Three-Dimensional Chiral Morphogenesis of Active Fluids.

Chirality is an essential nature of biological systems. However, it remains obscure how the handedness at the microscale is translated into chiral morphogenesis at the tissue level. Here, we investigate three-dimensional (3D) tissue morphogenesis using an active fluid theory invoking chirality. We show that the coordination of achiral and chiral stresses, arising from microscopic interactions and energy input of individual cells, can engender the self-organization of 3D papillary and helical structures. The achiral active stress drives the nucleation of asterlike topological defects, which initiate 3D out-of-plane budding, followed by rodlike elongation. The chiral active stress excites vortexlike topological defects, which favor the tip spheroidization and twisting of the elongated rod. These results unravel the chiral morphogenesis observed in our experiments of 3D organoids generated by human embryonic stem cells.

Dirac t-Boron Nitride Monolayer as an Appealing Binder-Free Anode for Alkali Metal Ion Batteries.

The development of universal anode materials with superlative electrochemical performance poses a great challenge for rechargeable alkali metal (AM) ion battery technologies. In the present work, the viability of the gapless Dirac t-BN (tetragonal boron nitride) monolayer as a lightweight binder-free anode has been systematically evaluated via comprehensive first-principles calculations. Aside from the desirable electronic conductivity, the t-BN monolayer exhibits an excellent ionic conductivity as well due to its moderate affinity for Li, Na, and K atoms with favorable in-plane barriers of 0.36, 0.18, and 0.19 eV, respectively. Meanwhile, the presence of B4N4 octagons allows the AM atoms to penetrate through the t-BN monolayer. Excitingly, the host material delivers an ultrahigh specific capacity up to 1080 mA h g-1 for Li, 5400 mA h g-1 for Na, and 2160 mA h g-1 for K in the wake of low mean open-circuit voltages of 0.033, 0.203, and 0.300 V at the half-cell level. According to the standard hydrogen electrode methodology, the energy densities are forecasted to be as large as 3240, 13500, and 5680 mW h g-1 for Li, Na, and K ion batteries, respectively, with robust thermal stability up to at least 400 K. The safety and cycling durability of the t-BN monolayer are jointly corroborated via the moderate mechanical strengths and ab initio molecular dynamics simulations at the maximum intercalated states, as well as via the small lattice changes and its ultrahigh tolerable ultimate tensile strain. These findings unambiguously promise that the t-BN monolayer can serve as an appealing candidate for anode applications in AM ion batteries.

Nucleon Energy Correlators for the Color Glass Condensate.

We demonstrate the recently proposed nucleon energy-energy correlator (NEEC) f_{EEC}(x,θ) can unveil the gluon saturation in the small-x regime in eA collisions. The novelty of this probe is that it is fully inclusive just like the deep-inelastic scattering (DIS), with no requirements of jets or hadrons but still provides an evident portal to the small-x dynamics through the shape of the θ distribution. We find that the saturation prediction is significantly different from the expectation of the collinear factorization.

First complete mitochondrial genomes of Ototretinae (Coleoptera, Lampyridae) with evolutionary insights into the gene rearrangement.

The subfamily Ototretinae represents an important and unusual lineage of fireflies. Here, we sequenced and annotated three mitogenomes for this subfamily, with two Stenocladius species and one Drilaster species as representatives. The mitogenome of Stenocladius exhibits a rearranged gene order between trnC and trnW caused by transposition, which is a novel finding in Lampyridae. Meanwhile, a long intergenic space (241 to 376 bp) exists between the two rearranged genes, and some remnants (23 bp) of trnW are present within this non-coding region. Moreover, phylogenetic analyses did not recover the monophyly of Ototretinae, in which Drilaster is shown at a basal lineage in Lampyridae, but Stenocladius seems more related to Luciolinae. Therefore, the gene rearrangement in Stenocladius is presumed to result from independent evolutionary events, suggesting that this genus should be placed in a separate lineage. Nevertheless, more representative mitogenomes from different groups are required to verify the present results.

Lactoferrin Attenuates Intestinal Barrier Dysfunction and Inflammation by Modulating the MAPK Pathway and Gut Microbes in Mice.

