Comparative analysis of the fatty acid profiles in goat milk during different lactation periods and their interactions with volatile compounds and metabolites.

This study aimed to compare the composition of fatty acids in goat milk during lactation with human milk, as well as analyze the differences in their interaction with odor and metabolites. Polyunsaturated fatty acids content was higher in human milk, while odd-chain, branched-chain, and monounsaturated fatty acids content were higher in goat milk with a decreasing trend during lactation. PUFAs in human milk undergo auto-oxidation to produce aldehydes (hexanal), giving it a mild aroma. Butyric acid in goat colostrum mediates the synthesis and auto-oxidation of PUFA, while taurine mediated the hydrolysis of amino acids. They produce a furanone compound (2(5H)-furanone) with a buttery flavor. The presence of butyric acid in goat transitional milk had an impact on flavor and metabolites. The medium chain fatty acid composition of the goat mature milk was affected by nucleic acid compounds, which then oxidized to produce methyl ketone (2-nonanone), giving it an unpleasant flavor.

Multi-omics reveals the molecular mechanism of the combined toxic effects of PFOA and 4-HBP exposure in MCF-7 cells and the key player: mTORC1.

With the discovery of evidence that many endocrine-disrupting chemicals (EDCs) in the environment influence human health, their toxic effects and mechanisms have become a hot topic of research. However, investigations into their endocrine-disrupting toxicity under combined binary exposure, especially the molecular mechanism of combined effects, have rarely been documented. In this study, two typical EDCs, perfluorooctanoic acid (PFOA) and 4-hydroxybenzophenone (4-HBP), were selected to examine their combined effects and molecular mechanism on MCF-7 cell proliferation at environmentally relevant exposure concentrations. We have successfully established a model to evaluate the binary combined toxic effects of endocrine disruptors, presenting combined effects in a simple and direct way. Results indicated that the combined effect changed from additive to synergistic from 1.25 × 10-8 M to 4 × 10-7 M. Metabolomics analyses suggested that exposure to PFOA and 4-HBP caused significant alterations in purine metabolism, arginine, and proline metabolism and had superimposed influences on metabolism. Enhanced combined effects were observed in glycine, serine, and threonine metabolic pathways compared to exposure to PFOS and 4-HBP alone. Additionally, the differentially expressed genes (DEGs) are primarily involved in Biological Processes, especially protein targeting the endoplasmic reticulum, and significantly impact the oxidative phosphorylation and thermogenesis-related KEGG pathway. By integrating metabolome and transcriptome analyses, PFOA and 4-HBP regulate purine metabolism, the TCA cycle, and endoplasmic reticulum protein synthesis in MCF-7 cells via mTORC1, which provides genetic material, protein, and energy for cell proliferation. Furthermore, molecular docking confirmed the ability of PFOA and 4-HBP to stably bind the estrogen receptor, indicating that they have different binding pockets. Collectively, these findings will offer new insights into understanding the mechanisms by which EDCs produce combined toxicity.

Comprehensive analysis of phospholipid in milk and their biological roles as nutrients and biomarkers.

Phospholipids (PL) have garnered significant attention due to their physiological activities. Milk and other dairy products are important dietary sources for humans and have been extensively used to analyze the presence of PL by various analytical techniques. In this paper, the analysis techniques of PL were reviewed with the eight trigrams of phospholipidomics and a comprehensive fingerprint of 1295 PLs covering 8 subclasses in milk and other dairy products, especially. Technology is the primary productive force. Based on phospholipidomics technology, we further review the relationship between the composition of PL and factors that may be involved in processing and experimental operation, and emphasized the significance of the biological role played by PL in dietary supplements and biomarkers (production, processing and clinical research), and providing the future research directions.

Levels, Toxic Effects, and Risk Assessment of Pyrrolizidine Alkaloids in Foods: A Review.

Pyrrolizidine alkaloids (PAs) are naturally occurring secondary metabolites of plants. To date, more than 660 types of PAs have been identified from an estimated 6000 plants, and approximately 120 of these PAs are hepatotoxic. As a result of PAs being found in spices, herbal teas, honey, and milk, PAs are considered contaminants in foods, posing a potential risk to human health. Here, we summarize the chemical structure, toxic effects, levels, and regulation of PAs in different countries to provide a better understanding of their toxicity and risk assessment. With recent research on the risk assessment of PAs, this review also discusses the challenges facing this field, aiming to provide a scientific basis for PA toxicity research and safety assessment.

