Ultrafine Iridium Nanoparticles Anchored on Co-Based Metal-Organic Framework Nanosheets for Robust Hydrogen Evolution in Alkaline Media.

A highly promising electrocatalyst has been designed and prepared for the hydrogen evolution reaction (HER). This involves incorporating well-dispersed Ir nanoparticles into a cobalt-based metal-organic framework known as Co-BPDC [Co(bpdc)(H2O)2, BPDC: 4,4'-biphenyldicarboxylic acid]. Ir@Co-BPDC demonstrates exceptional HER activity in alkaline media, surpassing both commercial Pt/C and recent noble-metal catalysts. Theoretical results indicate that electron redistribution, induced by interfacial bonds, optimizes the adsorption energy of water and hydrogen, thereby enhancing our understanding of the superior properties of Ir@Co-BPDC for HER.

Nickel Single-Atom Catalyst Boosts Electrochemiluminescence of Graphitic Carbon Nitride for Sensitive Detection of HBV DNA.

Owing to excellent catalytic activity, single-atom catalysts (SACs) have recently attracted considerable research interest in the electrochemiluminescence (ECL) field. However, the applications of SACs are mostly limited to conventional luminol ECL system. Hence, it is necessary to explore the application of SACs in more ECL systems. In this work, nickel single-atom catalysts (Ni SACs) were successfully applied in the graphitic carbon nitride (g-C3N4)-H2O2 ECL system to significantly enhance its cathodic emission. Notably, g-C3N4 acted not only as an ECL luminophore but also as a support to anchor Ni SACs. Ni SACs can significantly activate H2O2 to produce abundant OH• radicals for enhancing the cathodic ECL emission of g-C3N4. Ni SACs-anchored g-C3N4 (Ni SACs@g-C3N4) had a 10-fold enhanced ECL intensity as compared to g-C3N4. Finally, the Ni SACs@g-C3N4-H2O2 ECL system was developed to detect hepatitis B virus (HBV) DNA by incorporating an entropy-driven DNA walking machine-assisted CRISPR-Cas12a amplification strategy. The constructed biosensor exhibited excellent detection performance for HBV DNA with a limit of detection as low as 17 aM. This work puts forward a new idea for enhancing the cathodic ECL of g-C3N4-H2O2 and expands the application of SACs in the ECL system.

Coreactant-free dual-emitting conjugated polymer for ratiometric electrochemiluminescence detection of SARS-CoV-2 RdRp gene.

Constructing mono-luminophor-based electrochemiluminescence (ECL) ratio system is a great challenge due to the limitations of the luminescent species with dual-signal-output, luminescence efficiency and coreactant. This work developed carboxyl-functionalized poly[9,9-bis(3'-(N,N-dimethylamino) propyl)-2,7-fluorene]-alt-2,7-(9,9 dioctylfluorene)] nanoparticles(PFN NPs) as dual-emitting luminophors, which can synchronously output strong cathodic and anodic ECL signals without any exogenous coreactants. The inherent molecular structure enabled efficient intramolecular electron transfer between tertiary amine groups and backbone of PFN to generate strong cathodic and anodic ECL emission. Particularly, H+ in aqueous solution played an irreplaceable role for cathodic ECL emission. The silver nanoparticles (AgNPs) were developed as signal regulator because of their excellent hydrogen evolution reaction (HER) activity, which significantly quenched the cathodic signal while kept the anodic signal unchanged. The dual-emitting PFN NPs cleverly integrated signal regulator AgNPs and bicyclic strand displacement amplification (SDA) to construct a coreactant-free mono-luminophor-based ratiometric ECL sensing for SARS-CoV-2 RdRp gene assay. The strong dual-emitting of PFN NPs and excellent quenching effect of AgNPs on cathodic emission endowed the biosensor with a high detection sensitivity, and the detection limit was as low as 39 aM for RdRp gene. The unique dual-emitting properties of PFN NPs open up a new path to construct coreactant-free mono-luminophor-based ECL ratio platform, and excellent HER activity of AgNPs offers some new thoughts for realizing ECL signal changes.

An intelligent smartphone-test strip detection platform for rapid and on-site sensing of benzoyl peroxide in flour samples.

