A novel cuproptosis-related lncRNAs signature predicts prognostic and immune of bladder urothelial carcinoma

Bladder Urothelial Carcinoma (BLCA) remains the most common urinary system tumor, and its prognosis is poor. Cuproptosis is a recently discovered novel cell death involved in the development of tumor cells. However, the use of cuproptosis to predict the prognosis and immunity of Bladder Urothelial Carcinoma remains largely unclear, and this study was designed to verify cuproptosis-related long non-coding RNAs (lncRNAs) to estimate the prognosis and immunity of Bladder Urothelial Carcinoma. In our study, we first defined the expression of cuproptosis-related genes (CRGs) in BLCA, and 10 CRGs were up- or downregulated. We then constructed a co-expression network of cuproptosis-related mRNA and long non-coding RNAs using RNA sequence data from The Cancer Genome Atlas Bladder Urothelial Carcinoma (TCGA-BLCA), clinical features and mutation data from BLCA patients to obtain long non-coding RNAs by Pearson analysis. Afterward, univariate and multivariate COX analysis identified 21 long non-coding RNAs as independent prognostic factors and used these long non-coding RNAs to construct a prognostic model. Then, survival analysis, principal component analysis (PCA), immunoassay, and comparison of tumor mutation frequencies were performed to verify the accuracy of the constructed model, and GO and KEGG functional enrichment analysis was used to verify further whether cuproptosis-related long non-coding RNAs were associated with biological pathways. The results showed that the model constructed with cuproptosis-related long non-coding RNAs could effectively evaluate the prognosis of BLCA, and these long non-coding RNAs were involved in numerous biological pathways. Finally, we performed immune infiltration, immune checkpoint and drug sensitivity analyses on four genes (TTN, ARID1A, KDM6A, RB1) that were highly mutated in the high-risk group to evaluate the immune association of risk genes with BLCA. In conclusion, the cuproptosis-related lncRNA markers constructed in this study have evaluation value for prognosis and immunity in BLCA, which can provide a certain reference for the treatment and immunity of BLCA

Generalized Nonlinear Volterra-Fredholm Type Integral Inequality with Two Variables

We establish a class of new nonlinear retarded Volterra-Fredholm type integral inequalities, with two variables, where known function w in integral functions in Q.-H. Ma and J. Pečarić, 2008 is changed into the functions w1,w2. By adopting novel analysis techniques, such as change of variable, amplification method, differential and integration, inverse function, and the dialectical relationship between constants and variables, the upper bounds of the embedded unknown functions are estimated. The derived results can be applied in the study of solutions of ordinary differential equations and integral equations

Prognostic and immune correlation evaluation of a novel cuproptosis-related genes signature in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the world’s malignant tumors with high morbidity and mortality. Cuproptosis is a novel form of cell death. However, the prognostic evaluation and immune relevance of cuproptosis-related genes (CRGs) in HCC are largely unknown. In our study, we constructed a prognostic model of CRGs in HCC and performed immune infiltration, functional analysis, immune checkpoint and drug sensitivity analysis. Systematically elaborated the prognostic and immune correlation of CRGs in HCC. The results showed that 15 CRGs were up-regulated or down-regulated in HCC, and the mutation frequency of CRGs reached 10.33% in HCC, with CDKN2A having the highest mutation frequency. These 19 CRGs were mainly involved in the mitochondrion, immune response and metabolic pathways. Five selected genes (CDKN2A, DLAT, DLST, GLS, PDHA1) were involved in constructing a prognostic CRGs model that enables the overall survival in HCC patients to be predicted with moderate to high accuracy. Prognostic CRGs, especially CDKN2A, the independent factor of HCC prognosis, may be closely associated with immune-cell infiltration, tumor mutation burden (TMB), microsatellite instability(MSI), and immune checkpoints. CD274, CTLA4, LAG3, PDCD1, PDCD1LG2 and SIGLEC15 may be identified as potential therapeutic targets and CD274 correlated highly with prognostic genes. Quantitative Real-Time PCR (qRT-PCR) and immunohistochemical were performed to validate the mRNA and protein expression levels of CDKN2A in adjacent normal tissues and HCC tissues, and the results were consistent with gene difference analysis. In conclusion, CRGs, especially CDKN2A, may serve as potential prognostic predictors in HCC patients and provide novel insights into cancer therapy

The Contribution of the Underlying Factors to Socioeconomic Inequalities in Obesity: A Life Course Perspective

