Investigating critical brain area for EEG-based binocular color fusion and rivalry with EEGNet.

Introduction: Binocular color fusion and rivalry are two specific phenomena in binocular vision, which could be used as experimental tools to study how the brain processes conflicting information. There is a lack of objective evaluation indexes to distinguish the fusion or rivalry for dichoptic color. Methods: This paper introduced EEGNet to construct an EEG-based model for binocular color fusion and rivalry classification. We developed an EEG dataset from 10 subjects. Results: By dividing the EEG data from five different brain areas to train the corresponding models, experimental results showed that: (1) the brain area represented by the back area had a large difference on EEG signals, the accuracy of model reached the highest of 81.98%, and more channels decreased the model performance; (2) there was a large effect of inter-subject variability, and the EEG-based recognition is still a very challenge across subjects; and (3) the statistics of EEG data are relatively stationary at different time for the same individual, the EEG-based recognition is highly reproducible for an individual. Discussion: The critical channels for EEG-based binocular color fusion and rivalry could be meaningful for developing the brain computer interfaces (BCIs) based on color-related visual evoked potential (CVEP).

The protective mechanism of Dehydromiltirone in diabetic kidney disease is revealed through network pharmacology and experimental validation.

Background: Salvia miltiorrhiza (SM) is an effective traditional Chinese medicine for treating DKD, but the exact mechanism is elusive. In this study, we aimed to investigate and confirm the method underlying the action of the active components of SM in the treatment of DKD. Methods: Renal tissue transcriptomics and network pharmacology of DKD patients was performed to identify the active components of SM and the disease targets of DKD. Next, the point of convergence among these three groups was studied. Potential candidate genes were identified and analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The component-target networks were modelled and visualized with Cytoscape. In addition, docking studies were performed to validate our potential target predictions. Lastly, in vitro and in vivo experiments were performed to understand the role of Dehydromiltirone (DHT), the active component of SM, in the phenotypic switching of mesangial cells. Results: Transcriptomics of DKD patients' renal tissues screened 4,864 differentially expressed genes. Eighty-nine active components of SM and 161 common targets were found. Functional enrichment analysis indicated that 161 genes were enriched in apoptosis, the PI3K-AKT signaling pathway, and the AGE-RAGE signaling pathway in diabetes complications. Molecular docking and molecular dynamic simulations show that DHT can bind to functional PIK3CA pockets, thereby becoming a possible inhibitor of PIK3CA. In vitro study demonstrated that DHT reduced the expression of phenotypic switching markers α-SMA, Col-I, and FN in HMCs by downregulating the over-activation of the PI3K-AKT signaling pathway through the inhibition of PIK3CA. Furthermore, the DKD mouse model confirmed that DHT could reduce proteinuria and improve glomerular hypertrophy in vivo. Conclusion: DHT was identified as the key active component of SM, and its therapeutic effect on DKD was achieved by inhibiting the phenotypic switching of mesangial cells via the PIK3CA signaling pathway.

Protective Autophagy Attenuates the Cytotoxicity of MTI-31 in Renal Cancer Cells by Activating the ERK Pathway.

The mammalian target of rapamycin (mTOR) is a key regulatory molecular target to treat cancer, and MTI-31 is a potent mTOR inhibitory agent for the therapeutically target of the renal cell carcinoma (RCC). However, the therapeutic efficacy of MTI-31 is limited by multiple factors, including autophagy. MTI-31 can activate cells to generate autophagy, which may in turn indirectly affect cell proliferation and apoptosis. We aimed to observe changes in cell protective autophagy via the ERK pathway and explore the potential mechanism underlying drug resistance of RCC cells to MTI-31. Different concentrations of 786-O and RCC4 cells were co-cultured with MTI-31 for distinct durations. The result of autophagy marker detection by Western blot showed that MTI-31 could induce RCC cells to produce autophagy in a dose and time-dependent manner. After treating the RCC cells with the autophagy inhibitor chloroquine (CQ), CCK8 and Western blot assays demonstrated that CQ could effectively enhance cell apoptosis induced by MTI-31 and that the autophagy induced by MTI-31 was cytoprotective. In addition, CCK8 and Western blot demonstrated that MTI-31 exerted its effect by activating the ERK pathway rather than the JNK or p38 pathway. The use of the ERK inhibitor AZD6244 to block the ERK pathway could effectively promote cell apoptosis induced by MTI-31. AZD6244 attenuated the autophagy induced by MTI-31 and increased the cytotoxicity of MTI-31. Western blot also demonstrated that MTI-31-induced autophagy was mediated by the downstream regulators of ERK pathways, including Beclin-1 and Bcl-2. It demonstrated that the MTI-31 mediated activation ERK pathway is associated with the induction of autophagy, and autophagy can attenuate the cytotoxicity of MTI-31 on RCC cells. In summary, inhibition of ERK pathway-mediated autophagy can rectify drug resistance to MTI-31 effectively.