Evaluating the Impact of an Organic Trace Mineral mix on the Redox Homeostasis, Immunity, and Performance of Sows and their Offspring.

The objective of the study was to evaluate the effects of trace mineral supplementation in sows during gestation and lactation on the performance and health status of sows and their offspring. Sows (n = 30; Landrace × Yorkshire; avg parity = 3.9) were randomly allocated into two dietary treatments. Sows received a basal diet supplemented with 12 mg/kg Cu, 30 mg/kg Fe, 90 mg/kg Zn, 70 mg/kg Mn, 0.30 mg/kg Se, and 1.5 mg/kg I from an inorganic trace mineral source (ITM) or a blend of hydroxychloride and organic trace mineral source (HOTM) from day 1 of gestation until the end of the lactation period at day 21. Compared to the ITM, the HOTM supplementation increased (P < 0.05) both litter birth weight and individual piglet birth weight. Although not statistically significant, HOTM tended to increase (P = 0.069) the level of lactose in colostrum. HOTM increased (P < 0.05) the concentration of Mn and Se in the colostrum, milk, and serum of sows and/or piglets. Notably, the Zn concentration in the serum of sows was higher in sows supplemented with ITM compared to HOTM. Moreover, HOTM increased (P < 0.05) the activities of GPX and SOD in gestating sows and piglets, as well as increased (P < 0.05) cytokines (IL-1ß, TNF-α, and IL-10) in the serum of sows. The immunoglobulins (IgA, IgG, and IgM) also increased in sows and/or piglets at certain experimental time points. In conclusion, HOTM supplementation positively affected piglet development and improved the health status of sows and piglets potentially by regulating redox homeostasis and immunity.

AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken.

Dietary exposure to aflatoxin B1 (AFB1) is harmful to the health and performance of domestic animals. The hepatic cytochrome P450s (CYPs), CYP1A1 and CYP2A6, are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide (AFBO) in chicks. However, the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown. Dual-luciferase reporter assay, bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region -1,063/-948, -606/-541 of the CYP1A1 promoter as well as -636/-595, -503/-462, -147/-1 of the CYP2A6 promoter. Furthermore, overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6. Moreover, bioactivation of AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion of AP-1, rather than SP1, stimulated by AFB1-induced reactive oxygen species. Additionally, nano-selenium could reduce ROS, downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6, thus alleviating the toxicity of AFB1. In conclusion, AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver, which could provide novel targets for the remediation of aflatoxicosis in chicks.

CPK10 protein kinase regulates Arabidopsis tolerance to boron deficiency through phosphorylation and activation of BOR1 transporter.

Boron (B) is crucial for plant growth and development. B deficiency can impair numerous physiological and metabolic processes, particularly in root development and pollen germination, seriously impeding crop growth and yield. However, the molecular mechanism underlying boron signal perception and signal transduction is rather limited. In this study, we discovered that CPK10, a calcium-dependent protein kinase in the CPK family, has the strongest interaction with the boron transporter BOR1. Mutations in CPK10 led to growth and root development defects under B-deficiency conditions, while constitutively active CPK10 enhanced plant tolerance to B deficiency. Furthermore, we found that CPK10 interacted with and phosphorylated BOR1 at the Ser689 residue. Through various biochemical analyses and complementation of B transport in yeast and plants, we revealed that Ser689 of BOR1 is important for its transport activity. In summary, these findings highlight the significance of the CPK10-BOR1 signaling pathway in maintaining B homeostasis in plants and provide targets for the genetic improvement of crop tolerance to B-deficiency stress.

Estimation of Protein and Amino Acid Requirements in Layer Chicks Depending on Dynamic Model.

