We tested the hypothesis that the growth of fish exposed to high temperatures can be limited by available food energy whereas that of fish exposed to low temperatures can be limited by their metabolic capacity to exploit the available food energy. Under laboratory conditions we evaluated growth (%/d) and marginal metabolic scope (MMS; L·g⁻¹·h⁻¹) of juvenile red drum Sciaenops ocellatus exposed to two levels of dietary energy, low (LE; ∼4.1 kJ/g) and high (HE; ∼15.9 kJ/g), and to three temperatures, approximately 19, 25, and 29°C, for a period of 6 weeks. Growth rate and MMS increased with temperature, but only growth rate increased with dietary energy and then only at the higher two temperatures. The simulation model Ecophys. Fish was employed to elucidate experimental results potentially confounded by interactions between fish weight and the controlling effects of temperature on metabolism. The simulated and observed results both showed that performance is enhanced at higher temperatures, especially for fish consuming the HE diet. A subsequent 6‐week‐long experiment confirmed results for fish fed the two diets at ambient temperature (∼26°C) and sought to further resolve responses by examining body condition indices and proximate composition. Additionally, these fish were assayed for differential cortisol response to 15 min of confinement stress. The feed efficiency, hepatosomatic index, intraperitoneal fat ratio, and whole‐body fat of fish fed the LE diet were significantly lower than those of fish fed the HE diet, indicating relative energy malnutrition in the LE group. As with MMS, no apparent differential effect of feed energy on the pre‐ or poststress values of plasma cortisol was observed. These findings support the ideas that red drum obtain greater metabolic capacity when they are exposed to a near‐optimal temperature and that their ability to transform that capacity into growth is maximized only when they are provided a nutritious, high‐energy diet.

Background: Nuclear receptor coactivator 6 (NCoA6) is overexpressed in various cancers and considered a multifunctional coactivator of various transcription factors and nuclear receptors. However, the role of NCoA6 in pancreatic ductal adenocarcinoma (PDAC) remains unclear.Methods: NCoA6 expression data in PDAC were extracted from TCGA and GTEx databases, and their correlation with survival outcomes were analyzed using the Kaplan–Meier plotter database. NCoA6 protein expression in PDAC tissues was evaluated using immunohistochemistry. RNA‐sequencing technology was used to sequence the transcriptome of NCoA6‐silenced PANC‐1 cells, followed by differential expression, GO/KEGG and GSEA analyses. The effects of NCoA6 on cell proliferation, migration, invasion, cell cycle, and apoptosis were determined in two representative cell lines (PANC‐1 and SW1990). Western blotting, qPCR, and co‐immunoprecipitation were performed to explore the mechanism of action of NCoA6 in PDAC cells.Results: NCoA6 expression was markedly increased in PDAC tissues, and high NCoA6 expression was associated with poor survival prognosis. However, there was no significant relationship between NCoA6 expression and metastasis in PDAC patients. Our RNA‐sequencing data analysis found 1194 significant differentially expressed genes between the control and NCoA6‐silenced PANC‐1 cells. GO/KEGG analysis results mainly focused on cytokine production, cytokine activity, and cytokine‐cytokine receptor interactions. GSEA results showed that the knockdown of NCoA6 affected the expression of histone deacetylase 1 (HDAC1) targeted genes. NCoA6 knockdown suppressed proliferation, migration, and invasion of PDAC cells. Finally, western blotting, qPCR, and co‐immunoprecipitation results showed that NCoA6 interacted with HDAC1 and that NCoA6 expression was negatively correlated with F‐box and WD repeat domain‐containing 7 (FBW7) and caudal‐related homeobox transcription factor 2 (CDX2) expression in pancreatic cancer.Conclusions: NCoA6 has a profound effect on cell proliferation, migration, invasion, and prognosis of PDAC and is potentially related to the expression of HDAC1, FBW7, and CDX2. Our results may provide novel therapeutic strategies for PDAC patients.

Digestive system cancers (DSCs) are globally prevalent and account for a substantial proportion of cancer-related deaths. This study aimed to investigate the potential causal relationships between 35 blood and urine biomarkers and the risk of 4 major DSCs, including esophageal, gastric, colorectal, and pancreatic cancers. A 2-sample bidirectional Mendelian randomization (MR) approach was employed. Genome-wide association studies (GWAS) summary statistics for DSCs were obtained from public databases, and biomarker data were sourced from a GWAS meta-analysis of the UK Biobank. The inverse variance weighted (IVW), MR-Egger, and weighted median methods were used to examine causality. To evaluate robustness, we performed sensitivity analyses, including Cochran Q test for heterogeneity, MR-Egger and MR-PRESSO tests for pleiotropy, and leave-one-out analysis. Furthermore, reverse MR analyses were conducted for all significant causal relationships identified. We identified 14 significant associations: 6 with esophageal cancer, 1 with gastric cancer, 3 with colorectal cancer, and 4 with pancreatic cancer. Elevated serum uric acid was associated with increased pancreatic cancer risk (odds ratio [OR] = 1.230, 95% confidence interval [CI]: 1.015–1.490, P = .035) but decreased esophageal cancer risk (OR = 0.822, 95% CI: 0.683–0.989, P = .038). Increased insulin-like growth factor (IGF-1) levels were associated with higher risks of esophageal (OR = 1.228, 95% CI: 1.035–1.457, P = .019) and colorectal cancer (OR = 1.216, 95% CI: 1.125–1.314, P < .001). Subsequent sensitivity analyses revealed that our results were rarely influenced by pleiotropy or heterogeneity. Reverse MR analysis indicated that there were no causal associations between genetic predisposition to DSCs and the identified biomarkers. The identified biomarkers may serve as potential diagnostic markers, aiding in the early detection of cancer, which is crucial for improving treatment outcomes.