Cyclophilin A (CypA, also known as PPIA) is an essential member of the immunophilin family. As an intracellular target of the immunosuppressive drug cyclosporin A (CsA) or a peptidyl-prolyl cis/trans isomerase (PPIase), it catalyzes the cis-trans isomerization of proline amidic peptide bonds, through which it regulates a variety of biological processes, such as intracellular signaling, transcription and apoptosis. In this study, we found that intracellular CypA enhanced Twist1 phosphorylation at Ser68 and inhibited apoptosis in A549 cells. Mechanistically, CypA could mediate the phosphorylation of Twist1 at Ser68 via p38 mitogen-activated protein kinase (also known as MAPK14), which inhibited its ubiquitylation-mediated degradation. In addition, CypA increased interaction between Twist1 and p65 (also known as RELA), as well as nuclear accumulation of the Twist1-p65 complex, which regulated Twist1-dependent expression of CDH1 and CDH2. Our findings collectively indicate the role of CypA in Twist1-mediated apoptosis of A549 cells through stabilizing Twist1 protein.

Neonatal calves’ diarrhea, which can be severe enough to cause death, has a significant impact on the global cattle industry. In this study, alfalfa polysaccharides and seaweed polysaccharides were found to significantly improve the diarrhea condition in neonatal calves. To explore the underlying mechanisms, further microbiomic and metabolomic analyses were conducted. This study investigated the impact of alfalfa polysaccharides and seaweed polysaccharides on growth performance, serum metabolites, gut microbiota, and metabolomics in neonatal Holstein calves. A total of 24 newborn calves were randomly assigned to three groups, with 8 calves per treatment group. The control (CON) group was fed a basal diet, the alfalfa polysaccharide (AP) group received a basal diet supplemented with alfalfa polysaccharides (4 g/calf/day), and the seaweed polysaccharide group (SP) received a basal diet supplemented with seaweed polysaccharides (4 g/calf/day). These polysaccharides were plant extracts. Compared to the CON group, the results indicated that SP significantly enhanced the body weight, height, chest circumference, and average daily gain of Holstein calves (p < 0.05), while also reducing the diarrhea rate and improving manure scoring (p < 0.05). Compared to the CON, AP also reduced the diarrhea rate (p < 0.05). In terms of serum biochemistry, supplementation with AP and SP increased serum alkaline phosphatase (ALP) and insulin-like growth factor 1 (IGF-1) levels compared to the CON group (p < 0.05). Both AP and SP elevated serum catalase (CAT) and Total Antioxidant Capacity (T-AOC) levels, indicating enhanced antioxidant status (p < 0.05). Regarding immune responses, supplementation with AP and SP significantly increased serum complement component 3 (C3) and immunoglobulin M (IgM) levels, while significantly reducing pro-inflammatory cytokines interleukin-18 (IL-18), tumor necrosis factor alpha (TNF-α), and interferon-gamma (IFN-γ) compared to the CON group (p < 0.05). Microbiota analysis revealed that AP modulated the abundance of Firmicutes, while SP influenced the abundance of Prevotella and Succiniclasticum. AP and SP differentially influenced intestinal metabolites compared to the CON group, leading to enrichment in pathways related to immunity, antibacterial, and anti-inflammatory functions. These pathways included the biosynthesis of alkaloids from ornithine, lysine, and nicotinic acid, glucocorticoid and mineralocorticoid receptor canothersis/antagonists, secondary metabolite biosynthesis, and alkaloid biosynthesis from histidine and purine, thus alleviating intestinal inflammation. Therefore, by supplementing with AP and SP, the diarrhea rate in calves was reduced, and the immune function of Holstein calves was enhanced, while simultaneously promoting a higher relative abundance of beneficial gut bacteria and suppressing the relative abundance of pathogenic bacteria. Additionally, gut pathways associated with immune response and inflammation were modulated by AP and SP. This study provided valuable insights and theoretical underpinnings for the use of AP and SP in preventing diarrhea in neonatal calves.

