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Mcdaniel Klinge posted an update 6 months ago
Directly observing intracellular nanostructure formation remains challenging. In this work, using a rationally designed small-molecule 4-nitrobenzyl carbamate-Cys(SEt)-Asp-Asp-Phe(iodine)-2-cyano-benzothiazole (NBC-Iod-CBT), we directly observed intracellular nanoparticle formation with nanocomputed tomography (nano-CT). In vitro, upon glutathione reduction and nitroreductase (NTR) cleavage, NBC-Iod-CBT undergoes a CBT-Cys click condensation reaction to self-assemble nanoparticles Iod-CBT-NPs with an average linear absorption coefficient (LAC) value of 0.182 ± 0.078 μm-1 to x-ray. Nano-CT imaging of the NBC-Iod-CBT-treated, NTR-overexpressing HeLa cells showed the existence of Iod-CBT-NPs in their cytoplasm with an average LAC value of 0.172 ± 0.032 μm-1 We anticipate that our strategy could help people to deeply understand the formation mechanism of intracellular nanostructures in the near future.Ewing sarcoma (EwS) is an aggressive tumor that affects adolescents and young adults. EwS is defined by a chromosomal translocation, EWSR1-FLI1 being the most common, that causes genome reprogramming through remodeling of enhancers. Here, we describe an unexpected function of RING1B, which is highly expressed in EwS. While retaining its repressive activity at Polycomb developmental regulated genes, RING1B colocalizes with EWSR1-FLI1 at active enhancers. We demonstrate that RING1B is necessary for the expression of key EWSR1-FLI1 targets by facilitating oncogene recruitment to their enhancers. Knockdown of RING1B impairs growth of tumor xenografts and expression of genes regulated by EWSR1-FLI1 bound enhancers. Pharmacological inhibition of AURKB with AZD1152 increases H2Aub levels causing down-regulation of RING1B/EWSR1-FLI1 common targets. Our findings demonstrate that RING1B is a critical modulator of EWSR1-FLI1-induced chromatin remodeling, and its inhibition is a potential therapeutic strategy for the treatment of these tumors.Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing-related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel-induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)-gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.Football is a global game which is constantly evolving, showing substantial increases in physical and technical demands. Nutrition plays a valuable integrated role in optimising performance of elite players during training and match-play, and maintaining their overall health throughout the season. An evidence-based approach to nutrition emphasising, a ‘food first’ philosophy (ie, food over supplements), is fundamental to ensure effective player support. This requires relevant scientific evidence to be applied according to the constraints of what is practical and feasible in the football setting. The science underpinning sports nutrition is evolving fast, and practitioners must be alert to new developments. In response to these developments, the Union of European Football Associations (UEFA) has gathered experts in applied sports nutrition research as well as practitioners working with elite football clubs and national associations/federations to issue an expert statement on a range of topics relevant to elite football nutrition (1) match day nutrition, (2) training day nutrition, (3) body composition, (4) stressful environments and travel, (5) cultural diversity and dietary considerations, (6) dietary supplements, (7) rehabilitation, (8) referees and (9) junior high-level players. The expert group provide a narrative synthesis of the scientific background relating to these topics based on their knowledge and experience of the scientific research literature, as well as practical experience of applying knowledge within an elite sports setting. Our intention is to provide readers with content to help drive their own practical recommendations. In addition, to provide guidance to applied researchers where to focus future efforts.
To determine the relationship between corneal refractive surgery and the prevalence of glaucoma in the Korean population.
Data were obtained from the Korea National Health and Nutrition Examination Survey (KNHANES), a population-based cross-sectional study using a complex, stratified, multistage, probability-cluster survey. This study included 604 eyes that had undergone myopic corneal refractive surgery, and 3389 control eyes without a history of any ocular surgery and having a spherical equivalent (SE) <-3.00 D, obtained from the KNHANES database for the years 2010-2012. Glaucoma diagnosis was based on the International Society of Geographical and Epidemiological Ophthalmology criteria. The association between a history of corneal refractive surgery and the prevalence of glaucoma was analysed using logistic regression analysis, after adjusting for potential confounding factors.
Glaucoma prevalence did not differ between eyes that had and had not undergone corneal refractive surgery (p=0.675). After adjusting for age, sex, SE, and intraocular pressure, multivariate logistic regression analysis found that corneal refractive surgery was significantly associated with an increased risk of glaucoma (OR 9.14, p=0.002; 95% CI 2.22 to 37.69). Selleck Palazestrant Subgroup analysis that only included control eyes with a refraction cut-off <-3.70 D found that corneal refractive surgery was not significantly associated with glaucoma.
History of corneal refractive surgery was associated with a higher prevalence of glaucoma in the Korean population. However, this association was not observed in eyes with a higher degree of myopia.
History of corneal refractive surgery was associated with a higher prevalence of glaucoma in the Korean population. However, this association was not observed in eyes with a higher degree of myopia.