Pesticide residues in animal-derived food: Current state and perspectives.

Pesticides are widely used in the cultivation and breeding of agricultural products all over the world. However, their direct use or indirect pollution in animal breeding may lead to residual accumulation, migration, and metabolism in animal-derived foods, posing potential health risks to humans through the food chain. Therefore, it is necessary to detect pesticide residues in animal-derived food using simple, reliable, and sensitive methods. This review summarizes sample extraction and clean-up methods, as well as the instrumental determination technologies such as chromatography and chromatography-mass spectrometry for residual analysis in animal-derived foods, including meat, eggs and milk. Additionally, we perspectives on the future of this field. This information aims to assist relevant researchers in this area, contribute to the development of ideas and novel technical methods for residual detection, metabolic research and risk assessment of pesticides in animal-derived food.

Multiomics reveals new biomarkers and mechanistic insights into the combined toxicity effects of 2,2',4,4',5,5'-hexachlorobiphenyl and atrazine exposures in MCF-7 cells.

Humans are constantly exposed to complicated chemical mixtures from the environment and food rather than being exposed to a single pollutant. The underlying mechanisms of the complicated combined toxicity of endocrine disrupting chemicals (EDCs) are still mainly unexplored. In this study, two representative EDCs, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and atrazine (ATZ), were selected to explore their combined effects on MCF-7 cell proliferation at environmental exposure concentrations by an integrated analysis of metabolomics and transcriptomics. The results showed that 1 µM ATZ and PCB153 combined exposure significantly accelerated MCF-7 cell growth by 18.2%. More than 400 metabolites detected by UHPLC-QTOF/MS were used to observe metabolism differences induced by binary mixtures. Metabolomics analysis verified that ATZ and PCB153 exposure alone or in combination could have an additive effect on metabolism and induce significant disruption to glycolysis, purine metabolism and the TCA cycle, which provide energy demand and biosynthetic substrates for cell proliferation. Compared to PCB153 and ATZ exposure alone, a combined effect was observed in purine and pyrimidine metabolic pathways. Hexokinase 3 (HK3) and cytochrome P450 19 subfamily A1 (CYP19A1) were identified as differentially expressed genes based on transcriptomic analysis. By integrating metabolome and transcriptome analysis, the proliferation effects of ATZ and PCB153 were induced at low doses in MCF-7 cells through potential interference with the downstream transcription signaling of CYP19A1. Furthermore, molecular docking indicated that PCB153 and ATZ directly affected CYP19A1. Altogether, the regulation of pivotal metabolites and differentially expressed genes could provide helpful information to reveal the mechanism by which PCB153 and ATZ affect MCF-7 cell proliferation.

Use of Transcriptomics to Reveal the Joint Immunotoxicity Mechanism Initiated by Difenoconazole and Chlorothalonil in the Human Jurkat T-Cell Line.

It is very important to evaluate the immunotoxicity and molecular mechanisms of pesticides. In this study, difenoconazole and chlorothalonil were evaluated for immunotoxicity by using the human Jurkat T-cell line, and the EC50 were 24.66 and 1.17 mg/L, respectively. The joint exposure of difenoconazole and chlorothalonil showed a synergistic effect at low concentrations (lower than 10.58 mg/L) but an antagonistic effect at high concentrations (higher than 10.58 mg/L). With joint exposure at a concentration of EC10, the proportion of late apoptotic cells was 2.26- and 2.91-fold higher than that with exposure to difenoconazole or chlorothalonil alone, respectively. A transcriptomics analysis indicated that the DEGs for single exposure are associated with immunodeficiency disease. Single exposure to chlorothalonil was mainly involved in cation transportation, extracellular matrix organization, and leukocyte cell adhesion. Single exposure to difenoconazole was mainly involved in nervous system development, muscle contraction, and immune system processes. However, when the joint exposure dose was EC10, the DEGs were mainly involved in the formation of cell structures, but the DEGs were mainly involved in cellular processes and metabolism when the joint exposure dose was EC25. The results indicated that the immunotoxicological mechanisms underlying joint exposure to difenoconazole and chlorothalonil are different under low and high doses.

Comparative Transcriptome Analysis to Investigate the Immunotoxicity Mechanism Triggered by Dimethomorph on Human Jurkat T Cell Lines.

