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A method to prepare highly enantioenriched azaflavanones using an organocatalytic 6- endo aza-Michael addition has been described. A variety of 2-aryl-, 2-vinyl- and 2-methylazaflavanones were prepared in good yields (53-84%) and excellent enantioselectivities (97.6:2.4 to 99.3:0.7 er). [ABSTRACT FROM AUTHOR]

A variety of 3-substituted 1,2-oxazinanes (II) is obtained by quinine-catalyzed intramolecular aza-Michael reaction of enones (I) with moderate to high enantioselectivity. [ABSTRACT FROM AUTHOR]

The optimized conditions allow the highly enantioselective conversion of 2-aminochalcones into 2-substituted azaflavanones via intramolecular 6-endo aza-Michael addition. [ABSTRACT FROM AUTHOR]

Radiation-induced skin injury is a serious concern during radiotherapy and accidental exposure to radiation. This study aims to investigate the molecular events in early response to ionizing radiation of skin tissues and underlying mechanism. Mice and rats were irradiated with an electron beam. Skin tissues were used for liquid chromatography-mass spectrometry (LC-MS)-based metabolomics, mRNA-Seq and single-cell RNA sequencing (scRNA-Seq). Human keratinocytes (HaCaT) and skin fibroblasts (WS1) were used for functional studies. The integrated analysis of metabolomics and transcriptomics showed that 6 key fatty acid-associated metabolites, 9 key fatty acid-associated genes and multiple fatty acid-associated pathways were most obviously enriched and increased in the irradiated skins. Among them, acyl-CoA dehydrogenase very long chain (ACADVL) was investigated in greater detail due to its most obvious expression difference and significance in fatty acid metabolism. ScRNA-Seq of rat skin from irradiated individuals revealed that ACADVL was expressed in all subpopulations of skin tissues, with variations at different timepoints after radiation. Immunohistochemistry confirmed an increased ACADVL expression in the epidermis from human sample and various animal models, including monkeys, rats and mice. The knockdown of ACADVL increased the radiosensitivity of human keratinocytes and human skin fibroblasts. Silencing of ACADVL facilitated the expression of apoptosis and pyroptosis-related proteins following ionizing radiation. This study illustrated that cutaneous fatty acid metabolism was altered in the early response of ionizing radiation, and fatty acid metabolism-associated ACADVL is involved in radiation-induced cell death. ● Cutaneous fatty acid metabolism was altered in the early response of ionizing radiation. ● Fatty acid metabolism-associated ACADVL is involved in radiation-induced cell death. [ABSTRACT FROM AUTHOR]

Elucidation of the molecular mechanisms involving the initiation and progression of radiation-induced esophageal injury (RIEI) is important for prevention and treatment. Despite ongoing advances, the underlying mechanisms controlling RIEI remain largely unknown. In the present study, RNA-seq was performed to characterize mRNA profiles of the irradiated rat esophagus exposed to 0, 25, or 35 Gy irradiation. Bioinformatics analyses including dose-dependent differentially expressed genes (DEGs), Gene Ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG) pathway, protein-protein interaction (PPI) network, and immune infiltration were performed. 134 DEGs were screened out with a dose-dependent manner (35 Gy > 25 Gy > control, or 35 Gy < 25 Gy < control). GO and KEGG analyses showed that the most significant mechanism was IL-17 signaling-mediated inflammatory response. 5 hub genes, Ccl11, Cxcl3, Il17a, S100a8, and S100a9, were identified through the intersection of the DEGs involved in inflammatory response, IL-17 pathway, and PPI network. Additionally, immune infiltration analysis showed the activation of macrophages, monocytes, T cells, NKT cells, and neutrophils, among which macrophages, monocytes, and neutrophils might be the main sources of S100a8 and S100a9. Thus, these findings further our understanding on the molecular biology of RIEI and may help develop more effective therapeutic strategies. [ABSTRACT FROM AUTHOR]

To observe the effect of Prunella vulgaris polysaccharides (PVP) on cultured orbit fibroblasts in vitro from patients with thyroid-associated ophthalmopathy (TAO). PVP at different concentrations were used to treat different groups of fibroblasts from TAO patients and normal persons. Dexamethasone (Dex) was used as a positive control drug, and interferon-γ (IFN-γ) was used as a positive stimulant. The effects of PVP on the proliferation of orbital fibroblasts, the secretion of hyaluronic acid (HA), the expression of intercellular adhesion molecule-1 (ICAM-1/CD54) and apoptosis in orbital fibroblasts were determined. The experimental results showed when the concentration of PVP was greater than 400 μg/mL, it could significantly inhibit the proliferation of orbital fibroblasts from patients with TAO (P < 0.05). However, no definite inhibitory effect was observed in the orbital fibroblasts from the normal people. Dex could significantly inhibit the proliferation of orbital fibroblasts from patients with TAO and the normal people (P < 0.05). In contrast, every concentration of IFN-γ could promote the orbital fibroblasts from patients with TAO and the normal people proliferation. No groups had statistically significant stimulatory effect on HA secretion by orbital fibroblasts from normal people (P > 0.05). But the Dex group, IFN-γ+PVP-1600 group and IFN-γ+Dex group could significantly inhibit the secretion of HA from orbital fibroblasts of TAO patients. And there were no groups had statistically significant stimulatory effect on the expression of ICAM-1/CD54 in orbital fibroblasts from TAO patients (P > 0.05). PVP and Dex at all concentrations could significantly promote orbital fibroblast co-cultured with IFN-γ apoptosis (P < 0.05). But without IFN-γ, PVP and Dex at all concentrations could only significantly promote orbital fibroblast from TAO patients apoptosis (P < 0.05). These results suggest that PVP exerts its therapeutic effect by inhibiting the proliferation of orbital fibroblasts and promoting the apoptosis of orbital fibroblasts in TAO patients. In addition, in this process, HA secretion is suppressed. But the participation of IFN-γ is required. This effect is similar to that of Dex. And in the MTT experiment, the efficacy of PVP showed selectivity for TAO patients. This is different from Dex. This may be a feature of PVP that deserves attention. • Prunella vulgaris polysaccharides exerts its therapeutic effect by inhibiting the proliferation of orbital fibroblasts and promoting the apoptosis of orbital fibroblasts from TAO patients. • Prunella vulgaris polysaccharides exerts its therapeutic effect on the orbital fibroblasts from TAO patients. • Prunella vulgaris polysaccharides have not an inhibitory effect on intercellular adhesion molecule-1 (ICAM-1/CD54) expression by orbital fibroblasts from TAO patients. • Prunella vulgaris polysaccharides have some similar effects to that of dexamethasone. • Effect of Prunella vulgaris polysaccharides on the proliferation of orbital fibroblasts showed selectivity for TAO patients. [ABSTRACT FROM AUTHOR]