Objectives: The combination of gemcitabine (Gem) and hypericin (HY) enhances the apoptosis of Capan-2 cells, providing a promising option for the treatment of pancreatic cancer. Our study further explored the cytotoxic mechanism of HY combined with chemotherapy drugs on pancreatic cancer. Methods: The proliferation rate of the cells assayed with the MTT method. The ROS (reactive oxygen species) levels of each treatment were evaluated by DCFH-DA oxidisation methods. The activity of glutathione reductase and the levels of reduced glutathione (GSH) and oxidised glutathione (GSSG) were assessed using assay kits. The expression levels of apoptosis-related proteins were analysed by western blotting. Key findings: The activity of glucose-6-phosphate dehydrogenase (G6PDH), a key enzyme of the pentose phosphate pathway, significantly decreased in Gem + HY groups, however, the ROS level enhanced accompanying with GSH depleting, mitochondrial membrane depolarisation and cytochrome C release. Gem + HY inhibits the expression of Bcl-2 but stimulates Bax level, triggering caspase activation and PARP cleavage and thus promoted apoptosis of Capan-2 cells. Conclusions: We demonstrated that Gem combined HY-PDT could inhibit the proliferation of Capan-2 cells and induce cell apoptosis. HY-PDT combined with Gem had a great potential on pancreatic cancer treatment clinically.

Vitiligo is a kind of skin dysfunction on melanogenesis. The highly prevalent, chronic, and distinctive complexion changes on patients have imposed enormous psychic and economic burden on both individuals and society. Traditional Chinese Medicine (TCM) is a kind of precious source on chronic disease treatment, including skin dysfunctional diseases. In our previous study, a new compound named apigenin‐7‐butylene glucoside has been authenticated and purified from a prescription of Chinese traditional medicine formula which has been used clinically in vitiligo treatment. The aim of this work is to evaluate the effects of this compound on melanogenesis using melanoma cell B16‐F10 in vitro. The results showed that apigenin‐7‐butylene glucoside had almost no cytotoxicity on B16‐F10 cells within a lower dose of 5.0 μg ml⁻¹ and enhanced the melanin level to about 41% and tyrosinase activity to 1.32‐fold when compared with controls. The compound showed minor cytotoxicity to B16‐F10 cells at the higher concentration of 10 μg ml⁻¹ and 50 μg ml⁻¹, the inhibition rate was 8.4% and 11.8%, and the melanin level and tyrosinase activity showed a decreased trend because of the lower cell number at the higher concentrations. The results indicated that apigenin‐7‐butylene glucoside was safe to B16‐F10 cells within a lower concentration, <5.0 μg ml⁻¹. Incubated with 5.0 ug ml⁻¹of apigenin‐7‐butylene glucoside for 48 hours, the mRNA and protein levels of Tyr, Trp-1, and Trp-2 genes were all increased except Mitf in B16‐F10 cells. The stimulation of apigenin‐7‐butylene glucoside on melanogenesis of B16‐F10 cells through Tyr, Trp‐1, and Trp‐2 pathway highlighted the potential usage of the compound in vitiligo treatment.

Cyanobacteria represent an ancient group of photosynthetic microorganisms that offer unparalleled insights into evolutionarily conserved stress adaptation mechanisms essential for plant resilience. To investigate how photosynthetic organisms mitigate chemical stressors, we employed Synechocystis sp. PCC 6803—a keystone model for photosynthetic research due to its plant-like electron transport chain and stress-responsive plasticity. By implementing a genomic hypermutation strategy, we synergistically knocked out DNA replication fidelity genes and overexpressed error-prone replication elements, generating hypermutable strains HM24 and HM33 with relative mutation rates of 97 and 116-fold, respectively. Following triclosan (TCS) stress screening, the CRISPR-Cpf1 strategy was used to complement mutations and yielded transformants R-HM24 and R-HM33 that exhibited 96 h EC50 values of 4.963 and 5.238 mg/L representing 322- and 340-fold increases over wild-type levels, respectively. The strains demonstrated enhanced TCS and multidrug antibiotic tolerance. Whole-genome resequencing identified consistent missense mutation in fabI across resistant strains. Mechanistic analyses revealed that the hypermutated Synechocystis strains acquired resistance primarily by mutating the essential fabI protein to decrease its affinity for TCS. This study establishes the application of hypermutation-driven evolution for rapid dissection of pollutant resistance in photosynthetic microbes, thereby advocating for stricter regulation of antimicrobial pollutants in aquatic environments.

Background: Uterine corpus endometrial carcinoma (UCEC) is a prevalent gynaecologic malignancy. It has been demonstrated that the immune cell infiltration (ICI) pattern plays a critical role in the tumour progression of UCEC. Methods: To further investigate the immune microenvironment landscape of UCEC, we analysed the gene expression data of 539 UCEC patients from The Cancer Genome Atlas (TCGA) database using CIBERSORT and ESTIMATE for consensus clustering of immune cells. We used the limma package to compare differentially expressed genes (DEGs) among ICI patterns and constructed a prognostic model using Cox regression to calculate the risk score of UCEC patients. The immunophenoscore was downloaded to explore the immunotherapeutic effect between low- and high-risk score patients. Finally, the tumour mutation burden (TMB) was calculated using the somatic mutation data. Results: We identified two different immune infiltration patterns in 539 UCEC samples, the immune-desert and immune-inflamed phenotypes, which had distinct prognostic and biological features. We obtained 29 DEGs to construct the ICI-related prognostic model and established a four ICI-related gene-based prognostic model comprising LINC01871, CXCL13, IGKJ5, and LINC01281. The risk score was associated with distinct clinical outcomes, ICI, and immunotherapeutic effects. Patients with a low risk score had higher effective immune cells, which could be classified into the immune-inflamed phenotype. Additionally, patients with a low risk score had a significantly higher immunophenoscore, suggesting a better immunotherapeutic outcome. Finally, TMB was confirmed to be associated with prognosis, which was synergistic with the risk score. Conclusions: This study comprehensively analysed the ICI pattern in UCEC patients and established a four ICI-related gene-based prognostic model to predict prognosis and guide precise immunotherapy strategies.