Dimethomorph (DMM) is a broad-spectrum fungicide used globally in agricultural production, but little is known regarding the immunotoxicity of DMM in humans. In this study, the immunotoxicity of DMM on human Jurkat T cells was evaluated in vitro. The results indicated that the half-effective concentration (EC50) of DMM for Jurkat cells was 126.01 mg/L (0.32 mM). To further elucidate the underlying mechanism, transcriptomics based on RNA sequencing for exposure doses of EC25 (M21) and EC10 (L4) was performed. The results indicated that compared to untreated samples (Ctr), 121 genes (81 upregulated, 40 downregulated) and 30 genes (17 upregulated, 13 downregulated) were significantly differentially regulated in the L4 and M21 samples, respectively. A gene ontology analysis indicated that the significantly differentially expressed genes (DEGs) were mostly enriched in the negative regulation of cell activities, and a KEGG pathway analysis indicated that the DEGs were mainly enriched in the immune regulation and signal transduction pathways. A quantitative real-time PCR for the selected genes showed that compared to the high-dose exposure (M21), the effect of the low-dose DMM exposure (L4) on gene expression was more significant. The results indicated that DMM has potential immunotoxicity for humans, and this toxicity cannot be ignored even at low concentrations.

Integrated metabolomics and transcriptomics analysis reveals new biomarkers and mechanistic insights on atrazine exposures in MCF­7 cells.

Atrazine (ATZ) is a widely used herbicide worldwide and is a long-suspected endocrine-disrupting chemical. However, most endocrine-disrupting toxicity studies on ATZ have been based on animal models and those investigating inner mechanisms have only focused on a few genes. Therefore, the possible link between ATZ and endocrine-disrupting toxicity is still unclear. In this study, multi-omics and molecular biology techniques were used to elucidate the possible molecular mechanisms underlying the effect of ATZ exposure on MCF-7 proliferation at environmentally relevant concentrations. Our study is the first report on ATZ-induced one carbon pool by folate metabolic disorder in MCF-7 cells. A concentration of 1 µM ATZ yielded the highest cell viability and was selected for further mechanistic studies. A total of 34 significantly changed metabolites were identified based on metabolomic analysis, including vitamins, amino acids, fatty acids, and corresponding derivatives. Folate and pyridoxal have potential as biomarkers of ATZ exposure. One carbon pool by folate metabolic pathway was identified based on metabolic pathway analysis of the significantly altered pathways. Moreover, FTCD and MTHFD related to this pathway were further identified based on transcriptomic analysis and protein assays. Folate and different forms of 5,6,7,8-tetrahydrofolate, which participate in purine synthesis and associate with methyl groups (SOPC, arachidonic acid, and L-tryptophan) in one carbon pool by the folate metabolic pathway, potentially promote MCF-7 cell proliferation. These findings on the key metabolites and regulation of the related differentially expressed genes in folate metabolism will shed light on the mechanism of MCF-7 cell proliferation after ATZ exposure. Overall, this study provides new insights into the mechanistic understanding of toxicity caused by endocrine-disrupting chemicals.

A comprehensive analysis of metabolomics and transcriptomics reveals new biomarkers and mechanistic insights on DEHP exposures in MCF-7 cells.

Di-(2-ethylhexyl) phthalate (DEHP) is one of the most important environmental pollutants and affects multiple pathways upon human exposure. DEHP could induce MCF-7 cell proliferation at a very low dose; however, the possible linkage between DEHP and the cell proliferation effect is still unclear. Here, we carried out a comprehensive metabolome and transcriptome analysis to depict the possible molecular mechanisms of the effect of DEHP exposure on MCF-7 proliferation. In this paper, MCF-7 cells treated with DEHP at a dose of 1 µM for 48 h were selected for metabolome and transcriptome analysis. Untargeted and targeted metabolomics identified 8 differential metabolites, including amino acids, purine, pyrimidine and nucleotides. The metabolite changes were associated with 9 metabolic pathways. Disorders in riboflavin, histidine, beta-alanine metabolism, and nitrogen metabolism caused by DEHP exposure are important concerns for MCF-7 proliferation. Moreover, a transcriptomics study of the MCF-7 cells found a total of 500 differentially expressed genes (DEGs). KEGG enrichment analyses showed that pathways in cancer had stronger responses. The results of integrated analysis of the interactions between the DEGs and metabolites revealed significant changes in the purine metabolism pathway, which will shed light on the mechanism of MCF-7 cell proliferation after DEHP exposure. Overall, this study depicts the possible contribution of DEHP exposure to MCF-7 cell proliferation and highlights the power of omics platforms to deepen the mechanistic understanding of toxicity caused by endocrine disrupting chemicals.

