Development and experimental verification of a prognosis model for disulfidptosis-associated genes in HNSCC.

Disulfidptosis is a newly discovered cell death pattern that has been less studied in head and neck squamous carcinoma (HNSCC). Exploring the molecular features of different subtypes of HNSCC based on disulfidptosis-associated genes (DAGs) is important for HNSCC. In addition, immunotherapy plays a pivotal role in the treatment of HNSCC. Exploring the sensitivity of immunotherapies and developing predictive models is essential for HNSCC. We analyzed the expression and mutational status of DAGs in 790 HNSCC patients and correlated the dates with clinical prognosis. HNSCC patients were divided into 2 groups based on their DAG expression. The relationship between DAGs, risk genes, and the immune microenvironment was analyzed using the CIBERSORT algorithm. A disulfidptosis risk model was constructed based on 5 risk genes using the LASSO COX method. To facilitate the clinical applicability of the proposed risk model, we constructed column line plots and performed stem cell correlation analysis and antitumor drug sensitivity analysis. Two different disulfidptosis-associated clusters were identified using consistent unsupervised clustering analysis. Correlations between multilayer DAG alterations and clinical characteristics and prognosis were observed. Then, a well-performing disulfidptosis-associated risk model (DAG score) was developed to predict the prognosis of HNSCC patients. We divided patients into high-risk and low-risk groups based on the DAG score and found that patients in the low-risk group were more likely to survive than those in the high-risk group (P < .05). A high DAG score implies higher immune cell infiltration and increased mutational burden. Also, univariate and multivariate Cox regression analyses revealed that the DAG score was an independent prognostic predictor for patients with HNSCC. Subsequently, a highly accurate predictive model was developed to facilitate the clinical application of DAG scores, showing good predictive and calibration power. Overall, we present a comprehensive overview of the DAG profile in HNSCC and develop a new risk model for the therapeutic status and prognosis of patients with HNSCC. Our findings highlight the potential clinical significance of DAG and suggest that disulfidptosis may be a potential therapeutic target for patients with HNSCC.

OsbZIP18 Is a Positive Regulator of Phenylpropanoid and Flavonoid Biosynthesis under UV-B Radiation in Rice.

In plants exposed to ultraviolet B radiation (UV-B; 280-315 nm), metabolic responses are activated, which reduce the damage caused by UV-B. Although several metabolites responding to UV-B stress have been identified in plants, the accumulation of these metabolites at different time points under UV-B stress remains largely unclear, and the transcription factors regulating these metabolites have not been well characterized. Here, we explored the changes in metabolites in rice after UV-B treatment for 0 h, 6 h, 12 h, and 24 h and identified six patterns of metabolic change. We show that the rice transcription factor OsbZIP18 plays an important role in regulating phenylpropanoid and flavonoid biosynthesis under UV-B stress in rice. Metabolic profiling revealed that the contents of phenylpropanoid and flavonoid were significantly reduced in osbzip18 mutants compared with the wild-type plants (WT) under UV-B stress. Further analysis showed that the expression of many genes involved in the phenylpropanoid and flavonoid biosynthesis pathways was lower in osbzip18 mutants than in WT plants, including OsPAL5, OsC4H, Os4CL, OsCHS, OsCHIL2, and OsF3H. Electrophoretic mobility shift assays (EMSA) revealed that OsbZIP18 bind to the promoters of these genes, suggesting that OsbZIP18 function is an important positive regulator of phenylpropanoid and flavonoid biosynthesis under UV-B stress. In conclusion, our findings revealed that OsbZIP18 is an essential regulator for phenylpropanoid and flavonoid biosynthesis and plays a crucial role in regulating UV-B stress responses in rice.