Huynhehlers9466

Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absentETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs; probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease. This article is protected by copyright. All rights reserved.In cutaneous T-cell lymphoma (CTCL), global hypomethylation of the genome and hypermethylation of tumor suppressor genes were detected. Studies show that methylation dysregulation is often a starting point for processes that might lead to malignant transformation. In this review, all data regarding copy number variations (CNVs) and mutations in main methylation players DNA methyltransferases/TET in CTCL were summarized. An overview of studies on gene-specific hypomethylation and hypermethylation in CTCL, including methylation of microRNA genes, was presented. The possibility of using the methylation pattern in diagnosis and methylation inhibitors in treatment of CTCL was discussed. This article is protected by copyright. All rights reserved.Homogeneous electrocatalytic proton reduction is reported using cobalt complex [ 1 ](BF 4 ) 2 . This complex comprises two bis(1-methyl-4,5-diphenyl-1H-imidazol-2-yl)methane (HBMIM Ph2 ) ligands that contain an acidic methylene moiety in their backbone. Upon reduction of [ 1 ](BF 4 ) 2 by either electrochemical or chemical means, one of its HBMIM Ph2 ligands undergoes deprotonation under the formation of dihydrogen. Addition of a mild proton source (acetic acid) to deprotonated complex [ 2 ](BF 4 ) regenerates protonated complex [ 1 ](BF 4 ) 2 . In presence of acetic acid in acetonitrile solvent [ 1 ](BF 4 ) 2 shows electrocatalytic proton reduction with a k obs of ~200 s -1 at an overpotential of 590 mV. Mechanistic investigations supported by Density Functional Theory (BP86) reveal that dihydrogen formation takes place in an intramolecular fashion through the participation of a methylene C-H bond of the HBMIM Ph2 ligand and a Co II -H bond through formal heterolytic splitting of the latter. These results represent the joint involvement of a base metal-hydride and a C-H bond in electrocatalytic proton reduction and are of interest to the development of responsive ligands for molecular (base)metal (electro)catalysis. © 2020 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.OBJECTIVE The aim was to evaluate the effect of a home-based exercise program on functional capacity, health-related quality of life (HRQoL), and disability, in patients with systemic sclerosis (SSc). METHODS A 6-month randomized controlled trial was conducted on SSc patients by comparing a home-based minimally supervised exercise program (exercise on a stationary cycle and strengthening of upper limbs; stretching of the hands) with usual care. At baseline and after 3 and 6 months, the patients underwent 6 minutes walking test; hand mobility in scleroderma test; maximal exercise test on an ergocycle; strength measures (handgrip, quadriceps, and biceps). 10074-G5 chemical structure HRQoL (short-form 36 [SF-36]) and disability (health assessment questionnaire disability index [HAQ-DI]) were measured at the same time. RESULTS Forty-four patients participated in the study. Twenty-two were randomly assigned to the intervention group (IG, mean age 63.60 ± 10.40 years) and 22 to the control group (CG, 61.80 ± 14.40 years). At 6 months, the distance walked in 6 minutes increased by 46 m (baseline 486, 95% CI 458-513 m; 6 months 532, 95% CI 504-561 m) in IG, whereas it decreased by 5 m (baseline 464, 95% CI 431-497 m; 6 months 459, 95% CI 427-490 m) in CG with a significantly different temporal trend at the between-groups comparison (P  less then  .001). An improvement was also observed for strength measures (handgrip, P = .003; quadriceps, P  less then  .001; biceps, P  less then  .001), for the SF-36 physical component score (P  less then  .001) and for the HAQ-DI (P = .011). CONCLUSIONS This study indicates that in SSc patients, a minimally supervised home-based exercise program improves physical performance, quality of life, and disability in comparison with usual care. © 2020 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.RNA interference (RNAi) has become an integral part of mainstream research due to its versatility and ease of use. However, the potential nontarget effects associated with double-stranded RNAs (dsRNA) are poorly understood. To explore this, we used dsRNAs targeting the inhibitor of apoptosis (iap) gene from nine insect species and assayed their possible nontarget effects. For each assay, we used a control (dsRNA targeting the gene coding for green fluorescent protein, GFP) and a species-specific dsRNA targeting nine iap genes in insect species to evaluate target gene knockdown efficiency, apoptosis phenotype in cells and mortality in insects. Our results revealed that dsIAP efficiently knocks down iap gene expression and induces apoptosis phenotype and mortality in target insect species. In contrast, no significant knockdown of the iap gene expression, apoptosis phenotypes, or mortality were detected in cell lines developed from nontarget insects or nontarget insects treated with dsIAPs. Interestingly, even among closely related insects such as stink bugs, Nezara viridula, Halyomorpha halys, and Murgantia histrionica, with substantial sequence similarity among iap genes from these insects, no significant nontarget effects of dsIAP were observed under the conditions tested. These data demonstrate no significant nontarget effects for dsIAPs and