1,130 research outputs found

    MiR-22 alleviates the proliferation and metastasis of melanoma by targeting FASN

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    Purpose: To determine the role of microRNA-22 (miR-22) in the development of malignant melanoma, and the underlying mechanism. Methods: Potential miRNAs binding fatty acid synthase (FASN) were predicted by bioinformatics analysis, out of which miR-22 was selected. Their binding relationship was confirmed using dual-luciferase reporter assay. MicroRNA-22 and FASN levels in 40 clinical samples of melanoma were determined, and the correlation of the expression between miR-22 and FASN was assessed by Pearson correlation test. To uncover the role of miR-22 in regulating cell phenotypes of malignant melanoma, M21 and A375 cells were transfected with miRNA-NC, miR-22 mimics or miR-22 mimics + FASN-OE (FASN-over expression), respectively. Proliferative and metastatic abilities in each group were determined using cell counting kit-8 (CCK-8), 5-Ethynyl-2’- deoxyuridine (EdU) and Transwell assay, respectively. Results: MiR-22 was the target gene binding the oncogene, FASN. Downregulated miR-22 and upregulated FASN were observed in melanoma tissues, showing a negative correlation between them. An overexpression of miR-22 significantly inhibited proliferative, migratory and invasive capacities in M21 and A375 cells (p < 0.05). Notably, overexpression of FASN abolished the inhibitory effects of miR-22 on proliferative and metastatic abilities in melanoma. Conclusion: The level of expression of miR-22 in the malignant melanoma samples is low. Overexpression of miR-22 inhibits the proliferative and metastatic abilities of melanoma by targeting FASN and negatively regulating its level. Thus, miR-22 may be a promising therapeutic target of melanoma

    SIRT3 Protects Rotenone-induced Injury in SH-SY5Y Cells by Promoting Autophagy through the LKB1-AMPK-mTOR Pathway.

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    SIRT3 is a class III histone deacetylase that modulates energy metabolism, genomic stability and stress resistance. It has been implicated as a potential therapeutic target in a variety of neurodegenerative diseases, including Parkinson's disease (PD). Our previous study demonstrates that SIRT3 had a neuroprotective effect on a rotenone-induced PD cell model, however, the exact mechanism is unknown. In this study, we investigated the underlying mechanism. We established a SIRT3 stable overexpression cell line using lentivirus infection in SH-SY5Y cells. Then, a PD cell model was established using rotenone. Our data demonstrate that overexpression of SIRT3 increased the level of the autophagy markers LC3 II and Beclin 1. After addition of the autophagy inhibitor 3-MA, the protective effect of SIRT3 diminished: the cell viability decreased, while the apoptosis rate increased; α-synuclein accumulation enhanced; ROS production increased; antioxidants levels, including SOD and GSH, decreased; and MMP collapsed. These results reveal that SIRT3 has neuroprotective effects on a PD cell model by up-regulating autophagy. Furthermore, SIRT3 overexpression also promoted LKB1 phosphorylation, followed by activation of AMPK and decreased phosphorylation of mTOR. These results suggest that the LKB1-AMPK-mTOR pathway has a role in induction of autophagy. Together, our findings indicate a novel mechanism by which SIRT3 protects a rotenone-induced PD cell model through the regulation of autophagy, which, in part, is mediated by activation of the LKB1-AMPK-mTOR pathway

    Effects of Red Imported Fire Ants (Solenopsis invicta) on the Species Structure of Ant Communities in South China

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    We evaluated the effects of invasive red imported fire ants (RIFAs), Solenopsis invicta Buren, on native ant communities at three habitats in South China. By using paired control and treatment plots, the change in diversity and community structure of native ants due to the invasion of red imported fire ants could be observed. Ant species richness was reduced by 46 and 33% at RIFA-infested lawn and pasture habitats, respectively; however, the ant species richness in the lichee orchard was not affected by red imported fire ants. Our results indicated that red imported fire ants became one of several dominant species or the only dominant species in all three habitats in South China

    Efficient and Joint Hyperparameter and Architecture Search for Collaborative Filtering

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    Automated Machine Learning (AutoML) techniques have recently been introduced to design Collaborative Filtering (CF) models in a data-specific manner. However, existing works either search architectures or hyperparameters while ignoring the fact they are intrinsically related and should be considered together. This motivates us to consider a joint hyperparameter and architecture search method to design CF models. However, this is not easy because of the large search space and high evaluation cost. To solve these challenges, we reduce the space by screening out usefulness yperparameter choices through a comprehensive understanding of individual hyperparameters. Next, we propose a two-stage search algorithm to find proper configurations from the reduced space. In the first stage, we leverage knowledge from subsampled datasets to reduce evaluation costs; in the second stage, we efficiently fine-tune top candidate models on the whole dataset. Extensive experiments on real-world datasets show better performance can be achieved compared with both hand-designed and previous searched models. Besides, ablation and case studies demonstrate the effectiveness of our search framework.Comment: Accepted by KDD 202

    Melatonin enhances the anti-tumor effect of fisetin by inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways.

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    Melatonin is a hormone identified in plants and pineal glands of mammals and possesses diverse physiological functions. Fisetin is a bio-flavonoid widely found in plants and exerts antitumor activity in several types of human cancers. However, the combinational effect of melatonin and fisetin on antitumor activity, especially in melanoma treatment, remains unclear. Here, we tested the hypothesis that melatonin could enhance the antitumor activity of fisetin in melanoma cells and identified the underlying molecular mechanisms. The combinational treatment of melanoma cells with fisetin and melatonin significantly enhanced the inhibitions of cell viability, cell migration and clone formation, and the induction of apoptosis when compared with the treatment of fisetin alone. Moreover, such enhancement of antitumor effect by melatonin was found to be mediated through the modulation of the multiply signaling pathways in melanoma cells. The combinational treatment of fisetin with melatonin increased the cleavage of PARP proteins, triggered more release of cytochrome-c from the mitochondrial inter-membrane, enhanced the inhibition of COX-2 and iNOS expression, repressed the nuclear localization of p300 and NF-κB proteins, and abrogated the binding of NF-κB on COX-2 promoter. Thus, these results demonstrated that melatonin potentiated the anti-tumor effect of fisetin in melanoma cells by activating cytochrome-c-dependent apoptotic pathway and inhibiting COX-2/iNOS and NF-κB/p300 signaling pathways, and our study suggests the potential of such a combinational treatment of natural products in melanoma therapy

    Separate density and viscosity measurements of unknown liquid using quartz crystal microbalance

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    Aqueous liquids have a wide range of applications in many fields. Basic physical properties like the density and the viscosity have great impacts on the functionalities of a given ionic liquid. For the millions kinds of existing liquids, only a few have been systematically measured with the density and the viscosity using traditional methods. However, these methods are limited to measure the density and the viscosity of an ionic liquid simultaneously especially in processing micro sample volumes. To meet this challenge, we present a new theoretical model and a novel method to separate density and viscosity measurements with single quartz crystal microbalance (QCM) in this work. The agreement of experimental results and theocratical calculations shows that the QCM is capable to measure the density and the viscosity of ionic liquid
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