Danielsanderson7203

Moreover, the algorithm eliminates the prevalent cold start problem in the early stage of recommendation generation. Several experiments and benchmarking on different datasets are conducted to investigate the performance of the proposed personalized recommender engine. The experimental precision and recall results indicate that the proposed approach can achieve up to an approximately 28% higher F-score than conventional approaches. In general, the proposed hybrid approach outperforms other methods.The global incidence of breast cancer has increased. However, there are many impediments to the development of safe and effective anticancer drugs. The aim of the present study was to evaluate the effect of aviculin isolated from Lespedeza cuneata (Dum. Cours.) G. Don. (Fabaceae) on MCF-7 human breast cancer cells and determine the underlying mechanism. Using the bioassay-guided isolation by water soluble tetrazolium salt (WST-1)-based Ez-Cytox assay, nine compounds (four lignan glycosides (1-4), three flavonoid glycosides (5-7), and two phenolic compounds (8 and 9)) were isolated from the ethyl acetate (EA) fraction of the L. cuneata methanolic extract. Of these, aviculin (2), a lignan glycoside, was the only compound that reduced metabolic activity on MCF-7 cells below 50% (IC50 75.47 ± 2.23 μM). The underlying mechanism was analyzed using the annexin V Alexa Fluor 488 binding assay and Western blotting. Aviculin (2) was found to induce apoptotic cell death through the intrinsic apoptosis pathway, as indicated by the increased expression of initiator caspase-9, executioner caspase-7, and poly (ADP-ribose) polymerase (PARP). Aviculin (2)-induced apoptotic cell death was accompanied by an increase in the Bax/Bcl-2 ratio. These findings demonstrated that aviculin (2) could induce breast cancer cell apoptosis through the intrinsic apoptosis pathway, and it can therefore be considered an excellent candidate for herbal treatment of breast cancer.Patients with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) can present with life-threatening cardiac arrhythmias. The pathophysiological mechanism is unknown. We reprogrammed fibroblasts from one mildly and one severely affected VLCADD patient, into human induced pluripotent stem cells (hiPSCs) and differentiated these into cardiomyocytes (VLCADD-CMs). VLCADD-CMs displayed shorter action potentials (APs), more delayed afterdepolarizations (DADs) and higher systolic and diastolic intracellular Ca2+ concentration ([Ca2+]i) than control CMs. The mitochondrial booster resveratrol mitigated the biochemical, electrophysiological and [Ca2+]i changes in the mild but not in the severe VLCADD-CMs. Accumulation of potentially toxic intermediates of fatty acid oxidation was blocked by substrate reduction with etomoxir. Incubation with etomoxir led to marked prolongation of AP duration and reduced DADs and [Ca2+]i in both VLCADD-CMs. These results provide compelling evidence that reduced accumulation of fatty acid oxidation intermediates, either by enhanced fatty acid oxidation flux through increased mitochondria biogenesis (resveratrol) or by inhibition of fatty acid transport into the mitochondria (etomoxir), rescues pro-arrhythmia defects in VLCADD-CMs and open doors for new treatments.Enterovirus A71 (EV-A71) is a major pathogen that causes severe and fatal cases of hand-foot-and-mouth disease (HFMD). HFMD caused by EV-A71 seriously endangers children's health. Although autophagy is an important antiviral defense mechanism, some viruses have evolved strategies to utilize autophagy to promote self-replication. PF04957325 EV-A71 can utilize autophagy vesicles as replication scaffolds, indicating that EV-A71 infection is closely related to its autophagy induction mechanism. VP1, a structural protein of EV-A71, has been reported to induce autophagy, but the underlying mechanism is still unclear. In this study, we found that the C-terminus (aa 251-297) of VP1 induces autophagy. Mass spectrometry analysis suggested that prohibitin 2 (PHB2) interacts with the C-terminus of the EV-A71 VP1 protein, and this was further verified by coimmunoprecipitation assays. After PHB2 knockdown, EV-A71 replication, viral particle release, and viral protein synthesis were reduced, and autophagy was inhibited. The results suggest that PHB2 interaction with VP1 is essential for induction of autophagy and the infectivity of EV-A71. Furthermore, we confirmed that EV-A71 induced complete autophagy that required autolysosomal acidification, thus affecting EV-A71 infection. In summary, this study revealed that the host protein PHB2 is involved in an autophagy mechanism during EV-A71 infection.Crude ethyl acetate extract of Gerbera piloselloides (L.) Cass. was investigated by dual high-resolution PTP1B/α-glucosidase inhibition profiling and LC-PDA-HRMS. This indicated the presence of a series of unprecedented prenyl- and geranyl-substituted coumarin derivatives correlated with both α-glucosidase and PTP1B inhibitory activity. Repeated chromatographic separation targeting these compounds led to the isolation of 13 new compounds, of which ten could be isolated as both enantiomers after chiral separation. The structures of all isolated compounds were characterized by HRMS and extensive 1D and 2D NMR analysis. The absolute configurations of the isolated compounds were determined by comparison of experimental and calculated electronic circular dichroism spectra. Compound 6 features a rare furan-oxepane 5/7 ring system, possibly formed through addition of a geranyl unit to C-3 of 5-methylcoumarin, representing a new type of geranyl-substituted coumarin skeleton. Compounds 19 and 24 are the first examples of dimeric natural products consisting of both coumarin and chromone moieties.The theoretical relationship between Buddhism and subjective well-being has gained much academic attention in recent decades. However, the prominent determinants of religiosity remain limited for researchers to understand a holistic picture of religion-informed subjective well-being, particularly in the context of Buddhism. This study has applied a quantitative survey to verify the impact of the aesthetic effects of the Buddhist gesture symbol on Chinese people's subjective happiness through sequential mediators of life satisfaction and the perceived religiosity. The significance of this study is threefold. Firstly, it aims to enrich the current academic understanding of the religion-informed subjective well-being by introducing a new determinant of the Buddhist symbols. Secondly, the current study investigates the mechanism of how Buddhist symbols could influence happiness by analyzing the sequential mediating roles of religiosity and life satisfaction. Thirdly, this study empirically examines the topic in the context of China to confirm and underpin the theoretical relationship between Buddhism and subjective well-being in relevant research, which has previously focused on Western culture.