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Abstract Background Upper urinary tract urothelial carcinoma (UTUC) is a rare and highly aggressive malignancy characterized by poor prognosis, making the accurate identification of high-grade (HG) UTUC essential for subsequent treatment strategies. This study aims to develop and validate a nomogram model using computed tomography urography (CTU) images to predict HG UTUC. Methods A retrospective cohort study was conducted to include patients with UTUC who underwent radical nephroureterectomy and received a CTU examination prior to surgery. In the CTU images, tumor lesions located in the renal calyces, renal pelvis and ureter were segmented, and radiomics features from the unenhanced, medullary, and excretory phases were extracted. The maximum relevance minimum redundancy algorithm, least absolute shrinkage and selection operator, and various machine learning (ML) algorithms—including random forest, support vector machine, and eXtreme gradient boosting—were employed to select radiomics features and calculate radiomics scores. Logistic regression (LR) analysis was performed to identify the independent influencing factors of clinical baseline characteristics. Multiple datasets of radiomics features were constructed by integrating single-phase radiomics features with the most significant independent factor. Both LR and ML algorithms were utilized to develop predictive models. The area under the receiver operating characteristic curve (AUC values), accuracy, sensitivity, and specificity were assessed for model performance evaluation. Decision curve analysis was conducted to evaluate the clinical net benefits. Results A total of 167 patients were enrolled in this study. Among them, 56 were diagnosed with low-grade UTUC (including papillary urothelial neoplasms with low malignant potential and low-grade urothelial carcinoma) as confirmed by postoperative pathological examination results, and 111 were of HG. These patients were randomly allocated to the training set and the validation set at a ratio of 7:3. The training set comprised 116 patients with a mean age of 63.5 ± 9.38 years and 38 males. The validation set comprised 51 patients with a mean age of 65.6 ± 11.1 years and 18 males. Hydronephrosis was identified as the most significant independent factor in the clinical baseline features. Models that include mixed-phase development achieve better performance compared to models that rely simply on single-phase development. The nomogram model had excellent predictive ability for HG UTUC, with AUC values of 0.844 and an accuracy of 0.793 in the validation sets. The nomogram model can enhance accuracy by 14.1% (79.3% vs. 65.2%) and sensitivity by 32.8% (93.2% vs. 60.4%) compared to urinary cytology. Conclusions This study developed a nomogram model, which significantly improved the diagnostic ability for HG UTUC compared to urinary cytology. Furthermore, the results of the decision curve analysis showed that the model had a net benefit and could provide a non-invasive and potentially diagnostic reference tool for HG UTUC.

Abstract Objective To discuss the differences in the effectiveness and security of kidney stones in overweight or obese patients by mini percutaneous nephrolithotomy (MiniPCNL) and retrograde intrarenal surgery (RIRS). Materials and methods We exhaustively searched numerous databases, including PubMed, Embase, Web of Science, Cochrane Library, and CNKI, covering all records from their initiation date until September 2023. This included controlled trials focusing on the use of MiniPCNL and RIRS in the treatment of kidney stones in overweight or obese patients. The gathered data was then analyzed using the Review Manager 5.4 software. Results 9 studies including 1122 patients were included. Meta-analysis showed that: The MiniPCNL group had higher overall complications, grade I complications, length of hospital stay(LOS), first stone-free rate (SFR), and final SFR in obese patients, with no significant difference between the two groups in terms of operative time(OT), hemoglobin drop, and grade II complication rate. There were more overall complications, grade I complications, final SFR, and LOS with MiniPCNL in patients with stones > 2 cm compared to no significant difference in grade II complications. MiniPCNL performed in the prone position had higher final SFR, less OT, hemoglobin drop, and no statistically significant difference in overall complications or LOS. Sheaths using > 14 F had higher overall complication rates, final SFR, and LOS, and no statistical differences in OT and first SFR between the two modalities. In the MiniPCNL subgroup aged ≤ 50 years, there were higher first SFR, final SFR, and shorter OT, and in the MiniPCNL subgroup aged > 50 years, there were more OT, LOS, and hemoglobin drop, with no statistical difference in overall complications between the two groups. Conclusion Our study showed that MiniPCNL in obese patients had higher initial SFR and final SFR, fewer procedures, but more postoperative complications, LOS, and grade I complications compared with RIRS. Similar results were seen in patients in the prone position, with stones > 2 cm and age ≤ 50 years. Systematic review registration [ https://www.crd.york.ac.uk/PROSPERO/ ], identifier PROSPERO (CRD42023467284).

