RESUMO
The Crumbs homolog 1 (CRB1) gene is associated with retinal degeneration, most commonly Leber congenital amaurosis (LCA) and retinitis pigmentosa (RP). Here, we demonstrate that murine retinas bearing the Rd8 mutation of Crb1 are characterized by the presence of intralesional bacteria. While normal CRB1 expression was enriched in the apical junctional complexes of retinal pigment epithelium and colonic enterocytes, Crb1 mutations dampened its expression at both sites. Consequent impairment of the outer blood retinal barrier and colonic intestinal epithelial barrier in Rd8 mice led to the translocation of intestinal bacteria from the lower gastrointestinal (GI) tract to the retina, resulting in secondary retinal degeneration. Either the depletion of bacteria systemically or the reintroduction of normal Crb1 expression colonically rescued Rd8-mutation-associated retinal degeneration without reversing the retinal barrier breach. Our data elucidate the pathogenesis of Crb1-mutation-associated retinal degenerations and suggest that antimicrobial agents have the potential to treat this devastating blinding disease.
Assuntos
Proteínas do Tecido Nervoso , Degeneração Retiniana , Animais , Camundongos , Translocação Bacteriana , Proteínas do Olho/genética , Amaurose Congênita de Leber/genética , Mutação , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Retina/metabolismo , Degeneração Retiniana/genética , Retinose Pigmentar/genética , Retinose Pigmentar/metabolismo , Retinose Pigmentar/patologiaRESUMO
In this paper, Cu-BTC derived mesoporous CuS nanomaterial (m-CuS) was synthesized via a two-step process involving carbonization and sulfidation of Cu-BTC for colorimetric glutathione detection. The Cu-BTC was constructed by 1,3,5-benzenetri-carboxylic acid (H3BTC) and Cu2+ ions. The obtained m-CuS showed a large specific surface area (55.751 m2/g), pore volume (0.153 cm3/g), and pore diameter (15.380 nm). In addition, the synthesized m-CuS exhibited high peroxidase-like activity and could catalyze oxidation of the colorless substrate 3,3',5,5'-tetramethylbenzidine to a blue product. Peroxidase-like activity mechanism studies using terephthalic acid as a fluorescent probe proved that m-CuS assists H2O2 decomposition to reactive oxygen species, which are responsible for TMB oxidation. However, the catalytic activity of m-CuS for the oxidation of TMB by H2O2 could be potently inhibited in the presence of glutathione. Based on this phenomenon, the colorimetric detection of glutathione was demonstrated with good selectivity and high sensitivity. The linear range was 1-20 µM and 20-300 µM with a detection limit of 0.1 µM. The m-CuS showing good stability and robust peroxidase catalytic activity was applied for the detection of glutathione in human urine samples.
Assuntos
Colorimetria , Cobre , Glutationa , Peróxido de Hidrogênio , Nanoestruturas , Glutationa/análise , Glutationa/química , Colorimetria/métodos , Cobre/química , Nanoestruturas/química , Catálise , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/análise , Porosidade , Oxirredução , Ácidos Ftálicos/química , Humanos , Benzidinas/química , Limite de DetecçãoRESUMO
Air pollution poses a threat to human health. Public perceptions of air pollution are important for individual self-protection and policy-making. Given the uncertainty faced by residence-based exposure (RB) measurements, this study measures individuals' real-time mobility-based (MB) exposures and perceptions of air pollution by considering people's daily movement. It explores how contextual uncertainties may influence the disparities in perceived air quality by taking into account RB and MB environmental factors. In addition, we explore factors that are related to the mismatch between people's perceived air quality and actual air pollution exposure. Using K-means clustering to divide the PM2.5 values into two groups, a mismatch happens when the perceived air quality is poor but the air pollution level is lower than 15.536µg/m3 and when the perceived air quality is good but the air pollution level is higher than 15.608µg/m3. The results show that there is a mismatch between air pollution exposure and perception of air pollution. People with low income are exposed to higher air pollution. Unemployed people and people with more serious mental health symptoms (e.g., depression) have a higher chance of accurately assessing air pollution (e.g., perceiving air quality as poor when air pollution levels are high). Older people and those with a higher MB open space density tend to underestimate air pollution. Students tend to perceive air quality as good. People who are surrounded by higher MB transportation land-use density and green space density tend to perceive air quality as poor. The results can help policymakers to increase public awareness of high air pollution areas, and consider the health effects of landscapes during planning.