Objectives: Socioeconomic disparities in obesity have been observed in both childhood and adulthood. However, it remains unclear how the role of risk factors influencing these inequalities has evolved over time. Methods: Longitudinal data on 2,866 children and adolescents (6–17 years old) from the China Health and Nutrition Survey were used to track their BMI during childhood, adolescence, and adulthood. Concentration Index was utilized to measure socioeconomic inequalities in obesity, while Oaxaca decomposition was employed to determine the share of different determinants of inequality. Results: The concentration index for obesity during childhood and adulthood were 0.107 (95% CI: 0.023, 0.211) and 0.279 (95% CI: 0.203, 0.355), respectively. Changes in baseline BMI (24.6%), parental BMI (10.4%) and socioeconomic factors (6.7%) were found to be largely responsible for the increasing inequality in obesity between childhood and adulthood. Additionally, mother’s education (−7.4%) was found to contribute the most to reducing these inequalities. Conclusion: Inequalities in obesity during childhood and adulthood are significant and growing. Interventions targeting individuals with higher BMI, especially those who are wealthy, can significantly reduce the gap

Orsay virus CP-δ adopts a novel β-bracelet structural fold and incorporates into virions as a head fiber

Fiber proteins are commonly found in eukaryotic and prokaryotic viruses, where they play important roles in mediating viral attachment and host cell entry. They typically form trimeric structures and are incorporated into virions via noncovalent interactions. Orsay virus, a small RNA virus which specifically infects the laboratory model nematod

Prognostic value of fatty acid metabolism-related genes in colorectal cancer and their potential implications for immunotherapy

IntroductionColorectal cancer is one of the most common gastrointestinal cancers and the second leading cause of cancer-related death. Although colonoscopy screening has greatly improved the early diagnosis of colorectal cancer, its recurrence and metastasis are still significant problems. Tumour cells usually have the hallmark of metabolic reprogramming, while fatty acids play important roles in energy storage, cell membrane synthesis, and signal transduction. Many pathways of fatty acid metabolism (FAM) are involved in the occurrence and development of colon cancer, and the complex molecular interaction network contains a variety of genes encoding key enzymes and related products.MethodsClinical information and RNA sequencing data were collected from TCGA and GEO databases. The prognosis model of colon cancer was constructed by LASSO-Cox regression analysis among the selected fatty acid metabolism genes with differential expression. Nomogram for the prognosis model was also constructed in order to analyze its value in evaluating the survival and clinical stage of the colon cancer patients. The differential expression of the selected genes was verified by qPCR and immunohistochemistry. GSEA and GSVA were used to analyze the enrichment pathways for high- and low-risk groups. CIBERSORT was used to analyze the immune microenvironment of colon cancer and to compare the infiltration of immune cells in the high- and low-risk groups. The “circlize” package was used to explore the correlation between the risk score signature and immunotherapy for colon cancer.ResultsWe analysed the differential expression of 704 FAM-related genes between colon tumour and normal tissue and screened 10 genes with prognostic value. Subsequently, we constructed a prognostic model for colon cancer based on eight optimal FAM genes through LASSO Cox regression analysis in the TCGA-COAD dataset, and its practicality was validated in the GSE39582 dataset. Moreover, the risk score calculated based on the prognostic model was validated as an independent prognostic factor for colon cancer patients. We further constructed a nomogram composed of the risk score signature, age and American Joint Committee on Cancer (AJCC) stage for clinical application. The colon cancer cohort was divided into high- and low-risk groups according to the optimal cut-off value, and different enrichment pathways and immune microenvironments were depicted in the groups.DiscussionSince the risk score signature was significantly correlated with the expression of immune checkpoint molecules, the prognostic model might be able to predict the immunotherapy response of colon cancer patients. In summary, our findings expand the prognostic value of FAM-related genes in colon cancer and provide evidence for their application in guiding immunotherapy

Life-course social disparities in body mass index trajectories across adulthood: cohort study evidence from China health and nutrition survey

Background: The social disparities in obesity may originate in early life or in adulthood, and the associations of socioeconomic position (SEP) with obesity could alter over time. It is unclear how lifetime-specific and life-course SEP influence adult obesity development in China. Methods: Based on the China Health and Nutrition Survey (CHNS), three SEP-related indicators, including the father’s occupational position and the participant’s education and occupational position, were obtained. The life-course socioeconomic changes and a cumulative SEP score were established to represent the life-course SEP of the participants in the study. The growth mixture modeling was used to identify BMI trajectories in adulthood. Multinomial logistic regression was adopted to assess the associations between SEP and adult BMI trajectories. Results: A total of 3,138 participants were included in the study. A positive correlation was found between the paternal occupational position, the participants’ occupational position, education, and obesity in males, whereas an inverse correlation was observed among females. Males who experienced social upward mobility or remained stable high SEP during the follow-up had 2.31 and 2.52-fold risks of progressive obesity compared to those with a stable-low SEP. Among females, stable high SEP in both childhood and adulthood was associated with lower risks of progressive obesity (OR = 0.63, 95% CI: 0.43–0.94). Higher risks of obesity were associated with the life-course cumulative SEP score among males, while the opposite relationship was observed among females. Conclusions: The associations between life-course SEP and BMI development trajectories differed significantly by gender. Special emphasis should be placed on males experiencing upward and stable high socioeconomic change