Altered dynamic amplitude of low-frequency fluctuation in individuals at high risk for Alzheimer's disease.

The brain's dynamic spontaneous neural activity is significant in supporting cognition; however, how brain dynamics go awry in subjective cognitive decline (SCD) and mild cognitive impairment (MCI) remains unclear. Thus, the current study aimed to investigate the dynamic amplitude of low-frequency fluctuation (dALFF) alterations in patients at high risk for Alzheimer's disease and to explore its correlation with clinical cognitive assessment scales, to identify an early imaging sign for these special populations. A total of 152 participants, including 72 SCD patients, 44 MCI patients and 36 healthy controls (HCs), underwent a resting-state functional magnetic resonance imaging and were assessed with various neuropsychological tests. The dALFF was measured using sliding-window analysis. We employed canonical correlation analysis (CCA) to examine the bi-multivariate correlations between neuropsychological scales and altered dALFF among multiple regions in SCD and MCI patients. Compared to those in the HC group, both the MCI and SCD groups showed higher dALFF values in the right opercular inferior frontal gyrus (voxel P < .001, cluster P < .05, correction). Moreover, the CCA models revealed that behavioural tests relevant to inattention correlated with the dALFF of the right middle frontal gyrus and right opercular inferior frontal gyrus, which are involved in frontoparietal networks (R = .43, P = .024). In conclusion, the brain dynamics of neural activity in frontal areas provide insights into the shared neural basis underlying SCD and MCI.

FIP-nha, a fungal immunomodulatory protein from Nectria haematococca, induces apoptosis and autophagy in human gastric cancer cells via blocking the EGFR-mediated STAT3/Akt signaling pathway.

FIP-nha, a fungal immunomodulatory protein from Nectria haematococca, has been demonstrated a broad spectrum of antitumor activity and cell selectivity against human cancers in our previous study. However, the effect and mechanism of FIP-nha on gastric cancer remains unclear. In this study, we systematically observed the cytotoxicity, biological effect, regulatory mechanism and interaction target of FIP-nha on human gastric cancer cell lines, AGS and SGC7901. Our results demonstrated that FIP-nha inhibited the growth of AGS and SGC7901 cells in a dose-dependent manner and exerted proapoptotic effects on both cells as confirmed by flow cytometry, DAPI staining and western blot analysis. Additionally, the exposure of AGS and SGC7901 to FIP-nha induced autophagy as indicated by western blot analysis, GFP-LC3 and mCherry-GFP-LC3 transfection and acridine orange staining. Furthermore, we found that FIP-nha decreased the phosphorylation of EGFR, STAT3 and Akt and inhibited activation effect of ligand factor EGF to EGFR and its downstream signal molecule STAT3 and Akt. Finally, we proved that FIP-nha located on the surface of gastric cancer cells and bound directly to the transmembrane protein of EGFR by immunoprecipitation, cellular localization, molecular docking, microscale thermophoresis assay. The above findings indicated that FIP-nha inhibited the growth of gastric cancer and induced apoptosis and autophagy through competitively binding to EGFR with EGF to blocking the EGFR-mediated STAT3/Akt pathway. In summary, our study provided novel insights regarding the activity of FIP-nha against gastric cancer and contributed to the clinical application of FIP-nha as a potential chemotherapy drugs that targeted EGFR for human gastric cancer.

1H NMR-based chemometric metabolomics characterization of soymilk fermented by Bacillus subtilis BSNK-5.

Microbial fermentation can endow food with unique flavors, increase its nutritional value and enhance functional characteristics. Our previous research has shown that liquid fermentation of soymilk by Bacillus subtilis BSNK-5 imparted new functional properties of to the fermented product via production of nattokinase. In this study, in order to further investigate the changes in the flavor, nutritional quality and functional characteristics of soymilk during fermentation using proton nuclear magnetic resonance (1H NMR) metabolomics to monitor the metabolite profile of BSNK-5-fermented soymilk. A total of 44 differential metabolites were identified between BSNK-5-fermented soymilk and uninoculated/unfermented soymilk, among which the levels of flavor-related substances (acetate, isovalerate and 2-methylbutyrate), nutrient-related substances (12 free amino acids), and functional substances (taurine, GABA and genistein) significantly increased after fermentation. These metabolites were closely associated with eight potential metabolic pathways. This work highlighted the significance of BSNK-5 strain in improving the nutritional quality and functional characteristics of fermented soymilk; however, the use of the strain also caused flavor deterioration. This study lays a theoretical foundation for the improvement and development of fermented soy products via liquid fermentation with B. subtilis.