Wheat Flour, Enriched with γ-Oryzanol, Phytosterol, and Ferulic Acid, Alleviates Lipid and Glucose Metabolism in High-Fat-Fructose-Fed Rats.

(1) Background: Modern dietary patterns with a high intake of fat and fructose, as well as refined carbohydrates, closely relate to lipid/glucose metabolic disorders. The main objective of this study is to provide new thoughts in designing functional food with some lipid/glucose metabolism regulating effects for obese people. (2) Methods: The alleviating abilities of γ-oryzanol, phytosterol or ferulic acid-enriched wheat flour on lipid/glucose metabolic dysfunction were evaluated in male SD rats induced by a high-fat-fructose diet. The underlying mechanisms were clarified using western blot. (3) Results: In an in vitro cell model, γ-oryzanol, phytosterol and ferulic acid regulate lipid/glucose metabolism by increasing the phosphorylation of AMPK and Akt, and PI3K expression, as well as decreasing expressions of DGAT1 and SCD. The in vivo study shows that ferulic acid and γ-oryzanol-enriched flours are beneficial for managing body weight, improving glucose metabolism, hyperlipidemia and hepatic lipid accumulation. Phytosterol-enriched flour exerted remarkable effects in regulating hyperinsulinemia, insulin resistance and hyperuricemia. Western blot analysis of proteins from liver samples reveals that these enriched flours alleviated hepatic lipid accumulation and insulin resistance through their elevation in the phosphorylation of AMPK and Akt. (4) Conclusions: Our study indicates that these enriched flours can serve as a health-promoting functional food to regulate obesity-related lipid/glucose metabolic dysfunction in rats.

Polymer brushes-containing coordination polymer networks on monolith for rapid solid phase extraction of multi-class drug residues in meat samples.

A new solid phase extraction sorbent, based on poly(methacrylic acid) brushes-containing coordination polymer networks on monolith, was in-situ synthesized in a commercial syringe filter via surface grafting. Extraction of twenty model analytes, including nine sulfonamides, eight steroid hormones, and three quinolones, could be efficiently achieved by the monolithic hybrid filter due to multi-interactions. Through simple filtering steps, fast extraction (60 s of adsorption and 60 s of desorption) could be achieved. Furthermore, the monolithic hybrid filter was used to analyze the model compounds in chicken meat samples in combination with ultra-performance liquid chromatography-tandem mass spectrometry. Compared with other adsorption sorbents in reported literatures, the proposed monolithic hybrid filter allowed for shorter purification time, simplified sample pretreatment procedure, and comparable LODs and LOQs of 0.1-3 µg kg-1 and 0.4-10 µg kg-1, respectively. The recoveries for all analytes ranged from 83.9% to 103% with inter-day relative standard deviation lower than 10%. The results demonstrated that the developed analytical method was highly efficient and operationally convenient, and had a great potential for high throughput analysis of multi-residues.

Evidence from stable isotopes and 10Be for solar system formation triggered by a low-mass supernova.

About 4.6 billion years ago, some event disturbed a cloud of gas and dust, triggering the gravitational collapse that led to the formation of the solar system. A core-collapse supernova, whose shock wave is capable of compressing such a cloud, is an obvious candidate for the initiating event. This hypothesis can be tested because supernovae also produce telltale patterns of short-lived radionuclides, which would be preserved today as isotopic anomalies. Previous studies of the forensic evidence have been inconclusive, finding a pattern of isotopes differing from that produced in conventional supernova models. Here we argue that these difficulties either do not arise or are mitigated if the initiating supernova was a special type, low in mass and explosion energy. Key to our conclusion is the demonstration that short-lived 10Be can be readily synthesized in such supernovae by neutrino interactions, while anomalies in stable isotopes are suppressed.

New primary mechanisms for the synthesis of rare 9Be in early supernovae.

