Journal Articles

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    Identification of novel biomarkers for the prediction of subclinical coronary artery atherosclerosis in patients with rheumatoid arthritis: an exploratory analysis
    (BioMed Central Ltd, 2023-12) Bathon JM; Centola M; Liu X; Jin Z; Ji W; Knowlton NS; Ferraz-Amaro I; Fu Q; Giles JT; Wasko MC; Stein CM; Van Eyk JE
    Background: Cardiovascular (CV) risk estimation calculators for the general population underperform in patients with rheumatoid arthritis (RA). The purpose of this study was to identify relevant protein biomarkers that could be added to traditional CV risk calculators to improve the capacity of coronary artery calcification (CAC) prediction in individuals with RA. In a second step, we quantify the improvement of this prediction of CAC when these circulating biomarkers are added to standard risk scores. Methods: A panel of 141 serum and plasma proteins, which represent a broad base of both CV and RA biology, were evaluated and prioritized as candidate biomarkers. Of these, 39 proteins were selected and measured by commercial ELISA or quantitative mass spectroscopy in 561 individuals with RA in whom a measure of CAC and frozen sera were available. The patients were randomly split 50:50 into a training/validation cohort. Discrimination (using area under the receiver operator characteristic curves) and re-classification (through net reclassification improvement and integrated discrimination improvement calculation) analyses were performed first in the training cohort and replicated in the validation cohort, to estimate the increase in prediction accuracy for CAC using the ACA/AHA (American College of Cardiology and the American Heart Association) score with, compared to without, addition of these circulating biomarkers. Results: The model containing ACC/AHA score plus cytokines (osteopontin, cartilage glycoprotein-39, cystatin C, and chemokine (C–C motif) ligand 18) and plus quantitative mass spectroscopy biomarkers (serpin D1, paraoxonase, and clusterin) had a statistically significant positive net reclassifications index and integrated discrimination improvement for the prediction of CAC, using ACC/AHA score without any biomarkers as the reference category. These results were confirmed in the validation cohort. Conclusion: In this exploratory analysis, the addition of several circulating CV and RA biomarkers to a standard CV risk calculator yielded significant improvements in discrimination and reclassification for the presence of CAC in individuals with RA.
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    Characterizing the dynamics of the rumen microbiota, its metabolites, and blood metabolites across reproductive stages in Small-tailed Han sheep.
    (American Society for Microbiology, 2023-11-10) Sha Y; Liu X; Pu X; He Y; Wang J; Zhao S; Shao P; Wang F; Xie Z; Chen X; Yang W
    Different reproductive stages of mammals involve complex biological processes, and the intestinal microbiota, as an endocrine organ or an “invisible organ,” is involved in the regulation of hormone levels, immune function, and metabolism. However, the effects of the rumen microbiota, its metabolites, and blood metabolites on the reproductive performance of ruminants remain unclear. This study revealed that the Prevotella abundance increased significantly during pregnancy (P < 0.01); the Fibrobacter abundance increased significantly during lactation (P < 0.05); and rumen microbial carbohydrate metabolism, glucose biosynthesis, and metabolic functions were significantly enriched during pregnancy (P < 0.05). Microbial metabolic profile analysis showed that the differentially abundant microbial metabolites during pregnancy and lactation were mainly enriched in the biosynthesis of ubiquinone and other terpenoid quinones, and there was a certain correlation with the microbiota. Among them, sapindoside A was increased during pregnancy, nicotinamide riboside and β-cryptoxanthin were reduced during pregnancy, and L-tryptophan was significantly increased during lactation. In addition, the volatile fatty acid levels in lactation were significantly higher than those in non-pregnancy and pregnancy (P < 0.05), and the NH3-N content during pregnancy was significantly higher than that during lactation and non-pregnancy (P < 0.05). Moreover, there were differences in the serum metabolite levels at different reproductive stages, and similar metabolites existed when comparing the rumen metabolites, which were mainly enriched in arachidonic acid metabolism, vitamin B6 metabolism, and ABC transporter protein, resulting in significantly higher serum IgA and IgM levels during lactation than during non-pregnancy and pregnancy (P < 0.05).