Benzoyl peroxide (BPO) is a commonly used flour whitener, but its excessive usage can have adverse effects on human health, such as nutrient loss, vitamin deficiencies and certain diseases. In this study, a europium metal organic framework (Eu-MOF) fluorescence probe was prepared, which exhibited a strong fluorescence emission at 614 nm upon excitation at 320 nm, with a high quantum yield of 8.11%. The red fluorescence of the probe could be effectively quenched by BPO through the inner filter effect (IFE) and photoinduced electron transfer (PET) mechanism. The detection process offered several advantages, including a wide linear range of 0-0.95 mM, a low detection limit of 66 nM and a fast fluorescence response of 2 min. Furthermore, an intelligent detection platform was designed to enhance the practical application of the detection method. This platform combined the portability and visuality of a traditional test strip with the color recognition capability of a smartphone, allowing for the visualization and quantitative detection of BPO in a convenient and user-friendly manner. The detection platform was successfully applied to the analysis of BPO in real flour samples with satisfactory recoveries (99.79%-103.94%), suggesting a promising strategy for the rapid and on-site detection of BPO in food samples.

Effect of Two Particle Sizes of Nano Zinc Oxide on Growth Performance, Immune Function, Digestive Tract Morphology, and Intestinal Microbiota Composition in Broilers.

The effects of dietary supplementation with two particle sizes of nano zinc oxide (ZnO) on growth performance, immune function, intestinal morphology, and the gut microbiome were determined in a 42-day broiler chicken feeding experiment. A total of 75 one-day-old Arbor Acres broilers were randomized and divided into three groups with five replicates of five chicks each, including the conventional ZnO group (NC), the nano-ZnO group with an average particle size of 82 nm (ZNPL), and the nano-ZnO group with an average particle size of 21 nm (ZNPS). Each group was supplemented with 40 mg/kg of ZnO or nano-ZnO. Our results revealed that birds in the ZNPS group had a higher average daily gain and a lower feed-to-gain ratio than those in the NC group. ZNPS significantly increased the thymus index and spleen index, as well as the levels of serum metallothionein (MT), superoxide dismutase (SOD), and lysozyme (LZM). The ZNPS treatments reduced interleukin (IL)-1ß and tumor necrosis factor-alpha (TNF-α) levels and increased IL-2 and interferon (IFN)-γ levels compared to that in the NC group. Additionally, compared with the birds in the NC group, those in the nano-ZnO group had a higher villus height to crypt depth ratio of the duodenum, jejunum, and ileum. Bacteroides increased in the ZNPS group at the genus level. Further, unidentified_Lachnospiraceae, Blautia, Lachnoclostridium, unidentified_Erysipelotrichaceae, and Intestinimonas were significantly increased in the ZNPL group. In conclusion, nano-ZnO improved the growth performance, promoted the development of immune organs, increased nonspecific immunity, improved the villus height to crypt depth ratio of the small intestine, and enriched the abundance of beneficial bacteria. Notably, the smaller particle size (21 nm) of nano-ZnO exhibited a more potent effect.

The Universally Conserved Unconventional G Protein YchF Is Critical for Growth and Stress Response.

The ancient guanine nucleotide-binding (G) proteins are a group of critical regulatory and signal transduction proteins, widely involved in diverse cellular processes of all kingdoms of life. YchF is a kind of universally conserved novel unconventional G protein that appears to be crucial for growth and stress response in eukaryotes and bacteria. YchF is able to bind and hydrolyze both adenine nucleoside triphosphate (ATP) and guanosine nucleoside triphosphate (GTP), unlike other members of the P-loop GTPases. Hence, it can transduce signals and mediate multiple biological functions by using either ATP or GTP. YchF is not only a nucleotide-dependent translational factor associated with the ribosomal particles and proteasomal subunits, potentially bridging protein biosynthesis and degradation, but also sensitive to reactive oxygen species (ROS), probably recruiting many partner proteins in response to environmental stress. In this review, we summarize the latest insights into how YchF is associated with protein translation and ubiquitin-dependent protein degradation to regulate growth and maintain proteostasis under stress conditions.