Four trials were conducted to establish a protein and amino acid requirement model for layer chicks over 0-6 weeks by using the analytical factorization method. In trial 1, a total of 90 one-day-old Jing Tint 6 chicks with similar body weight were selected to determine the growth curve, carcass and feather protein deposition, and amino acid patterns of carcass and feather proteins. In trials 2 and 3, 24 seven-day-old and 24 thirty-five-day-old Jing Tint 6 chicks were selected to determine the protein maintenance requirements, amino acid pattern, and net protein utilization rate. In trial 4, 24 ten-day-old and 24 thirty-eight-day-old Jing Tint 6 chicks were selected to determine the standard terminal ileal digestibility of amino acids. The chicks were fed either a corn-soybean basal diet, a low nitrogen diet, or a nitrogen-free diet throughout the different trials. The Gompertz equation showed that there is a functional relationship between body weight and age, described as BWt(g) = 2669.317 × exp(-4.337 × exp(-0.019t)). Integration of the test results gave a comprehensive dynamic model equation that could accurately calculate the weekly protein and amino acid requirements of the layer chicks. By applying the model, it was found that the protein requirements for Jing Tint 6 chicks during the 6-week period were 21.15, 20.54, 18.26, 18.77, 17.79, and 16.51, respectively. The model-predicted amino acid requirements for Jing Tint 6 chicks during the 6-week period were as follows: Aspartic acid (0.992-1.284), Threonine (0.601-0.750), Serine (0.984-1.542), Glutamic acid (1.661-1.925), Glycine (0.992-1.227), Alanine (0.909-0.961), Valine (0.773-1.121), Cystine (0.843-1.347), Methionine (0.210-0.267), Isoleucine (0.590-0.715), Leucine (0.977-1.208), Tyrosine (0.362-0.504), Phenylalanine (0.584-0.786), Histidine (0.169-0.250), Lysine (0.3999-0.500), Arginine (0.824-1.147), Proline (1.114-1.684), and Tryptophan (0.063-0.098). In conclusion, this study constructed a dynamic model for the protein and amino acid requirements of Jing Tint 6 chicks during the brooding period, providing an important insight to improve precise feeding for layer chicks through this dynamic model calculation.

Effective protective agents against the organ toxicity of T-2 toxin and corresponding detoxification mechanisms: A narrative review.

T-2 toxin is one of the most widespread and toxic fungal toxins in food and feed. It can cause gastrointestinal toxicity, hepatotoxicity, immunotoxicity, reproductive toxicity, neurotoxicity, and nephrotoxicity in humans and animals. T-2 toxin is physicochemically stable and does not readily degrade during food and feed processing. Therefore, suppressing T-2 toxin-induced organ toxicity through antidotes is an urgent issue. Protective agents against the organ toxicity of T-2 toxin have been recorded widely in the literature, but these protective agents and their molecular mechanisms of detoxification have not been comprehensively summarized. In this review, we provide an overview of the various protective agents to T-2 toxin and the molecular mechanisms underlying the detoxification effects. Targeting appropriate targets to antagonize T-2 toxin toxicity is also an important option. This review will provide essential guidance and strategies for the better application and development of T-2 toxin antidotes specific for organ toxicity in the future.

Optimum Doses and Forms of Selenium Maintaining Reproductive Health via Regulating Homeostasis of Gut Microbiota and Testicular Redox, Inflammation, Cell Proliferation, and Apoptosis in Roosters.

BACKGROUND: There is a U-shaped relationship between dietary selenium (Se) ingestion and optimal sperm quality. OBJECTIVES: This study aimed to investigate the optimal dietary dose and forms of Se for sperm quality of breeder roosters and the relevant mechanisms. METHODS: In experiment 1, 18-wk-old Jingbai laying breeder roosters were fed a Se-deficient base diet (BD, 0.06 mg Se/kg), or the BD + 0.1, 0.2, 0.3, 0.4, 0.5, or 1.0 mg Se/kg for 9 wk. In experiment 2, the roosters were fed the BD or the BD + sodium selenite (SeNa), seleno-yeast (SeY), or Se-nanoparticles (SeNPs) at 0.2 mg Se/kg for 9 wk. RESULTS: In experiment 1, added dietary 0.2 and 0.3 mg Se/kg led to higher sperm motility and lower sperm mortality than the other groups at weeks 5, 7, and/or 9. Furthermore, added dietary 0.2-0.4 mg Se/kg produced better testicular histology and/or lower testicular 8-hydroxy-deoxyguanosine than the other groups. Moreover, integrated testicular transcriptomic and cecal microbiomic analysis revealed that inflammation, cell proliferation, and apoptosis-related genes and bacteria were dysregulated by Se deficiency or excess. In experiment 2, compared with SeNa, SeNPs slightly increased sperm motility throughout the experiment, whereas SeNPs slightly reduced sperm mortality compared with SeY at week 9. Both SeY and SeNPs decreased malondialdehyde in the serum than those of SeNa, and SeNPs led to higher glutathione peroxidase (GPX) and thioredoxin reductase activities and GPX1 and B-cell lymphoma 2 protein concentrations in the testis compared with SeY and SeNa. CONCLUSIONS: The optimal dietary Se dose for reproductive health of breeder roosters is 0.25-0.35 mg Se/kg, and SeNPs displayed better effects on reproductive health than SeNa and SeY in laying breeder roosters. The optimal doses and forms of Se maintain reproductive health of roosters associated with regulation intestinal microbiota homeostasis and/or testicular redox balance, inflammation, cell proliferation, and apoptosis.