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    Interaction between Rumen Epithelial miRNAs-Microbiota-Metabolites in Response to Cold-Season Nutritional Stress in Tibetan Sheep.
    (MDPI (Basel, Switzerland), 2023-09-23) Lv W; Sha Y; Liu X; He Y; Hu J; Wang J; Li S; Guo X; Shao P; Zhao F; Li M; Freking B
    Tibetan sheep are already well adapted to cold season nutrient stress on the Tibetan Plateau. Rumen, an important nutrient for metabolism and as an absorption organ in ruminants, plays a vital role in the cold stress adaptations of Tibetan sheep. Ruminal microbiota also plays an indispensable role in rumen function. In this study, combined multiomics data were utilized to comprehensively analyze the interaction mechanism between rumen epithelial miRNAs and microbiota and their metabolites in Tibetan sheep under nutrient stress in the cold season. A total of 949 miRNAs were identified in the rumen epithelium of both cold and warm seasons. A total of 62 differentially expressed (DE) miRNAs were screened using FC > 1.5 and p value < 0.01, and a total of 20,206 targeted genes were predicted by DE miRNAs. KEGG enrichment analysis revealed that DE miRNA-targeted genes were mainly enriched in axon guidance(ko04360), tight junction(ko04530), inflammatory mediator regulation of TRP channels(ko04750) and metabolism-related pathways. Correlation analysis revealed that rumen microbiota, rumen VFAs and DE miRNAs were all correlated. Further study revealed that the targeted genes of cold and warm season rumen epithelial DE miRNAs were coenriched with differential metabolites of microbiota in glycerophospholipid metabolism (ko00564), apoptosis (ko04210), inflammatory mediator regulation of TRP channels (ko04750), small cell lung cancer (ko05222), and choline metabolism in cancer (ko05231) pathways. There are several interactions between Tibetan sheep rumen epithelial miRNAs, rumen microbiota, and microbial metabolites, mainly through maintaining rumen epithelial barrier function and host homeostasis of choline and cholesterol, improving host immunity, and promoting energy metabolism pathways, thus enabling Tibetan sheep to effectively respond to cold season nutrient stress. The results also suggest that rumen microbiota have coevolved with their hosts to improve the adaptive capacity of Tibetan sheep to cold season nutrient stress, providing a new perspective for the study of cold season nutritional stress adaptation in Tibetan sheep.
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    Synergistic Responses of Tibetan Sheep Rumen Microbiota, Metabolites, and the Host to the Plateau Environment.
    (MDPI (Basel, Switzerland), 2023-10-03) Sha Y; Guo X; He Y; Li W; Liu X; Zhao S; Hu J; Wang J; Li S; Zhao Z; Hao Z; Miccheli A; Docea AO; Fukui H
    Plateau adaptation in animals involves genetic mechanisms as well as coevolutionary mechanisms of the microbiota and metabolome of the animal. Therefore, the characteristics of the rumen microbiome and metabolome, transcriptome, and serum metabolome of Tibetan sheep at different altitudes (4500 m, 3500 m, and 2500 m) were analyzed. The results showed that the rumen differential metabolites at 3500 m and 4500 m were mainly enriched in amino acid metabolism, lipid metabolism, and carbohydrate metabolism, and there was a significant correlation with microbiota. The differentially expressed genes and metabolites at middle and high altitudes were coenriched in asthma, arachidonic acid metabolism, and butanoate and propanoate metabolism. In addition, the serum differential metabolites at 3500 m and 4500 m were mainly enriched in amino acid metabolism, lipid metabolism, and metabolism of xenobiotics by cytochrome P450, and they were also related to microbiota. Further analysis revealed that rumen metabolites accounted for 7.65% of serum metabolites. These common metabolites were mainly enriched in metabolic pathways and were significantly correlated with host genes (p < 0.05). This study found that microbiota, metabolites, and epithelial genes were coenriched in pathways related to lipid metabolism, energy metabolism, and immune metabolism, which may be involved in the regulation of Tibetan sheep adaptation to plateau environmental changes.
