Integrated lipidomics and network pharmacology analysis of the protective effects and mechanism of Yuanzhi San on rats with cognitive impairment.

Cognitive impairment (CI) can seriously affect people's mental and physical health. Yuanzhi San (YZS) is a classic prescription for treating CI, but the mechanisms need further exploration. The aim of this study is to explore the effect of YZS on promoting the learning and memory ability of CI rats induced by d-galactose combined with aluminum chloride. Behavioral experiments had been used to comprehensively evaluate the established CI model. Brain histological morphology and the expressions of calcium ion signaling pathway related factors in serum were used to evaluate the effect of YZS against CI. Lipids in rat serum were analyzed by ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS) and chemical pattern recognition methods. Network pharmacology was used to find potential chemical compounds, targets, and related signaling pathways against CI with treatment of YZS. The integrated lipidomics and network pharmacology analysis were conducted by Cytoscape software. The results showed that YZS could alleviate neurodegenerative impairment. It was verified that model rats had longer latency time, shorter exploration paths, lower new objects recognition indexes, and shorter exercise time and distances compared with the normal rats in behavioral experiments, indicating that the model rats were successfully established. Rats of YZS 6.67 had significant differences in retention time (p < 0.05), number of entrances (p < 0.01), new object recognition indexes (p < 0.05, p < 0.01), exercise time (p < 0.05), and content of Ca [2]+, CAM, APP, CREB (p < 0.01), CAMK2 (p < 0.05). Rats of YZS 6.67 had five cell layers in hippocampus histological morphology. Behavioral experiments results showed that YZS had an active effect on CI rats. From lipidomics analysis, 129 lipids were screened out by conditions of VIP > 1 and p < 0.05, and 17 lipid markers were identified from the databases, which were divided mainly into five types. Pathway analysis indicated that linoleic acid, α-linolenic acid, arachidonic acid, and glycerophospholipid metabolisms were potential target pathways closely involved in the mechanism YZS's effects against CI. Network pharmacology focused on 84 chemical compounds, 130 intersection targets, and 10 hub genes of YZS's effects against CI. Six hub genes and four lipid compounds had intrinsic contact with arachidonic acid metabolism, glycerophospholipid metabolism and linoleate metabolism. The study revealed that YZS could improve animal cognitive behaviors, the expression of factors associated with memory in serum and the histological morphology of hippocampus. Four lipid compounds, three metabolic pathways, and six hub genes of YZS could effectively modulated CI. These results collectively suggest that the main mechanism of YZS in improving CI involves lipid metabolism, which affects biological processes and targets of action in the body.

Insight into the mechanism of nitrogen sufficiency conversion strategy for microalgae-based ammonium-rich wastewater treatment.

The strategy of nitrogen sufficiency conversion can improve ammonium nitrogen (NH4+-N) removal with microalgal cells from ammonium-rich wastewater. We selected and identified one promising isolated algal strain, NCU-7, Chlorella sorokiniana, which showed a high algal yield and tolerance to ammonium in wastewater, as well as strong adaptability to N deprivation. The transition from N deprivation through mixotrophy (DN, M) to N sufficiency through autotrophy (SN, P) achieved the highest algal yields (optical density = 1.18 and 1.59) and NH4+-N removal rates (2.5 and 4.2 mg L-1 d-1) from synthetic wastewaters at two NH4+-N concentrations (160 and 320 mg L-1, respectively). Algal cells in DN, M culture obtained the lowest protein content (20.6%) but the highest lipid content (34.0%) among all cultures at the end of the stage 2. After transferring to stage 3, the lowest protein content gradually recovered to almost the same level as SN, P culture on the final day. Transmission electron microscopy and proteomics analysis demonstrated that algal cells had reduced intracellular protein content but accumulated lipids under N deprivation by regulating the reduction in synthesis of protein, carbohydrate, and chloroplast, while enhancing lipid synthesis. After transferring to N sufficiency, algal cells accelerated their growth by recovering protein synthesis, leading to excessive uptake of NH4+-N from wastewater. This study provides specific insights into a nitrogen sufficiency conversion strategy to enhance algal growth and NH4+-N removal/uptake during microalgae-based ammonium-rich wastewater treatment.

The transcriptome analysis on urea response mechanism in the process of ergosterol synthesis by Cordyceps cicadae.

Nitrogen source is required for the growth of Cordyceps cicadae and involved in the regulation of metabolite synthesis. In order to further investigate the regulatory effects of nitrogen sources on the ergosterol synthesis by C. cicadae. We first confirmed that urea could significantly increase the ergosterol synthesis. The transcriptome analysis showed that compared with biomass cultured in the control fermentation medium (CFM), 1340 differentially expressed genes (DEGs) were obtained by Gene Ontology (GO) annotation, and 312 DEGs were obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) annotation from the biomass cultured in CFM + CO(NH2)2. Urea up-regulated D-3-phosphoglycerate dehydrogenase gene transcription level and down-regulated enolase and L-serine/L-threonine ammonialyase gene transcription level, increased serine synthesis, allosterically activate pyruvate kinase, to promote the synthesis of pyruvate and CH3CO ~ SCOA, the primer of ergosterol; Urea increase the genes transcription related with ergosterol synthesis by up-regulating the steroid regulatory element binding protein gene transcription levels. The transcriptome results were provided by those of qRT-PCR. Collectively, our finding provided valuable insights into the regulatory effect of nitrogen source on the ergosterol synthesis by C. cicadae.