An integrated mycotoxin-mitigating agent can effectively mitigate the combined toxicity of AFB1, DON and OTA on the production performance, liver and oviduct health in broiler breeder hens.

This study was to evaluate the efficacy of an integrated mycotoxin-mitigating agent in reducing the adverse effects of co-occurring dietary aflatoxin B1 deoxynivalenol and ochratoxin A on broiler breeder hens. 360 30-week-old Hubbard Efficiency Plus broiler breeder hens were allocated into four groups and received a basal diet (BD; Control), BD added 0.15 mg/kg aflatoxin B1+1.5 mg/kg deoxynivalenol+0.12 mg/kg ochratoxin A (Toxins), BD plus Toxins with 0.1% TOXO-XL (Toxins + XL1), and BD plus Toxins with 0.2% TOXO-XL (Toxins + XL2), respectively, for 8 weeks, and then received the same BD for another 4 weeks. Compared with control, mycotoxins decreased total egg weigh, egg laying rate, settable eggs rate, hatch of total eggs rate, egg quality, but increased feed/egg ratio and mortality rate, and impaired the liver and oviduct health during weeks 1-8 and(or) 9-12. It also increased PC and MDA concentrations, TUNEL-positive cells and IL-1ß and IL-6 expression, and decreased T-AOC, GPX and CAT activities in liver and/or oviduct. Notably, most of these negative changes were mitigated by both dosages of TOXO-XL. Generally, 0.2% TOXO-XL displayed better mitigation effects than 0.1% TOXO-XL. Conclusively, these findings revealed that TOXO-XL could mitigate the combined mycotoxins-induced toxicity on the performance, liver and oviduct health, through the regulation of redox, immunity, and apoptosis in broiler breeder hens.

Heat Stress Impairs Male Reproductive System with Potential Disruption of Retinol Metabolism and Microbial Balance in the Testis of Mice.

BACKGROUND: Heat stress (HS) has a harmful impact on the male reproductive system, primarily by reducing the sperm quality. The testicular microenvironment plays an important role in sperm quality. OBJECTIVES: This study aimed to explore the underlying mechanism by which HS impairs the male reproductive system through the testicular microenvironment. METHODS: Ten-week-old male mice (n = 8 mice/group) were maintained at a normal temperature (25°C, control) or subjected to HS (38°C for 2 h each day, HS) for 2 wk. The epididymides and testes were collected at week 2 to determine sperm quality, histopathology, retinol concentration, the expression of retinol metabolism-related genes, and the testicular microbiome. The testicular microbiome profiles were analyzed using biostatistics and bioinformatics; other data were analyzed using a 2-sided Student's t test. RESULTS: Compared with the control, HS reduced (P < 0.05) sperm count (42.4%) and motility (97.7%) and disrupted the integrity of the blood-testis barrier. Testicular microbial profiling analysis revealed that HS increased the abundance of the genera Asticcacaulis, Enhydrobacter, and Stenotrophomonas (P < 0.05) and decreased the abundance of the genera Enterococcus and Pleomorphomonas (P < 0.05). Notably, the abundance of Asticcacaulis spp. showed a significant negative correlation with sperm count (P < 0.001) and sperm motility (P < 0.001). Moreover, Asticcacaulis spp. correlated significantly with most blood differential metabolites, particularly retinol (P < 0.05). Compared with the control, HS increased serum retinol concentrations (25.3%) but decreased the testis retinol concentration by 23.7%. Meanwhile, HS downregulated (P < 0.05) the expression of 2 genes (STRA6 and RDH10) and a protein (RDH10) involved in retinol metabolism by 27.3%-36.6% in the testis compared with the control. CONCLUSIONS: HS reduced sperm quality, mainly because of an imbalance in the testicular microenvironment potentially caused by an increase in Asticcacaulis spp. and disturbed retinol metabolism. These findings may offer new strategies for improving male reproductive capacity under HS.