suggest that the threat of nontarget effects of RNAi technology may not be substantial. © 2020 Wiley Periodicals, Inc.OBJECTIVE Whether bridging therapy (intravenous thrombolysis [IVT] followed by endovascular treatment) is superior to IVT alone in minor stroke with large vessel occlusion (LVO) is unknown. METHODS Multicentric retrospective observational study including, in intention-to-treat, consecutive IVT-treated minor strokes (National Institutes of Health Stroke Scale [NIHSS] ≤ 5) with LVO, with or without additional mechanical thrombectomy. Propensity-score (inverse probability of treatment weighting) was used to reduce baseline between-groups differences. The primary outcome was excellent outcome, that is, modified Rankin score 0 to 1 at 3 months follow-up. RESULTS Overall, 598 patients were included (214 and 384 in the bridging therapy and IVT groups, respectively). Following propensity-score weighting, the distribution of baseline clinical and radiological variables was similar across the two patient groups. Compared with IVT alone, bridging therapy was not associated with excellent outcome (odds ratio [OR] = 0.96;vor IVT alone in M2 occlusions. ANN NEUROL 2020. © 2020 American Neurological Association.There are currently no proven or approved treatments for coronavirus disease 2019 (COVID-19). Early anecdotal reports and limited in vitro data led to the significant uptake of hydroxychloroquine (HCQ), and to lesser extent chloroquine (CQ), for many patients with this disease. As an increasing number of patients with COVID-19 are treated with these agents and more evidence accumulates, there continues to be no high-quality clinical data showing a clear benefit of these agents for this disease. Moreover, these agents have the potential to cause harm, including a broad range of adverse events including serious cardiac side effects when combined with other agents. In addition, the known and potent immunomodulatory effects of these agents which support their use in the treatment of auto-immune conditions, and provided a component in the original rationale for their use in patients with COVID-19, may, in fact, undermine their utility in the context of the treatment of this respiratory viral infection. Specificallase-by-case basis after rigorous consideration of the risks and benefits of this therapeutic approach. © 2020 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.The Colorado potato beetle (CPB; Leptinotarsa decemlineata) is one of the most notorious and difficult to control pests of potato and other solanaceous crops in North America. This insect has evolved a remarkable ability to detoxify both plant and synthetic toxins, allowing it to feed on solanaceous plants containing toxic alkaloids and to develop resistance to synthetic chemicals used for its control. RNA interference (RNAi) is a natural mechanism that evolved as an immune response to double-stranded RNA (dsRNA) viruses where dsRNA triggers silencing of target gene expression. RNAi is being developed as a method to control CPB. Here, we evaluated four CPB-specific genes to identify targets for RNAi-mediated control of this insect. Out of the four dsRNAs evaluated in CPB larvae and adults, dsIAP (dsRNA targeting inhibitor of apoptosis, iap gene) performed better than dsActin, dsHSP70, and dsDynamin in inducing larval mortality. However, in adults, the mortality induced by dsActin is significantly higher than the mortality induced by dsIAP, dsHSP70, and dsDynamin. Interestingly, a combination of dsIAP and dsActin performed better than either dsIAP or dsActin alone by inducing feeding inhibition in 24 hr and mortality in 48 hr in larvae. When the dsIAP and dsActin were expressed in the Escherichia coli HT115 strain and applied as a heat-killed bacterial spray on potato plants, it protected the plants from CPB damage. These studies show that the combination of dsIAP and dsActin shows promise as an insecticide to control CPB. © 2020 Wiley Periodicals, Inc.Invited for the cover of this issue is the group of Yuanhua Wang at Sichuan University. The image depicts the reported dirhodium complexes depicted as Chinese lanterns. Read the full text of the article at 10.1002/chem.201905855. © 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.Brown adipose tissue (BAT) has long been recognized as an energy-consuming organ and a possible target for combating metabolism disorder. Although numerous studies have demonstrated the ability of phytochemical phenolic acids to improve obesity by activating BAT, the underlying mechanism or mechanism therein remain obscure. In this study, diet-induced obese mice, genetically obese mice, and C3H10T1/2 cells were used to examine the effects of p-Coumaric acid (CA) on metabolism profiles. The results showed that CA prevented metabolic syndromes in the two mice models through the activation of BAT. This phenomenon was closely linked to the upregulation of uncoupling protein 1 (UCP1) and the accelerated burning of fatty acids and glucose, which consequently enhanced the energy expenditure and thermogenesis. Similar results were also obtained in vitro. Importantly, these effects were mediated by the mammalian target of rapamycin complex 1 (mTORC1)-RPS6 pathway. These findings reveal, to the best of our knowledge for the first time, the close correlation between mTORC1-RPS6 and BAT-mediated thermogenesis, and, in addition, the key role played by mTORC1-RPS6 in mediating phenolic acids-induced activation of BAT, thus preventing obesity.