理学最新文献

There is increasing interest in developing reduced-crude protein (CP) diets for broiler chickens because their commercial adoption would generate a diverse range of advantages that would enhance the sustainability of the chicken-meat industry. However, the development of reduced-CP broiler diets is proving to be not straightforward, particularly when dietary CP reductions exceed 30 g/kg. The capacity of broilers to accommodate dietary CP reductions when offered maize-based diets is superior to their counterparts offered wheat-based diets. Numerous factors could be contributing to this difference but have yet to be identified with certainty. Maize-based, reduced-CP diets characteristically support better weight gains and efficiencies of feed conversion than wheat-based diets, but this better growth performance is associated with increased fat deposition, monitored as heavier relative abdominal fat-pad weights. This is an intriguing dichotomy. Insulin is a powerful anabolic hormone in mammalian species capable of promoting fat deposition, protein accretion and growth, but the importance of insulin in avian species is usually dismissed. This is because broiler chickens are considered both hyperglycaemic and resistant to insulin. However, the likelihood is that young broiler chickens are more sensitive to insulin than is generally recognised and the anabolic properties of insulin may be contributing to the diverse responses observed between maize and wheat in the context of reduced-CP diets. Dietary CP reductions may trigger increased plasma ammonia concentrations and metabolic acidosis, but both factors can influence insulin secretion and insulin resistance. Maize has slower rates of starch digestion and glucose absorption than wheat and it has been suggested that this generates a more sustained insulin release resulting in increased weight gains and fat deposition. If so, this could be driving the differences generated by the feed grain selected as the basis of reduced-CP diets. The intention of this review is to explore this proposition because if the causal factors of the differences between maize and wheat can be identified the development and acceptance of reduced-CP broiler diets should be accelerated.

Backgrounds: Deoxynivalenol (DON) is an abundant environmental pollutant in feed, posing serious health hazards to animals. However, whether DON triggers an imbalance in mitochondrial fission/fusion and the underlying mechanisms involved remain poorly understood. Our aim was to clarify whether mitochondrial fission or fusion proteins participated in DON-caused intestinal damage in pigs.

Methods: Firstly, two groups of weaning pigs were fed a basal diet, or basal diet supplemented with 4 mg DON/kg for 3 weeks. Additionally, another two groups of weaning pigs were given an oral gavage with 2 mg/kg body weight DON or an equivalent amount of normal saline. In addition, the involvement of mitochondrial fission or fusion proteins in DON-induced intestinal damage was further verified in intestinal porcine epithelial cell line (IPEC-1) by overexpressed plasmids of dynamin related protein 1 (Drp1) and mitofusin 2 (Mfn2) which were determined by animal studies. Finally, a mitochondrial fusion promotor M1 was used in IPEC-1 cells to explore the role of Mfn2 in DON-induced intestinal damage.

Results: Dietary DON caused jejunal damage and inflammation, reduced intestinal Drp1, mitofusin 1 (Mfn1) and Mfn2, and induced cell apoptosis. DON gavage also impaired jejunal structure and led to decreased Drp1 and Mfn2, and increased cell apoptosis. Moreover, DON challenge also resulted in cell damage and mitochondrial dysfunction, accompanied by abnormal protein expression of mitochondrial fission/fusion proteins and increased cell apoptosis in IPEC-1 cells. Subsequently, Mfn2, but not Drp1 overexpression plasmid restored mitochondrial fission/fusion protein expression, suppressed cell apoptosis, mitigated cell damage and mitochondrial dysfunction in IPEC-1 cells after DON challenge. Finally, M1 alleviated DON-induced reduction of Mfn2 protein and cell apoptosis, rescued mitochondrial dysfunction, barrier function impairment and cell damage.

Conclusions: Overall, our study demonstrates that DON exposure triggers Mfn2 protein dysregulation, which in turn mediates DON-induced intestinal epithelial damage in piglets.