Abstract Prostate cancer (PCa), with high heterogeneity and poor prognosis, is one of the most common malignant tumors in men. Circular RNAs (circRNAs) have been identified in tumor progression and resistance to medication in numerous studies. However, the role of circ_0001047 in PCa is unclear. In this research, we found that circ_0001047 had low expression in PCa cells and tissues and was negatively correlated with testosterone secretion in vivo. Overexpression of circ_0001047 inhibited the proliferation, migration, invasion, and anti-apoptotic abilities of human PCa cells in vitro. Mechanistically, circ_0001047 promoted the expression of FKBP5 through sponge adsorption of miR-122-5p and then inhibited the proliferation, anti-apoptotic migration, and invasion abilities of PCa cells. In addition, overexpression of circ_0001047 enhanced the sensitivity of PCa cells to abiraterone by inhibiting AKT phosphorylation activation through upregulation of FKBP5/PHLPP1. This study revealed a novel mechanism by which circ_0001047 regulates PCa progression and treatment sensitivity via the miR-122-5p/FKBP5/PHLPP1/AKT axis. These findings deepen our comprehension of the molecular mechanisms in latent PCa progression and treatment resistance. Graphical Abstract

This study addresses the challenges of power output and durability in anion-exchange membrane (AEM) fuel cells (AEMFCs) through the use of graphene-based materials. Graphene oxide (GO) and partially reduced graphene oxide (prGO) with varying degrees of reduction were synthesized and characterized via Raman spectroscopy, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). AEMs were coated with the synthesized graphene materials and tested with Pt catalyst. The addition of GO and prGO with high degrees of reduction improved power output by 12 % and 5 %, respectively, and increased durability by 29 %. Optimal reduction degree of prGO showed significant improvements, enhancing power output by 53 % and doubling membrane life. When FeCo-N-C replaced Pt/C at the cathode, the power enhancement with intermediate prGO was reduced to 16 %, and durability increased by only 13 %, indicating a specific synergy with Pt. X-ray computed tomography (XCT) analysis showed that graphene addition maintained membrane integrity and prevented Pt nucleation within the membrane. However, after 140 h, the membrane interface became rough, causing electrical shorts. It is hypothesized that the hexagonal carbon ring structure of graphene allows OH− migration but blocks larger Pt ions, preventing degradation. Further investigation is needed to understand the significant power enhancement with minimal prGO addition.