Effects of anti-stress agents on the growth performance and immune function in broiler chickens with vaccination-induced stress.

The aim of this study was to evaluate the effects of anti-stress agents on the growth performance and immune function of broilers under immune stress conditions induced by vaccination. A total of 128, 1-day-old Arbor Acres broilers were randomly divided into four groups. Group normal control (NC) was the control group. Group vaccination control (VC), T 0.5%, and T 1% were the treatment groups, which were nasally vaccinated with two doses of the Newcastle disease virus (NDV) vaccine. The chicks in groups T 0.5% and T 1% were fed conventional diets containing 0.5% and 1% anti-stress agents. Thereafter, these broilers were slaughtered on 1, 7, 14, and 21 days post-vaccination. The results indicated that anti-stress agents could significantly reduce serum adrenocorticotropic hormone (ACTH) (P < 0.01) and cortisol (CORT) (P < 0.05) levels, and improve the growth performance (P < 0.05) and immune function of broilers (P < 0.05); However, the levels of malondialdehyde (MDA) (P < 0.05) were decreased, and the decreased total antioxidant capacity (T-AOC) (P < 0.01) levels mediated by vaccination were markedly improved. In addition, anti-stress agents could attenuate apoptosis in spleen lymphocytes (P < 0.01) by upregulating the ratio of Bcl-2 to BAX (P < 0.01) and downregulating the expression of caspase-3 and -9 (P < 0.01), which might be attributed to the inhibition of the enzymatic activities of caspase-3 and -9 (P < 0.05). In conclusion, anti-stress agents may improve growth performance and immune function in broilers under immune-stress conditions.RESEARCH HIGHLIGHTS Investigation of effects and mechanism of immune stress induced by vaccination.Beneficial effect of anti-stress agents on growth performance, immune function, oxidative stress, and regulation of lymphocyte apoptosis.Demonstration of the effects of apoptosis on immune function in the organism.

Ameliorative effect of betulinic acid against zearalenone exposure triggers testicular dysfunction and oxidative stress in mice via p38/ERK MAPK inhibition and Nrf2-mediated antioxidant defense activation.

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin, which mainly contaminates grains and has estrogen-like effects on the reproductive system. Betulinic acid (BA), a natural lupane-type pentacyclic triterpene, has anti-oxidative and anti-inflammatory properties. This study aimed to investigate whether BA alleviates ZEA-induced testicular damage and explore the possible mechanism. Here, BA ameliorated testicular damage by mitigating the disordered arrangement of seminiferous tubules, the exfoliation of lumen cells, and the increase of cell apoptosis caused by ZEA. Meanwhile, BA alleviated ZEA-triggered testicular damage by restoring hormone levels and sperm motility, and reconstructing the blood-testis-barrier. Moreover, BA alleviated ZEA-exposed testicular oxidative stress by activating Nrf2 pathway. Furthermore, BA moderated ZEA-evoked testicular inflammation by inhibiting p38/ERK MAPK pathway. Overall, our results revealed that BA has a therapeutic protective effect on ZEA-induced testicular injury and oxidative stress via p38/ERK MAPK inhibition and Nrf2-mediated antioxidant defense activation, which provides a viable alternative to alleviate ZEA-induced male reproductive toxicology.

Betulinic acid attenuates cognitive dysfunction, oxidative stress, and inflammation in a model of T-2 toxin-induced brain damage.

T-2 toxin is a mycotoxin that has harmful effects on the immune system and cognitive function. Betulinic acid (BA) is a plant-derived pentacyclic lupane-type triterpenoid which possesses a wide spectrum of bioactivities. The study was aimed to explore whether BA has a protective effect on cognitive impairment and oxidative stress caused by T-2 toxin. BA was suspended in 1% soluble starch by continuous intragastric administration for 14 days, then the brain damage in mice was induced by a single intraperitoneal injection of T-2 toxin (4 mg/kg). It was found that BA alleviated the reduction of discrimination index in T-2 toxin-treated mice, and enhanced dopamine (DA), 5-hydroxytryptamine (5-HT), and acetylcholine (ACH) levels of brain neurotransmitter. Meanwhile, BA pretreatment ameliorated oxidative stress through increase of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione (GSH) levels, and inhibition of the generation of reactive oxygen species (ROS) and malondialdehyde (MDA) in the brain of mice exposed to T-2 toxin. Moreover, BA reduced brain hemorrhage and ecchymosis, improved the mitochondrial morphology, enriched the number of organelles, and inhibited cell apoptosis in brain challenged with T-2 toxin. Furthermore, BA inhibited mRNA expression of pro-inflammatory cytokines such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) as well as enhanced mRNA expression of anti-inflammatory cytokine such as IL-10 in the brain of T-2 toxin-triggered mice. Therefore, BA could improve the cognitive function, enhance the antioxidant capacity, and inhibit the secretion of proinflammatory cytokines in brain, thereby playing a preventive and protective role against brain damage caused by T-2 toxin.