Avian colibacillosis is a bacterial disease caused by avian pathogenic Escherichia coli (APEC) that results in great losses in the poultry industry every year. Individual Silkie chickens of the same breed that are given the same feed in the same feeding conditions have different levels of resistance or susceptibility to APEC. Differences in gut microbes, gut metabolites, and gene expression in the spleen of APEC-resistant and APEC-susceptible chickens were compared, and multiple omics associations were analyzed to explore the mechanism of resistance to APEC in Silkie chickens. Compared with those in the APEC-susceptible group, the APEC-resistant group showed significantly increased abundances of many gut microorganisms, including Bacillus, Thermoactinomyces, Arthrobacter, and Ureibacillus, which were positively correlated with norvaline, l-arginine, and valyl-glycine levels. Intestinal tryptophan, indole, and indole derivative-related differentially abundant metabolites played an active role in combatting APEC infection. In the spleen, "response to stimulus" was the most significantly enriched GO term, and "cytokine‒cytokine receptor interaction" was the most significantly enriched KEGG pathway. The arginine biosynthesis and PPAR signaling pathways were the KEGG pathways that were significantly enriched with differentially abundant metabolites and differentially expressed genes. This study provides new insight into the prevention and treatment of APEC infection in Silkie chickens and lays a foundation to study the mechanism of APEC infection in poultry.

MicroRNAs (miRNAs) are short noncoding RNAs that can regulate target gene expression at the posttranscriptional level. It has been reported that bta-miR-145 shows differential expression between the different lactation stages of bovine mammary glands, but the function of bta-miR-145 in normal mammary glands remains unknown. The overexpression of bta-miR-145 significantly decreased the proliferation of mammary epithelial cells (p < .05), and this effect was reversed upon bta-miR-145 inhibition. Using several miRNA prediction programmes, insulin receptor substrate 1 (IRS1) was predicted to be a potential target of miR-145. Using the DAVID database, many predicted targets of bta-miR-145 were found to be involved in the MAPK signalling pathway associated with cell proliferation, including IRS1. Bovine IRS1 3’RACE sequencing and reference comparison revealed that possible binding sites for bta-miR-145 still exist in IRS1. The IRS1 mRNA level was not affected by the transfection of primary bovine mammary epithelial cells with 150 pmol of a bta-miR-145 mimic or 300 pmol of a bta-miR-145 inhibitor for 24 h (pBMEC, p > .05), whereas the IRS1 protein level was changed significantly after bta-miR-145 mimic or inhibitor transfection for 72 h (p < .05). Taken together, these results suggest that bta-miR-145 is involved in the proliferation of bovine mammary epithelial cells by targeting IRS1, which is related to the MAPK signalling pathway.

Objective: The study aimed to compare the growth performance, rumen fermentation, and rumen bacterial community of fattening Hu sheep fed either total mixed ration (TMR) or pelleted total mixed ration (PTMR) and to assess the feeding efficiency.Methods: In a 58-day feeding experiment, forty-eight Hu sheep were randomly assigned to two groups (TMR and PTMR), with six pens per group and four sheep per pen. Body weight and feed intake were measured throughout the experiment to assess growth performance. On the final day of the experiment, rumen fluid was collected from sheep using a rumen fluid collector two hours post-feeding.Results: The sheep in the PTMR group exhibited significantly higher body weight (p<0.05) and average daily gain (p0.05). No statistically significant differences were observed in rumen fermentation parameters between the TMR and PTMR groups. However, analysis of rumen bacteria revealed that the Sob, Ace, Bootstrap, Shannon, and Chao indices were significantly lower in the PTMR group compared to the TMR group (p<0.05). Bacteroidetes and Firmicutes were the predominant bacteria in all groups, with the abundance of Succinivibrionaceae_UCG-001 significantly lower in the PTMR group. The relative abundance of Rikenellaceae_RC9_gut_group, NK4A214_group, and Streptococcus was significantly higher in the TMR group than in the PTMR group (p<0.05). Bacterial function prediction showed downregulation of the energy production and conversion pathway in the PTMR group (p<0.05). Correlation analysis indicated that norank_f_Bacteroidales_RF16 positively correlated with butyric acid (p<0.05), while Anaerovibrio negatively correlated with acetic acid, propionic acid, butyric acid, and total volatile fatty acids (p<0.05).Conclusion: In summary, the results demonstrate that PTMR significantly enhances average daily gain in Hu sheep while maintaining rumen fermentation parameters, although accompanied by modifications in rumen bacterial community structure.