Although small interfering RNA (siRNA) holds great therapeutic promise, its delivery to the disease site remains a paramount obstacle. In this study, we tested whether brain endothelial cell-derived exosomes could deliver siRNA across the blood-brain barrier (BBB) in zebrafish. Natural exosomes were isolated from brain endothelial bEND.3 cell culture media and vascular endothelial growth factor (VEGF) siRNA was loaded in exosomes with the assistance of a transfection reagent. While fluorescence-activated cell flow cytometry and immunocytochemistry staining studies indicated that wild-type exosomes significantly increased the uptake of fluorescence-labeled siRNA in the autologous brain endothelial cells, decreased fluorescence intensity was observed in the cells treated with the tetraspanin CD63 antibody-blocked exosome-delivered formulation (p < 0.05). In the transport study, exosomes also enhanced the permeability of rhodamine 123 in a co-cultured monolayer of brain endothelial bEND.3 cell and astrocyte. Inhibition at the expression of VEGF RNA and protein levels was observed in glioblastoma-astrocytoma U-87 MG cells treated with exosome-delivered siRNAs. Imaging results showed that exosome delivered more siRNAs across the BBB in Tg(fli1:GFP) zebrafish. In a xenotransplanted brain tumor model, exosome-delivered VEGF siRNAs decreased the fluorescence intensity of labeled cancer cells in the brain of zebrafish. Brain endothelial cell-derived exosomes could be potentially used as a natural carrier for the brain delivery of exogenous siRNA.

A chitin-sourced 3-aminocyclopentenone building block is an effective platform for the diversity-oriented synthesis of nitrogen compounds in processes independent of Haber ammonia.

The chitin obtained from crustacean shell waste and other renewable resources may be used as a primary feedstock in the biorefineries of the future. Accordingly, the incorporation of chitin‐derived building blocks into new synthesis processes will accentuate the utility of this biopolymer, particularly in the production of bio‐based small molecules that contain one or more nitrogen atoms. Herein we report that enantioenriched 2‐amino sugars are readily accessible from the chitin‐derived platform 3‐acetamido‐5‐acetylfuran (3A5AF). Subjecting 3A5AF to a Noyori reduction–Achmatowicz rearrangement sequence gave N‐acetyl‐l‐rednose (RedNAc) in excellent yield and enantiopurity. Acetamide hydrolysis gave l‐rednose, a rare 2‐amino sugar found in natural anthracycline and angucycline antibiotics. RedNAc was subsequently shown to be a versatile platform from which a variety of stereochemically pure 2‐amino sugars are readily attainable. The synthesis of chiral, bio‐based N‐compounds from chitin emphasises the rapidly expanding utility of this biopolymer as a viable platform for fine chemical production.

Level II.

Prospective comparative study.

No abstract

The Coonrad-Morrey prosthesis provides satisfactory results with follow-up. The rate of complications remains high even if the rate of implant revision stayed low.

The synthesis of 3‐amidofurans is laborious due to the difficulty installing a nitrogen substituent at the C3 position of the furan heterocycle. 3‐Acetamido‐5‐acetylfuran (3A5AF), readily available from chitin, is a versatile biorenewable platform that can be converted into a range of functionally rich 3‐amidofurans, streamlining access to this underexplored heteroaromatic chemical space.