Purified diet versus whole food diet and the inconsistent results in studies using animal models.

In animal models, purified diets (PDs) and whole food diets (WFDs) are used for different purposes. In similar studies, different dietary patterns may lead to inconsistent results. The aim of this study was to evaluate and compare the effects of WFDs and PDs on changes in the metabolism of mice. We found that different dietary patterns produced different results in lipid metabolism experiments. Compared with those of the PD-fed mice, the WFD-fed mice had higher body weights and serum glucose, serum lipid, and liver lipid levels (p < 0.01), as well as low glucose tolerance (p < 0.01) and insulin sensitivity (p < 0.05). The body weight and fasting blood glucose increased by 20% in the WFD-fed mice, and the white adipose tissue weight increased by ∼50%. The WFD-fed mice also had a comparatively higher abundance of Lactobacillus, Turicibacter, Bifidobacterium, Desulfovibrio, and Candidatus saccharimonas (p < 0.01), which were positively correlated with lipid accumulation. Dietary patterns should be chosen cautiously in studies that use rodents as models. Inappropriate selection of animal dietary patterns may lead to experimental systematic errors and paradoxical results.

Structural comparison of unconventional G protein YchF with heterotrimeric G protein and small G protein.

Guanine nucleotide-binding (G) proteins, namely, phosphate-binding (P) loop GTPases, play a critical role in life processes among different species. Based on the structural characteristics, G proteins can be divided into heterotrimeric G proteins, small G proteins and multiple unique unconventional G proteins. The highly conserved unconventional G protein YchF is composed of a core G domain, an inserted coiled-coil domain, and a TGS domain from the N-terminus to the C-terminus. In this review, we compared the structural characteristics of the G domain in rice OsYchF1 with those of Rattus norvegicus heterotrimeric G protein α-subunit and human small G protein Ras-related G protein C and analyzed the binding modes of these G proteins with GTP or ATP by performing molecular dynamics simulations. In summary, it will provide new insights into the enormous diversity of biological function of G proteins.

Two Co(II)/Ni(II) complexes based on nitrogenous heterocyclic ligands as high-performance electrocatalysts for the hydrogen evolution reaction.

Two transition metal complexes {[Co2(bpda)4(H2O)2]·4H2O}n(Co-1) and {[Ni(bpda)2(H2O)2]·2H2O}(Ni-2) (H2bpda = 2,2'-bipyridine-4,4'-dicarboxylic acid) have been synthesized by a hydrothermal method and characterized. These two compounds can be explored as stable electrocatalysts in the hydrogen evolution reaction (HER) using two important parameters: the overpotential and Tafel slope (TS). Electrochemical studies suggest that the reaction kinetics of a Co-1 catalyst is more favorable than that of a Ni-2 catalyst. Co-1 exhibits better HER performance with an overpotential of 182 mV at a current density of 10 mA cm-2, a small TS of 87.21 mV dec-1 and superior long-term durability (of up to 3000 cycles). Structural analysis shows that its catalytic activity is improved due to the two mixed valence cobalt ions and the pore structure formed by hydrogen bonds in Co-1, which is different from that of Ni-2. In addition, the mechanism of the HER is also explained theoretically by DFT molecular orbital and free energy calculations in this article.

A turn-off Eu-MOF@Fe2+ sensor for the selective and sensitive fluorescence detection of bromate in wheat flour.

