ABSTRACT
Fracture of the lateral process of the talus (FLPT) is uncommon in clinical practice and can be easily missed or misdiagnosed. In recent years, as researchers from all over the world have further deepened their research on FLPT, there has been a breakthrough in the classification, and the methods and principles of clinical management have changed accordingly; however, there is still no standardized guideline for the diagnosis and management of FLPT, and there have been few relevant literature review articles related to this kind of fracture in the past at least 5 years. In this article, we review the clinical classification, classification-based therapeutic recommendations, and prognosis of FLPT, with the aim of providing a reference for the clinical diagnosis and management of this infrequent fracture.
ABSTRACT
A series of novel propargylamine-modified pyrimidinylthiourea derivatives (1-3) were designed and synthesized as multifunctional agents for Alzheimer's disease (AD) therapy, and their potential was evaluated through various biological experiments. Among these derivatives, compound 1b displayed good selective inhibitory activity against AChE (vs BuChE, IC50 = 0.324 µM, SI > 123) and MAO-B (vs MAO-A, IC50 = 1.427 µM, SI > 35). Molecular docking study showed that the pyrimidinylthiourea moiety of 1b could bind to the catalytic active site (CAS) of AChE, and the propargylamine moiety interacted directly with the flavin adenine dinucleotide (FAD) of MAO-B. Moreover, 1b demonstrated mild antioxidant ability, good copper chelating property, effective inhibitory activity against Cu2+-induced Aß1-42 aggregation, moderate neuroprotection, low cytotoxicity, and appropriate blood-brain barrier (BBB) permeability in vitro and was capable of ameliorating scopolamine-induced cognitive impairment in mice. These results indicated that 1b has the potential to be a multifunctional candidate for the treatment of Alzheimer's disease.
