Lymphatic metastasis is recognized as the leading manner of metastasis in bladder cancer (BLCa), but hematogenous metastasis accounts for a majority of cancer-associated deaths. The past two decades have witnessed tremendous attention in long non-coding RNAs (lncRNAs), which are a new hope for the development of targeted drug therapy for metastatic cancers; however, the underlying mechanism of lncRNAs involved in BLCa hematogenous metastasis remains to be elucidated. Here, we identified BLCa-associated transcript 3 (BLACAT3), a lncRNA, which was aberrantly upregulated in BLCa and corelated with poor prognosis of patients with muscle-invasive bladder cancer. Methodologically, m6A epitranscriptomic microarray, RNA sequencing and mass spectrometry (MS) were used to screen the key molecules of the regulatory axis. Functional assays, animal models and clinical samples were used to explore the roles of BLACAT3 in BLCa in vitro and in vivo. Mechanistically, m6A modification contributes to BLACAT3 upregulation by stabilizing RNA structure. BLACAT3 recruits YBX3 to shuttle into the nucleus, synergistically enhances NCF2 transcription, and promotes BLCa angiogenesis and hematogenous metastasis by activating downstream NF-κB signaling. Our findings will develop prognosis prediction tools for BLCa patients and discover novel therapeutic biological targets for metastatic BLCa.

Kidney cancer is a common urological tumour. Owing to its high prevalence and mortality rate, it is the third most malignant tumour of the urinary system, followed by prostate and bladder cancers. It exerts a high degree of malignancy, and most of the distant metastasis occurs at an early stage; it is insensitive to chemoradiotherapy and easily develops drug resistance. The current treatment for kidney cancer mainly includes surgery, interventional embolization and targeted therapy; however, the treatment efficacy is poor. In recent years, the role of exosomes as mediators of intercellular communication and information exchange in the tumour microenvironment in tumour pathogenesis has attracted much attention. Exosomes are rich in bioactive substances such as nucleic acids, proteins and lipids and are involved in angiogenesis, immune regulation, drug resistance, formation of pre-metastatic niche, invasion and metastasis. This article reviews the ongoing research and applications of exosomes for the diagnosis and treatment of kidney cancer.

Immune checkpoint therapy for prostate cancer (PCa), a classic ‘immune-cold’ tumor characterized by an immunosuppressive tumor microenvironment, failed previously in clinical trials, but the underlying causes remain elusive. Here we find that YY1⁺, immunosuppressive macrophages aggregate in the hypoxic areas of PCa. Mechanistically, hypoxia promotes the phase separation of YY1 in the nucleus, where YY1 binds to NUSAP1 and promotes the SUMOylation, phase separation and stabilization of HIF-1α. Either myeloid-specific conditional knockout of YY1 or a treatment with tenapanor for decreasing the YY1–NUSAP1–HIF-1α interaction impairs subcutaneous PCa tumor formation in mouse prostate tumor models. Lastly, a first-generation tetrahedral DNA nanostructure based on the proteolysis targeting chimera technique, termed YY1-DcTAC, allows targeting and degrading YY1 in tumor-associated macrophages for inducing antitumor effects and CD8⁺ T cell tumor infiltration in mouse tumor models. In summary, our findings underscore the pivotal role of YY1 in the hypoxia/HIF-1α pathway in tumor-associated macrophages and support the targeting of YY1 for treating PCa.

Background: Body mass index (BMI) is a vital risk factor for kidney stones, but physical activity may reduce the incidence of kidney stones. However, it remains unknown whether physical activity reduces the effect of high BMI on kidney stones in diabetes participants.Methods: We included clinical information from 4,008 adult participants with diabetes from the National Health and Nutrition Examination Survey (NHANES) database from 2007 to 2018. Univariate and multivariate logistic regression analyses were used to analyze the relationship between BMI and kidney stones, as well as the risk of BMI and kidney stones in different physical activity subgroups.Results: A total of 4,008 diabetic participants were included in this study, of whom 652 (16.3%) self-reported a history of kidney stones. Logistic regression analysis showed a positive association between BMI and kidney stones. After adjusting for other confounders, the adjusted ORs for the risk of kidney stones was 1.514 (95% CI, 1.134–2.022, p = 0.005) for participants with BMI ≥30 kg/m² among all participants; the risk of kidney stones was elevated (OR = 1.572, 95% CI, 1.134–2.022, p = 0.005) in group without physical activity, and a reduced risk (OR = 1.421, 95% CI, 0.847–2.382, p = 0.183) in the group with physical activity. Furthermore, similar results were found in most subgroups.Conclusion: Our study suggests that high BMI is a risk factor for diabetes kidney stone participants and that physical activity may moderate this relationship to some extent.

Background: Trace metals are essential trace elements for the human body, but insufficient or excessive levels of metal ions can lead to the development of disease. The purpose of this study was to examine the relationship between dietary intake of copper and the prevalence of kidney stones in U.S. adult population.Methods: We included data on dietary intake of trace metals from 28,623 adult participants in the National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2018. Multivariate logistic regression and restricted cubic spline (RCS) dose-response curves were used to explore the association between trace metals and kidney stones, and 1:1 propensity score matching (PSM) was performed between the stone formers and non-stone formers to test the validity of the results.Results: Dose-response curves showed a non-linear negative association between dietary copper intake and kidney stones, and an increase in copper intake reduced the risk of kidney stones. Multivariate logistic regression analysis showed that the odds ratio (95% confidence interval) for kidney stones in each quartile of copper intake compared to the lowest quartile were 0.905 (0.808–1.011, p = 0.075), 0.880 (0.785–0.987, p = 0.028) and 0.853 (0.756–0.959, p = 0.009). In addition, similar conclusions were reached after analysis of PSM in the stone formers and non-stone formers groups.Conclusion: Dietary copper intake was negatively and non-linearly correlated with kidney stones, which is worthy of further research and application in clinical practice.

Background: Sarcopenia as the loss of skeletal muscle mass is related with poor postoperative survival. This work purposed to evaluate the prognostic prediction of the total psoas index (TPI), albumin–globulin score (AGS), and the combination of TPI and AGS (CTA) in bladder cancer (BCa) patients after radical cystectomy. Methods: BCa patients that received radical cystectomy between 2012 and 2020 were retrieved from our medical center. The calculation of TPI was based on the plain computed tomography images. The predictive effects of TPI, AGS, and CTA grade on survival of BCa patients were analyzed and compared with the albumin–globulin ratio (AGR) through the receiver operating characteristic (ROC) curves. A nomogram was further established based on the Cox regression results from CTA grade and clinicopathological characteristics, which are verified by the decision curve analysis (DCA). Results: A total of 112 eligible patients diagnosed as BCa were included in this study for retrospective analysis. The patients with lower TPI or higher AGS grade (1/2) contained poorer overall survival (OS) and disease-free survival (DFS). Divided by CTA grade, there were 35 (31.25%) patients in grade 1 associated with the best postoperative prognosis, which was accompanied with increased TPI and decreased AGS. The CTA grade could better predict postoperative outcomes compared with TPI, AGR, and AGS for the highest area under the curve (AUC; 0.674 of OS and 0.681 of DFS). The 3- and 5-year OS and DFS nomograms were conducted based on CTA grade and clinical variables, with a higher predictive performance than the TNM stage. Conclusion: This study revealed that the novel index CTA functioned as an effective prognostic predictor for postoperative OS and DFS of BCa patients after radical cystectomy. Preoperative assessment of CTA would contribute to optimizing clinical therapies.