A new europium metal-organic framework (Eu-MOF) was prepared by simple hydrothermal method. The product exhibited intense red fluorescence, long fluorescence lifetime (0.454 ms) and excellent fluorescence stability. The fluorescence titration result showed that Fe3+ could completely quench the fluorescence of Eu-MOF, while the fluorescence quenching effect of Fe2+ or bromate was negligible. Considering the strong oxidizing property of bromate, a "turn off" Eu-MOF@Fe2+ sensor toward bromate was designed by generating Fe3+ due to the redox reaction. The results showed that the sensor displayed a wide linear range (0-0.2 mM), high sensitivity (LOD = 3.7 × 10-6 mol/L), good selectivity and resistant to possible interferences in real four sample. Furthermore, the detection mechanism was investigated by PXRD, XPS and UV-Vis methods. More importantly, the Eu-MOF@Fe2+ sensor was further applied to detect bromate in wheat flour with satisfactory recovery (95.30%-104.38%) and accuracy (RSD < 2.85%). These results suggest that Eu-MOF@Fe2+ can be used as a potential sensor to detect bromate in food industry.

Benzyl Isothiocyanate, a Vegetable-Derived Compound, Induces Apoptosis via ROS Accumulation and DNA Damage in Canine Lymphoma and Leukemia Cells.

Treatment of neoplastic diseases in companion animals is one of the most important problems of modern veterinary medicine. Given the growing interest in substances of natural origin as potential anti-cancer drugs, our goal was to examine the effectiveness of benzyl isothiocyanate (BITC), a compound found in cruciferous vegetables, against canine lymphoma and leukemia. These are the one of the most common canine cancer types, and chemotherapy is the only treatment option. The study involved established cell lines originating from various hematopoietic malignancies: CLBL-1, GL-1, CLB70 and CNK-89, immortalized noncancerous cell lines: MDCK and NIH-3T3 and canine peripheral blood mononuclear cells (PBMCs). The cytotoxic activity of BITC, apoptosis induction, caspase activity and ROS generation were evaluated by flow cytometry. H2AX phosphorylation was assessed by western blot. The study showed that the compound was especially active against B lymphocyte-derived malignant cells. Their death resulted from caspase-dependent apoptosis. BITC induced ROS accumulation, and glutathione precursor N-acetyl-l-cysteine reversed the effect of the compound, thus proving the role of oxidative stress in BITC activity. In addition, exposure to the compound induced DNA damage in the tested cells. This is the first study that provides information on the activity of BITC in canine hematopoietic malignancies and suggests that the compound may be particularly useful in B-cell neoplasms treatment.

Involvement of endoplasmic reticulum stress-activated PERK-eIF2α-ATF4 signaling pathway in T-2 toxin-induced apoptosis of porcine renal epithelial cells.

T-2 toxin is a highly toxic trichothecene that can induce toxic effects in a variety of organs and tissues, but the pathogenesis of its nephrotoxicity has not been elucidated. In this study, we assessed the involvement of protein kinase RNA-like ER kinase (PERK)-mediated endoplasmic reticulum (ER) stress and apoptosis in PK-15 cells cultured at different concentrations of T-2 toxin. Cell viability, antioxidant capacity, intracellular calcium (Ca2+) content, apoptotic rate, levels of ER stress, and apoptosis-related proteins were studied. T-2 toxin inhibited cell proliferation; increased the apoptosis rate; and was accompanied by increased cleaved caspase-3 expression, altered intracellular oxidative stress marker levels, and intracellular Ca2+ overloading. The ER stress inhibitor 4-phenylbutyrate (4-PBA) and PERK selective inhibitor GSK2606414 prevented the decrease of cell activity and apoptosis caused by T-2 toxin. The altered expression of glucose regulatory protein 78 (GRP78), C/EBP homologous protein (CHOP), and caspase-12 proved that ER stress was involved in cell injury triggered by T-2 toxin. T-2 toxin activated the phosphorylation of PERK and the alpha subunit of eukaryotic initiation factor 2 (eIF2α) and upregulated the activating transcription factor 4 (ATF4), thereby triggering ER stress via the GRP78/PERK/CHOP signaling pathway. This study provides a new perspective for understanding the nephrotoxicity of T-2 toxin.

