α-Azido ketones. Part 7: synthesis of 1,4-disubstituted triazoles by the “click” reaction of various terminal acetylenes with phenacyl azides or α-azidobenzo(hetera)cyclanones

Copper(I)-catalyzed alkyne-azide 1,3-cycloaddition reaction (CuAAC, Sharpless–Meldal reaction) of various α-azido ketones such as substituted 2-azidoacetophenones, 2-azidobenzosuberone and 3-azido(thio)chromanones with terminal alkynes was studied. The reaction resulted in the formation of the expected 1,2,3-triazoles in moderate to good yields although the reactivity was somewhat lower than in the case of simple azides. Reaction of ethynylchromones as alkynes gave interesting dichromonoid systems bridged by a triazole unit.     

New Coordination Compounds Based on a Pyrazine Derivative: Design,Characterization, and Biological Study

New coordination compounds of Mn(II), Fe(III), Co(II), and Ni(II) and the biologically active ligand L (N′-benzylidenepyrazine-2-carbohydrazonamide) were synthesized and characterized by appropriate analytical techniques: elemental analysis (EA), thermogravimetric analysis (TG–DTG), infrared spectroscopy (FTIR), and flame-atomic absorption spectrometry (F-AAS). The biological activity of the obtained compounds was then comprehensively investigated. Rational use of these compounds as potential drugs was proven by ADME analysis. All obtained compounds were screened in vitro for antibacterial, antifungal, and anticancer activities. Some of the studied complexes exhibited significantly higher activity than the ligand alone.     

Latrophilin-2 is a novel receptor of LRG1 that rescues vascular and neurological abnormalities and restores diabetic erectile function

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by inappropriate hyperglycemia, which causes endothelial dysfunction and peripheral neuropathy, ultimately leading to multiple complications. One prevalent complication is diabetic erectile dysfunction (ED), which is more severe and more resistant to treatment than nondiabetic ED. The serum glycoprotein leucine-rich ɑ-2-glycoprotein 1 (LRG1) is a modulator of TGF-β-mediated angiogenesis and has been proposed as a biomarker for a variety of diseases, including DM. Here, we found that the adhesion GPCR latrophilin-2 (LPHN2) is a TGF-β-independent receptor of LRG1. By interacting with LPHN2, LRG1 promotes both angiogenic and neurotrophic processes in mouse tissue explants under hyperglycemic conditions. Preclinical studies in a diabetic ED mouse model showed that LRG1 administration into the penile tissue, which exhibits significantly increased LPHN2 expression, fully restores erectile function by rescuing vascular and neurological abnormalities. Further investigations revealed that PI3K, AKT, and NF-κB p65 constitute the key intracellular signaling pathway of the LRG1/LPHN2 axis, providing important mechanistic insights into LRG1-mediated angiogenesis and nerve regeneration in DM. Our findings suggest that LRG1 can be a potential new therapeutic option for treating aberrant peripheral blood vessels and neuropathy associated with diabetic complications, such as diabetic ED.Subject terms: Biological therapy, Cytokines, Recombinant protein therapy, Extracellular signalling molecules     

Revealing the Origin of Transition-Metal Migration in Layered Sodium-Ion Battery Cathodes: Random Na Extraction and Na-Free Layer Formation

Cation migration often occurs in layered oxide cathodes of lithium-ion batteries due to the similar ion radius of Li and transition metals (TMs). Although Na and TM show a big difference of ion radius, TMs in layered cathodes of sodium-ion batteries (SIBs) can still migrate to Na layer, leading to serious electrochemical degeneration. To elucidate the origin of TM migration in layered SIB cathodes, we choose NaCrO₂, a typical layered cathode suffering from serious TM migration, as a model material and find that the TM migration is derived from the random desodiation and subsequent formation of Na-free layer at high charge potential. A Ru/Ti co-doping strategy is developed to address the issue, where the doped active Ru is first oxidized to create a selective desodiation and the doped inactive Ti can function as a pillar to avoid complete desodiation in Ru-contained TM layers, leading to the suppression of the Na-free layer formation and subsequent enhanced electrochemical performance.     

A Dual-Metal-Catalyzed Sequential Cascade Reaction in an Engineered Protein Cage**

Herein, we describe the creation of an artificial protein cage housing a dual-metal-tagged guest protein that catalyzes a linear, two-step sequential cascade reaction. The guest protein consists of a fusion protein of HaloTag and monomeric rhizavidin. Inside the protein capsid, we established a ruthenium-catalyzed allylcarbamate deprotection reaction followed by a gold-catalyzed ring-closing hydroamination reaction that led to indoles and phenanthridines with an overall yield of up to 66 % in aqueous solutions. Furthermore, we show that the encapsulation stabilizes the metal catalysts against deactivation by air, proteins and cell lysate.     

Riesz Transform for a Flow Laplacian on Homogeneous Trees

Journal of Fourier Analysis and Applications - We introduce and study the notion of weak semi-greedy systems—which is inspired in the concepts of semi-greedy and branch semi-greedy systems...