Paternally imprinted LATE-FLOWERING2 transcription factor contributes to paternal-excess interploidy hybridization barriers in wheat.

Interploidy hybridization between hexaploid and tetraploid genotypes occurred repeatedly during genomic introgression events throughout wheat evolution, and is commonly employed in wheat breeding programs. Hexaploid wheat usually serves as maternal parent because the reciprocal cross generates progeny with severe defects and poor seed germination, but the underlying mechanism is poorly understood. Here, we performed detailed analysis of phenotypic variation in endosperm between two interploidy reciprocal crosses arising from tetraploid (Triticum durum, AABB) and hexaploid wheat (Triticum aestivum, AABBDD). In the paternal- versus the maternal-excess cross, the timing of endosperm cellularization was delayed and starch granule accumulation in the endosperm was repressed, causing reduced germination percentage. The expression profiles of genes involved in nutrient metabolism differed strongly between these endosperm types. Furthermore, expression patterns of parental alleles were dramatically disturbed in interploidy versus intraploidy crosses, leading to increased number of imprinted genes. The endosperm-specific TaLFL2 showed a paternally imprinted expression pattern in interploidy crosses partially due to allele-specific DNA methylation. Paternal TaLFL2 binds to and represses a nutrient accumulation regulator TaNAC019, leading to reduced storage protein and starch accumulation during endosperm development in paternal-excess cross, as confirmed by interploidy crosses between tetraploid wild-type and clustered regularly interspaced palindromic repeats (CRISPR) - CRISPR-associated protein 9 generated hexaploid mutants. These findings reveal a contribution of genomic imprinting to paternal-excess interploidy hybridization barriers during wheat evolution history and explains why experienced breeders preferentially exploit maternal-excess interploidy crosses in wheat breeding programs.

Accurate diagnosis of pulmonary inflammatory myofibroblastic tumor by imaging technology before operation: A case report.

RATIONALE: Pulmonary inflammatory myofibroblastic tumor (IMT) is a rare borderline tumor, which has the potential of malignant including invasion of surrounding tissues, distant metastasis and recurrence. However, the preoperative diagnosis is difficult and it can also be difficult to distinguish from malignancy in small tissue samples. Preoperative accurate diagnosis has important clinical significance for patients to choose treatment measures and improve the quality of rehabilitation. We was examined by computed tomography (CT) plain scan plus enhanced scan, magnetic resonance diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) imaging technology in an adult female, compared with lung cancer and pulmonary cryptococcus infection for diagnosis of pulmonary IMT. PATIENT CONCERNS: A 32-year-old female patient was admitted to the hospital "physical examination revealed nodules in the right upper lung for 1 week". DIAGNOSES: The patient was diagnosed with Pulmonary inflammatory myofibroblastic tumor. INTERVENTIONS: Single-port thoracoscopic lobectomy was performed after multidisciplinary consultation. OUTCOMES: DWI and ADC improves the accuracy of preoperative diagnosis and well guides the formulation of treatment measures. The combined CT, DWI, and ADC magnetic resonance imaging technology has more important significance in the diagnosis and differential diagnosis of IMT and lung malignant tumors. LESSONS: Although accurate preoperative diagnosis of pulmonary IMT is difficult. Chest CT examination combined with DWI and ADC imaging technology has high clinical significance for the diagnosis of IMT.

