Organophosphorus flame retardant TDCPP induces neurotoxicity via mitophagy-related ferroptosis in vivo and in vitro.

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP) has neurotoxicity, but its mechanism remains unclear. Evidence recently showed that ferroptosis might be associated with TDCPP-induced neurotoxicity. To explore the role and underlying mechanism of ferroptosis in TDCPP-induced neurotoxicity, the occurrence of ferroptosis was examined in mice and PC12 cells upon TDCPP exposure. The mechanism of TDCPP-induced ferroptosis was clarified in vitro combined with the RNA sequencing assay. The in vivo results showed that orally TDCPP exposure (100 mg/kg, 30 d) inhibited the learning and memory ability of mice, reduced hippocampus neurons, induced malondialdehyde (MDA) accumulation, and decreased glutathione (GSH) and superoxide dismutase (SOD) levels in the hippocampus. Moreover, TDCPP exposure (100 mg/kg, 30 d) altered the ferroptosis and autophagy-related protein abundances in the hippocampus. The in vitro results showed that TDCPP exposure (0, 5, 20, 50, 100, and 200 µM) for 24 h induced dose-dependent cell death in PC12 cells, and the cell death was ameliorated by the co-treatment with ferrostatin-1 (1 µM, 24 h). Similarly, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased the levels of MDA and LPO, but decreased the reduced GSH in PC12 cells. Furthermore, TDCPP exposure (0, 50, 100, and 200 µM) for 24 h altered the ferroptosis and autophagy-related protein abundances in PC12 cells. The RNA-sequencing revealed that TDCPP exposure (100 µM, 24 h) induced mitophagy activation in SH-SY5Y cells. Meanwhile, the in vitro experiments confirmed that TDCPP exposure (0, 50, 100, and 200 µM) for 24 h increased abundances of mitophagy-related protein phosphatase and tensin homolog induced kinase 1(PINK1), Parkinson protein 2 E3 ubiquitin-protein ligase (PARKIN), inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), and voltage-dependent anion channel 1 (VDAC1) in PC12 cells. Moreover, TDCPP treatment (100 µM, 24 h) increased the mitochondrial recruitment of PARKIN, decreased the mitochondrial membrane potential (MMP) level, and increased the Fe2+ level in mitochondria. In addition, decreased ATP levels and increased reactive oxygen species (ROS) levels were observed in PC12 cells upon TDCPP exposure (0, 50, 100, and 200 µM) for 24 h. In summary, ferroptosis was associated with TDCPP-induced neurotoxicity, and the mechanism might be related to PINK1/PARKIN-mediated mitophagy initiated by mitochondrial damage.

Angiotensin-Converting Enzyme (ACE) Inhibitory Activity and Mechanism Analysis of N-(1-Deoxy-d-fructos-1-yl)-histidine (Fru-His), a Food-Derived Amadori Compound.

N-(1-Deoxy-d-fructos-1-yl)-histidine (Fru-His), one of the Amadori compounds, widely presents in processed foods, and its potential functional activities have attracted extensive attention in recent years. In this work, the angiotensin-converting enzyme (ACE) inhibitory activity and mechanism of Fru-His were investigated. The IC50 value of Fru-His was 0.150 ± 0.019 mM, and there was no obvious degradation of Fru-His after digestion simulation, showing that Fru-His has good ACE inhibition and digestive stability. Fru-His was a competitive inhibitor according to the enzyme inhibition kinetic analysis. The interaction between ACE and Fru-His occurred spontaneously mainly through hydrogen bonding, and the process was accompanied by fluorescence quenching and the alteration of the secondary structure of ACE. The molecular docking data supported the above results. Fru-His was attached to ACE's S1 active pocket through hydrogen bonds and interacted with zinc ions in active sites. The present study demonstrates that food-derived Fru-His has the potential to relieve hypertension.

Analysis of Microbial Community Diversity on the Epidermis of Wine Grapes in Manasi's Vineyard, Xinjiang.

Epiphytic microbial communities significantly impact the health and quality of grape berries. This study utilized high-performance liquid chromatography and high-throughput sequencing to explore the epiphytic microbial diversity and physicochemical indicators in nine different wine grape varieties. In total, 1,056,651 high-quality bacterial 16S rDNA sequences and 1,101,314 fungal ITS reads were used for taxonomic categorization. Among the bacteria, Proteobacteria and Firmicutes were the dominant phyla, and Massilia, Pantoea, Pseudomonas, Halomonas, Corynebacterium, Bacillus, Anaerococcus, and Acinetobacter were the dominant genera. Among the fungi, Ascomycota and Basidiomycota were the dominant phyla, and Alternaria, Filobasidium, Erysiphe, Naganishia, and Aureobasidium were the dominant genera. Notably, Matheran (MSL) and Riesling (RS) exhibited the highest microbial diversity among the nine grape varieties. Moreover, pronounced differences in epiphytic microorganisms in red and white grapes suggested that the grape variety significantly influences the structure of surface microbial communities. Understanding the composition of epiphytic microorganisms on the grape skin can provide a direct guide to winemaking.

Vacuum Dehydration: An Excellent Method to Promote the Formation of Amadori Compounds (ACs, N-(1-Deoxy-d-fructos-1-yl)-amino Acid) in Aqueous Models and Tomato Sauce.

Amadori compounds (ACs; N-(1-deoxy-d-fructos-1-yl)-amino acid) are superior flavor precursors and potential functional ingredients in food processing. In this study, vacuum dehydration as an excellent and universal method for the formation of ACs in both simulation systems and food processing was revealed. In total, 12 amino acids referring to all six categories were selected to conduct simulated reactions with glucose in aqueous models. At 90 °C, yields of 11 ACs were significantly increased by vacuum dehydration, reaching 4-198 times compared to a heat sealing reaction in aqueous systems, and formation of 5-hydroxymethyl-2-furaldehyde (5-HMF) and browning were slower than that by a dry powder reaction. In particular, the yields of Fru-Arg, Fru-His, and Fru-Glu reached 87.03, 90.73, and 89.88 mol %, respectively. The order of promotion effect was acid ACs > basic ACs > unique ACs > polar neutral ACs > aliphatic ACs > aromatic ACs. The excellent effect was mainly attributed to the control of water activity (Aw) and pH, which enabled the models to reach the optimal reaction state quickly by adjusting the vacuum degree at mild temperatures. The method was also applied to AC enrichment in tomato sauce processing; the AC content could rise to 30.72 mg/g, which was more than 17 times than those in samples without vacuum dehydration and two commercial tomato sauces.