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Toxoplasma gondii is an obligate protozoon that can infect all warm-blooded animals including humans. T. gondii afflicts one-third of the human population and is a detriment to the health of livestock and wildlife. Thus far, traditional drugs such as pyrimethamine and sulfadiazine used to treat T. gondii infection are inadequate as therapeutics due to relapse, long treatment period, and low efficacy in parasite clearance. Novel, efficacious drugs have not been available. Lumefantrine, as an antimalarial, is effective in killing T. gondii but has no known mechanism of action. We combined metabolomics with transcriptomics to investigate how lumefantrine inhibits T. gondii growth. We identified significant alternations in transcripts and metabolites and their associated functional pathways that are attributed to lumefantrine treatment. RH tachyzoites were used to infect Vero cells for three hours and subsequently treated with 900 ng/mL lumefantrine. Twenty-four hours post-drug treatment, we observed significant changes in transcripts associated with five DNA replication and repair pathways. Metabolomic data acquired through liquid chromatography-tandem mass spectrometry (LC-MS) showed that lumefantrine mainly affected sugar and amino acid metabolism, especially galactose and arginine. To investigate whether lumefantrine damages T. gondii DNA, we conducted a terminal transferase assay (TUNEL). TUNEL results showed that lumefantrine significantly induced apoptosis in a dose-dependent manner. Taken together, lumefantrine effectively inhibited T. gondii growth by damaging DNA, interfering with DNA replication and repair, and altering energy and amino acid metabolisms. [ABSTRACT FROM AUTHOR]

To study the effects of mineral fulvic acid (FuA) on broiler performance, slaughter performance, blood biochemistry index, antioxidant function, immune performance, and intestinal microflora, 360 Arbor Acres (AA) broiler chickens with similar body weights were randomly divided into 5 groups with 6 replicates in each group and 12 chickens in each replicate in the current study. Chickens in the control group (C) were fed with the basal diet, and chickens in the test groups (I, II, III, and IV) were fed with the diet supplemented with 0.05%, 0.1%, 0.2%, and 0.3% mineral FuA, respectively. The indicators were measured on the hatching day, d 21 and d 35. From the whole experimental period, FuA supplement significantly increased average body weight (ABW) (P < 0.05), average daily gain (ADG) of broilers (P < 0.05), and thymus weight (P < 0.05) in II and IV groups, but bascially reduced the pH value of thigh meat. FuA supplement significantly improved aspartate aminotransferase (AST) activity in the group III on d 35 (P < 0.05) and the serum levels of IgA and IgG on d 21 and d 35 (P < 0.05), but reduced glutathione peroxidase (GSH-Px) level on d 21 (P < 0.05) and malondialdehyde (MDA) level in serum on d 35 (P < 0.05). FuA supplement significantly affected the abundance of Barnesiella, Lachnospiraceae, Alistipes, Lactobacillus , and Christensenellaceae on genus level. Differences between group III and other groups were significant in the genera microflora composition on d 21 and d 35. Functional analysis showed that the cecum microbiota were mainly enriched in carbohydrate metabolism, amino acid metabolism, and energy metabolism. In conclusion, FuA may potentially have significant positive effects on the growth performance and immune function of AA chickens through the modulation of the gut microbiota, and the 0.1% FuA was the best in broiler diet based on the present study. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effect of different germination times (0–48 h) on the quality characteristics, especially the volatile compounds, of fermented brown rice cake (FBRC). Post-germination treatment, the viscoelasticity of the rice pulp decreased, also the hardness of FBRC steadily decreased. The 24 h germination time FBRC is considered to have the best quality including the smallest pore average area on the sliced surface and highest sensory score. In addition, the germination treatment also positively impacted the flavor of FBRC. Compared with the non-germination, the germinated groups had higher contents of alcohols, ketones, and heterocyclic compounds. The flavor volatile compounds could be generated via the amino acid metabolism and lipid oxidation pathways. A close correlation was found between the free amino acids, the free fatty acids and the main flavor volatile compounds. Principal component analysis indicated that the germination treatment improved the yeast flavor of brown rice cake; a short germination time was found best to provide a richer flavor. Overall, this study proved that moderate germination treatment effectively could improve the whole quality of FBRC. • The application of whole germinated brown rice flour in the preparation of gluten-free fermented rice cake was investigated. • Post-germination treatment reduced the hardness and springiness of fermented brown rice cake. • Germination increased the contents of alcohols, ketones, and heterocyclic compounds of fermented brown rice cake. • 24 h germination brown rice flour provided fermented rice cake with the most acceptable properties. [ABSTRACT FROM AUTHOR]

Halomonas spp. are moderately halophilic bacteria with the ability to tolerate various heavy metals. However, the role of basic cellular metabolism, particularly amino acid metabolism, has not been investigated in Halomonas spp. under excess Mn(Ⅱ). The strain Halomonas sp. MNB13 was isolated from a deep-sea ferromanganese nodule and can tolerate 80 mM Mn(Ⅱ). To comprehensively explore the mechanisms underlying its resistance to excess Mn(Ⅱ), we conducted a comparative proteome analysis. The data revealed that both 10 mM and 50 mM Mn(Ⅱ) significantly up-regulated the expression of proteins involved in Mn(Ⅱ) transport (MntE), oxidative stress response (alkyl hydroperoxide reductase and the Suf system), and amino acid metabolism (arginine, cysteine, methionine, and phenylalanine). We further investigated the role of cysteine metabolism in Mn(Ⅱ) resistance by examining the function of its downstream product, H 2 S. Consistent with the up-regulation of cysteine desulfurase, we detected an elevated level of H 2 S in Halomonas sp. MNB13 cells under Mn(Ⅱ) stress, along with increased intracellular levels of H 2 O 2 and O 2 •−. Upon exogenous addition of H 2 S, we observed a significant restoration of the growth of Halomonas sp. MNB13. Moreover, we identified decreased intracellular levels of H 2 O 2 and O 2 •− in MNB13 cells, which coincided with a decreased formation of Mn-oxides during cultivation. In contrast, in cultures containing NaHS, the residual Mn(Ⅱ) levels were higher than in cultures without NaHS. Therefore, H 2 S improves Mn(Ⅱ) tolerance by eliminating intracellular reactive oxygen species rather than decreasing Mn(Ⅱ) concentration in solution. Our findings indicate that cysteine metabolism, particularly the intermediate H 2 S, plays a pivotal role in Mn(Ⅱ) resistance by mitigating the damage caused by reactive oxygen species. These findings provide new insights into the amino acid mechanisms associated with Mn(Ⅱ) resistance in bacteria. • High levels of Mn(Ⅱ) affected the metabolism of certain amino acids in MNB13. • Cysteine desulfurase responsible for H 2 S production was significantly up-regulated. • Increased amounts of H 2 S, H 2 O 2 , and O 2.•− were detected in MNB13 under Mn(Ⅱ) stress • H 2 S restored the growth of MNB13 and reduced H 2 O 2 and O 2.•− intracellular levels • H 2 S decreased the formation of Mn(Ⅱ)-oxides by MNB13. [ABSTRACT FROM AUTHOR]