Polymorphisms in the Presumptive Promoter Region of the SLC2A9 Gene Are Associated with Gout in a Chinese Male Population

BACKGROUND: Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate transporter. To date, several recent genome-wide association studies (GWAS) and follow-up studies have identified genetic variants of SLC2A9 associated with urate concentrations and susceptibility to gout. We therefore investigated associations between gout and polymorphisms and haplotypes in the presumptive promoter region of GLUT9 in Chinese males. METHODOLOGY/PRINCIPAL FINDINGS: The approximately 2000 bp presumptive promoter region upstream of the start site of exon 1 of GLUT9 was sequenced and subjected to genetic analysis. A genotype-phenotype correlation was performed and polymorphisms-induced changes in transcription factor binding sites were predicted. Of 21 SNPs identified in GLUT9, five had not been previously reported. Two of the SNPs (rs13124007 and rs6850166) were associated with susceptibility to gout (p = 0.009 and p = 0.042, respectively). The C allele of rs13124007 appeared to be the risk allele for predisposition to gout (p = 0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p = 0.029, OR 1.645 [95% CI 1.050-2.577]). After Bonferroni correction, there was statistically difference in rs13124007 allele frequencies between gout cases and controls (P = 0.042). Haplotype analyses showed that haplotype GG was a protective haplotype (p = 0.0053) and haplotype CA was associated with increased risk of gout (p = 0.0326). Genotype-phenotype analysis among gout patients revealed an association of rs13124007 with serum triglycerides levels (P = 0.001). The C to G substitution in polymorphism rs13124007 resulted in a loss of a binding site for transcription factor interferon regulatory factor 1 (IRF-1). CONCLUSIONS/SIGNIFICANCE: Polymorphisms rs13124007 and rs6850166 are associated with susceptibility to gout in Chinese males

Effect of Pulse Frequency on Microstructure and Mechanical Properties of 2198 Al-Li Alloy Joints Obtained by Ultrahigh-Frequency Pulse AC CMT Welding

In this study, 2198 Al-Li alloy, a low density and high-performance material for aerospace equipment, was welded using ultrahigh-frequency pulse alternating current with cold metal transfer (UHF-ACCMT). Influence of different ultrahigh-frequency on the formation, porosity, microstructure, microhardness and tensile strength of the welded joints were investigated. The results showed that the coupled ultrahigh-frequency current generated electromagnetic force to stir the liquid metal of molten pool. The weld formation became much better with metallic luster and uniform ripples at frequency of 60 kHz and 70 kHz. The porosity was the minimum at frequency of 60 kHz. Furthermore, the molten pool was scoured and stirred by the electromagnetic force which provided the thermal and dynamic conditions for nucleation and grain refinement, the width of fine equiaxed grain zone became larger, and the number of equiaxed non-dendrite grains increased. With the grain refining and crystallize transition, the average microhardness and tensile strength of the joints at frequency of 60 kHz reached up the highest value, 116 HV0.1 and 338 MPa, respectively. The fracture of the welded joints presented the characteristics of quasi-cleavage fracture

P2X4 receptor modulates gut inflammation and favours microbial homeostasis in colitis

Abstract Background Inflammatory bowel disease (IBD) is a non‐specific chronic inflammatory disease of the intestine. In addition to genetic susceptibility, environmental factors and dysregulated host immunity, the gut microbiota is implicated in the pathogenesis of Crohn's disease (CD) or ulcerative colitis (UC), the two primary types of IBD. The P2X4 receptor has been demonstrated to have a crucial role in preventing infection, inflammation, and organ damage. However, it remains unclear whether the P2X4 receptor affects IBD and the underlying mechanisms. Methods Colitis was induced in mice administrated with dextran sodium sulphate (DSS). 16S rDNA sequencing was used to analyze the gut microbiota in knockout and wild‐type mice. Clinical and histopathological parameters were monitored throughout the disease progression. Results Gene Expression Omnibus analysis showed the downregulation of P2RX4 (P2rx4) expression in colonic tissues from patients or mice with IBD. However, its expression at the protein levels was upregulated on day 4 or 6 and then downregulated on day 7 in C57BL/6 mice treated with DSS. Gene ablation of P2rx4 aggravated DSS‐induced colitis accompanying gut microbiota dysbiosis in mice. Moreover, P2X4 receptor‐positive modulator ivermectin alleviated colitis and corrected dysregulated microbiota in wild‐type C57BL/6 mice. Further antibiotic‐treated gut microbiota depletion, cohousing experiment, and fecal microbiota transplantation proved that gut microbiota dysbiosis was associated with the aggravation of colitis in the mouse model initiated by P2rx4. Conclusions Our findings elaborate on an unrevealed etiopathophysiological mechanism by which microbiota dysbiosis induced by the P2X4 receptor influences the development of colitis, indicating that the P2X4 receptor represents a promising target for treating patients with CD and UC

