理学最新文献

Fiber, the most abundant organic polymer in nature, is widely recognized as a foundational sustainable material with diverse applications across industrial, medical, and consumer domains. Owing to its renewability and widespread availability, it also serves as a critical alternative energy source in agriculture, enabling more sustainable livestock production through the efficient conversion of fibrous feedstuffs, thereby supporting the principles of a circular bioeconomy. Cellulose, which constitutes up to 80% of plant fiber, contains tightly packed crystalline regions that confer strong resistance to microbial degradation. Other key obstacles to efficient cellulose digestion in the gut include the absence of critical cellulolytic genes, low enzymatic activity, a lack of natural activators, and the presence of cellulase inhibitors. Synthetic biology provides innovative molecular-level strategies to overcome key technical barriers in cellulose degradation. These approaches employ targeted modifications at nucleic acid and protein levels, including the introduction of engineered genes, synthetic regulators, and optimized enzymes, to develop high-performance microbial systems with enhanced cellulose-degrading capabilities. Furthermore, genetic modifications like the knockout of inhibitory genes and knock-in of activator genes, combined with rational redesign of multi-enzyme complexes, can significantly improve the secretion and catalytic efficiency of cellulases. When integrated with artificial intelligence, synthetic biology enables predictive screening and precision engineering of microbial strains for highly efficient cellulose degradation. This review comprehensively summarizes recent advances in synthetic biology approaches for improving cellulose degradation and highlights how these tools can optimize fiber utilization in sustainable agricultural and industrial applications.

Background: Post-weaning diarrhea (PWD) in piglets, primarily caused by enterotoxigenic Escherichia coli (ETEC) K88 (F4) infection, presents a major challenge in swine production. This study aimed to isolate bacteriophages (phages) specific to ETEC K88, utilizing ETEC K88 as the host strain, and to assess the efficacy of dietary supplementation with the isolated phages in weaned piglets over a two-week period using an ETEC K88 challenge model in a pilot study.

Results: Three ETEC K88-specific phages (EC-P1, EC-P2, and EC-P3) were isolated and identified as tailed phages. These phages displayed a short latency period, broad acid-base stability, and thermal stability, effectively inhibiting ETEC K88 growth and disrupting ETEC K88 biofilms in vitro. Lyophilized phage powder was prepared and supplemented at 400, 600 or 800 mg/kg in the diets. Compared to the ETEC K88 group, piglets in the ETEC K88 + 600 or 800 mg/kg phages group exhibited markedly lower diarrhea scores and rectal temperatures at 12, 24, and 48 h post-infection. Supplementation with 600 mg/kg phages enhanced intestinal integrity of ETEC K88-infected piglets, as evidenced by an increased jejunal villus height and villus height-to-crypt depth ratio, reduced serum diamine oxidase and D-lactate levels, and upregulated jejunal ZO-1 protein expression. Concomitantly, systemic and jejunal inflammatory responses were attenuated by supplementation with 600 mg/kg of phages, as evidenced by decreased serum LPS, IL-1β, IL-10 and TNF-α levels, down-regulated jejunal IL-1β and IL-6 mRNA expression, and suppressed NF-κB signalling (downregulated p-IκBα/IκBα and p-p65/p65 ratios). Supplementation with 600 mg/kg phages also shifted the faecal microbiota toward eubiosis, increasing the Shannon index, decreasing Proteobacteria and Enterobacteriaceae abundances, and elevating beneficial taxa (Patescibacteria, Muribaculaceae, and Subdoligranulum). Correlation analysis further revealed that Proteobacteria and Enterobacteriaceae abundances were positively associated with diarrhoea characteristics, whereas Muribaculaceae showed a negative correlation.

Conclusions: Three ETEC K88-targeting phages were successfully isolated, characterized, and prepared as lyophilized phage powder for dietary supplementation. Dietary supplementation with 600 mg/kg of lyophilized phage powder alleviated PWD in piglets by modulating gut microbiota and inflammatory responses.

Background: Normal testicular development is essential for maintaining male fertility and reproductive performance in livestock. Leydig cells (LCs) play a central role in testicular physiology; however, the epigenetic mechanisms regulating their development remain largely unclear. Methyltransferase-like 3 (METTL3), a key m⁶A methylation enzyme, and microRNAs are increasingly recognised as critical regulators of this process.

Results: METTL3 expression in goat LCs markedly decreased during testicular development. This downregulation reduced m⁶A modification on pri-miR-145, impairing DiGeorge syndrome critical region 8-mediated processing and resulting in decreased levels of mature miR-145-3p. This reduction in miR-145-3p increased the expression of phosphoenolpyruvate carboxykinase 1 (PCK1), which activated gluconeogenesis, increased intracellular glucose levels, and increased mitochondrial membrane potential. Consequently, this metabolic shift upregulated cell cycle-related genes (cyclin B1 and cyclin E2), promoting LC proliferation and testicular growth.

Conclusions: Our findings demonstrate that the METTL3/miR-145-3p/PCK1 axis is a key regulatory pathway linking epigenetic modification to the metabolic activity and proliferation of LCs. This mechanism provides novel insights into the molecular control of testicular development in male goats and may offer new targets for improving male reproductive capacity in livestock.