Remediation Strategies for Mycotoxins in Animal Feed.

Mycotoxins occur widely in various animal feedstuffs, with more than 500 mycotoxins identified so far [...].

Translocation of gut microbes to epididymal white adipose tissue drives lipid metabolism disorder under heat stress.

Heat stress induces multi-organ damage and serious physiological dysfunction in mammals, and gut bacteria may translocate to extra-intestinal tissues under heat stress pathology. However, whether gut bacteria translocate to the key metabolic organs and impair function as a result of heat stress remains unknown. Using a heat stress-induced mouse model, heat stress inhibited epididymal white adipose tissue (eWAT) expansion and induced lipid metabolic disorder but did not damage other organs, such as the heart, liver, spleen, or muscle. Microbial profiling analysis revealed that heat stress shifted the bacterial community in the cecum and eWAT but not in the inguinal white adipose tissue, blood, heart, liver, spleen, or muscle. Notably, gut-vascular barrier function was impaired, and the levels of some bacteria, particularly Lactobacillus, were higher in the eWAT, as confirmed by catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH) staining when mice were under heat stress. Moreover, integrated multi-omics analysis showed that the eWAT microbiota was associated with host lipid metabolism, and the expression of genes involved in the lipid metabolism in eWAT was upregulated under heat stress. A follow-up microbial supplementation study after introducing Lactobacillus plantarum to heat-stressed mice revealed that the probiotic ameliorated heat stress-induced loss of eWAT and dyslipidemia and reduced gut bacterial translocation to the eWAT by improving gut barrier function. Overall, our findings suggest that gut bacteria, particularly Lactobacillus spp., play a crucial role in heat stress-induced lipid metabolism disorder and that there is therapeutic potential for using probiotics, such as Lactobacillus plantarum.

Alternative splicing of TaHSFA6e modulates heat shock protein-mediated translational regulation in response to heat stress in wheat.

Heat stress greatly threatens crop production. Plants have evolved multiple adaptive mechanisms, including alternative splicing, that allow them to withstand this stress. However, how alternative splicing contributes to heat stress responses in wheat (Triticum aestivum) is unclear. We reveal that the heat shock transcription factor gene TaHSFA6e is alternatively spliced in response to heat stress. TaHSFA6e generates two major functional transcripts: TaHSFA6e-II and TaHSFA6e-III. TaHSFA6e-III enhances the transcriptional activity of three downstream heat shock protein 70 (TaHSP70) genes to a greater extent than does TaHSFA6e-II. Further investigation reveals that the enhanced transcriptional activity of TaHSFA6e-III is due to a 14-amino acid peptide at its C-terminus, which arises from alternative splicing and is predicted to form an amphipathic helix. Results show that knockout of TaHSFA6e or TaHSP70s increases heat sensitivity in wheat. Moreover, TaHSP70s are localized in stress granule following exposure to heat stress and are involved in regulating stress granule disassembly and translation re-initiation upon stress relief. Polysome profiling analysis confirms that the translational efficiency of stress granule stored mRNAs is lower at the recovery stage in Tahsp70s mutants than in the wild types. Our finding provides insight into the molecular mechanisms by which alternative splicing improves the thermotolerance in wheat.

Mitigating the adverse effects of Aflatoxin B1 in LMH, IPEC-J2 and 3D4/21 cells by a novel integrated agent.