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    Age Differences in Ileum Microbiota Density: VFAs and Their Transport-Related Gene Interactions in Tibetan Sheep
    (MDPI (Basel, Switzerland), 2024-10-03) Wang F; Sha Y; He Y; Liu X; Chen X; Yang W; Chen Q; Gao M; Huang W; Wang J; Hao Z; Wang L; Yang F
    Microbiota density plays an important role in maintaining host metabolism, immune function, and health, and age has a specific effect on the composition of intestinal microbiota. Therefore, the age-specific effects of age differences on the structure and function of the ileum microbiota in Tibetan sheep were investigated by determining the density of the ileum microbiota, the content of VFAs, and the expression levels of their transporter-related genes at different ages. The results showed that the contents of acetic acid and propionic acid in the ileum of Tibetan sheep in the 1.5-year-old group were significantly higher (p < 0.05) than those in other age groups, and that the contents of total VFAs were also significantly higher (p < 0.05) than those in other age groups. The relative densities of ileum Rf, Ra, and Fs were significantly higher in the 1.5-year-old group than in the other age groups (p < 0.05). The ileum epithelial VFAs transport-related genes AE2, MCT-4, and NHE1 had the highest expression in the 1.5-year-old group, and the expression of DRA was significantly lower in the 1.5-year-old group than in the 6-year-old group (p < 0.05). Correlation analysis showed that Cb, Sr, and Tb were significantly positively correlated with butyric acid concentration (p < 0.05) and negatively correlated with acetic acid, but the difference was not significant (p > 0.05); MCT-1, MCT-4, and AE2 were significantly positively correlated (p < 0.05) with acetic, propionic, and isobutyric acid concentrations; NHE1, NHE2, and MCT-4 were highly significantly positively correlated (p < 0.01) with Romboutsia and unclassified_Peptostreptococcaceae, while acetic acid was significantly positively correlated (p < 0.05) with NK4A214_group; Romboutsia, and unclassified_Peptostreptococcaceae were significantly positively correlated (p < 0.05). Therefore, compared with other ages, the 1.5-year-old Tibetan sheep had a stronger fermentation and metabolic capacity in the ileum under traditional grazing conditions on the plateau, which could provide more energy for Tibetan sheep during plateau acclimatization.
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    Large-scale synthesis of N-doped carbon capsules supporting atomically dispersed iron for efficient oxygen reduction reaction electrocatalysis
    (Elsevier B.V. on behalf of Nankai University, 2022-05-17) Yang H; Liu Y; Liu X; Wang X; Tian H; Waterhouse GIN; Kruger PE; Telfer SG; Ma S
    The large-scale synthesis of platinum-free electrocatalysts for the oxygen reduction reaction (ORR) remains a grand challenge. We report the large-scale production of stable and active ORR electrocatalysts based on iron, an earth-abundant element. A core–shell zeolitic imidazolate framework–tannic acid coordination polymer composite (ZIF-8@K-TA) was utilized as the catalyst precursor, which was transformed into iron atoms dispersed in hollow porous nitrogen-doped carbon capsules (H-Fe-Nx-C) through ion exchange and pyrolysis. H-Fe-Nx-C features site-isolated single-atom iron centers coordinated to nitrogen in graphitic layers, high levels of nitrogen doping, and high permeability to incoming gases. Benefiting from these characteristics, H-Fe-Nx-C demonstrated efficient electrocatalytic activity (E1/2 ​= ​0.92 ​V, vs. RHE) and stability towards the ORR in both alkaline and acidic media. In ORR performance, it surpassed the majority of recently reported Fe-N-C catalysts and the standard Pt/C catalyst. In addition, H-Fe-Nx-C showed outstanding tolerance to methanol.
