AGF-PPIS: A protein-protein interaction site predictor based on an attention mechanism and graph convolutional networks.

Protein-protein interactions play an important role in various biological processes. Interaction among proteins has a wide range of applications. Therefore, the correct identification of protein-protein interactions sites is crucial. In this paper, we propose a novel predictor for protein-protein interactions sites, AGF-PPIS, where we utilize a multi-head self-attention mechanism (introducing a graph structure), graph convolutional network, and feed-forward neural network. We use the Euclidean distance between each protein residue to generate the corresponding protein graph as the input of AGF-PPIS. On the independent test dataset Test_60, AGF-PPIS achieves superior performance over comparative methods in terms of seven different evaluation metrics (ACC, precision, recall, F1-score, MCC, AUROC, AUPRC), which fully demonstrates the validity and superiority of the proposed AGF-PPIS model. The source codes and the steps for usage of AGF-PPIS are available at https://github.com/fxh1001/AGF-PPIS.

Dissymmetric pyridyl-substituted 3,5-bis(arylidene)-4-piperidones as anti-hepatoma agents by inhibiting NF-κB pathway activation.

To get new anti-hepatoma agents with anti-inflammatory activity and hypotoxicity, a series of dissymmetric pyridyl-substituted 3,5-bis(arylidene)-4-piperidones (BAPs, 25-82) were designed and synthesized. Many of them exhibited potential anti-hepatoma properties against human hepatocellular carcinoma cell lines (HepG2, QGY-7703, SMMC-7721) and hypotoxicity for human normal heptical cell line (HHL-5, LO2), and prominently inhibited lipopolysaccharides (LPS) induced IL-6, TNF-α secretion to exert its anti-inflammatory effect. Combining the data of cytotoxicity, cytocompatibility and anti-inflammatory activity, 3-pyridyl and -CF3 substituted 67 may be the potential anti-hepatoma agent. 67 effectively promoted cell apoptosis through up-regulating cleaved caspase-3 and Bax expression and down-regulating Bcl-2 expression. Furthermore, 67 prominently inhibited NF-κB pathway activation by blocking the phosphorylation of IκBα, p65 and the nuclear translocation of NF-κB induced by TNF-α and LPS. In addition, 67 could reasonably bind to the active site of Bcl-2 and NF-κB/p65 protein proved by Molecular docking analyses. Moreover, 67 significantly suppressed the growth and inflammatory response of HepG2 xenografts in nude mice and was relatively nontoxic to mice. These results suggest that 67 may be effective and hypotoxicity anti-hepatoma agent for the clinical treatment of liver cancers.