BACKGROUND: Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products) that induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear. OBJECTIVES: This study aimed to investigate the effects of LF on DON-induced intestinal dysfunction in mice, and its underlying protective mechanism. METHODS: Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh [peroral vehicle daily, commercial (C) diet]; LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by 2-factor ANOVA or Kruskal-Wallis test. RESULTS: The DON group exhibited lower final body weight (-12%), jejunal villus height (VH; -41%), and jejunal occludin expression (-36%), and higher plasma IL-1ß concentration (+85%) and jejunal Il1b mRNA expression (+98%) compared with the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal VH (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P < 0.05). Additionally, jejunal Il1b mRNA expression (-31%) and phosphorylation of p38 and extracellular signal regulated kinase 1/2 (-40% and - 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, the relative abundance of Clostridium XIVa (+181%) and colonic butyrate concentration (+53%) were greater in LF + DON compared with DON (P < 0.05). CONCLUSIONS: Our study highlights a promising antimycotoxin approach using LF to alleviate DON-induced intestinal dysfunction by modulating the mitogen-activated protein kinase pathway and gut microbial community in mice.

Targeted inhibition of PPARα ameliorates CLA-induced hypercholesterolemia via hepatic cholesterol biosynthesis reprogramming.

BACKGROUND & AIMS: Disruption of lipid metabolism is largely linked to metabolic disorders, such as hypercholesterolemia (HCL) and liver steatosis. While cholesterol metabolic re-programmers can serve as targets for relevant interventions. Here we explored the dietary conjugated linoleic acids (CLA)-induced HCL in mice and the molecular regulation behind it. METHODS: A high dose of CLA supplementation in the diet was used to induce HCL in mice and was found to cause a hyper-activated cholesterol biosynthesis programme in the liver, leading to cholesterol metabolism dysregulation. The effects of a small-molecule drug targeting PPARα, i.e., GW6471 were studied in vivo in mice fed diets with CLA supplementation for 28 days, and in primary hepatocytes derived from HCL-mice in vitro. RESULTS: We demonstrate that CLA induced HCL and liver steatosis through multiple pathways. Among which was the PPARα-mediated cholesterogenesis. It was found to cooperate with SREBP2 via binding to Hmgcr and Dhcr7 (genes encoding key enzymes of the cholesterol biosynthetic pathway) and recruits the histone marks H3K27ac and H3K4me1 and cofactors. PPARα inhibition disrupts its physical association with SREBP2 by blocking cobinding of PPARα and SREBP2 to the genomic DNA response element. We showed that NR RORγ functions as an essential mediator that facilitates the interaction of PPARα and SREBP2 to modulate the cholesterol biosynthesis genes expression. CONCLUSIONS: Our study unravels that the small-molecule compound GW6471 exerts an attractive therapeutic effect for CLA-induced HCL, involving multiple pathways with the "PPARα-RORγ-SREBP2" being a potential complex player in this hepatic cholesterol biosynthesis programming.

Co-option of PPARα in the regulation of lipogenesis and fatty acid oxidation in CLA-induced hepatic steatosis.

Nonalcoholic-fatty-liver-disease (NAFLD) is the result of imbalances in hepatic lipid partitioning and is linked to dietary factors. We demonstrate that conjugated linoleic acid (CLA) when given to mice as a dietary supplement, induced an enlarged liver, hepatic steatosis, and increased plasma levels of fatty acid (FA), alanine transaminase, and triglycerides. The progression of NAFLD and insulin resistance was reversed by GW6471 a small-molecule antagonist of peroxisome proliferator-activated receptor α (PPARα). Transcriptional profiling of livers revealed that the genes involved in FA oxidation and lipogenesis as two core gene programs controlled by PPARα in response to CLA and GW6471 including Acaca and Acads. Bioinformatic analysis of PPARα ChIP-seq data set and ChIP-qPCR showed that GW6471 blocks PPARα binding to Acaca and Acads and abolishes the PPARα-mediated local histone modifications of H3K27ac and H3K4me1 in CLA-treated hepatocytes. Thus, our findings reveal a dual role of PPARα in the regulation of lipid homeostasis and highlight its druggable nature in NAFLD.

Maternal high-protein diet modulates hepatic growth axis in weaning piglets by reprogramming the IGFBP-3 gene.