Betulinic acid attenuates T-2 toxin-induced cytotoxicity in porcine kidney cells by blocking oxidative stress and endoplasmic reticulum stress.

T-2 toxin is highly cytotoxic to animals, which causes damage to animal health and great economic losses to agriculture and livestock production. Betulinic acid (BA), a naturally occurring pentacyclic lupane-type triterpenoid, has various biological and medicinal activities in vivo and in vitro. The objective of the present study was to investigate the toxic effects of T-2 toxin and the reversal effect of BA on porcine kidney (PK-15) cells. We evaluated T-2 toxin-induced apoptotic responses via oxidative stress and endoplasmic reticulum stress pathways by assessing the repair effect of BA in PK-15 cells. The results proved that T-2 toxin (1 µM, treated for 24 h) is highly toxic to PK-15 cells. After pre-treatment with BA (0.25, 0.5, and 1 µM) for 24 h, the cell viabilities were significantly increased, and the lactate dehydrogenase (LDH) in the culture media was dramatically decreased compared to that in the T-2 toxin treatment group. BA also enhanced the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and catalase (CAT) and reduced the production of reactive oxygen species (ROS) and malondialdehyde (MDA) in cells. BA also dose-dependently increased the expression of glucose regulated protein (GRP78), reduced expression of activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP), the phosphorylation of protein kinase R-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2α (eIF2α), and intracellular Ca2+ concentration in a dose-dependent manner. In addition, BA significantly decreased the expression of cleaved-caspase-3 and caspase-12, consequently reducing T-2 toxin-induced PK-15 cell apoptosis in a dose-dependent manner. Collectively, we suggest that BA has a protective effect on T-2 toxin-induced cytotoxicity by ameliorating oxidative stress and endoplasmic reticulum stress in PK-15 cells.

Tannic acid repair of zearalenone-induced damage by regulating the death receptor and mitochondrial apoptosis signaling pathway in mice.

Zearalenone (ZEA) is an estrogenic toxin produced by Fusarium strains, that is widely present in crops, and endangers the reproductive system of animals. Tannic acid (TA) is a natural polyphenolic substance that is widespread in the roots, stems, and leaves of plants, and has special pharmacological activity. This study was designed to investigate the therapeutic effect of TA on ZEA-induced ovarian damage in mice and to explore the molecular mechanism involved. Ninety healthy Kunming female mice were divided into six equal groups. All the groups but the control group were administered daily with ZEA [10 mg/kg body weight (bw)] orally, for 7 days, to induce damage to the reproductive system. Some groups were also administered with TA (50, 100, and 200 mg/bw) for 7 days. Mice were euthanized 24 h later to allow for collection of serum and ovaries. TA can effectively alleviate the appearance of congestion and redness of the ovary, caused by ZEA, and increase the number of healthy growing follicles. Moreover, the estrogen content and the levels of MDA and ROS in the ovaries can be effectively reduced by TA. It can also reduce the apoptosis of ovarian cells, decreases the protein expression of the estrogen receptor, Fas, Fasl, caspase-3, caspase-8, caspase-9, and Bax, and increases the protein expression of Bcl-2. Our study indicates that TA reduces the strong estrogen and oxidative damage induced by ZEA, and these therapeutic effects may be partially mediated by the death receptor and mitochondrial apoptosis signaling pathway.

Effects of ND vaccination combined LPS on growth performance, antioxidant performance and lipid metabolism of broiler.

