Single-cell sequencing technologies have noteworthily improved our understanding of the genetic map and molecular characteristics of bladder cancer (BC). Here we identify CD39 as a potential therapeutic target for BC via single-cell transcriptome analysis. In a subcutaneous tumor model and orthotopic bladder cancer model, inhibition of CD39 (CD39i) by sodium polyoxotungstate is able to limit the growth of BC and improve the overall survival of tumor-bearing mice. Via single cell RNA sequencing, we find that CD39i increase the intratumor NK cells, conventional type 1 dendritic cells (cDC1) and CD8 + T cells and decrease the Treg abundance. The antitumor effect and reprogramming of the tumor microenvironment are blockaded in both the NK cells depletion model and the cDC1-deficient Batf3^−/− model. In addition, a significant synergistic effect is observed between CD39i and cisplatin, but the CD39i + anti-PD-L1 (or anti-PD1) strategy does not show any synergistic effects in the BC model. Our results confirm that CD39 is a potential target for the immune therapy of BC.

Background: A series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain.Methods: We incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women (including premenopausal and postmenopausal groups). Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones.Results: Total 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/m²).Conclusion: In all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results.

Background: Some VOCs are identified as endocrine-disrupting chemicals (EDCs), interfering with the effect of sex hormones. However, no studies focused on the common spectrum of environmental VOCs exposure affecting sex hormones in the average male population.Objectives: We aimed to explore the association between VOCs and sex hormones in American adult males using multiple statistical models.Methods: The generalized linear (GLM), eXtreme Gradient Boosting (XGBoost), weighted quantile sum (WQS), Bayesian kernel machine regression (BKMR) and stratified models were used to evaluate the associations between Specific Volatile Organic Compounds and sex hormones in American adult male from NHANES 2013–2016.Results: Pearson correlation model revealed the potential co-exposure pattern among VOCs. XGBoost algorithm models and the WQS model suggested the relative importance of VOCs. BKMR models reveal that co-exposure to the VOCs was associated with increased Testosterone (TT), Estradiol (E₂), SHBG and decreased TT/E₂. GLM models revealed specific VOC exposure as an independent risk factor causing male sex hormones disorders. Stratified analysis identified the high-risk group on the VOCs exposures. We found Blood 2,5-Dimethylfuran in VOCs was the most significant effect on sex hormones in male. Testosterone increased by 213.594 (ng/dL) (124.552, 302.636) and estradiol increased by 7.229 (pg/mL) for each additional unit of blood 2,5-Dimethylfuran (ng/mL).Conclusion: This study is an academic illustration of the association between VOCs exposure and sex hormones, suggesting that exposure to VOCs might be associated with sex hormone metabolic disorder in American adult males.

(1) Background: Increasing evidence indicates that lipid metabolism may influence the concentration of prostate-specific antigen (PSA). However, the association between triglycerides and PSA remains unclear and complicated. Hence, we evaluated the correlation between triglycerides and PSA based on the U.S. National Health and Nutrition Examination Survey (NHANES) database. (2) Methods: A total of 2910 participants out of 41,156 participants fit into our study after conducting the screening from the 2003 to 2010 NHANES survey. Serum triglycerides were the independent variable of our study, and PSA was the dependent variable; (3) Results: In our study, the average age of chosen participants was 59.7 years (±12.7). After adjusting for covariates, the result indicated that for each additional unit of serum triglyceride (mg/dL), the PSA concentrations were reduced by 0.0043 ng/mL (−0.0082, −0.0005) with a statistical difference. Furthermore, we used machine learning of the XGBoost model to determine the relative importance of selected variables as well as constructed a smooth curve based on the fully adjusted model to investigate the possible linear relationship between the triglyceride and PSA concentrations. (4) Conclusions: The serum triglyceride is independently and negatively correlated with PSA among American males, which may make it hard to detect asymptomatic prostate cancer and diagnose at an advance stage with higher triglycerides due to detection bias.

Carboxypeptidase A4 (CPA4) has shown the potential to be a biomarker in the early diagnosis of certain cancers. However, no previous research has linked CPA4 to therapeutic or prognostic significance in bladder cancer. Using data from The Cancer Genome Atlas (TCGA) database, we set out to determine the full extent of the link between CPA4 and BLCA. We further analyzed the interacting proteins of CPA4 and infiltrated immune cells via the TIMER2, STRING, and GEPIA2 databases. The expression of CPA4 in tumor and normal tissues was compared using the TCGA + GETx database. The connection between CPA4 expression and clinicopathologic characteristics and overall survival (OS) was investigated using multivariate methods and Kaplan–Meier survival curves. The potential functions and pathways were investigated via gene set enrichment analysis. Furthermore, we analyze the associations between CPA4 expression and infiltrated immune cells with their respective gene marker sets using the ssGSEA, TIMER2, and GEPIA2 databases. Compared with matching normal tissues, human CPA4 was found to be substantially expressed. We confirmed that the overexpression of CPA4 is linked with shorter OS, DSF(Disease-specific survival), PFI(Progression-free interval), and increased diagnostic potential using Kaplan–Meier and ROC analysis. The expression of CPA4 is related to T-bet, IL12RB2, CTLA4, and LAG3, among which T-bet and IL12RB2 are Th1 marker genes while CTLA4 and LAG3 are related to T cell exhaustion, which may be used to guide the application of checkpoint blockade and the adoption of T cell transfer therapy.