Fungal keratitis, a severe ocular disease, is one of the leading causes of ocular morbidity and blindness, yet it is often neglected, especially in developing countries. Therapeutic efficacy of traditional treatment such as eye drops is very limited due to poor bioavailability, whereas intraocular injection might cause serious side effects. Herein, we designed and fabricated a hybrid hydrogel-based contact lens which comprises quaternized chitosan (HTCC), silver nanoparticles, and graphene oxide (GO) with a combination of antibacterial and antifungal functions. The hydrogel is cross-linked through electrostatic interactions between GO and HTCC, resulting in strong mechanical properties. Voriconazole (Vor), an antifungal drug, can be loaded onto GO which retains the drug and promotes its sustained release from the hydrogel-based contact lenses. The contact lenses also exhibited good antimicrobial functions in view of glycidyltrimethylammonium chloride and silver nanoparticles. The results from in vitro and in vivo experiments demonstrate that contact lenses loaded with Vor have excellent efficacy in antifungal activity in vitro and could significantly enhance the therapeutic effects on a fungus-infected mouse model. The results indicate that this hydrogel contact lenses-based drug delivery system might be a promising therapeutic approach for a rapid and effective treatment of fungal keratitis.

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BACKGROUND: Accumulating evidence has shown that disorders in the gut microbiota and derived metabolites affect the development of atherosclerotic cardiovascular disease (ASCVD). However, which and how specific gut microbial metabolites contribute to the progression of atherosclerosis and the clinical relevance of their alterations remain unclear. METHODS: We performed integrated microbiome–metabolome analysis of 30 patients with coronary artery disease (CAD) and 30 age- and sex-matched healthy controls to identify CAD-associated microbial metabolites, which were then assessed in an independent population of patients with ASCVD and controls (n=256). We further investigate the effect of CAD-associated microbial metabolites on atherosclerosis and the mechanisms of the action. RESULTS: Indole-3-propionic acid (IPA), a solely microbially derived tryptophan metabolite, was the most downregulated metabolite in patients with CAD. Circulating IPA was then shown in an independent population to be associated with risk of prevalent ASCVD and correlated with the ASCVD severity. Dietary IPA supplementation alleviates atherosclerotic plaque development in ApoE −/− mice. In murine- and human-derived macrophages, administration of IPA promoted cholesterol efflux from macrophages to ApoA-I through an undescribed miR-142-5p/ABCA1 (ATP-binding cassette transporter A1) signaling pathway. Further in vivo studies demonstrated that IPA facilitates macrophage reverse cholesterol transport, correlating with the regulation of miR-142-5p/ABCA1 pathway, whereas reduced IPA production contributed to the aberrant overexpression of miR-142-5p in macrophages and accelerated the progression of atherosclerosis. Moreover, the miR-142-5p/ABCA1/reverse cholesterol transport axis in macrophages were dysregulated in patients with CAD, and correlated with the changes in circulating IPA levels. CONCLUSIONS: Our study identify a previously unknown link between specific gut microbiota-derived tryptophan metabolite and ASCVD. The microbial metabolite IPA/miR-142-5p/ABCA1 pathway may represent a promising therapeutic target for ASCVD.

Purpose. To compare the prevalence of and factors associated with Demodex brevis and Demodex folliculorum in patients with cylindrical dandruff (CD group) and healthy controls. Methods. Eyelashes were taken from 1680 patients with CD and 1700 healthy controls in China from March 2015 to May 2017. All patients underwent a complete eye examination, and Demodex spp. were counted. The prevalence was analyzed according to age, gender, and clinical features. Results. Mean patient age was 42.93 ± 16.52 (3–88) and 39.4 ± 13.6 (7–81) years old in the CD and healthy control groups, respectively. In the CD and healthy groups, the positive rate for Demodex folliculorum was 27.92% and 8.47%, respectively, while that for Demodex brevis was 31.67% and 6.65%, respectively. In the CD group, the prevalence of Demodex brevis was higher than that of Demodex folliculorum, no matter in the females (33.65% versus 29.01%) or the males (28.54% versus 23.88%) in the CD group. Moreover, the numbers of Demodex folliculorum and Demodex brevis were significantly and positively correlated with age, in both children and old patients (both P<0.001), as well as with the severity of eyelid congestion (all P<0.05). Conclusions. In a large sample population, the prevalence of Demodex brevis and Demodex folliculorum was higher in the CD group than in healthy volunteers. In addition, the severity of eyelid congestion might be exacerbated by the number of Demodex spp., which may therefore provide a good clinical reference and objective guide.