PURPOSE: The aim of this study was to investigate the effects of maternal high dietary protein intake on the hepatic growth axis in offspring. METHODS: Fourteen primiparous purebred Meishan sows were fed either a standard-protein (SP, n = 7) diet or a high-protein (HP, 150% of SP, n = 7) diet during pregnancy. Offspring (one male and one female per group, n = 14) on day 70 of the embryonic stage and on days 1, 35 and 180 after birth were selected, weighed and killed. Serum samples were analyzed for Tch, insulin and insulin-like growth factor-binding protein 3 (IGFBP-3) levels. Liver samples were analyzed for IGFBP-3 and IGF-I mRNA expression by qRT-PCR and for IGFBP-3, IGF1R and growth hormone receptor (GHR) protein expression by Western blotting. The underlying mechanism of IGFBP-3 regulation was determined by methylated DNA immunoprecipitation (MeDIP) and chromatin immunoprecipitation (ChIP). RESULTS: High-protein exposure resulted in significantly higher body and liver weights of piglets, and it increased their serum T3 and T4 levels at birth and/or at weaning. Furthermore, the IGFBP-3 protein content in the liver and serum was significantly reduced in the HP-exposed weaning piglets, whereas at the transcriptional level IGFBP-3 mRNA expression was downregulated in the livers of HP group piglets. Finally, DNA hypermethylation and higher enrichment of the histone repressive marks H3K27me3 and H3K9me3 were observed. CONCLUSIONS: Taken together, these results suggest that a maternal high-protein diet during gestation epigenetically reprograms IGFBP-3 gene expression to modulate the hepatic growth axis in weaning piglets.

Genistein Binding to Copper(II)-Solvent Dependence and Effects on Radical Scavenging.

Genistein, but not daidzein, binds to copper(II) with a 1:2 stoichiometry in ethanol and with a 1:1 stoichiometry in methanol, indicating chelation by the 5-phenol and the 4-keto group of the isoflavonoid as demonstrated by the Jobs method and UV-visible absorption spectroscopy. In ethanol, the stability constants had the value 1.12 × 1011 L²âˆ™mol-2 for the 1:2 complex and in methanol 6.0 × 105 L∙mol-1 for the 1:1 complex at 25 °C. Binding was not detected in water, as confirmed by an upper limit for the 1:1 stability constant of K = 5 mol-1 L as calculated from the difference in solvation free energy of copper(II) between methanol and the more polar water. Solvent molecules compete with genistein as demonstrated in methanol where binding stoichiometry changes from 1:2 to 1:1 compared to ethanol and methanol/chloroform (7/3, v/v). Genistein binding to copper(II) increases the scavenging rate of the stable, neutral 2,2-diphenyl-1-picrylhydrazyl radical by more than a factor of four, while only small effects were seen for the short-lived but more oxidizing ß-carotene radical cation using laser flash photolysis. The increased efficiency of coordinated genistein is concluded to depend on kinetic rather than on thermodynamic factors, as confirmed by the small change in reduction potential of -0.016 V detected by cyclic voltammetry upon binding of genistein to copper(II) in methanol/chloroform solutions.

Expression of heat shock proteins 27 and 72 correlates with specific commensal microbes in different regions of porcine gastrointestinal tract.

The gastrointestinal (GI) tract of mammals is inhabited by trillions of microorganisms, resulting in exceedingly complex networking. The interaction between distinct bacterial species and the host immune system is essential in maintaining homeostasis in the gut ecosystem. For instance, the gut commensal microbiota dictates intestinal mucosa maturation and its abundant immune components, such as cytoprotective heat shock proteins (HSP). Here we examined physiological expression of HSP in the normal porcine GI tract and found it to be gut region- and cell type-specific in response to dietary components, microbes, and microbial metabolites to which the mucosa surface is exposed. Correlations between HSP72 expression and ileal Lactobacillus spp. and colonic clostridia species, and between HSP27 expression and uronic acid ingestion, were important interplays identified here. Thus this study provides novel insights into host-microbe interactions shaping the immune system that are modifiable by dietary regime.

Dose-dependent effects of Lactobacillus rhamnosus on serum interleukin-17 production and intestinal T-cell responses in pigs challenged with Escherichia coli.