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    Rumen Epithelial Development- and Metabolism-Related Genes Regulate Their Micromorphology and VFAs Mediating Plateau Adaptability at Different Ages in Tibetan Sheep.
    (MDPI (Basel, Switzerland), 2022-12-16) Sha Y; He Y; Liu X; Zhao S; Hu J; Wang J; Li S; Li W; Shi B; Hao Z; Martinez-Pastor F
    The rumen is an important hallmark organ of ruminants and plays an important role in the metabolism and immune barrier of Tibetan sheep on the Plateau. However, there are few studies on rumen development and metabolism regulation in Tibetan sheep at different ages. Here, we comprehensively analyzed the immune function, fermentation function, rumen epithelial micromorphology and transcriptome profile of Tibetan sheep at different ages. The results showed that the concentration of IgG decreased and the concentration of IgM increased with age (p < 0.05), and the highest concentration of IgA was observed at 1.5 and 3.5 years of age. In terms of rumen fermentation characteristics, VFAs of 4-month-old lambs were the highest, followed by VFAs and NH3-N of Tibetan sheep at 3.5 years of age. Hematoxylin-eosin staining and transmission electron microscopy section examination of rumen epithelial tissue showed that the rumen papilla width increased with age (p < 0.001), the thickness of the stratum corneum decreased, the cells in the stratum corneum showed accelerated migration and the thickness of the rumen muscle layer increased (p < 0.001). Desmosomal junctions between the layers of rumen epithelium increased at 1.5 and 3.5 years old, forming a compact barrier structure, and the basal layer had more mitochondria involved in the regulation of energy metabolism. RNA-seq analysis revealed that a total of 1006 differentially expressed genes (DEGs) were identified at four ages. The DEGs of Tibetan sheep aged 4 months and 6 years were mainly enriched in the oxidation−reduction process and ISG15-protein conjugation pathway. The 1.5 and 3.5-year-olds were mainly enriched in skeletal muscle thin filament assembly, mesenchyme migration and the tight junction pathway. WGCNA showed that DEGs related to rumen microbiota metabolite VFAs and epithelial morphology were enriched in “Metabolism of xenobiotics by cytochrome P450, PPAR signaling pathway, Butanoate metabolism pathways” and participated in the regulation of rumen epithelial immune and fermentation metabolism functions of Tibetan sheep at different ages. This study systematically revealed the regulatory mechanism of rumen epithelial development and metabolism in the plateau adaptation of Tibetan sheep, providing a new approach for the study of plateau adaptation.
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    Study of the Interactions between Muscle Fatty Acid Composition, Meat Quality-Related Genes and the Ileum Microbiota in Tibetan Sheep at Different Ages.
    (MDPI (Basel, Switzerland), 2024-02-23) Wang F; Sha Y; Liu X; He Y; Hu J; Wang J; Li S; Shao P; Chen X; Yang W; Chen Q; Gao M; Huang W; Panea B
    The intestinal microbiota of ruminants is an important factor affecting animal production and health. Research on the association mechanism between the intestinal microbiota and meat quality of ruminants will play a positive role in understanding the formation mechanism of meat quality in ruminants and improving production efficiency. In this study, the fatty acid composition and content, expression of related genes, and structural characteristics of the ileum microbiota of ewes of Tibetan sheep at different ages (4 months, 1.5 years, 3.5 years, and 6 years) were detected and analyzed. The results revealed significant differences in fatty acid composition and content in the muscle of Tibetan sheep at different ages (p < 0.05); in addition, the content of MUFAs in the longissimus dorsi muscle and leg muscle was higher. Similarly, the expressions of muscle-related genes differed among the different age groups, and the expression of the LPL, SCD, and FABP4 genes was higher in the 1.5-year-old group. The ileum microbiota diversity was higher in the 1.5-year-old group, the Romboutsia abundance ratio was significantly higher in the 1.5-year-old group (p < 0.05), and there was a significant positive correlation with oleic acid (C18:1n9c) (p < 0.05). In conclusion, the content of beneficial fatty acids in the longissimus dorsi muscle and leg muscle of Tibetan sheep was higher at 1.5 years of age, and the best slaughter age was 1.5 years. This study provides a reference for in-depth research on the mechanism of the influence of the gut microbiota on meat quality and related regulation.