Background: Goat milk is increasingly recognized for high digestibility and a distinctive compositional profile. Protein acetylation, an important post-translational modification, regulates biosynthetic and metabolic pathways. This study aimed to identify critical acetylated proteins and specific modification sites involved in milk production and component synthesis in dairy goats, thereby elucidating the molecular mechanisms of lactation. We performed a comparative TMT-based acetylomic and proteomic analysis of mammary tissues from Saanen dairy goats during peak lactation and the dry period using LC-MS/MS. A candidate acetylation site was further investigated in goat mammary epithelial cells (GMECs) through site-directed mutagenesis and lipid metabolic assays, establishing functional links between acetylation and mammary lipid metabolism and providing a foundation for molecular strategies to improve milk quality and yield.

Results: We established a comprehensive mammary acetylome, identifying 862 significantly acetylated proteins and 2,028 modification sites across the two physiological phases. Differentially acetylated proteins were predominantly localized to the cytoplasm (39.98%). From these, 54 key acetylated proteins, including MTOR, BCAT2, QARS1, GOT1, GOT2, BDH1, ACSS1, STAT5B, FABP5, and GPAM were prioritized as candidates involved in milk protein synthesis, milk fat synthesis, lactose synthesis, and other lactation-related processes. Among them, β-hydroxybutyrate dehydrogenase 1 (BDH1) acetylation was characterized in detail. Members of the HDAC family were identified as primary regulators mediating BDH1 deacetylation. BDH1 acetylation promoted lipid droplet formation and triglyceride synthesis in GMECs. At the transcriptional level, BDH1 acetylation upregulated LXRα, ACSL1 and SCD1, whereas deacetylation downregulated SCD1, FASN, and ACSL1. Notably, BDH1 acetylation/deacetylation significantly reduced SREBP1 expression, linking this modification to coordinated control of lipogenic gene networks.

Conclusions: This study established, for the first time, the comprehensive acetylome of mammary gland tissues in dairy goats, revealing a substantial number of differentially acetylated proteins and modification sites. We demonstrate that acetylation of BDH1 regulated by HDACs promotes lipid droplet biogenesis and triglyceride synthesis in GMECs through transcriptional modulation of key lipogenic genes and suppression of SREBP1. These findings provide mechanistic insights into the post-translational regulation of mammary lipid metabolism and offer molecular targets for future genetic and nutritional strategies aimed at enhancing milk quality and yield in dairy goats.

Background: Multibreed genomic prediction (MBGP) is crucial for improving prediction accuracy for breeds with small populations, for which limited data are often available. Recent studies have demonstrated that partitioning the genome into nonoverlapping blocks to model heterogeneous genetic (co)variance in multitrait models can achieve higher joint prediction accuracy. However, the block partitioning method, a key factor influencing model performance, has not been extensively explored.

Results: We introduce mbBayesABLD, a novel Bayesian MBGP model that partitions each chromosome into nonoverlapping blocks on the basis of linkage disequilibrium (LD) patterns. In this model, marker effects within each block are assumed to follow normal distributions with block-specific parameters. We employ simulated data as well as empirical datasets from pigs and beans to assess genomic prediction accuracy across different models using cross-validation. The results demonstrate that mbBayesABLD significantly outperforms conventional MBGP models, such as GBLUP and BayesR. For the meat marbling score trait in pigs, compared with GBLUP, which does not account for heterogeneous genetic (co)variance, mbBayesABLD improves the prediction accuracy for the small-population breed Landrace by 15.6%. Furthermore, our findings indicate that a moderate level of similarity in LD patterns between breeds (with an average correlation of 0.6) is sufficient to improve the prediction accuracy of the target breed.

Conclusions: This study presents a novel LD block-based approach for multibreed genomic prediction. Our work provides a practical tool for livestock breeding programs and offers new insights into leveraging genetic diversity across breeds for improved genomic prediction.

Background: Fast-growing broilers are poorly adapted to heat. Adjusting feed composition may mitigate heat stress (HS) effects in temperate climates, while maintaining performance and health during cooler days.

Methods: One thousand nine hundred and twenty Ross 308 male broilers were housed in 64 pens in 4 climate-controlled rooms, 2 under cyclical HS (d 28-43; 32 ± 2 °C; 60%-70% RH; 09:30-15:30) and 2 under thermoneutral (TN) conditions. In the finisher phase, broilers were allocated to 4 dietary treatments, analyzed values are given except for metabolizable energy (ME): low crude protein (CP) and control fat (LowCP-ConF; 17.0% CP, 5.9% crude fat (CF), 2,925 kcal/kg ME), low CP and high fat (LowCP-HighF; 17.2% CP, 7.9% CF, 3,019 kcal/kg ME), control CP and high fat (ConCP-HighF; 18.1% CP, 8.0% CF, 2,992 kcal/kg ME) and a basal control (ConCP-ConF; 18.7% CP, 6.3% CF, 2,913 kcal/kg ME). LowCP diets contained control levels of digestible amino acids.

