GCN2-eIF2α signaling pathway negatively regulates the growth of triploid crucian carp.

GCN2-eIF2α signaling pathway plays crucial roles in cell growth,development, and protein synthesis. However, in polyploid fish, the function of this pathway is rarely understood. In this study, genes associated with the GCN2-eIF2α pathway (pkr, pek, gcn2, eif2α) are founded lower expression levels in the triploid crucian carp (3nCC) muscle compared to that of the red crucian carp (RCC). In muscle effect stage embryos of the 3nCC, the mRNA levels of this pathway genes are generally lower than those of RCC, excluding hri and fgf21. Inhibiting gcn2 in 3nCC embryos downregulates downstream gene expression (eif2α, atf4, fgf21), accelerating embryonic development. In contrast, overexpressing of eif2α can alter the expression levels of downstream genes (atf4 and fgf21), and decelerates the embryonic development. These results demonstrate the GCN2-eIF2α pathway's regulatory impact on 3nCC growth, advancing understanding of fish rapid growth genetics and offering useful molecular markers for breeding of excellent strains.

Integrative analyses reveal prognostic and immunogenic characteristics of m7G methylation regulators in patients with glioma.

OBJECTIVES: The expression profiles, biological mechanisms, and clinical relevance of m7G regulators in glioma were studied in this research. METHODS: Based on the Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA) datasets, glioma patients, can be categorized into three groups according to 29 m7G regulators, and different subtypes of glioma show different immune cell infiltration characteristics, function enrichment, and clinical prognosis. Three gene clusters were confirmed by utilizing the differentially expressed genes (DEGs) across the three m7G clusters. RESULTS: A prognostic signature based on 12 m7G regulators was established and validated, producing an effective tool for predicting overall survival (OS) in glioma patients. High m7G scores indicated elevated tumor mutation burden and activation of immunity, suggesting an inflamed tumor microenvironment phenotype with poor overall survival. Low m7G scores characterized by a lack of immune infiltration and low mutation burden indicated a non-inflamed phenotype with a favorable clinical prognosis. It was also found that the m7G risk scores can affect chemotherapy sensitivity and prognosis of patients who received immunotherapy. The hub gene EIF4E1B of m7G regulators can inhibit the in vitro progression of glioma cells by regulating PD-L1 expression through p53 signaling pathway-related inactivation. CONCLUSIONS: The m7G prognostic signature can be a biomarker of the overall survival of patients with glioma. An initial in-vitro experiment suggested the potential biological mechanisms of immune regulation, with m7G regulators affecting glioma progression by modulating immune responses. The present research provides a better understanding of how m7G regulators function in glioma progression as well as the impact on clinical outcomes, which can provide new insights that might be beneficial for precision therapy of glioma.

Volumetric modulated arc therapy versus tomotherapy for late T-stage nasopharyngeal carcinoma.

Purpose: To compare the dosimetric parameters and clinical outcomes between volumetric modulated arc therapy (VMAT) and tomotherapy for treating late T-stage nasopharyngeal carcinoma (NPC). Methods: Patients with non-metastatic late T-stage NPC who received definitive radiotherapy with tomotherapy or VMAT were selected. 1:1 propensity score matching (PSM) was used to control the balance of confounding factors. The dosimetric parameters and clinical outcomes were compared. Results: A total of 171 patients were enrolled before matching, with 61 patients in the VMAT group and 110 patients in the tomotherapy group. In the post-PSM cohort, 54 sub-pairs of 108 patients were included after matching. Tomotherapy was superior to VMAT in the dosimetric parameters of planning target volumes, brainstem, spinal cord, lenses, and parotid glands but inferior in the optic nerves and optic chiasm. The tomotherapy group had a lower incidence of grade ≥ 3 acute mucositis (22.2% vs. 40.7%, p = 0.038) and a higher rate of complete response (83.3% vs. 66.7%, p = 0.046) after radiotherapy. However, there were no significant differences in locoregional failure-free survival (p = 0.375), distant metastasis-free survival (p = 0.529), or overall survival (p = 0.975) between the two groups. Conclusion: Tomotherapy is superior to VMAT in terms of most dosimetric parameters, with less acute mucositis and better short-term efficacy. There are no significant differences in the survival outcomes between the VMAT and tomotherapy groups.