1,3-Dipolar Cycloaddition of SF-Alkynes with Nonstabilized Diazo: Synthesis of Highly Substituted SF-3-Pyrazoles.

This work presents the 1,3-dipolar cycloaddition of SF-alkynes with nonstabilized diazo compounds under mild conditions, producing highly substituted SF-3-pyrazoles. Eighteen examples are given, with yields of up to 91%. The two regioisomers were obtained in ratios ranging from 27:73 to 73:27.

Bioadhesive Hyaluronic Acid/Dopamine Hydrogels for Vascular Applications Prepared by Initiator-Free Crosslinking.

Intimal hyperplasia, a vascular pathology characterized by vessel wall thickening, is implicated in vein graft failures. For efficient prevention, a biodegradable drug delivery system should be applied externally to the graft for an extended time. Finding a gel suitable for such a system is challenging.

Mir-21 Suppression Promotes Mouse Hepatocarcinogenesis.

The microRNA 21 (miR-21) is upregulated in almost all known human cancers and is considered a highly potent oncogene and potential therapeutic target for cancer treatment. In the liver, miR-21 was reported to promote hepatic steatosis and inflammation, but whether miR-21 also drives hepatocarcinogenesis remains poorly investigated in vivo. Here we show using both carcinogen (Diethylnitrosamine, DEN) or genetically (PTEN deficiency)-induced mouse models of hepatocellular carcinoma (HCC), total or hepatocyte-specific genetic deletion of this microRNA fosters HCC development-contrasting the expected oncogenic role of miR-21.

Squalene-PEG-Exendin as High-Affinity Constructs for Pancreatic Beta-Cells.

Novel drug delivery systems targeting native, transplanted, or cancerous beta-cells are of utmost importance. Herein, we present new exendin-4 derivatives with modified unnatural amino acids at strategic positions within the polypeptide sequence. The modified peptides allowed modular orthogonal chemical modifications to attach imaging agents and amphiphilic squalene-PEG groups.

Pannexin1 links lymphatic function to lipid metabolism and atherosclerosis.

Extracellular ATP is a central signaling molecule in inflammatory responses. Pannexin1 (Panx1) channels release ATP in a controlled manner and have been implicated in various inflammatory pathologies, but their role in atherogenesis remains elusive. Using atherosclerosis-susceptible mouse models with ubiquitous deletion of Panx1 (Panx1 Apoe ) or with Cre recombinase-mediated deletion of Panx1 in endothelial cells and monocytes (Tie2-Cre Panx1 Apoe ; Panx1 Apoe ), we identified a novel role for Panx1 in the lymphatic vasculature.