Introduction: Sepsis is a worldwide epidemic, with high morbidity and mortality. Cuproptosis is a form of cell death that is associated with a wide range of diseases. This study aimed to explore genes associated with cuproptosis in sepsis, construct predictive models and screen for potential targets. Methods: The LASSO algorithm and SVM-RFE model has been analysed the expression of cuproptosis-related genes in sepsis and immune infiltration characteristics and identified the marker genes under a diagnostic model. Gene-drug networks, mRNA-miRNA networks and PPI networks were constructed to screen for potential biological targets. The expression of marker genes was validated based on the GSE57065 dataset. Consensus clustering method was used to classify sepsis samples. Results: We found 381 genes associated with the development of sepsis and discovered significantly differentially expressed cuproptosis-related genes of 16 cell types in sepsis and immune infiltration with CD8/CD4 T cells being lower. NFE2L2, NLRP3, SLC31A1, DLD, DLAT, PDHB, MTF1, CDKN2A and DLST were identified as marker genes by the LASSO algorithm and the SVM-RFE model. AUC > 0.9 was constructed for PDHB and MTF1 alone respectively. The validation group data for PDHB (P=0.00099) and MTF1 (P=7.2e-14) were statistically significant. Consistent clustering analysis confirmed two subtypes. The C1 subtype may be more relevant to cellular metabolism and the C2 subtype has some relevance to immune molecules.The results of animal experiments showed that the gene expression was consistent with the bioinformatics analysis. Discussion: Our study systematically explored the relationship between sepsis and cuproptosis and constructed a diagnostic model. And, several cuproptosis-related genes may interfere with the progression of sepsis through immune cell infiltration.

A novel ratiometric fluorescent probe was constructed for sensitive assay of hydrogen peroxide (H₂O₂) and glucose, which utilized the synergistically enhanced effects of Ce³⁺ and Fe²⁺ on copper nanoclusters (CuNCs) and coumarin. In the CuNCs-Ce³⁺/Fe²⁺-coumarin system, Ce³⁺ triggered the aggregation-induced emission phenomenon of CuNCs, and Fe²⁺ catalyzed the Fenton reaction to efficiently yield hydroxyl radical (•OH). In the presence of H₂O₂, the 625-nm red fluorescence of CuNCs was sharply quenched owing to the oxidation of CuNCs to Cu(II) by •OH, but the 460-nm blue fluorescence of 7-hydroxycoumarin from the oxidation of coumarin by •OH dramatically increased. Based on the reversible changes in two fluorescence signals, a satisfactorily ratiometric probe was constructed for H₂O₂ assay with a detection limit (LOD) of 0.6 μM accompanied by a visual color variation from red to blue. For glucose assay, this ratiometric probe gave a linear range of 3.2-160 μM and LOD of 0.96 μM owing to the oxidization of glucose to yield H₂O₂ in the presence of glucose oxidase and O₂. Overall, the newly developed ratiometric probe shows a great prospect in real applications for visual assay of H₂O₂ and glucose by our naked eyes.

Despite the wide application of radiotherapy in HCC, radiotherapy efficacy is sometimes limited due to radioresistance. Although radioresistance is reported with high glycolysis, the underlying mechanism between radioresistance and cancer metabolism, as well as the role of cathepsin H (CTSH) within it, remain unclear. In this study, tumor-bearing models and HCC cell lines were used to observe the effect of CTSH on radioresistance. Proteome mass spectrometry, followed by enrichment analysis, were used to investigate the cascades and targets regulated by CTSH. Technologies such as immunofluorescence co-localization flow cytometry and Western blot were used for further detection and verification. Through these methods, we originally found CTSH knockdown (KD) perturbed aerobic glycolysis and enhanced aerobic respiration, and thus promoted apoptosis through up-regulation and the release of proapoptotic factors such as AIFM1, HTRA2, and DIABLO, consequently reducing radioresistance. We also found that CTSH, together with its regulatory targets (such as PFKL, HK2, LDH, and AIFM1), was correlated with tumorigenesis and poor prognosis. In summary, our study found that the cancer metabolic switch and apoptosis were regulated by CTSH signaling, leading to the occurrence of radioresistance in HCC cells and suggesting the potential value of HCC diagnosis and therapy.

The cardiovascular system effects of environmental low-dose radiation exposure on radiation practitioners remain uncertain and require further investigation. The aim of this study was to initially investigate and explore the mechanisms by which low-dose radiation may contribute to atherosclerosis through a multi-omics joint comprehensive basic experiment. We used WGCNA and differential analyses to identify shared genes and potential pathways between radiation injury and atherosclerosis sequencing datasets, as well as tissue transcriptome immune infiltration level extrapolation and single-cell transcriptome data correction using the CIBERSORT deconvolution algorithm. Animal models were constructed by combining a high-fat diet with 5 Gy γ-ray whole-body low-dose ionizing radiation. The detection of NETs release was validated by enzyme-linked immunosorbent assay. Analysis reveals shared genes in both datasets of post-irradiation and atherosclerosis, suggesting that immune system neutrophils may be a key node connecting radiation to atherosclerosis. NETs released by neutrophil death can influence the development of atherosclerosis. Animal experiments showed that the number of neutrophils decreased (P < 0.05) and the concentration of NETs reduced after low-dose radiation compared with the control group, and the concentration of NETs significantly increased (P < 0.05) in the HF group. Endothelial plaques were significantly increased in the high-fat feed group and significantly decreased in the low-dose radiation group compared with the control group. Long-term low-dose ionizing radiation exposure stimulates neutrophils and inhibits their production of NETs, resulting in inhibition of atherosclerosis.

Background: Keratoconus is a diseased corneal dilation of unknown etiology. Studies have shown that inflammation may play a role in keratoconus. Inflammatory enteritis (IBD), including ulcerative colitis (UC), is a chronic, systemic inflammatory disease. We used Mendelian randomization to assess the causal relationship among IBD, UC and keratoconus.Methods: The instrumental variable of IBD and UC was selected, the information of the instrumental variable in keratoconus outcome was extracted, and the causal relationship was assessed by the inverse variance weighted method by primary analysis, and its relevant sensitivity analysis.Results: A causal relationship between IBD and keratoconus was observed significantly (P = 0.017, OR = 1.21, 95% CI = 1.03–1.41), and same as to UC and keratoconus (P = 0.038, OR = 1.25, 95% CI = 1.01–1.54).Conclusion: IBD may play a causal role in the development of keratoconus, but the mechanism needs to be further elucidated.