This study was to evaluate the efficacy of TOXO-XL (XL), an integrated mycotoxin-mitigating agent, on aflatoxin B1 (AFB1)-induced damage in Leghorn male hepatoma (LMH), porcine jejunum epithelial cell line (IPEC-J2) and porcine alveolar macrophages (3D4/21) cells, and to explore its potential mechanisms. The results showed that 30% inhibition concentration (IC30) of AFB1 in LMH, IPEC-J2 and 3D4/21 cells was 0.5, 15.0, and 2.5 mg/L, respectively. Notably, cell viability, ROS, apoptosis and DNA lesion induced by AFB1 (IC30) could be ameliorated by the supplementation with XL at the dosage of 0.025, 0.025 and 0.005%, respectively. Additionally, the migration and phagocytosis abilities impaired by AFB1 were also restored by XL in 3D4/21. Further experiments revealed that XL supplementation markedly attenuated AFB1-induced inflammatory response by decreasing IL-1ß, IL-6 and IL-10 in LMH, IL-6 in IPEC-J2 and IL-1ß in 3D4/21 cells. Meanwhile, XL supplementation reversed the alterations of BAX, BCL-2 and caspase-3 induced by AFB1 in the three cells, suggesting that AFB1-induced apoptosis may be suppressed via the mitochondria-dependent pathway. Furthermore, XL may have a protective effect on the intestinal barrier through the restoration of occludin protein. Conclusively, these findings indicated that XL could alleviate AFB1-induced cytotoxicity in the three cells, potentially through the regulation of cytokines, ROS, apoptotic and DNA damage signaling.

The effect of posterior cruciate ligament tibial avulsion fracture on functional outcomes in knees with concomitant ipsilateral lower limb fractures: a matched-cohort analysis.

BACKGROUND: At present, the optimal treatment for posterior cruciate ligament tibial avulsion fracture (PCLTAF) combined with concomitant ipsilateral lower limb fractures remains unclear. The present study aimed to assess the preliminary outcomes of treatment for PCLTAF with concomitant ipsilateral lower limb fractures by open reduction and internal fixation (ORIF). MATERIALS AND METHODS: The medical records of patients who sustained PCLTAF with concomitant ipsilateral lower limb fractures between March 2015 and February 2019 and underwent treatment at a single institution were retrospectively reviewed. Imaging examinations performed at the time of injury were applied to identify concomitant ipsilateral lower limb fractures. We used 1:2 matching between patients with PCLTAF combined with concomitant ipsilateral lower limb fractures (combined group; n = 11) and those with isolated PCLTAF (isolated group; n = 22). Outcome data were collected, including the range of motion (ROM) and visual analogue scale (VAS), Tegner, Lysholm, and International Knee Documentation Committee (IKDC) scores. At the final follow-up, the clinical outcomes were compared between the combined and isolated groups and between patients who underwent early-stage surgery and those who underwent delayed treatment for PCLTAF. RESULTS: Thirty-three patients (26 males, 7 females) were included in this study, with eleven patients having PCLTAF and concomitant ipsilateral lower limb fractures and a follow-up of 3.1 to 7.4 years (average, 4.8 years). Compared to patients in the isolated group, patients in the combined group demonstrated significantly worse Lysholm scores (85.7 ± 5.8 vs. 91.5 ± 3.9, p = 0.040), Tegner scores (4.4 ± 0.9 vs. 5.4 ± 0.8, p = 0.006), and IKDC scores (83.6 ± 9.3 vs. 90.5 ± 3.0, p = 0.008). Inferior outcomes were found in patients with delayed treatment. CONCLUSIONS: Inferior results were found in patients with concomitant ipsilateral lower limb fractures, while better outcomes were obtained in patients with PCLTAF through early-stage ORIF using the posteromedial approach. The present findings may help determine the prognoses of patients with PCLTAF combined with concomitant ipsilateral lower limb fractures treated through early-stage ORIF.

Selenium Deficiency Dysregulates One-Carbon Metabolism in Nutritional Muscular Dystrophy of Chicks.