Abstract Background The benefits of first-line, cisplatin-based chemotherapy for muscle-invasive bladder cancer are limited due to intrinsic or acquired resistance to cisplatin. Increasing evidence has revealed the implication of cancer stem cells in the development of chemoresistance. However, the underlying molecular mechanisms remain to be elucidated. This study investigates the role of LASS2, a ceramide synthase, in regulating Wnt/β-catenin signaling in a subset of stem-like bladder cancer cells and explores strategies to sensitize bladder cancer to cisplatin treatment. Methods Data from cohorts of our center and published datasets were used to evaluate the clinical characteristics of LASS2. Flow cytometry was used to sort and analyze bladder cancer stem cells (BCSCs). Tumor sphere formation, soft agar colony formation assay, EdU assay, apoptosis analysis, cell viability, and cisplatin sensitivity assay were used to investigate the functional roles of LASS2. Immunofluorescence, immunoblotting, coimmunoprecipitation, LC–MS, PCR array, luciferase reporter assays, pathway reporter array, chromatin immunoprecipitation, gain-of-function, and loss-of-function approaches were used to investigate the underlying mechanisms. Cell- and patient-derived xenograft models were used to investigate the effect of LASS2 overexpression and a combination of XAV939 on cisplatin sensitization and tumor growth. Results Patients with low expression of LASS2 have a poorer response to cisplatin-based chemotherapy. Loss of LASS2 confers a stem-like phenotype and contributes to cisplatin resistance. Overexpression of LASS2 results in inhibition of self-renewal ability of BCSCs and increased their sensitivity to cisplatin. Mechanistically, LASS2 inhibits PP2A activity and dissociates PP2A from β-catenin, preventing the dephosphorylation of β-catenin and leading to the accumulation of cytosolic phospho-β-catenin, which decreases the transcription of the downstream genes ABCC2 and CD44 in BCSCs. Overexpression of LASS2 combined with a tankyrase inhibitor (XAV939) synergistically inhibits tumor growth and restores cisplatin sensitivity. Conclusions Targeting the LASS2 and β-catenin pathways may be an effective strategy to overcome cisplatin resistance and inhibit tumor growth in bladder cancer patients.

Abstract Bladder cancer (BC) is a heterogeneous disease with varying clinical outcomes. Recent evidence suggests that cancer progression involves the acquisition of stem-like signatures, and assessing stemness indices help uncover patterns of intra-tumor molecular heterogeneity. We used the one-class logistic regression algorithm to compute the mRNAsi for each sample in BLCA cohort. We subsequently classified BC patients into two subtypes based on 189 mRNAsi-related genes, using the unsupervised consensus clustering. Then, we identified nine hub genes to construct a stemness-related prognostic index (SRPI) using Cox regression, LASSO regression and Random Forest methods. We further validated SRPI using two independent datasets. Afterwards, we examined the molecular and immune characterized of SRPI. Finally, we conducted multiply drug screening and experimental approaches to identify and confirm the most proper agents for patients with high SRPI. Based on the mRNAsi-related genes, BC patients were classified into two stemness subtypes with distinct prognosis, functional annotations, genomic variations and immune profiles. Using the SRPI, we identified a specific subgroup of BC patients with high SRPI, who had a poor response to immunotherapy, and were less sensitive to commonly used chemotherapeutic agents, FGFR inhibitors, and EGFR inhibitors. We further identified that dasatinib was the most promising therapeutic agent for this subgroup of patients. This study provides further insights into the stemness classification of BC, and demonstrates that SRPI is a promising tool for predicting prognosis and therapeutic opportunities for BC patients.

Background: The metabolism of arginine, a conditionally essential amino acid, plays a crucial role in cancer progression and prognosis. However, a more detailed understanding of the influence of arginine biosynthesis genes in cancer is currently unavailable. Methods: We performed an integrative multi-omics analysis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to determine the characteristics of these genes across multiple cancer types. To measure the overall activity of arginine biosynthesis genes in cancer, we calculated arginine biosynthesis scores based on gene expression. Results: Our results indicated that the arginine biosynthesis score was negatively correlated with immune-related pathways, immune infiltration, immune checkpoint expression, and patient prognosis, and single-cell data further clarified that patients with high arginine biosynthesis scores showed a reduced proportion of T and B cells in an immune desert tumor microenvironment and were insensitive to immunotherapy. We also identified several potential drugs through the Cancer Therapeutic Response Portal (CTRP) and Genomics of Drug Sensitivity in Cancer (GDSC) databases that could target arginine biosynthesis genes and potentially improve the response rate to immunotherapy in patients with a high arginine biosynthesis fraction. Conclusion: Overall, our analyses emphasize that arginine biosynthesis genes are associated with immune evasion in several cancers. Targeting these genes may facilitate more effective immunotherapy.