Noncoding RNAs are increasingly promising drug targets yet ligand design is hindered by a paucity of methods that reveal driving factors in selective small molecule : RNA interactions, particularly given the difficulties of high-resolution structural characterization. HIV RNAs are excellent model systems for method development given their targeting history, known structure-function relationships, and the unmet need for more effective treatments. Herein we report a strategy combining synthetic diversification, profiling against multiple RNA targets, and predictive cheminformatic analysis to identify driving factors for selectivity and affinity of small molecules for distinct HIV RNA targets. Using this strategy, we discovered improved ligands for multiple targets and the first ligands for ESSV, an exonic splicing silencer critical to replication. Computational analysis revealed guiding principles for future designs and a predictive cheminformatics model of small molecule : RNA binding. These methods are expected to facilitate progress toward selective targeting of disease-causing RNAs.
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http://dx.doi.org/10.1039/c9ob01702j | DOI Listing |
ACS Appl Mater Interfaces
January 2025
Department of Pharmaceutics, School of Pharmacy, Ningxia Medical University, No. 1160 Shengli South Street, Yinchuan 750004, PR China.
The structural disruption of intestinal barrier and excessive reactive oxygen/nitrogen species (RONS) generation are two intertwined factors that drive the occurrence and development of ulcerative colitis (UC). Synchronously restoring the intestinal barrier and mitigating excess RONS is a promising strategy for UC management, but its treatment outcomes are still hindered by low drug accumulation and retention in colonic lesions. Inspired by intestine colonizing bacterium, we developed a mucoadhesive probiotic -mimic entinostat-loaded hollow mesopores prussian blue (HMPB) nanotherapeutic (AM@HMPB@E) for UC-targeted therapy via repairing intestinal barrier and scavenging RONS.
View Article and Find Full Text PDFACS EST Air
January 2025
Environmental Engineering Program, University of Colorado Boulder, 1111 Engineering Drive, Boulder, Colorado 80309-0428, United States.
Quantifying changes in the properties of smoke aerosols under varying conditions is important for understanding the health and environmental impacts of exposure to smoke. Smoke composition, aerosol liquid water content, effective density (ρ), and other properties can change significantly as smoke travels through areas under different ambient conditions and over time. During this study, we measured changes in smoke composition and physical properties due to oxidative aging and exposure to humidity.
View Article and Find Full Text PDFAnn Transl Med
December 2024
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Background: Osteoarthritis (OA) is increasingly thought to be a multifactorial disease in which sustained gut inflammation serves as a continued source of inflammatory mediators driving degenerative processes at distant sites such as joints. The objective of this study was to use the equine model of naturally occurring obesity associated OA to compare the fecal microbiome in OA and health and correlate those findings to differential gene expression synovial fluid (SF) cells, circulating leukocytes and cytokine levels (plasma, SF) towards improved understanding of the interplay between microbiome and immune transcriptome in OA pathophysiology.
Methods: Feces, peripheral blood mononuclear cells (PBMCs), and SF cells were isolated from healthy skeletally mature horses (n=12; 6 males, 6 females) and those with OA (n=6, 2 females, 4 males).
ACS ES T Water
January 2025
Department of Geological Sciences, University of Saskatchewan, 114 Science Pl, Saskatoon, Saskatchewan, Canada, S7N 5E2.
Metals are ubiquitous in Earth's Critical Zone and play key roles in ecosystem function, human health, and water security. They are essential nutrients at low concentrations, yet some metals are toxic at a high dose. Permafrost thaw substantially alters all the physical and chemical processes governing metal mobility, including water movement and solute transport and (bio)geochemical interactions involving water, organic matter, minerals, and microbes.
View Article and Find Full Text PDFR Soc Open Sci
January 2025
Centre for Integrative Anatomy, Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK.
The mechanical properties of dietary items are known to influence skull morphology, either through evolution or by phenotypic plasticity. Here, we investigated the impact of supplementary feeding of peanuts on the morphology of red squirrels () from five populations in Britain (North Scotland, Borders, Jersey and two temporally distinct populations from Formby (Merseyside)). Stable isotope analysis confirmed dietary ecology in 58 specimens.
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