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Typhimurium-increased paracellular permeability. Further study showed that Gli1 was cross-activated by the MAP and PI-3 kinase pathways. S. Typhimurium devoid of sopB, an effector of the Type 3 secretion system (T3SS) responsible for AKT activation, was unable to induce Snail expression and to decrease the expression of apical junction proteins. Our study uncovered a novel role of Gli1 in mediating the Salmonella-induced disruption of the intestinal epithelial barrier. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.Methylation is the main form of RNA modification. N6-methyladenine (m6A) regulates the splicing and translation of mRNA. Alk B homologue 5 (ALKBH5) participates in the biological regulation of various cancers. However, its role in ovarian carcinogenesis has not been unveiled. In the present study, ALKBH5 showed higher expression in ovarian cancer tissue than in normal ovarian tissue, but lower expression in ovarian cancer cell lines than in normal ovarian cell lines. Interestingly, Toll-like receptor (TLR4), a molecular functioning in tumour microenvironment (TME), demonstrated the same expression trend. To investigate the effect of abnormal TME on ovarian carcinogenesis, we established an in vitro model in which macrophages and ovarian cancer cells were co-cultured. In the ovarian cancer cells co-cultured with M2 macrophages, the expression of ALKBH5 and TLR4 increased. We also verified that TLR4 up-regulated ALKBH5 expression via activating NF-κB pathway. Depending on transcriptome sequencing, m6A-Seq and m6A MeRIP, we found that NANOG served as a target in ALKBH5-mediated m6A modification. NANOG expression increased after mRNA demethylation, consequently enhancing the aggressiveness of ovarian cancer cells. In conclusion, highly expressed TLR4 activated NF-κB pathway, up-regulated ALKBH5 expression and increased m6A level and NANOG expression, all contributing to ovarian carcinogenesis. Our study revealed the role of m6A in ovarian carcinogenesis, providing a clue for inventing new target therapy. © 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley &amp; Sons Ltd.Vacancy defects of catalyst has been extensively studied and proven to be beneficial to various electrocatalytic reactions. [https://www.selleckchem.com/products/ms-275.html click here] However, it remains a great challenge to systematically study the effects of vacancy defects on the electrocatalytic reaction during electrochemical process. Herein, an ultra-stable three-dimensional PtCu nanowire networks (NNWs) with ultrafine size, self-supporting rigid structure, and Cu vacancy defects has been successfully developed. The vacancy defect-rich PtCu NNWs exhibits an outstanding performance for oxygen reduction reaction (ORR), in which the mass activity is 14.1 times higher than that of the commercial Pt/C catalyst (20%.wt, JM), and is the best performance currently. In addition, the mass activity of the PtCu NNWs for methanol oxidation reaction (MOR) is 17.8 times higher than that of the commercial Pt/C catalyst. Density-functional theory (DFT) calculations indicate that the introduction of Cu vacancy enhances the adsorption capacity of Pt atoms to HO* intermediate and simultaneously weakens the adsorption for O* intermediate. The excellent performances of PtCu NNWs for ORR and MOR can be attributed to the self-supporting structure, massive Cu vacancy defects, and synergistic electronic interaction on various active sites. This work presents a facile strategy to assemble efficient electrocatalysts with abundant vacancy defects, at the same time, provides an insight into the ORR mechanism in acidic solution. © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.Boosting charge transfer in materials is critical for applications involving charge carriers. Engineering ionic channels in electrode materials can create a skeleton to manipulate their ion and electron behaviors with favorable parameters to promote their capacity and stability. Here, tailoring of the atomic structure in layered potassium niobate (K4 Nb6 O17 ) nanosheets and facilitating their application in lithium and potassium storage by dehydration-triggered lattice rearrangement is reported. The spectroscopy results reveal that the interatomic distances of the NbO coordination in the engineered K4 Nb6 O17 are slightly elongated with increased degrees of disorder. Specifically, the engineered K4 Nb6 O17 shows enhanced electrical and ionic conductivity, which can be attributed to the enlarged interlamellar spacing and subtle distortions in the fine atomic arrangements. Moreover, subsequent experimental results and calculations demonstrate that the energy barrier for Li+ /K+ diffusion is significantly lower than that in pristine K4 Nb6 O17 . Interestingly, the diffusion coefficient of K+ is one order of magnitude higher than that of Li+ , and the engineered K4 Nb6 O17 presents superior electrochemical performance for K+ to Li+ . This work offers an ionic engineering strategy to enable fast and durable charge transfer in materials, holding great promise for providing guidance for the material design of related energy storage systems. © 2020 WILEY-VCH Verlag GmbH &amp; Co. KGaA, Weinheim.OBJECTIVES Hearing impairment (HI) is a leading impairment worldwide and identifying modifiable risk factors of HI may have major public health implications. The aim of this study was to investigate the association between obstructive sleep apnea (OSA) and HI. DESIGN Observational longitudinal study (the Paris Prospective Study 3). SETTING Population-based. PARTICIPANTS Volunteers aged 50-75 years and consulting at a preventive medical center were included between 2008 and 2012. 