Background: During the weaning phase, piglets are exposed to significant physiological and environmental stressors, which disrupt the balance of their intestinal microbiota and often lead to severe diarrhea. Previous studies have demonstrated that alfalfa fiber, derived from the stems and leaves of alfalfa, can effectively alleviate diarrhea in piglets. Additionally, multiple studies have highlighted the potential of fecal microbiota transplantation (FMT) in mitigating diarrhea in various models of intestinal diseases in young animals. However, the specific mechanisms by which FMT from targeted sources alleviates diarrhea in weaned piglets remain to be fully elucidated.

Results: In this study, FMT from donor piglets fed an alfalfa fiber-supplemented diet effectively alleviated diarrhea, improved intestinal morphology, and enhanced gut barrier function in weaned piglets. FMT further promoted the colonization of beneficial bacterial genera (including UCG-005, unclassified Lachnospiraceae, Lachnospiraceae AC2044 group, UCG-002, Candidatus Saccharimonas, and Lachnospiraceae ND3007 group) while inhibiting the detrimental genus Tyzzerella, consequently enhancing the production of short-chain fatty acids (SCFAs). Additionally, FMT upregulated riboflavin metabolism, leading to elevated flavin adenine dinucleotide (FAD) levels and increased glutathione reductase activity, thereby collectively attenuating lipopolysaccharide (LPS)-induced oxidative stress and contributing to intestinal health.

Conclusions: We found that FMT modulates the structure of the gut microbiota, enhances microbial diversity and composition, increases the production of SCFAs, and upregulates riboflavin metabolism to elevate FAD levels. These changes collectively enhance immune and antioxidant capacities, thereby alleviating diarrhea.

Background: The gut is primarily responsible for digestion and nutrient absorption, plays essential roles in immune regulation and metabolic balance, and is supported by a diverse microbiome essential for digestion, absorption, and defence from pathogens. Understanding gut physiology and pathophysiology in pre-weaned calves is essential, as infections like cryptosporidiosis can lead to gut dysbiosis, impair growth, and negatively affect long-term productivity. Faeces are considered easily accessible biological specimens that can be used to monitor gastrointestinal disorders. The methods employed in this study aimed to investigate the potential use of faecal extracellular vesicles (fEVs) as a non-invasive tool for assessing gut health and infections in calves. Particularly, considering Cryptosporidiosis as a model for gut infectious disease.

Results: The analysis using a hybrid reference-based metaproteomic approach revealed that the proteomic profiles of fEVs significantly differed from that of faecal crude (FC) suspensions. Both sample types contained microbial and host proteins, which are important for maintaining gut defence and microbial homeostasis. However, Cryptosporidium spp. infection significantly shifted the fEV proteome, reducing both host and microbial proteins involved in gut defence. It also reduced proteins from microbes that are important for maintaining microbial homeostasis, while increasing stress-related proteins. Further, lyophilisation of fEVs significantly altered the protein profiles.

Conclusion: These findings underscore that fEVs contain host and microbial proteins that are a valuable resource for studying gut physiology, pathophysiology, host-microbe-pathogen interactions, and microbiome dynamics. Changes in the proteomic profile of fEVs during Cryptosporidium spp. infection demonstrates the pathogen's ability to manipulate host immune defences and microbiome composition for its survival and replication. Overall, these findings support the utility of fEV proteomics as a non-invasive platform for biomarker discovery and advancing research in gastrointestinal health and disease in livestock.

Background: Heat stress (HS) can impair boar testicular function, leading to reproductive issues. However, chlorogenic acid (CGA) has been shown to mitigate HS-induced damage in various livestock and poultry species. Prepuberty is an important stage of testicular development in boars after birth. However, the protective effect of CGA on testicular HS injury during prepuberty boars and the underlying mechanisms are still not fully understood.

Results: In vivo, a total of 30 healthy boars with similar body weights and ages were obtained and randomly divided into 3 groups, which were fed a basal diet supplemented with CGA 0 (the ND_TN group), 0 (the ND_HS group) or 1,000 (the CGA_HS group) mg/kg. After being fed for 28 d, all the groups, except the ND_TN group, were treated with high temperature for 7 d, after which samples were collected from the boars and analysed. The results showed that CGA significantly mitigated the HS-induced reduction in T-AOC content in testicular tissue and sperm density. Mechanistically, multiomics analysis revealed that the genes differentially expressed by CGA and HS were predominantly associated with the glutathione metabolism pathway. The combined analysis of transcriptomics and proteomics revealed that only BLVRA was affected by both HS and CGA when the mRNA and protein levels of a gene showed differential expression with the same trend. In vitro studies confirmed that CGA modulated GPX3 expression via BLVRA, affected GPx activity, and attenuated HS-induced ROS accumulation.

Conclusions: In conclusion, prepubertal HS impairs the spermatogenic capacity of boars. BLVRA may mediate the testicular protective effect of CGA, although in vivo validation of this pathway is needed. This study contributes to elucidating the mechanisms underlying the effects of HS on prepubertal boar testicular development using multiomics approaches, laying a foundation for the potential utilization of CGA in swine production.