The combination of radiation therapy (radiotherapy) with immunotherapy is changing the landscape of cancer treatment. Radiation damage tumor cell DNA through high-energy rays directly causes cell death or growth arrest; Immunotherapy works by boosting a patient’s own immune system’s ability to recognize and destroy cancer cells. The combination of the two not only enhances the local control of the tumor, but may also activate the systemic anti-tumor immune response, transforming the “cold” tumor into a “hot” tumor, thereby improving the survival rate and quality of life of patients. In recent years, this combined treatment approach has shown remarkable efficacy in a variety of cancers, especially non-small cell lung cancer and melanoma, among others. However, how to optimize radiation dose, timing and combination with immunotherapy drugs remains the focus of research. This paper first discusses the effect of radiotherapy on immune system, then analyzes the killing effect of radiotherapy and its mechanism, and finally discusses the latest progress and challenges of the combined application of radiotherapy and immunotherapy. Each section aims to provide clinicians and researchers with an in-depth understanding with a view to optimizing treatment strategies and improving outcomes for cancer patients.

The escalating crisis of bacterial antimicrobial resistance necessitates the discovery of novel antibacterial agents with distinct mechanisms of action. Ursolic acid (UA), a naturally abundant pentacyclic triterpenoid, serves as a promising scaffold for structural modification. In this study, a series of 26 novel UA derivatives (A1–A7 and B1–B19) were designed and synthesized by introducing various substituents at the C-28 carboxyl group via a chloroacetyl chloride linker. Their antibacterial activities were evaluated against S. aureus, S. epidermidis, E. coli, and P. aeruginosa using the microbroth dilution method. Among them, compound B1 exhibited the most potent activity, with a minimum inhibitory concentration (MIC) of 37.5 μg/mL against S. aureus and 75 μg/mL against E. coli. Antibacterial kinetic and time-kill curve assays confirmed the sustained bactericidal effect of B1. Furthermore, B1 significantly inhibited biofilm formation in both S. aureus and E. coli in a time-dependent manner. Molecular docking studies revealed that B1 binds spontaneously to the S. aureus SarA protein through three hydrogen bonds and π-π stacking interactions, providing a structural basis for its antibacterial and anti-biofilm activities. This study demonstrates that piperazine-modified UA derivative B1 is a promising antibacterial candidate and offers a new strategy for the structural optimization of ursolic acid.

Gastric cancer remains a major health burden, and the molecular events that accompany the transition from normal gastric epithelium to malignancy (and the factors that facilitate dissemination) are incompletely defined. In particular, the cellular phenotypes that precede overt transformation and the role of copper-linked metabolic stress in this process are not well understood. We integrated 2 public single-cell RNA-seq datasets of gastric tissues (gene expression omnibus) using canonical correlation analysis-based batch correction and performed quality control and pre/post-integration assessments. Epithelial subclusters were annotated and analyzed by dimensionality reduction, pseudotime inference (monocle; natural-spline model ~sm.ns[Pseudotime]), gene ontology/Kyoto encyclopedia of genes and genomes enrichment, and pathway activity scoring (gene set variation analysis/gene set enrichment analysis). Immune dysfunction/exclusion was evaluated (e.g., tumor immune dysfunction and exclusion). To evaluate genetic evidence, we conducted two-sample Mendelian randomization (MR) using circulating copper as the exposure and benign gastric tumors (FinnGen) and gastric cancer (Genome-Wide Association Study Catalog) as outcomes; standard diagnostics (e.g., F -statistics, I²_GX, pleiotropy/heterogeneity tests, MR-PRESSO) were applied. We identified a putative transitional epithelial phenotype between normal and malignant states, characterized by attenuation of lineage functions (e.g., gastric-acid-related signatures) and enrichment of stress-adaptation programs. Along pseudotime, module scores for stress response to copper ion increased from normal to transition cells and decreased along the tumor branch; metastatic epithelial cells showed attenuated copper-stress signatures together with enhanced motility/tumor programs, consistent with phenotypic convergence across metastatic sites. Primary tumor epithelium exhibited reinforced cell-cycle activity and immune-response attenuation, with immune dysfunction exceeding that of normal epithelium. In MR analyses, genetically proxied variation in circulating copper was positively associated with risk of both benign and malignant gastric tumors, with directions concordant across estimators and diagnostics not indicating major violations (findings consistent with a deleterious causal contribution under standard MR assumptions). Single-cell and genetic evidence prioritize copper-linked metabolic stress and epithelial remodeling (together with immune dysfunction) as testable axes in early gastric epithelial transformation and dissemination. While the patterns are consistent with a causal contribution of higher systemic copper, they do not constitute proof; orthogonal tissue validation and functional perturbation of copper-handling/cuproptosis pathways, alongside expanded genetic analyses (e.g., multivariable/colocalization), are warranted. These insights suggest potential avenues for prevention and targeted intervention.