Efficiency, Safety, and Efficacy of High-Power Short-Duration Radiofrequency Ablation in Patients with Atrial Fibrillation

Pulmonary vein isolation (PVI) is the cornerstone therapy of atrial fibrillation (AF). Radiofrequency catheter ablation (RFCA) is performed using a point-by-point method to achieve durable PVI. However, this procedure remains complex and time-consuming, and the long-term clinical outcomes are still not satisfactory. Recently, there has been increasing interest in the clinical application of high-power short-duration (HPSD) approaches in the field of RFCA. HPSD ablation, distinguishing it from the conventional ablation strategy, delivers RF energy at a high power and saves the dwell time at each site. It is unknown whether the HPSD approach can bring some gratifying changes in the field of RF energy ablation. A number of experimental studies and clinical studies have been conducted regarding this topic. The review aimed to summarize the research findings and evaluate the procedural efficiency, safety, and clinical outcomes of the HPSD approach based on the evidence available to date

Highly Perfluorinated Covalent Triazine Frameworks Derived from a Low-Temperature Ionothermal Approach Towards Enhanced CO2 Electroreduction

Perfluorinated covalent triazine frameworks (F-CTFs) have shown unique features and attractive performance in separation and catalysis. However, state-of-the-art F-CTFs synthesized via the ZnCl2-promoted procedure have quite low fluorine contents due to C-F bond cleavage induced by chloride (a Lewis base) and the harsh conditions deployed (400–700 °C). Fabricating F-CTFs with high fluorine contents (>30 wt %) remains challenging. Herein, we present a low-temperature ionothermal approach (275 °C) to prepare F-CTFs, which is achieved via polymerization of tetrafluoroterephthalonitrile (TFPN) over the Lewis superacids, e.g., zinc triflimide [Zn(NTf2)2] without side reactions. With low catalyst loading (equimolar), F-CTFs are afforded with high fluorine content (31 wt %), surface area up to 367 m2 g-1, and micropores around 1.1nm. The highly hydrophobic F-CTF-1 exhibits good capability to boost electroreduction of CO2 to CO, with faradaic efficiency of 95.7 % at -0.8 V and high current density (-141 mA cm-2) surpassing most of the metal-free electrocatalysts.This is a manuscript of an article published as Suo, Xian, Fengtao Zhang, Zhenzhen Yang, Hao Chen, Tao Wang, Zongyu Wang, Takeshi Kobayashi et al. "Highly Perfluorinated Covalent Triazine Frameworks Derived from a Low‐Temperature Ionothermal Approach Towards Enhanced CO2 Electroreduction." Angewandte Chemie International Edition 60, no. 49 (2021): 25688-25694. DOI: 10.1002/anie.202109342. Copyright 2021 Wiley-VCH GmbH. DOE Contract Number(s): AC02-07CH11358; AC05-00OR22725. Posted with permission

Demographic and clinical characteristics (Mean±SD) of the study population.

<p>Demographic and clinical characteristics (Mean±SD) of the study population.</p

Association between the polymorphisms (rs13124007 and rs6850166) and characteristics among gout patients.

<p>*The major allele was referred to as allele 1 and the minor allele as allele 2.</p>#<p>Hypertension was defined as systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg or receiving antihypertensivedrug treatment in a patient with a history of hypertension.</p> <p>Diabetes was defined on the basis of fasting blood glucose ≥7.0 mmol/l (126 mg/dl) or non-fasting blood glucose ≥11.1 mmol/l(200 mg/dl) and/or treatment of diabetes.</p>&<p>Obesity is defined as a BMI of 30 and above by World Health Organization (WHO).</p