Quantitative assessment of the associations between XRCC1 polymorphisms and bladder cancer risk

BACKGROUND: The XRCC1 polymorphisms have been implicated in bladder cancer risk, but individually published studies show inconsistent results. The aim of our study was to clarify the effects of XRCC1 variants on bladder cancer risk. METHODS: A systematic literature search up to September 13, 2012 was carried out in PubMed, EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios with 95% confidence intervals were used to assess the associations between XRCC1 Arg194Trp and Arg399Gln polymorphisms and bladder cancer risk. Heterogeneity and publication bias were also evaluated. RESULTS: A total of 14 and 18 studies were eligible for meta-analyses of Arg194Trp and Arg399Gln, respectively. Regrouping was adopted in accordance with the most probable appropriate genetic models. No obvious heterogeneity between studies was found. For overall bladder cancer, the pooled odds ratios for Arg194Trp and Arg399Gln were 1.69 (95% confidence interval: 1.25 to 2.28; P = 0.001) and 1.10 (95% confidence interval: 1.03 to 1.19; P = 0.008), respectively. After excluding the studies that were not in Hardy–Weinberg equilibrium, the estimated pooled odds ratio still did not change at all. CONCLUSIONS: The meta-analysis results suggest that XRCC1 Arg194Trp and Arg399Gln polymorphisms may be associated with elevated bladder cancer risk

Surface micromorphology and strength formation mechanisms of steering knuckles produced by casting-forging technology

Casting technology plays a crucial role in the advanced production of vehicle parts due to its relatively low manufacturing cost and flexibility. However, a major challenge is to improve surface strength, surface finish, and production efficiency in order to produce the next generation of lightweight, long-lasting, energy-efficient vehicles. In this study, we propose an efficient AlSi7Mg casting-forging technology that significantly enhances the mechanical properties of the samples compared to those produced by casting alone. The ultimate tensile strength (UTS) and elongation were increased from 290 MPa to 11% to 311 MPa and 13%, respectively, which represents an improvement of 7.2% and 18%. Our research results demonstrate that the casting-forging technique introduces favorable and stable microstructural features, including optimized surface quality and refined grains, which improve mechanical properties

Exploration of Prognostic Biomarkers of Muscle-Invasive Bladder Cancer (MIBC) by Bioinformatics

We aimed to discover prognostic factors of muscle-invasive bladder cancer (MIBC) and investigate their relationship with immune therapies. Online data of MIBC were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus database (GEO) database. Weighted gene co-expression network analysis (WGCNA) and univariate Cox analysis were applied to classify genes into different groups. Venn diagram was used to find the intersection of genes, and prognostic efficacy was proved by Kaplan-Meier analysis. Heatmap was utilized for differential analysis. Riskscore (RS) was calculated according to multivariate Cox analysis and evaluated by receiver operating characteristic curve (ROC). MIBC samples from TCGA and GEO were analyzed by WGCNA and univariate Cox analysis and intersected at 4 genes, CLK4, DEDD2, ENO1, and SYTL1. Higher SYTL1 and DEDD2 expressions were significantly correlated with high tumor grades. Riskscore based on genes showed great prognostic efficiency in predicting overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in TCGA dataset ( P  < .001). The area under the ROC curve (AUC) of RS reached 0.671 in predicting 1-year survival and 0.653 in 3-year survival. KEGG pathways enrichment filtered 5 enriched pathways. xCell analysis showed increased T cell CD4+ Th2 cell, macrophage, macrophage M1, and macrophage M2 infiltration in high RS samples ( P  < .001). In immune checkpoints analysis, PD-L1 expression was significantly higher in patients with high RS. We have, therefore, constructed RS as a convincing prognostic index for MIBC patients and found potential targeted pathways

Effects of PYCR1 on prognosis and immunotherapy plus tyrosine kinase inhibition responsiveness in metastatic renal cell carcinoma patients

Background: Immunotherapy plus tyrosine kinase inhibitor (IO-TKI) has become the first-line management for metastatic renal cell carcinoma (RCC), despite the absence of biomarkers. Recently, pyrroline-5-carboxylate reductase 1 (PYCR1) and proline metabolism have been reported regulatory roles in the anti-tumor response. Methods: There were three cohorts enrolled: two from our institution (ZS-MRCC and ZS-HRRCC) and one from a clinical trial (JAVELIN-101). The PYCR1expression in each sample was evaluated by RNA sequencing. Flow cytometry and immunohistochemistry were performed to assess immune infiltration. Single-cell RNA-seq (scRNA-seq) data was used for cluster analysis of T cells and macrophages. Primary endpoints were set as response and progression-free survival (PFS). Results: Patients in the low-PYCR1 group had greater objective response rate (52.2% vs 18.2%) and longer PFS in both cohorts (ZS-MRCC cohort, P=0.01, HR=2.80; JAVELIN-101 cohort, P<0.001, HR=1.85). In responders, PYCR1 expression was decreased (P<0.05). In the high PYCR1 group, CD8+ T cells exhibited an exhausted phenotype with decreased GZMB (Spearman's ρ=-0.36, P=0.02). scRNA-seq revealed tissue-resident memory T (Trm) (P<0.05) and tissue-resident macrophage (P<0.01) were decreased in samples with high PYCR1 expression. A machine learning score was further built by random forest, involving PYCR1 and Trm markers. Only in the subgroup with the lower RFscore did IO+TKI show a favorable outcome, compared to TKI monotherapy. Conclusions: Immunosuppression and IO+TKI resistance were correlated with high PYCR1 expression. T cell exhaustion and dysfunction were also related with the expression of PYCR1. PYCR1 has the potential to be employed as a biomarker to discriminate between IO+TKI and TKI monotherapy as the optimal patient treatment strategy

2-Diphenylphosphinoyl-acetyl as a remote directing group for the highly stereoselective synthesis of β-glycosides

The configuration of the anomeric glycosidic linkages is crucial for maintaining the biological functions and activities of carbohydrate molecules. However, their stereochemistry control in glycosylation represents one of the most challenging tasks in carbohydrate chemistry. In this report, the easily accessible 2-diphenylphosphinoyl-acetyl (DPPA) group was developed as a highly stereodirecting group for catalytic glycosylation via hydrogen-bond mediated delivery of the alcoholic acceptors. TMSOTf-catalyzed glycosylation with 6-O-DPPA glycosyl imidate donors displayed excellent β-selectivity and broad substrate scope, particularly applicable to synthesize the challenging β-configured 2-deoxy- and 2-azido-2-deoxy-glycosides from electron-deficient or bulky acceptors. Chemoselective removal of the DPPA group could be readily achieved under the mild catalysis of Ni(OTf)2, and further application was demonstrated in the synthesis of biologically important oligosaccharides, uronic acids, and 2,6-dideoxy-glycosides

Characteristics of cohort studies of diabetes and bladder cancer based on standardized incidence ratio.

<p>NA, data not applicable; m, male; f, female.</p