Recent advances in endocrine organoids for therapeutic application.

The endocrine system, consisting of the hypothalamus, pituitary, endocrine glands, and hormones, plays a critical role in hormone metabolic interactions. The complexity of the endocrine system is a significant obstacle to understanding and treating endocrine disorders. Notably, advances in endocrine organoid generation allow a deeper understanding of the endocrine system by providing better comprehension of molecular mechanisms of pathogenesis. Here, we highlight recent advances in endocrine organoids for a wide range of therapeutic applications, from cell transplantation therapy to drug toxicity screening, combined with development in stem cell differentiation and gene editing technologies. In particular, we provide insights into the transplantation of endocrine organoids to reverse endocrine dysfunctions and progress in developing strategies for better engraftments. We also discuss the gap between preclinical and clinical research. Finally, we provide future perspectives for research on endocrine organoids for the development of more effective treatments for endocrine disorders.

Iridium-catalyzed selective 1,2-hydrosilylation of N-heterocycles.

A silylene-bridged Ir dimer in situ generated from [Ir(coe)2Cl]2 and Et2SiH2 was found to catalyze the hydrosilylation of N-heteroaromatics to furnish dearomatized azacyclic products with high activity (up to 1000 TONs), excellent selectivity, and good functional group tolerance. The substrate scope was highly broad, including (iso)quinolines, substituted pyridines, pyrimidines, pyrazines, deazapurines, triazines, and benzimidazoles. Mechanistic studies such as a kinetic profile, rate-order assessment, and investigation of the electronic substituent effects on the initial rates were performed to access the detailed pathways. One pathway is proposed to involve an intramolecular insertion of the C[double bond, length as m-dash]N moiety of the substrates into the Ir-H bond of a resting species to form an Ir-amido silyl intermediate, followed by reductive elimination. The synthetic utility was proven by successful application to cinchona alkaloids, and facile post-synthetic transformations of the 1,2-dihydroquinoline products.

Boron-Catalyzed Silylative Reduction of Nitriles in Accessing Primary Amines and Imines.

Silylative reduction of nitriles was studied under transition metal-free conditions by using B(C6F5)3 as a catalyst with hydrosilanes as a reductant. Alkyl and (hetero)aryl nitriles were efficiently converted to primary amines or imines under mild conditions. The choice of silanes was found to determine the selectivity: while a full reduction of nitriles was highly facile, the use of sterically bulky silanes allowed for the partial reduction leading to N-silylimines.

Chemoselective Silylative Reduction of Conjugated Nitriles under Metal-Free Catalytic Conditions: ß-Silyl Amines and Enamines.

The B(C6F5)3-catalyzed silylative reduction of conjugated nitriles has been developed to afford synthetically valuable ß-silyl amines. The reaction is chemoselective and proceeds under mild conditions. Mechanistic elucidation indicates that it proceeds by rapid double hydrosilylation of the conjugated nitrile to an enamine intermediate which is subsequently reduced to the ß-silyl amine, thus forming a new C(sp(3))-Si bond. Based on this mechanistic understanding, a preparative route to enamines was also established using bulky silanes.

Inactivation of Pseudomonas aeruginosa biofilm by dense phase carbon dioxide.

Dense phase carbon dioxide (DPCD) is one of the most promising techniques available to control microorganisms as a non-thermal disinfection method. However, no study on the efficiency of biofilm disinfection using DPCD has been reported. The efficiency of DPCD in inactivating Pseudomonas aeruginosa biofilm, which is known to have high antimicrobial resistance, was thus investigated. P. aeruginosa biofilm, which was not immersed in water but was completely wet, was found to be more effectively inactivated by DPCD treatment, achieving a 6-log reduction within 7 min. The inactivation efficiency increased modestly with increasing pressure and temperature. This study also reports that the water-unimmersed condition is one of the most important operating parameters in achieving efficient biofilm control by DPCD treatment. In addition, observations by confocal laser scanning microscopy revealed that DPCD treatment not only inactivated biofilm cells on the glass coupons but also caused detachment of the biofilm following weakening of its structure as a result of the DPCD treatment; this is an added benefit of DPCD treatment.