RESUMEN
In this study, three phenylpyridine diamide ligands, namely, 2,2'-((pyridine-2,6-diylbis(3,1-phenylene))bis(oxy))bis(N,N-diethylacetamide) (PPEA, L1), 2,2'-((pyridine-2,6-diylbis(3,1-phenylene))bis(oxy))bis(N-ethyl-N-phenylacetamide) (PEPA, L2), and 2,2'-(((4-phenylpyridine-2,6-diyl)bis(3,1-phenylene))bis(oxy))bis(N,N-dioctylacetamide) (PPOA, L3), were synthesized and explored for the solvent extraction of Pu(iv) in a HNO3 medium using 1-(trifluoromethyl)-3-nitrobenzene as the diluent. The effects of HNO3 concentration, extractant concentration, and temperature on the Pu(iv) extraction efficiency were studied. All three extractants displayed high selectivity for Pu(iv) over other metals such as U(vi), Np(v), Am(iii), and various fission elements. At 3 M HNO3, the distribution ratio for Pu(iv) reached 27.18, in contrast to 1.11, 0.3, and 0.03 for U(vi), Np(v), Am(iii), respectively. Slope analysis and UV titration revealed the formation of 1 : 1 Pu(NO3)4/ligand complexes during extraction. The extraction reactions had negative Gibbs free energies, indicating the spontaneous nature of Pu(iv) extraction at room temperature. Furthermore, the extractants demonstrated good stripping ability and reusability, and their radiolytic stability was reasonable up to an absorbed dose of 100 kGy, underscoring their potential for practical applications. Overall, this study broadens our understanding of actinide-diamide ligand coordination and actinide chemistry during coordination, paving the way for the design and synthesis of new extractants.
RESUMEN
Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with no cure. Bufotalin (BT), an active component extracted from Venenum Bufonis, has been prescribed as a treatment for chronic inflammatory diseases. However, whether BT has antifibrotic properties has never been investigated. In this study, we report on the potential therapeutic effect and mechanism of BT on IPF. BT was shown to attenuate lung injury, inflammation, and fibrosis as well as preserve pulmonary function in bleomycin (BLM)-induced pulmonary fibrosis model. We next confirmed BT's ability to inhibit TGF-ß1-induced epithelial-mesenchymal transition (EMT) and myofibroblast activation (including differentiation, proliferation, migration, and extracellular matrix production) in vitro. Furthermore, transcriptional profile analysis indicated the Wnt signaling pathway as a potential target of BT. Mechanistically, BT effectively prevented ß-catenin from translocating into the nucleus to activate transcription of profibrotic genes. This was achieved by blunting TGF-ß1-induced increases in phosphorylated Akt Ser437 (p-Akt S437) and phosphorylated glycogen synthase kinase (GSK)-3ß Ser9 (p-GSK-3ß S9), thereby reactivating GSK-3ß. Additionally, the antifibrotic effects of BT were further validated in another in vivo model of radiation-induced pulmonary fibrosis. Collectively, these data demonstrated the potent antifibrotic actions of BT through inhibition of Akt/GSK-3ß/ß-catenin axis downstream of TGF-ß1. Thus, BT could be a potential option to be further explored in IPF treatment.