BACKGROUND: Nutritional muscular dystrophy (NMD) in animals is induced by dietary selenium (Se) deficiency. OBJECTIVES: This study was conducted to explore the underlying mechanism of Se deficiency-induced NMD in broilers. METHODS: One-day-old male Cobb broilers (n = 6 cages/diet, 6 birds/cage) were fed a Se-deficient diet (Se-Def, 47 µg Se/kg) or the Se-Def supplemented with 0.3 mg Se/kg (control) for 6 wk. Thigh muscles of broilers were collected at week 6 for measuring Se concentration, histopathology, and transcriptome and metabolome assays. The transcriptome and metabolome data were analyzed with bioinformatics tools and other data were analyzed with Student's t tests. RESULTS: Compared with the control, Se-Def induced NMD in broilers, including reduced (P < 0.05) final body weight (30.7%) and thigh muscle size, reduced number and cross-sectional area of fibers, and loose organization of muscle fibers. Compared with the control, Se-Def decreased (P < 0.05) the Se concentration in the thigh muscle by 52.4%. It also downregulated (P < 0.05) GPX1, SELENOW, TXNRD1-3, DIO1, SELENOF, H, I, K, M, and U by 23.4-80.3% in the thigh muscle compared with the control. Multi-omics analyses indicated that the levels of 320 transcripts and 33 metabolites were significantly altered (P < 0.05) in response to dietary Se deficiency. Integrated transcriptomics and metabolomics analysis revealed that one-carbon metabolism, including the folate and methionine cycle, was primarily dysregulated by Se deficiency in the thigh muscles of broilers. CONCLUSIONS: Dietary Se deficiency induced NMD in broiler chicks, potentially with the dysregulation of one-carbon metabolism. These findings may provide novel treatment strategies for muscle disease.

Both selenium deficiency and excess impair male reproductive system via inducing oxidative stress-activated PI3K/AKT-mediated apoptosis and cell proliferation signaling in testis of mice.

Selenium (Se) deficiency or excess impairs testicular development and spermatogenesis, while the underlying mechanisms in this regard remain unclear. This study was designed to explore the molecular biology of Se deficiency or excess in spermatogenesis in mice. Three-week-old male mice (n = 10 mice/diet) were fed with Se-deficient diet (SeD, 0.02 mg Se/kg), adequate-Se diet (SeA, 0.2 mg Se/kg), or excess-Se diet (SeE, 2.0 mg Se/kg) for 5 months. Compared with SeA, SeD reduced (P < 0.05) the body weight (10.4%) and sperm density (84.3%) but increased (P < 0.05) sperm deformity (32.8%); SeE decreased (P < 0.05) the sperm density (78.5%) and sperm motility (35.9%) of the mice. Meanwhile, both SeD and SeE increased (P < 0.05) serum FSH concentrations (10.4-25.6%) and induced testicular damage in mice in comparison with the SeA. Compared with SeA, SeD increased (P < 0.05) the 8-OHdG concentration by 25.5%; SeE increased (P < 0.05) both MDA and 8-OHdG concentrations by 118.8-180.3% in testis. Furthermore, transcriptome analysis showed that there 1325 and 858 transcripts were altered (P < 0.05) in the testis by SeD and SeE, respectively, compared with SeA. KEGG pathway analysis revealed that these differentially expressed genes were mainly enriched in the PI3K-AKT signaling pathway, which is regulated by oxidative stress. Moreover, western blotting analysis revealed that SeD and SeE dysregulated PI3K-AKT-mediated apoptosis and cell proliferation signaling, including upregulating (P < 0.05) caspase 3, cleaved-caspase 3, BCL-2 and (or) P53 and downregulating (P < 0.05) PI3K, p-AKT, p-mTOR, 4E-BP1, p-4E-BP1 and (or) p-p70S6K in the testis of mice compared with SeA. Additionally, compared with SeA, both SeD and SeE increased (P < 0.05) GPX3 and SELENOO; SeD decreased (P < 0.05) GPX1, TXRND3 and SELENOW, but SeE increased (P < 0.05) production of three selenoproteins in the testis. Conclusively, both Se deficiency and excess impairs male reproductive system in mice, potentially with the induction of oxidative stress and activation of PI3K/AKT-mediated apoptosis and cell proliferation signaling in the testis.

Alpha-class glutathione S-transferases involved in the detoxification of aflatoxin B1 in ducklings.