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    Response of Ruminal Microbiota-Host Gene Interaction to High-Altitude Environments in Tibetan Sheep.
    (MDPI (Basel, Switzerland), 2022-10-17) Sha Y; Ren Y; Zhao S; He Y; Guo X; Pu X; Li W; Liu X; Wang J; Li S; Wahli W
    Altitude is the main external environmental pressure affecting the production performance of Tibetan sheep, and the adaptive evolution of many years has formed a certain response mechanism. However, there are few reports on the response of ruminal microbiota and host genomes of Tibetan sheep to high-altitude environments. Here, we conducted an integrated analysis of volatile fatty acids (VFAs), microbial diversity (16S rRNA), epithelial morphology, and epithelial transcriptome in the rumen of Tibetan sheep at different altitudes to understand the changes in ruminal microbiota−host interaction in response to high altitude. The differences in the nutritional quality of forage at different altitudes, especially the differences in fiber content (ADF/NDF), led to changes in rumen VFAs of Tibetan sheep, in which the A/P value (acetic acid/propionic acid) was significantly decreased (p < 0.05). In addition, the concentrations of IgA and IgG in Middle-altitude (MA) and High-altitude Tibetan sheep (HA) were significantly increased (p < 0.05), while the concentrations of IgM were significantly increased in MA (p < 0.05). Morphological results showed that the width of the rumen papilla and the thickness of the basal layer increased significantly in HA Tibetan sheep (p < 0.05). The 16S rRNA analysis found that the rumen microbial diversity of Tibetan sheep gradually decreased with increasing altitude, and there were some differences in phylum- and genus-level microbes at the three altitudes. RDA analysis found that the abundance of the Rikenellaceae RC9 gut group and the Ruminococcaceae NK4A214 group increased with altitudes. Furthermore, a functional analysis of the KEGG microbial database found the “lipid metabolism” function of HA Tibetan sheep to be significantly enriched. WGCNA revealed that five gene modules were enriched in “energy production and conversion”, “lipid transport and metabolism”, and “defense mechanisms”, and cooperated with microbiota to regulate rumen fermentation and epithelial immune barrier function, so as to improve the metabolism and immune level of Tibetan sheep at high altitude.
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    Effect of iron-manganese oxide on the degradation of deoxynivalenol in feed and enhancement of growth performance and intestinal health in weaned piglets.
    (Elsevier B.V., 2024-10-28) Wu C; Song J; Liu X; Zhang Y; Zhou Z; Thomas DG; Wu B; Yan X; Li J; Zhang R; Wu F; Cheng C; Pu X; Wang X
    Deoxynivalenol (DON), a prevalent and highly toxic mycotoxin in animal feed, poses significant risks to livestock health and productivity. This study evaluates the effectiveness of iron-manganese oxide (Fe/Mn oxides) in degrading DON. The DON degradation rate of Fe/Mn oxide reached 98.46 % in a controlled solution under specific conditions (0.2 % concentration, 37-85 °C, pH 6-7, 1-minute reaction time). When applied to actual feed, it reduced DON levels by approximately 49.3 % and remained stable in simulated gastrointestinal environments of weaned piglets. A 28-day trial involving 48 weaned piglets assessed the impacts of Fe/Mn oxides on health and growth. Results indicated that piglets consuming contaminated feed without the treatment exhibited reduced growth and compromised gut integrity, which were significantly mitigated by the addition of Fe/Mn oxides. Therefore, Fe/Mn oxides effectively reduce DON in feed and alleviate adverse health effects in piglets, making them a viable option to enhance safety and performance in mycotoxin-prone environments.