Results: During the finisher phase, compared to control CP levels, LowCP increased average daily feed intake (ADFI) (+ 2.15%; P = 0.020) and affected average daily gain (ADG) and feed conversion ratio (FCR) negatively under TN (-3.77% and +6.49%; P = 0.003 and P < 0.001, respectively), but not during HS. Compared to control CF, HighF decreased ADFI during TN and HS (-3.16% and -3.17%; P < 0.001 and P = 0.022) and reduced ADG in TN groups (-3.17%; P = 0.010), but not during HS. Mortality was higher in broilers receiving HighF during HS (P = 0.040). Slaughter weights were unaffected. LowCP decreased plasma uric acid and lactate dehydrogenase levels during TN, but increased plasma glucose during HS. LowCP increased breast meat redness (a*) during TN and HS (P < 0.05). HighF decreased fat (-1.68%; P = 0.017), but increased protein levels (+1.53%; P < 0.001) in breast meat of HS-broilers.

Conclusion: LowCP and HighF impaired performance under TN but not under HS. HighF increased mortality under HS, yet improved breast meat composition. These findings highlight the challenge of designing an optimal diet for both conditions and underscore the need to better understand amino acid needs and energy-to-protein ratios during HS.

Background: As a unique livestock adapted to the harsh environment, grazing yaks frequently suffer from malnutrition and even death because of the lower yield and quality of forage in the Qinghai-Tibet Plateau during the cold season. Certain stress conditions, such as environmental changes, disease, and malnutrition, can lead to a decrease in glutamine (Gln) synthesis, which fails to cover the physiological needs of the organism. Supplementation with exogenous Gln can promote nutrient digestion and improve rumen fermentation in ruminant animals under malnutrition. However, whether Gln could alleviate the barrier function injury induced by malnutrition and its mechanism is still unclear.

Methods: In the in vivo experiments, 24 healthy yaks (31 months, 265.35 ± 25.81 kg) were randomly divided into 3 groups, namely control group (Con, free access to the basal diet), feed restriction group (FR, 50% level of ad libitum feed intake), and feed restriction + Gln group (FR + Gln, 50% level of ad libitum feed intake from d 1 to 30, 50% level of ad libitum feed intake + 1% Gln from d 31 to 60). In the in vitro experiments, the yak rumen epithelial cells (YRECs) were divided into 4 groups: Con group (complete medium), Gln group (complete medium + 10 mmol/L Gln), Gln deficiency group (Gln-D, Gln-free medium), and Gln deficiency + Gln group (Gln-D + Gln, Gln-free medium + 10 mmol/L Gln).

Results: In the in vivo experiments, FR significantly decreased the ruminal concentrations of acetate, propionate, butyrate, iso-butyrate, and total volatile fatty acid (VFA) (P < 0.05). FR also reduced the mRNA expression of NHE1, Na⁺/K⁺-ATPase, and Ca²⁺/Mg²⁺-ATPase, and the concentrations of lactate, histone acetyltransferase (p300), histone deacetylase (HDAC), as well as the histone lysine lactylation level compared to Con group, while Gln supplementation alleviated them (P < 0.05). In the in vitro experiments, Gln alleviated the Gln-D-induced down-regulation of NHE1, Na⁺/K⁺-ATPase, and Ca²⁺/Mg²⁺-ATPase mRNA expressions and reduction of lactate, p300, HDAC concentrations, and histone lysine lactylation level (P < 0.05). Besides, p300 inhibitor abrogated Gln repair of barrier function damage in YRECs (P < 0.05).

Conclusions: Overall, our results revealed the potential mechanism of Gln supplementation to repair malnutrition-induced damage of rumen epithelial barrier function in yaks, which might be related to histone lysine lactylation. However, because we do not have a control group receiving glutamine alone, we cannot determine the impact of Gln on the rumen epithelial function of normal yaks.