The objective of this study was to identify the key glutathione S-transferase (GST) isozymes involved in the detoxification of Aflatoxin B1 (AFB1) in ducks' primary hepatocytes. The full-length cDNA encoding the 10 GST isozymes (GST, GST3, GSTM3, MGST1, MGST2, MGST3, GSTK1, GSTT1, GSTO1 and GSTZ1) were isolated/synthesized from ducks' liver and cloned into the pcDNA3.1(+) vector. The results showed that pcDNA3.1(+)-GSTs plasmids were successfully transferred into the ducks' primary hepatocytes and the mRNA of the 10 GST isozymes were overexpressed by 1.9-3274.7 times. Compared to the control, 75 µg/L (IC30) or 150 µg/L (IC50) AFB1 treatment reduced the cell viability by 30.0-50.0% and increased the LDH activity by 19.8-58.2% in the ducks' primary hepatocytes. Notably, the AFB1-induced changes in cell viability and LDH activity were mitigated by overexpression of GST and GST3. Compared to the cells treated with AFB1, exo-AFB1-8,9-epoxide (AFBO)-GSH, as the major detoxified product of AFB1, was increased in the cells overexpression of GST and GST3. Moreover, the sequences, phylogenetic and domain analysis revealed that the GST and GST3 were orthologous to Meleagris gallopavo GSTA3 and GSTA4. In conclusion, this study found that the ducks' GST and GST3 were orthologous to Meleagris gallopavo GSTA3 and GSTA4, which were involved in the detoxification of AFB1 in ducks' primary hepatocytes.

Selenium deficiency-induced multiple tissue damage with dysregulation of immune and redox homeostasis in broiler chicks under heat stress.

Broiler chicks are fast-growing and susceptible to dietary selenium (Se) deficiency. This study sought to reveal the underlying mechanisms of how Se deficiency induces key organ dysfunctions in broilers. Day-old male chicks (n=6 cages/diet, 6 chicks/cage) were fed with a Se-deficient diet (Se-Def, 0.047 mg Se/kg) or the Se-Def+0.3 mg Se/kg (Control, 0.345 mg Se/kg) for 6 weeks. The serum, liver, pancreas, spleen, heart, and pectoral muscle of the broilers were collected at week 6 to assay for Se concentration, histopathology, serum metabolome, and tissue transcriptome. Compared with the Control group, Se deficiency induced growth retardation and histopathological lesions and reduced Se concentration in the five organs. Integrated transcriptomics and metabolomics analysis revealed that dysregulation of immune and redox homeostasis related biological processes and pathways contributed to Se deficiency-induced multiple tissue damage in the broilers. Meanwhile, four metabolites in the serum, daidzein, epinephrine, L-aspartic acid and 5-hydroxyindoleacetic acid, interacted with differentially expressed genes with antioxidative effects and immunity among all the five organs, which contributed to the metabolic diseases induced by Se deficiency. Overall, this study systematically elucidated the underlying molecular mechanisms in the pathogenesis of Se deficiency-related diseases, which provides a better understanding of the significance of Se-mediated heath in animals.

T-2 toxin-induced intestinal damage with dysregulation of metabolism, redox homeostasis, inflammation, and apoptosis in chicks.

T-2 toxin is a worldwide problem for feed and food safety, leading to livestock and human health risks. The objective of this study was to explore the mechanism of T-2 toxin-induced small intestine injury in broilers by integrating the advanced microbiomic, metabolomic and transcriptomic technologies. Four groups of 1-day-old male broilers (n = 4 cages/group, 6 birds/cage) were fed a control diet and control diet supplemented with T-2 toxin at 1.0, 3.0, and 6.0 mg/kg, respectively, for 2 weeks. Compared with the control, dietary T-2 toxin reduced feed intake, body weight gain, feed conversion ratio, and the apparent metabolic rates and induced histopathological lesions in the small intestine to varying degrees by different doses. Furthermore, the T-2 toxin decreased the activities of glutathione peroxidase, thioredoxin reductase and total antioxidant capacity but increased the concentrations of protein carbonyl and malondialdehyde in the duodenum in a dose-dependent manner. Moreover, the integrated microbiomic, metabolomic and transcriptomic analysis results revealed that the microbes, metabolites, and transcripts were primarily involved in the regulation of nucleotide and glycerophospholipid metabolism, redox homeostasis, inflammation, and apoptosis were related to the T-2 toxin-induced intestinal damage. In summary, the present study systematically elucidated the intestinal toxic mechanisms of T-2 toxin, which provides novel ideas to develop a detoxification strategy for T-2 toxin in animals.