to investigate their roles in in vitro fertilization outcomes in mouse oocytes. 53 samples were classified as Group 1 (high quality) if the day-3 embryos had seven and more cells or as Group 2 (low quality) if the embryos had six and fewer cells. TaqMan Human microRNAs cards and qRT-PCR were performed to verify differently expressed miRNAs. The function of the corresponding miRNA was investigated in mouse oocytes by injecting them with miRNA-inhibitor oligonucleotides. We found that hsa-miR-320a and hsa-miR-197 had significantly higher expression levels in the Group 1 follicular fluids than in Group 2 (p = 0.0073 and p = 0.008, respectively). Knockdown of mmu-miR-320 in mouse oocytes strongly decreased the proportions of MII oocytes that developed into two-cell and blastocyst stage embryos (p = 0.0048 and p = 0.0069, respectively). Wnt signaling pathway components had abnormal expression level in miR-320 inhibitor-injected oocytes. This study provides the first evidence that miRNAs in human follicular fluid are indicative of and can influence embryo quality. [ABSTRACT FROM AUTHOR]