Co-delivery of microRNA-150 and quercetin by lipid nanoparticles (LNPs) for the targeted treatment of age-related macular degeneration (AMD).

Age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV), which leads to severe vision loss in middle-aged and elderly patients. Current treatments for CNV show weak, transient efficacy, and they can cause several adverse effects. A potential new treatment is to use microRNA-150 (mR150), which regulates physiological and pathological angiogenesis by modulating the expression of CXCR4 at the post-transcriptional level. Here, we developed solid lipid nanoparticles that we modified with an Asp-Gly-Arg peptide to target endothelial cells during abnormal angiogenesis, then we co-loaded them with mR150 and the anti-angiogenic drug quercetin. The resulting nanoparticles had an average size around 200 nm and showed strong ability to target the fundus and inhibit CNV for up to two weeks in a mouse model without causing retinal toxicity. They significantly enhanced the uptake of mR150 in vitro compared to free mR150 or nanoparticles without peptide. Our study suggests that co-administration of mR150 and quercetin has potential for treating age-related macular degeneration and that nanoparticles modified with Asp-Gly-Arg peptide are an effective platform for the co-delivery of small-molecule and nucleic acid drugs via intravitreal injection.

Slope aspect determines the abundance and composition of nitrogen-cycling microbial communities in an alpine ecosystem.

Slope aspect is an important topographic feature that can influence local environmental conditions. While strong effects of slope aspect on aboveground and belowground communities have been frequently elucidated, how slope aspect affects soil nitrogen (N) cycling microbes remains unclear. Here, we characterized the communities of soil N-cycling microbes on south- and north-facing slopes in an alpine ecosystem, by quantifying (qPCR) and high-throughput sequencing six genes involved in N-fixation (nifH), nitrification (archaeal and bacterial amoA) and denitrification (nirK, nirS and nosZ). We found that the abundance, diversity and community composition of major N-cycling microbes differed dramatically between the two slope aspects, and these variances could be well explained by the aspect-driven differences in environmental conditions, especially soil temperature and moisture. The response patterns of different N-cycling groups to slope aspect were much inconsistent, especially for those with similar functions (i.e. ammonia-oxidizing archaea vs. bacteria, nirK- vs. nirS-reducers), indicating strong niche differentiation between these counterparts. We also observed strong preferences and distinct co-occurrence patterns of N-cycling microbial taxa for the two slope aspects. These findings highlight the importance of slope aspect in determining the abundance, species distribution and community structure of N-cycling microbes, and consequently influencing N-cycling processes and ecosystem functioning.