Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 promotes collagen cross-linking and ECM stiffening to induce liver fibrosis.

Procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (Plod2) is a key collagen lysyl hydroxylase mediating the formation of collagen fiber and stabilized collagen cross-links, and has been identified in several forms of fibrosis. However, the potential role and regulatory mechanism of Plod2 in liver fibrosis remain unclear yet. Mouse liver fibrosis models were induced by injecting carbon tetrachloride (CCl4) intraperitoneally. The morphology and alignment of collagen was observed under transmission and scanning electron microscopy, and extracellular matrix (ECM) stiffness was measured by atomic force microscopy. Large amounts of densely packed fibrillar collagen fibers produced by myofibroblasts (MFs) were deposited in fibrotic liver of mice reaching very large diameters in the cross section, accompanied with ECM stiffening, which was positively correlated with collagen-crosslinking. The expression of Plod2 was dynamically up-regulated in fibrotic liver of mouse and human. In MFs transfection of Plod2 siRNA made collagen fibers more orderly and linear aligned which can be easily degraded and protected from ECM stiffness. Administration of Plod2 siRNA preventatively or therapeutically in CCl4 mice reduced the average size of collagen bundles in transverse section, increased collagen solubility, decreases the levels of crosslinking products hydroxylysylpyridinoline and lysylpyridinoline, prevented ECM stiffening and alleviated liver fibrosis. Altogether, Plod2 mediates the formation of stabilized profibrotic collagen cross-links in MFs, leading to the alteration of collagen solubility and ECM stiffness, and eventually aggravates liver fibrosis, which provide potential target for the treatment of liver disease.

Characterization of Lung Microbiomes in Pneumonic Hu Sheep Using Culture Technique and 16S rRNA Gene Sequencing.

Hu sheep, a locally bred species in China known for its high productivity, is currently suffering from pneumonia. Here, we combine high-throughput 16SrRNA gene sequencing and bacterial culturing to examine the bacterial community in pneumonic Hu Sheep lungs (p < 0.05). The results showed that the abundance and diversity of lung bacteria in healthy sheep were significantly higher than those in pneumonia sheep (p = 0.139), while there was no significant difference between moderate and severe pneumonia. Furthermore, the composition of the lung microbiota community underwent significant alterations between different levels of pneumonia severity. The application of LEfSe analysis revealed a notable enrichment of Mannheimiae within the lungs of sheep afflicted with moderate pneumonia (p < 0.01), surpassing the levels observed in their healthy counterparts. Additionally, Fusobacterium emerged as the prevailing bacterial group within the lungs of sheep suffering from severe pneumonia. Integrating the results of bacterial isolation and identification, we conclusively determined that Mannheimia haemolytica was the primary pathogenic bacterium within the lungs of sheep afflicted with moderate pneumonia. Furthermore, the exacerbation of pneumonia may be attributed to the synergistic interplay between Fusobacterium spp. and other bacterial species. Our results provide new insights for guiding preventive and therapeutic measures for pneumonia of different severities in sheep.

Probiotics and vitamins modulate the cecal microbiota of laying hens submitted to induced molting.

Induced molting enables laying hens to relax, restore energy and prolong the laying hen cycle, resolving problems such as poor egg quality and minimizing economic losses caused by rising global feeding costs. However, traditional molting methods may disrupt gut microflora and promote potential pathogens infections. This study used a customized additive with a mixture of probiotics and vitamins to induce molting and examine the cecal microbiota post molting. A total of two hundred 377 day-of-ISA Brown laying hens were randomly assigned to four groups: non-molt with basal diet (C), 12-day feeding restriction (FR) in earlier-molting (B), feed again to 27.12% egg production in middle-molting (A) and reach second peak of egg production over 81.36% in post-molting (D). Sequencing 16S rRNA to analyze cecal microbial composition revealed that there is no significant change in bacterial community abundance post-molting. In contrast to group C, the number of potentially harmful bacteria such as E. coli and Enterococcus was not found to increase in groups B, A, or D. This additive keeps cecal microbiota diversity and community richness steady. In cecal contents, hens in group B had lower Lactobacillus, Lachnospiraceae and Prevotellaceae (vsC, A, and D), no significant differences were found between post-molting and the non-molting. Furthermore, cecal microbiota and other chemicals (antibodies, hormones, and enzymes, etc.) strongly affect immunological function and health. Most biochemical indicators are significantly positively correlated with Prevotellaceae, Ruminococcaceae and Subdoligranulum, while negatively with Phascolarctobacterium and Desulfovibrio. In conclusion, the additive of probiotics and vitamins improved the cecal microbiota composition, no increase in the associated pathogenic microbial community due to traditional molting methods, and enhances hepatic lipid metabolism and adaptive immunological function, supporting their application and induced molting technology in the poultry breeding industry.

Isolation and Identification of Aeromonas veronii in Sheep with Fatal Infection in China: A Case Report.

According to the findings of a sheep breeding farm in Shaanxi, China, 2.53% (15/594) of sheep exhibited respiratory (clinical) symptoms such as dyspnoea, nasal discharge, wet cough, fever, and progressive emaciation. Although multi-drug treatment strategies (including ampicillin, tylosin, florfenicol, and ceftiofur) have been attempted to improve clinical outcomes, they have only been met with limited success, with a mortality rate of 40%. Ultimately, Aeromonas veronii (A. veronii) was identified as the causative pathogen for respiratory disease. The rates of symptomatic and asymptomatic sheep positive to A. veronii were 64.28% (95% CI 52.25-76.31%) and 8.02% (95% CI 6.96-9.08%), respectively. Pathogenicity tests demonstrated that the A. veronii is pathogenic to sheep and mice. The results of the antibiotic susceptibility tests revealed that the strain was sensitive to cefotaxime, gentamicin, and enrofloxacin and resistant to ampicillin, ceftiofur, amoxicillin, kanamycin, neomycin, streptomycin, tetracycline, florfenicol, and tylosin. We suggest that the combination of cefotaxime and gentamicin is an effective treatment based on the results of an antimicrobial susceptibility test, which exhibited good therapeutic efficacy. To the best of our knowledge, this is the first report in which pathogenic A. veronii has been documented as the cause of death in sheep in China. We concluded that pathogenic A. veronii poses a potential risk to the industry of sheep husbandry. This study's findings can help guide prevention and treatment plans for A. veronii infection in sheep.