Fine-scale mapping of chromosome 9q22.33 identifies candidate causal variant in ovarian cancer.

Ovarian cancer is a complex polygenic disease in which genetic factors play a significant role in disease etiology. A genome-wide association study (GWAS) identified a novel variant on chromosome 9q22.33 as a susceptibility locus for epithelial ovarian cancer (EOC) in the Han Chinese population. However, the underlying mechanism of this genomic region remained unknown. In this study, we conducted a fine-mapping analysis of 130 kb regions, including 1,039 variants in 200 healthy women. Ten variants were selected to evaluate the association with EOC risk in 1,099 EOC cases and 1,591 controls. We identified two variants that were significantly associated with ovarian cancer risk (rs7027650, P = 1.91 × 10-7; rs1889268, P = 3.71 × 10-2). Expression quantitative trait locus (eQTL) analysis found that rs7027650 was significantly correlated with COL15A1 gene expression (P = 0.009). The Luciferase reporter gene assay confirmed that rs7027650 could interact with the promoter region of COL15A1, reducing its activity. An electrophoretic mobility shift assay (EMSA) showed the allele-specific binding capacity of rs7027650. These findings revealed that rs7027650 could be a potential causal variant at 9q22.33 region and may regulate the expression level of COL15A1. This study offered insight into the molecular mechanism behind a potential causal variant that affects the risk of ovarian cancer.

ABO blood groups and expression of blood group antigens of epithelial ovarian cancer in Chinese women.

BACKGROUND: ABO blood groups has been associated with risk of several cancers; however, the results for an association with ovarian cancer are inconsistent and little is known about the expression of histo-blood group (ABH) antigens and ABO gene in ovarian tumor tissues. METHODS: To assess the impact of genotype-derived ABO blood types on the risk of EOC, we conducted a case-control study in 1,870 EOC and 4,829 controls. Expression of A and B antigen in 70 pairs of ovarian tumor tissues and adjacent normal tissues were detected by immunohistochemistry. Gene expression and DNA methylation profiling was conducted in ovarian tumor tissues. RESULTS: We identified that blood group A was associated with increased risk for EOC compared to blood group O (OR = 1.18, 95% CI = 1.03-1.36, p = 0.019). Increased frequency of aberrant expression of histo-blood group antigens was observed in patients with blood group A (76.5%) compared to patients with blood group O (21.1%) and B (5.0%) by immunohistochemistry (p < 0.001). ABO gene expression was down-regulated in ovarian tumor tissues compared with paired adjacent normal tissues (p = 0.027). In addition, ABO gene expression was positively correlated with NFYB (r = 0.38, p < 0.001) and inversely correlated with DNA methylation level of four CpG sites on ABO gene (cg11879188, r = - 0.3, p = 0.002; cg22535403, r = - 0.30, p = 0.002; cg13506600, r = - 0.22, p = 0.025; cg07241568, r = - 0.21, p = 0.049) in ovarian tumor tissues. CONCLUSION: We identified blood group A was associated with increased EOC risk in Chinese women and provided the clues of the possible molecular mechanisms of blood group A related to ovarian cancer risk.

Hierarchically Structured FeNiOx Hy Electrocatalyst Formed by In†Situ Transformation of Metal Phosphate for Efficient Oxygen Evolution Reaction.

A simple and low-cost fabrication method is needed to obtain effective and robust heterogeneous catalysts for the oxygen evolution reaction (OER). In this study, an electrocatalyst FeNiOx Hy with a hierarchical structure is synthesized on nickel foam by a simple fabrication method through anion exchange from a metal phosphate to a metal hydroxide. The as-fabricated FeNiOx Hy electrode requires overpotentials of 206 and 234 mV to deliver current densities of 10 and 50 mA cm-2 , respectively. The catalytic performance of FeNiOx Hy is superior to that of most previously reported FeNi-based catalysts, including NiFe layered double hydroxide. The catalyst also shows good long-term durability at a current density of 50 mA cm-2 over 50 h with no activity decay under 1 m KOH. By comparison to the directly electrodeposited FeNi hydroxide in morphology and electrochemical properties, the improved activity of the catalyst could be mainly attributed to an enhancement of its intrinsic activity, which was caused by the anion exchange of phosphate to (oxy)hydroxide. Further studies by cyclic voltammetry indicated a stronger interaction between Ni and Fe from the negative shift of the oxidation peak of Ni2+ /Ni3+ in comparison with reported FeNiOx Hy , which promoted the generation of active Ni3+ species more easily. This work may provide a new approach to the simple preparation of effective and robust OER catalysts by anion exchange.

Facile Synthesis of a Ternary Metal Hydroxide with Acid Treatment as an Effective and Durable Electrocatalyst in Water Oxidation.

Developing low-cost, effective, and durable oxygen-evolution catalysts (OECs) is still a huge challenge owing to the uphill thermodynamic reaction and the involvement of a four-electron and four-proton kinetics process. Herein, a facilely prepared NiCoFe(OH)x /NiOOH/NF electrode affords current densities of 10 and 100 mA cm-2 at overpotentials of 223 and 254 mV, respectively, and a Tafel slope as low as 33.5 mV dec-1 in 1 m KOH, which is superior to NiCoFe(OH)x /NF electrodes electrodeposited with a traditional method. This electrode also displays surprisingly high durability at a current density of 50 mA cm-2 for over 50 hours under alkaline conditions. Component analysis and an electrochemical study revealed that the catalytic activity enhancement of this newly prepared electrode is mainly attributed to the formation of the electrically conductive NiOOH interlayer.