ABSTRACT
Background: Hepatocellular carcinoma (HCC), one of the highest causes of cancer-associated death, has effective treatments, especially for patients with advanced HCC. Circadian rhythm participates in several important physiological functions, and its chronic disruption results in many disordered diseases, including cancer. However, the role of circadian rhythm in the overall survival (OS) of patients with HCC remains unclear. Methods: We investigated the expression, copy number variation (CNV), and mutation profiles of core circadian clock genes in normal and tumor tissues. We developed and validated a messenger RNA signature (mRNASig) based on prognostic circadian clock genes. A set of bioinformatic tools were applied for functional annotation and tumor-associated microenvironment (TME) analysis. Results: Core circadian clock genes were disrupted in terms of the transcription and CNV of HCC samples. The mRNASig, including NPAS2, NR1D1, PER1, RORC, and TIMELESS, was constructed. We divided patients with HCC into high-risk group and low-risk group based on the median value of the risk score. The high-risk group had a poorer prognosis than the low-risk group. The high-risk group was associated with malignant processes (e.g., proliferation, oncogenic pathway, DNA repair), metabolism, and tumor mutational burden (TMB). Surprisingly, the low-risk group was associated with enriched angiogenesis and was linked to enhanced response to sorafenib. Moreover, the high-risk group showed poor infiltration of CD8 T cells and natural killer cells accompanied by higher expression of CTLA4, PDCD1, TIGIT, and TIM3. Additionally, the mRNASig was associated with TMB. Conclusions: The mRNASig based on core circadian clock genes is a potential prognostic signature and therapeutic strategy and is significantly associated with the malignant biology of HCC.
ABSTRACT
The use of the electro-Fenton process to continuously generate H2O2 and efficiently degrade organic pollutants is considered a promising technology. The ratio of generation of H2O2 is usually regarded as the critical step; however, how the H2O2 is utilized is also of particular importance. Herein, activated carbon was activated at different temperatures and used to explore the effect of nitrogen doping on the production and utilization of H2O2 in the electro-Fenton-based degradation of organic pollutants. The experimental results indicate that nitrogen-doped activated carbon simultaneously promotes the generation and utilization of H2O2, which is attributed to the regulation of the competition between phenol and O2 adsorption by the doped nitrogen. Nitrogen doping not only improves 2e-ORR selectivity but also aggregates phenol near the cathode to balance the concentrations of phenol and ·OH. Density functional theory (DFT) calculations further confirmed that pyrrole-N as a dopant promoted the adsorption of phenol, while pyridine-N was more favorable for O2 adsorption. The unique balance of nitrogen types possessed by modified activated carbon NAC-750 permits the efficient synergistic generation and utilization of H2O2 in a balanced manner during the degradation of phenol. This work provides a new direction for the rational nitrogen-doping modification of activated carbon for the electro-Fenton-based degradation of organic pollutants.
ABSTRACT
Given the rising popularity of post-retirement work and its potential benefits for older adults' mental health, this study examined older adults' adaptation ability as a conditional factor for the impact of post-retirement work on depression. Quantitative data from 1433 working older adults and 1433 non-working older adults were analyzed using the PROCESS macro in SPSS to test a moderated regression model with adaptation ability as the moderator. Results showed that older adults with lower adaptation ability demonstrated significantly lower depression if they worked (vs. did not work). Older adults with higher adaptation ability exhibited significantly higher depression if they worked (vs. did not work). These findings were subsequently verified with a robustness check. Overall, post-retirement work did not prevent depression for the entire sample; working only alleviated depression among older adults with limited adaptation ability. Older adults with stronger adaptation ability could better maintain their mental health by staying retired. This study fills a knowledge gap regarding the relationship between post-retirement work and mental health. Implications for aging societies are also discussed.
ABSTRACT
Background: Small cell lung cancer (SCLC) is an aggressive lung malignancy with high relapse rates and poor survival outcomes. Ferroptosis is a recently identified type of cell death caused by excessive intracellular iron accumulation and lipid peroxidation, which may mediate tumor-infiltrating immune cells to influence anti-cancer immunity. But prognostic value of ferroptosis-related genes and its relationship with the treatment response of immunotherapies in SCLC have not been elucidated. Methods: The RNA-sequencing and clinical data of SCLC patients were downloaded from the cBioPortal database. A ferroptosis-related prognostic risk-scoring model was constructed based on univariable and multivariable Cox-regression analysis. Kaplan-Meier (K-M) survival curves and receiver operating characteristics (ROC) curves were constructed to assess the sensitivity and specificity of the risk-scoring model. And the correlations between ferroptosis-related prognostic genes and immune microenvironment were explored. The IC50 values of anti-cancer drugs were downloaded from the Genomics of Drug Sensitivity in Cancer (GDSC) database and the correlation analysis with the key gene thioredoxin-interacting protein (TXNIP) was performed. In addition, immunohistochemistry (IHC) staining was employed to detect the expression of TXNIP in 20 SCLC patients who received first-line chemo-immunotherapy. Immunotherapeutic response according to iRECIST (Response Evaluation Criteria in Solid Tumours for immunotherapy trials) were recorded. Results: We constructed a risk-score successfully dividing patients in the low- and high-risk groups (with better and worse prognosis, respectively). The area under the curve (AUC) of this risk-scoring model was 0.812, showing it had good utility in predicting the prognosis of SCLC. Moreover, ferroptosis-related genes were associated with the degree of immune infiltration of SCLC. Most importantly, we found that the TXNIP expression was highly correlated with the degree of immune invasion and the efficacy of chemotherapy in combination with immunotherapy in SCLC patients. Conclusions: The ferroptosis-related prognostic risk-scoring model proposed in this study can potentially predict the prognosis of SCLC patients. TXNIP may serve as a potential biomarker to predict the prognosis and efficacy of chemotherapy combined with immunotherapy in SCLC patients.