We present two new primary mechanisms for the synthesis of the rare nucleus (9)Be, both triggered by ν-induced production of (3)H followed by (4)He((3)H,γ)(7)Li in the He shells of core-collapse supernovae. For progenitors of ∼ 8M(⊙), (7)Li((3)H,n(0))(9)Be occurs during the rapid expansion of the shocked He shell. Alternatively, for ultra-metal-poor progenitors of ∼ 11-15 M(⊙), (7)Li(n,γ)(8)Li(n,γ)(9)Li(e(-)ν(e))(9)Be occurs with neutrons produced by (4)He(ν(e),e(+)n)(3)H, assuming a hard effective ν(e) spectrum from oscillations (which also leads to heavy element production through rapid neutron capture) and a weak explosion (so the (9)Be survives shock passage). We discuss the associated production of (7)Li and (11)B, noting patterns in LiBeB production that might distinguish the new mechanisms from others.

Supernova-driven outflows and chemical evolution of dwarf spheroidal galaxies.

We present a general phenomenological model for the metallicity distribution (MD) in terms of [Fe/H] for dwarf spheroidal galaxies (dSphs). These galaxies appear to have stopped accreting gas from the intergalactic medium and are fossilized systems with their stars undergoing slow internal evolution. For a wide variety of infall histories of unprocessed baryonic matter to feed star formation, most of the observed MDs can be well described by our model. The key requirement is that the fraction of the gas mass lost by supernova-driven outflows is close to unity. This model also predicts a relationship between the total stellar mass and the mean metallicity for dSphs in accord with properties of their dark matter halos. The model further predicts as a natural consequence that the abundance ratios [E/Fe] for elements such as O, Mg, and Si decrease for stellar populations at the higher end of the [Fe/H] range in a dSph. We show that, for infall rates far below the net rate of gas loss to star formation and outflows, the MD in our model is very sharply peaked at one [Fe/H] value, similar to what is observed in most globular clusters. This result suggests that globular clusters may be end members of the same family as dSphs.

Long, cold, early r process? Neutrino-induced nucleosynthesis in He shells revisited.

We revisit a ν-driven r-process mechanism in the He shell of a core-collapse supernova, finding that it could succeed in early stars of metallicity Z ≲ 10⁻³ Z(⊙), at relatively low temperatures and neutron densities, producing A ~ 130 and 195 abundance peaks over ~10-20 s. The mechanism is sensitive to the ν emission model and to ν oscillations. We discuss the implications of an r process that could alter interpretations of abundance data from metal-poor stars, and point out the need for further calculations that include effects of the supernova shock.

Flavor evolution of the neutronization neutrino burst from an O-Ne-Mg core-collapse supernova.

We present results of 3-neutrino flavor evolution simulations for the neutronization burst from an O-Ne-Mg core-collapse supernova. We find that nonlinear neutrino self-coupling engineers a single spectral feature of stepwise conversion in the inverted neutrino mass hierarchy case and in the normal mass hierarchy case, a superposition of two such features corresponding to the vacuum neutrino mass-squared differences associated with solar and atmospheric neutrino oscillations. These neutrino spectral features offer a unique potential probe of the conditions in the supernova environment and may allow us to distinguish between O-Ne-Mg and Fe core-collapse supernovae.

Neutrino mass hierarchy and stepwise spectral swapping of supernova neutrino flavors.

We examine a phenomenon recently predicted by numerical simulations of supernova neutrino flavor evolution: the swapping of supernova nu(e) and nu(mu,tau) energy spectra below (above) energy E(C) for the normal (inverted) neutrino mass hierarchy. We present the results of large-scale numerical calculations which show that in the normal neutrino mass hierarchy case, E(C) decreases as the assumed effective 2x2 vacuum nu(e)<==>nu(mu,tau) mixing angle (approximately theta13) is decreased. In contrast, these calculations indicate that E(C) is essentially independent of the vacuum mixing angle in the inverted neutrino mass hierarchy case. With a good neutrino signal from a future galactic supernova, the above results could be used to determine the neutrino mass hierarchy even if theta13 is too small to be measured by terrestrial neutrino oscillation experiments.

Coherent development of neutrino flavor in the supernova environment.

We calculate coherent neutrino and antineutrino flavor transformation in the supernova environment, for the first time including self-consistent coupling of intersecting neutrino and antineutrino trajectories. For neutrino mass-squared difference /deltam2/ = 3 x 10(-3) eV2 we find that in the normal (inverted) mass hierarchy the more tangentially-propagating (radially-propagating) neutrinos and antineutrinos can initiate collective, simultaneous medium-enhanced flavor conversion of these particles across broad ranges of energy and propagation direction. Accompanying alterations in neutrino and antineutrino energy spectra and fluxes could affect supernova nucleosynthesis and the expected neutrino signal.