Background: Heat stress (HS) is posing as a tremendous threat to the swine industry, due to the thermos-sensitive gonads of boars. Testes are immune-privileged organs in which spermatogenesis needs to remain undisturbed, whereas immune cells are thermo-sensitive, especially macrophages, which are the most abundant testicular immune cells. Our study aimed to unveil the underlying immune responses and assess their consequences on the semen quality of boars under HS. The results will aid in addressing environmental temperature-related seasonal infertility and in selecting the best boar for use in artificial insemination.

Methods: The 3-week experiment assigned 26 8-week-old Rongchang male pigs into thermal neutral pair-feed (TN-PF) and HS groups. During the last 2 weeks, which served as the HS period, the HS group was subjected to 14-day 35 ± 1 °C, while the TN-PF group was kept at 26 ± 1 °C. Pig gonad tissues were sampled at the end of HS period for assessments and measurements.

Results: Our findings confirmed HS-related reactions such as elevated respiration rate (P < 0.05) and elevated heat shock protein 60 (HSP60; P < 0.05) and heat shock protein 90 (HSP90; P < 0.05) expression levels. Sperm motility (P = 0.06) and progressive sperms (P = 0.08) were decreased under HS as was a significant reduction in average straight-line velocity (VSL; P < 0.05). Additionally, total abnormality levels increased (P < 0.05). Fibrosis, caspase-3 expression, and accumulations of tumor necrosis factor-α (TNF-α; P < 0.05) and interleukin-1β (IL-1β; P < 0.05), along with an elevated macrophage composition (P < 0.05) characterized the orchitis under HS. Single cell RNA sequencing (scRNA-seq) revealed fluctuations in engulfing and inflammatory signals in testicular macrophages (TMs). In particular, the complement cascade was promoted by CD163⁺ macrophages, resulting in membrane attack complex (C5b-9) assembly (P < 0.05). Linear regressions further revealed a negative correlation between C5b-9 and sperm motility (P < 0.05), as well as near-negative correlations between the C5b-9 and both progressive motility (P = 0.08) and VSL (P = 0.06).

Conclusions: Our findings highlighted the relationship between HS, the onset of orchitis, and the activation of the complement system, all of which decreased the boar semen quality.

Background: Hypoxia is a pervasive challenge in aquaculture that poses a significant threat to aquatic organisms. Since fish cannot synthesize vitamin A endogenously, it must be supplied through diet, and it plays a vital role in supporting fish stress resistance. This study aimed to investigate the protective effects of VA on the gills of adult grass carp (Ctenopharyngodon idella) against hypoxia and to elucidate the underlying mechanisms.

Methods: Six experimental diets with graded VA levels (375, 862, 1,614, 2,099, 2,786, and 3,118 IU/kg) were fed to grass carp (initial weight: 726 ± 1.2 g) for 60 d. After the trial, 24 fish per treatment were selected, divided equally into normoxic and hypoxic groups, fasted for 24 h, and then subjected to a 96-h acute hypoxic challenge.

Results: The results demonstrated that VA supplementation mitigated hypoxia-induced damage in gill tissue, as evidenced by histological examination. Furthermore, VA alleviated oxidative stress, as indicated by reduced levels of lactate (LD), lactate dehydrogenase (LDH), reactive oxygen species (ROS), protein carbonyl (PC), and malondialdehyde (MDA). Further investigations indicated that VA alleviated mitochondrial stress, potentially through suppressing the canonical UPR^mt axis while activating both the UPR^mt sirtuin axis and the UPR^IMS/Erα axis. VA also modulated mitochondrial mass via multiple mechanisms, including the promotion of mitochondrial biogenesis, maintenance of dynamics by stimulating fusion and reducing fission, and inhibition of mitophagy. The suppression of mitophagy likely involved downregulating both the Pink1/Parkin-dependent pathway and the Hif1a-Bnip3 pathway. Taken together, these adaptations suggested an essential role for VA in preserving mitochondrial homeostasis. Based on the quadratic regression analysis of ROS and MDA levels from the hypoxic group, the estimated VA requirements for adult grass carp were 2,013 and 2,056 IU/kg diet, respectively.

Conclusions: In summary, this study provided the first evidence that VA conferred protective effects against hypoxia-induced gill damage in grass carp.