The mechanism underlying the dose effect of probiotics on ameliorating diarrhea has not been fully elucidated. Here, low (1 × 10(9) CFU/ml) or high (1 × 10(11) CFU/ml) doses of Lactobacillus rhamnosus ATCC 7469 were administered orally to piglets for 1 week before F4 (K88)-positive enterotoxigenic Escherichia coli (F4(+) ETEC) challenge. Administration of a low, but not a high, dose of L. rhamnosus decreased the percentage of CD3(+) CD4(+) CD8(-) T cells in the peripheral blood. Notably, transiently increased serum concentrations of interleukin-17A (IL-17A) were observed after F4(+) ETEC challenge in pigs pretreated with a high dose of L. rhamnosus. Administration of L. rhamnosus increased the percentage of the small intestinal lamina propria CD3(+) CD4(+) CD8(-) cells and Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells. The percentage of ileal intraepithelial CD3(+) CD4(-) CD8(+) cells increased only in the high-dose piglets. Administration of L. rhamnosus downregulated expression of ileal IL-17A after F4(+) ETEC challenge but had no effect on expression of gamma interferon (IFN-γ), IL-12, IL-4, and FOXP3 mRNA in the small intestine. Expression of jejunal IL-2, ileal transforming growth factor ß1 (TGF-ß1), and ileal IL-10 was upregulated in the low-dose piglets after F4(+) ETEC challenge. Our findings suggest that amelioration of infectious diarrhea in piglets by L. rhamnosus is associated with the generation of lamina propria CD3(+) CD4(+) CD8(-) T cells, the expansion of Peyer's patch CD3(+) CD4(-) CD8(-) and CD3(-) CD4(-) CD8(+) cells, and the attenuation of F4(+) ETEC-induced increase in CD3(+) CD4(+) CD8(+) T cells in the small intestine. However, consumption of high doses of L. rhamnosus may increase levels of serum IL-17A after F4(+) ETEC challenge, thus eliciting a strong proinflammatory response.

Alternatives to antibiotics in pig production: looking through the lens of immunophysiology.

In the livestock production system, the evolution of porcine gut microecology is consistent with the idea of "The Hygiene Hypothesis" in humans. I.e., improved hygiene conditions, reduced exposure to environmental microorganisms in early life, and frequent use of antimicrobial drugs drive immune dysregulation. Meanwhile, the overuse of antibiotics as feed additives for infectious disease prevention and animal growth induces antimicrobial resistance genes in pathogens and spreads related environmental pollutants. It justifies our attempt to review alternatives to antibiotics that can support optimal growth and improve the immunophysiological state of pigs. In the current review, we first described porcine mucosal immunity, followed by discussions of gut microbiota dynamics during the critical weaning period and the impacts brought by antibiotics usage. Evidence of in-feed additives with immuno-modulatory properties highlighting probiotics, prebiotics, and phytobiotics and their cellular and molecular networking are summarized and reviewed. It may provide insights into the immune regulatory mechanisms of antibiotic alternatives and open new avenues for health management in pig production.

Natural products for Gut-X axis: pharmacology, toxicology and microbiology in mycotoxin-caused diseases.

Introduction: The gastrointestinal tract is integral to defending against external contaminants, featuring a complex array of immunological, physical, chemical, and microbial barriers. Mycotoxins, which are toxic metabolites from fungi, are pervasive in both animal feed and human food, presenting substantial health risks. Methods: This review examines the pharmacological, toxicological, and microbiological impacts of natural products on mycotoxicosis, with a particular focus on the gut-x axis. The analysis synthesizes current understanding and explores the role of natural products rich in polysaccharides, polyphenols, flavonoids, and saponins. Results: The review highlights that mycotoxins can disrupt intestinal integrity, alter inflammatory responses, damage the mucus layer, and disturb the bacterial balance. The toxins' effects are extensive, potentially harming the immune system, liver, kidneys, and skin, and are associated with serious conditions such as cancer, hormonal changes, genetic mutations, bleeding, birth defects, and neurological issues. Natural products have shown potential anticancer, anti-tumor, antioxidant, immunomodulatory, and antitoxic properties. Discussion: The review underscores the emerging therapeutic strategy of targeting gut microbial modulation. It identifies knowledge gaps and suggests future research directions to deepen our understanding of natural products' role in gut-x axis health and to mitigate the global health impact of mycotoxin-induced diseases.

Lithocholic Acid Alleviates Deoxynivalenol-Induced Inflammation and Oxidative Stress via PPARγ-Mediated Epigenetically Transcriptional Reprogramming in Porcine Intestinal Epithelial Cells.