Newcastle Disease Virus (NDV) is the important pathogen of Newcastle Disease (ND) attacking chicken, turkey and other birds. Therefore, the purpose of this study was to assess the effects of immune stress induced by ND vaccination and lipopolysaccharide (LPS) on growth performance, antioxidant ability, and lipid metabolism of broilers. In total, 128 one-day-old broilers were randomly assigned to the following four groups and were treated as indicated: normal control (NC); vaccinated with live LaSota ND vaccine (CV); administered ND vaccine and 0.25 mg/kg body weight (BW) LPS (L-LPS); and administered ND vaccine and 0.5 mg/kg BW LPS (H-LPS). The results demonstrated that broiler feed conversion ratio (FCR) was increased in the groups CV, L-LPS and H-LPS from d 0 to 42 days compared with the group NC. The antioxidant function of broilers was decreased as indicated by the malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) levels in the serum of the treated groups. ND vaccination combined LPS increased the concentration of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), but decreased the concentration of high-density lipoprotein cholesterol (HDLC) compared with the group NC. The reverse transcription (RT)-PCR results revealed that the mRNA expression of acetyl-CoA carboxylase gene (ACC) and 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR) in the liver were downregulated, whereas the mRNA expression of carnitine palmitoyltransferase-1 (CPT-1) and peroxisome proliferator-activated receptor (PPAR)-α were upregulated compared with the group NC. These results suggest that ND vaccination combined LPS reduced broiler growth performance and antioxidant ability, whereas it activated AMPK-mediated lipid metabolism.

Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway.

T-2 toxin, a trichothecene mycotoxin produced by Fusarium, is widely distributed in crops and animal feed and frequently induces intestinal damage. Betulinic acid (BA), a plant-derived pentacyclic lupane-type triterpene, possesses potential immunomodulatory, antioxidant and anti-inflammatory biological properties. The current study aimed to explore the protective effect and molecular mechanisms of BA on intestinal mucosal impairment provoked by acute exposure to T-2 toxin. Mice were intragastrically administered BA (0.25, 0.5, or 1 mg/kg) daily for 2 weeks and then injected intraperitoneally with T-2 toxin (4 mg/kg) once to induce an intestinal impairment. BA pretreatment inhibited the loss of antioxidant capacity in the intestine of T-2 toxin-treated mice by elevating the levels of CAT, GSH-PX and GSH and reducing the accumulation of MDA. In addition, BA pretreatment alleviated the T-2 toxin-triggered intestinal immune barrier dysregulation by increasing the SIgA level in the intestine at dosages of 0.5 and 1 mg/kg, increasing IgG and IgM levels in serum at dosages of 0.5 and 1 mg/kg and restoring the intestinal C3 and C4 levels at a dosage of 1 mg/kg. BA administration at a dosage of 1 mg/kg also improved the intestinal chemical barrier by decreasing the serum level of DAO. Moreover, BA pretreatment improved the intestinal physical barrier via boosting the expression of ZO-1 and Occludin mRNAs and restoring the morphology of intestinal villi that was altered by T-2 toxin. Furthermore, treatment with 1 mg/kg BA downregulated the expression of p-NF-κB and p-IκB-α proteins in the intestine, while all doses of BA suppressed the pro-inflammatory cytokines expression of IL-1ß, IL-6 and TNF-α mRNAs and increased the anti-inflammatory cytokine expression of IL-10 mRNA in the intestine of T-2 toxin-exposed mice. BA was proposed to exert a protective effect on intestinal mucosal disruption in T-2 toxin-stimulated mice by enhancing the intestinal antioxidant capacity, inhibiting the secretion of inflammatory cytokines and repairing intestinal mucosal barrier functions, which may be associated with BA-mediated inhibition of the NF-κB signaling pathway activation.

Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway.

T-2 toxin, the most toxic of the trichothecenes, is widely found in grains and feeds, and its intake poses serious risks to the health of humans and animals. An important cytotoxicity mechanism of T-2 toxin is the production of excess free radicals, which in turn leads to oxidative stress. Betulinic acid (BA) has many biological activities, including antioxidant activity, which is a plant-derived pentacyclic triterpenoid. The protective effects and mechanisms of BA in blocking oxidative stress caused by acute exposure to T-2 toxin in the thymus of mice was studied. BA pretreatment reduced ROS production, decreased the MDA content, and increased the content of IgG in serum and the levels of SOD and GSH in the thymus. BA pretreatment also reduced the degree of congestion observed in histopathological tissue sections of the thymus induced by T-2 toxin. Besides, BA downregulated the phosphorylation of the p38, JNK, and ERK proteins, while it upregulated the expression of the Nrf2 and HO-1 proteins in thymus tissues. The results indicated that BA could protect the thymus against the oxidative damage challenged by T-2 toxin by activating Nrf2 and suppressing the MAPK signaling pathway.