Squaramide-catalyzed enantioselective Michael addition of nitromethane to 2-enoylazaarenes: synthesis of chiral azaarene-containing γ-nitroketones.

Bifunctional chiral squaramide-catalyzed highly enantioselective Michael addition of nitromethane to diverse 2-enoylazaarenes was successfully performed. This protocol provided a set of chiral azaarene-containing γ-nitroketones with up to 98% yield and 98% ee in a solvent-free catalytic system under mild conditions. Furthermore, gram-scale synthetic utility was also showcased.

Dehydroabietane-type bifunctional organocatalysts in asymmetric synthesis: recent progress.

Dehydroabietane-type bifunctional organocatalysts derived from rosane-type diterpenes of dehydroabietic acid (DHAA) and dehydroabietylamine (DA) have been utilized in a wide variety of highly enantioselective reactions. Since one well-documented review exclusively reported on the development of terpene-derived bifunctional thioureas in asymmetric organocatalysis in 2013, fragmentary progress on the dehydroabietane-type bifunctional thioureas and squaramides has been mentioned in other reviews. In this mini-review, we systematically analyze and reorganize the published literature on dehydroabietane-type bifunctional organocatalysts in the recent decade according to the type of catalysts. Our aim is for this review to provide helpful research information and serve as a foundation for further design and application of rosin-based organocatalysts.

Neuron secrete exosomes containing miR-9-5p to promote polarization of M1 microglia in depression.

BACKGROUND: Neuroinflammation is an important component mechanism in the development of depression. Exosomal transfer of MDD-associated microRNAs (miRNAs) from neurons to microglia might exacerbate neuronal cell inflammatory injury. RESULTS: By sequence identification, we found significantly higher miR-9-5p expression levels in serum exosomes from MDD patients than healthy control (HC) subjects. Then, in cultured cell model, we observed that BV2 microglial cells internalized PC12 neuron cell-derived exosomes while successfully transferring miR-9-5p. MiR-9-5p promoted M1 polarization in microglia and led to over releasing of proinflammatory cytokines, such as interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), which exacerbated neurological damage. Furthermore, we identified suppressor of cytokine signaling 2 (SOCS2) as a direct target of miR-9-5p. Overexpression of miR-9-5p suppressed SOCS2 expression and reactivated SOCS2-repressed Janus kinase (JAK)/signal transducer and activator of transcription 3 (STAT3) pathways. Consistently, we confirmed that adeno-associated virus (AAV)-mediated overexpression of miR-9-5p polarized microglia toward the M1 phenotype and exacerbated depressive symptoms in chronic unpredictable mild stress (CUMS) mouse mode. CONCLUSION: MiR-9-5p was transferred from neurons to microglia in an exosomal way, leading to M1 polarization of microglia and further neuronal injury. The expression and secretion of miR-9-5p might be novel therapeutic targets for MDD.