Deoxynivalenol (DON) is a common mycotoxin that induces intestinal inflammation and oxidative damage in humans and animals. Given that lithocholic acid (LCA) has been suggested to inhibit intestinal inflammation, we aimed to investigate the protective effects of LCA on DON-exposed porcine intestinal epithelial IPI-2I cells and the underlying mechanisms. Indeed, LCA rescued DON-induced cell death in IPI-2I cells and reduced DON-stimulated inflammatory cytokine levels and oxidative stress. Importantly, the nuclear receptor PPARγ was identified as a key transcriptional factor involved in the DON-induced inflammation and oxidative stress processes in IPI-2I cells. The PPARγ function was found compromised, likely due to the hyperphosphorylation of the p38 and ERK signaling pathways. In contrast, the DON-induced inflammatory responses and oxidative stress were restrained by LCA via PPARγ-mediated reprogramming of the core inflammatory and antioxidant genes. Notably, the PPARγ-modulated transcriptional regulations could be attributed to the altered recruitments of coactivator SRC-1/3 and corepressor NCOR1/2, along with the modified histone marks H3K27ac and H3K18la. This study emphasizes the protective actions of LCA on DON-induced inflammatory damage and oxidative stress in intestinal epithelial cells via PPARγ-mediated epigenetically transcriptional reprogramming, including histone acetylation and lactylation.

[Interrelation between the hypothalamic arcuate nucleus and the bone variation of osteoporosis in rats].

This study investigated the interrelation between the hypothalamic arcuate nucleus (ARC) and the bone variation of osteoporosis in rats. Four animal models of ovariectomy-induced osteoporosis (OVX), glucocorticoid-induced osteoporosis (GIOP), retinoic acid-induced osteoporosis (RAOP) and senile osteoporosis (SOP) were used to study the influence of osteoporosis on ARC. Ovariectomized rats were further treated with thymopeptide, ciclosporin and exercise respectively to detect the changes of ARC nerve cells number. The results showed that: (1) The OVX, GIOP, RAOP and SOP models were successfully established, showing osteoporosis as well as decrease of the number of ARC nerve cells; (2) Thymopeptide and exercise respectively alleviated the bone loss induced by ovariectomy, accompanied by increase of the number of ARC nerve cells, while ciclosporin further increased the bone loss of ovariectomized rats, accompanied by further decrease of the number of ARC nerve cells. These results suggest that there is a close interrelationship between ARC and osteoporosis in rat. There is a hypothalamus-pituitary-bone (HPB) axis, and HPB axis regulates the mechanism of osteoporosis in rats.

First record of Noctitrella Gorochov from China, with description of a new species (Orthoptera: Gryllidae: Podoscirtinae).

The genus Noctitrella Gorochov, 1990 is recorded to China for the first time. A new species is described and illustrated, N. denticulata sp. nov. (CHINA: Yunnan). A key to and a distribution map of the known species of this genus in the world are presented.

Lactoferrin Restores the Deoxynivalenol-Impaired Spermatogenesis and Blood-Testis Barrier Integrity via Improving the Antioxidant Capacity and Modifying the Cell Adhesion and Inflammatory Response.

Deoxynivalenol (DON) is among the most prevalent contaminants in cereal crops and has been demonstrated to impair male spermatogenesis and induce oxidative stress, testicular apoptosis, and disruption of the blood-testis barrier (BTB). Lactoferrin (LF) is an iron-binding glycoprotein with multifunctions including anti-inflammation and antioxidation. Thus, this study aimed to investigate the effects of LF on the spermatogenesis and integrity of the BTB in DON-exposed mice. Thirty-two male mice were allotted to four groups for a 35-day feeding period: vehicle (basal diet), DON (12 mg/kg), LF (10 mg/d, p.o.), and DON + LF. The results showed that DON induced vacuolization of the spermatogenic epithelium, broke the adhesion junction between Sertoli cells and spermatids established by N-cadherin and induced testicular oxidative stress. LF administration restored sperm production, attenuated the DON-induced oxidative stress and reduced the breakages in adhesion junction. DON exposure enhanced the protein expression of occludin. Transcriptional profiling of the testis observed a disturbance in the expression profiles of cell adhesion and inflammatory response genes, and LF administration reversed these gene expressions. Furthermore, down-regulated signaling pathways, including the apical junction, TNFα signaling via NF-κB, and TGF-ß in the DON group were observed. These were restored by LF. Enrichment analysis between DON + LF group and vehicle also confirmed the absence of these pathways. These findings indicated that LF eliminated the DON-induced detriment to spermatogenesis and cell connections between Sertoli cells and spermatids via improving antioxidant capacity and modifying the inflammatory response and cell adhesion genes.

