XA pH-Responsive and Colitis-Targeted Nanoparticle Loaded with Shikonin for the Oral Treatment of Inflammatory Bowel Disease in Mice

Epidemiology shows that more than 6.8 million people in the world are influenced by inflammatory bowel disease (IBD) each year. IBD is a refractory inflammatory disease, and the disease mainly affects the colon. Shikonin (SK) was originally extracted from traditional Chinese medicine “Zicao” (with an English name Lithospermum erythrorhizon) and found to inhibit inflammation, regulate immunity, and be involved in healing wounds. Herein, we used chitosan (CS), hyaluronic acid (HA), and pH-responsive polymer Eudragits S100 (ES100) to design SK-loaded ES100/HA/CS nanoparticles (SK@SAC) as an oral delivery system to treat the colitis mice. Particle size of SK@SAC was 190.3 nm and drug loading efficiency was 6.6%. SAC nanoparticles accumulated in RAW264.7 macrophages and exhibited colitis-targeted ability by increasing the local drug concentration as well as reducing nonspecific distribution after oral gavage. In TNBS-induced IBD mice, SK@SAC treatment had significant therapeutic effects, regulated of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10 and TGF-β), and also inhibited COX-2 and iNOS activity. SK@SAC also increased tight junction protein ZO-1 and occludin to some extent. These promising results showed that this novel oral SK-loaded nanoparticle drug delivery system for targeted treatment provides a new strategy for the management of IBD

Whole-brain annotation and multi-connectome cell typing of Drosophila.

The fruit fly Drosophila melanogaster has emerged as a key model organism in neuroscience, in large part due to the concentration of collaboratively generated molecular, genetic and digital resources available for it. Here we complement the approximately 140,000 neuron FlyWire whole-brain connectome1 with a systematic and hierarchical annotation of neuronal classes, cell types and developmental units (hemilineages). Of 8,453 annotated cell types, 3,643 were previously proposed in the partial hemibrain connectome2, and 4,581 are new types, mostly from brain regions outside the hemibrain subvolume. Although nearly all hemibrain neurons could be matched morphologically in FlyWire, about one-third of cell types proposed for the hemibrain could not be reliably reidentified. We therefore propose a new definition of cell type as groups of cells that are each quantitatively more similar to cells in a different brain than to any other cell in the same brain, and we validate this definition through joint analysis of FlyWire and hemibrain connectomes. Further analysis defined simple heuristics for the reliability of connections between brains, revealed broad stereotypy and occasional variability in neuron count and connectivity, and provided evidence for functional homeostasis in the mushroom body through adjustments of the absolute amount of excitatory input while maintaining the excitation/inhibition ratio. Our work defines a consensus cell type atlas for the fly brain and provides both an intellectual framework and open-source toolchain for brain-scale comparative connectomics