6797 participants were included in the present analysis. MAIN OUTCOME MEASURES Audiometry testing was performed in both ears in all participants and HI was defined by a pure tone average (PTA) &gt;25 decibels (dB) hearing level in the better ear. RESULTS OSA (estimated by the Berlin questionnaire) was present in 18.6% (n=1267) and HI in 13.9% (n=947) of the participants. Mean age was 59.5 years (SD 6.2) and 63.5% were male (n=4317). In multiple logistic regression modeling, OSA was significantly associated with a 1.21-increased odd of HI (95% confidence interval 1.01 - 1.44). Several sensitivity analyses supported this finding. CONCLUSION OSA is associated with a 21% increased odds of HI. These results support active screening of HI in subjects with OSA, and future studies should evaluate whether the treatment of OSA can delay the onset of HI. This article is protected by copyright. All rights reserved.BACKGROUND Allergic rhinitis (AR) is a major public health problem and is increasing worldwide. Allergic rhinitis affects children's learning efficiency, sleep quality and other major aspects of life. Sublingual immunotherapy (SLIT) is effective and safe for children with seasonal allergic rhinitis, but for children with perennial allergic rhinitis (PAR) caused by house dust mites (HDM), its effectiveness and safety is less convincing. METHODS Medical literature databases up to 2019 were searched for published and unpublished pieces of evidence. Studies were individually screened by two reviewers against the eligibility criteria. Primary outcomes were total nasal symptoms scores (TNSS) and total medication scores (TMS). The secondary outcomes were total ocular symptoms scores and adverse events (AEs). Random effect models and fixed-effect models were used to calculate the standard mean difference (SMD) and risk ratio (RR), respectively. RESULTS We identified 3,772 abstracts, of which only 16 studies met our established criteria. SLIT significantly reduced TNSS (SMD -1.73 [95 % Cl -2.62, -0.84]; p = 0.0001) and TMS (SMD -1.21 [95% CI -1.75, -0.67]; P less then 0.00001). Compared with children taking placebo, children taking SLIT were 1.08 [95% CI 1 to 1.17, p = 0.05], 1.15 [95% CI 0.87 to 1.51, p = 0.32], and 1.68 [95% CI 0.68 to 4.11, p = 0.26] times more likely to develop mild, moderate, and severe AEs, respectively. CONCLUSION HDM SLIT can effectively alleviate TNSS and TMS in children with PAR, but care should be taken to avoid harm due to possible adverse drug reactions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.INTRODUCTION Maternal viral load monitoring (mVL) and early infant diagnosis (EID) are necessary to achieve elimination of mother-to-child transmission of HIV. Point-of-care testing can achieve better outcomes compared to centralized laboratory testing (CLT). We describe the first implementation of point-of-care (POC) mVL and EID testing around delivery at four high volume tertiary obstetric units (TOUs) in Gauteng, South Africa. METHODS Prospective study of pregnant women living with HIV (WLHIV) and their infants. During the period 1 June 2018 to 31 March 2019, routine staff collected blood specimens from women and their infants around delivery. Specimen collection occurred throughout the week while dedicated POC operators, conducted testing during working hours on weekdays. Descriptive statistics and multivariable Poisson regression with robust error variance were used to describe outcomes and associated factors. Outcomes determined were (i) coverage of mVL and EID testing defined as a proportion of live bis vs. 2.9&nbsp;hours, p-value sign test less then 0.001). POC results were comparable to those from laboratory testing. CONCLUSION Accurate and timely POC mVL and EID testing around delivery was implemented with variable success across TOUs. Further scale up would need to address health system factors at facility level and high analytical error rates. © 2020 The Authors. Journal of the International AIDS Society published by John Wiley &amp; Sons Ltd on behalf of the International AIDS Society.Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with one of the poorest prognosis among all malignancies. The initiation and evolution of this kind of tumor depends on a complex interaction between cancer cells and the tumor microenvironment (TME). In an elegant study, Steins et&nbsp;al [1] used a combination of relevant disease models to show that mesenchymal subtype of PDAC shows a distinct deactivation of stellate cells in a CSF1-dependent fashion. This study shedding light on a new role for the stroma driving an aggressive PDAC subtypes shifts the current paradigm for the requirement of an activated TME to regulate PDAC growth and maintenance. © 2020 The Authors.BACKGROUND/AIM Sildenafil induces smooth muscle relaxation of the esophagus by blocking type 5 phosphodiesterase that degrades cyclic guanine monophosphate. We aimed to characterize the effects of sildenafil on esophageal peristalsis and contraction reserve using high-resolution manometry (HRM). METHODS Fifteen healthy adults (12 men, age 21-39, mean 27&nbsp;years) participated in this study using HRM following either sildenafil 50&nbsp;mg or placebo. HRM with ten wet swallows and five multiple rapid swallows was performed in all participants. HRM metrics included esophagogastric junction contractile integral (EGJ-CI), basal lower esophageal sphincter (LES) pressure, 4-second integrated relaxation pressure (IRP-4s), distal contractile integral (DCI), distal latency, resting upper esophageal sphincter pressure (UESP), and the response to MRS. RESULTS Sildenafil significantly lowered EGJ-CI (P&nbsp; less then &nbsp;.001), LES pressure (P&nbsp;=&nbsp;.04), IRP-4s (P&nbsp;=&nbsp;.02), and DCI (P&nbsp; less then &nbsp;.001). There was no difference in UESP (P&nbsp;=&nbsp;.