Sodium Butyrate Ameliorates Deoxynivalenol-Induced Oxidative Stress and Inflammation in the Porcine Liver via NR4A2-Mediated Histone Acetylation.

Mycotoxin-induced liver injury is often accompanied by oxidative stress (OS) and inflammation. This research aimed to explore the potential mechanism of sodium butyrate (NaBu) in modulating hepatic anti-oxidation and anti-inflammation pathways in deoxynivalenol (DON)-exposed piglets. The results show that DON induced liver injury, increased mononuclear cell infiltration, and decreased serum total protein and albumin concentrations. Transcriptomic analysis revealed that reactive oxygen species (ROS) and TNF-α pathways were highly activated upon DON exposure. This is associated with disturbed antioxidant enzymes and increased inflammatory cytokines secretion. Importantly, NaBu effectively reversed the alterations caused by DON. Mechanistically, the ChIP-seq result revealed that NaBu strongly depressed DON-increased enrichment of histone mark H3K27ac at the genes involved in ROS and TNF-α-mediated pathways. Notably, we demonstrated that nuclear receptor NR4A2 was activated by DON and remarkably recovered with the treatment of NaBu. In addition, the enhanced NR4A2 transcriptional binding enrichments at the promoter regions of OS and inflammatory genes were hindered by NaBu in DON-exposed livers. Consistently, elevated H3K9ac and H3K27ac occupancies were also observed at the NR4A2 binding regions. Taken together, our results indicated that a natural antimycotic additive, NaBu, could mitigate hepatic OS and inflammatory responses, possibly via NR4A2-mediated histone acetylation.

Curcumin derived from medicinal homologous foods: its main signals in immunoregulation of oxidative stress, inflammation, and apoptosis.

It has been for thousands of years in China known medicinal homologous foods that can be employed both as foods and medicines to benefit human and animal health. These edible herbal materials perform divert roles in the regulation of metabolic disorders, cancers, and immune-related diseases. Curcumin, the primary component derived from medicinal homologous foods like curcuma longa rhizome, is reported to play vital actions in organic activities, such as the numerous pharmacological functions including anti-oxidative stress, anti-inflammation and anti/pro-apoptosis in treating various diseases. However, the potential mechanisms of curcumin-derived modulation still need to be developed and attract more attention worldwide. Given that these signal pathways are enrolled in important bioactive reactions, we collected curcumin's last achievements predominantly on the immune-regulation signals with the underlying targetable strategies in the last 10 years. This mini-review will be helpful to accelerate curcumin and other extracts from medicinal homologous foods use in future human clinical applications.

Lactoferrin Relieves Deoxynivalenol-Induced Oxidative Stress and Inflammatory Response by Modulating the Nrf2/MAPK Pathways in the Liver.

Deoxynivalenol (DON), one of the most common mycotoxins contaminating food and feed, has been shown to induce hepatotoxicity. Lactoferrin (LF) enriched in human milk is a critical functional food component and performs the hepatoprotection function. Here, we aimed to explore whether dietary LF supplementation can protect from DON-induced hepatotoxicity and uncover the underlying mechanism in mice and alpha mouse liver 12 (AML12) hepatocytes. In vivo results revealed that LF alleviated DON-induced liver injury, reflected by repairing the hepatic histomorphology and decreasing the plasma alanine aminotransferase (ALT) level and the number of blood white blood cells (WBC) and neutrophils (Neu). Moreover, LF decreased the hepatic reactive oxygen species (ROS) and malondialdehyde (MDA) accumulation and enhanced the hepatic GSH-px activity and protein expression of Nrf2 and GPX4 to reverse the DON-induced hepatic oxidative stress. Furthermore, LF downregulated the pro-inflammatory-response-related gene expressions (IL1ß, TNFα, and Tlr4) and the phosphorylation levels of IKK, IκBα, and p38 in the liver of DON-exposed mice. Additionally, in vitro studies confirmed that LF ameliorated the DON-induced oxidation-reduction imbalance, inflammatory responses, and associated core modulators of the Nrf2 and MAPK pathways in DON-induced hepatotoxicity. In conclusion, LF performs hepatic antioxidative and anti-inflammatory functions by regulating the Nrf2/MAPK signaling pathways, thus reducing DON-induced hepatotoxicity.