Search

Abstract Atherosclerosis is a chronic inflammatory disease characterized with innate and adaptive immunity but also involves pyroptosis. Few studies have explored the role of pyroptosis in advanced atherosclerotic plaques from different vascular beds. Here we try to identify the different underlying function of pyroptosis in the progression of atherosclerosis between carotid arteries and femoral. arteries. We extracted gene expression levels from 55 advanced carotid or femoral atherosclerotic plaques. The pyroptosis score of each sample was calculated by single-sample-gene-set enrichment analysis (ssGSEA). We then divided the samples into two clusters: high pyroptosis scores cluster (PyroptosisScoreH cluster) and low pyroptosis scores cluster (PyroptosisScoreL cluster), and assessed functional enrichment and immune cell infiltration in the two clusters. Key pyroptosis related genes were identified by the intersection between results of Cytoscape and LASSO (Least Absolute Shrinkage and Selection Operator) regression analysis. Finally, all key pyroptosis related genes were validated in vitro. We found all but one of the 29 carotid plaque samples belonged to the PyroptosisScoreH cluster and the majority (19 out of 26) of femoral plaques were part of the PyroptosisScoreL cluster. Atheromatous plaque samples in the PyroptosisScoreL cluster had higher proportions of gamma delta T cells, M2 macrophages, myeloid dendritic cells (DCs), and cytotoxic lymphocytes (CTLs), but lower proportions of endothelial cells (ECs). Immune full-activation pathways (e.g., NOD-like receptor signaling pathway and NF-kappa B signaling pathway) were highly enriched in the PyroptosisScoreH cluster. The key pyroptosis related genes GSDMD, CASP1, NLRC4, AIM2, and IL18 were upregulated in advanced carotid atherosclerotic plaques. We concluded that compared to advanced femoral atheromatous plaques, advanced carotid atheromatous plaques were of higher grade of pyroptosis. GSDMD, CASP1, NLRC4, AIM2, and IL18 were the key pyroptosis related genes, which might provide a new sight in the prevention of fatal strokes in advanced carotid atherosclerosis.

Abstract Background This study aims to establish an in vitro monitoring approach to evaluate the pesticide exposures. We studied the in vitro cytotoxicity of three different body fluids of rats to the respective corresponding tissue-derived cells. Methods Wistar rats were orally administrated daily with three different doses of chlorpyrifos (1.30, 3.26, and 8.15 mg/kg body weight/day, which is equal to the doses of 1/125, 1/50, and 1/20 LD50, respectively) for consecutive 90 days. Blood samples as well as 24-hour urine and fecal samples were collected and processed. Then, urine, serum, and feces samples were used to treat the correspondent cell lines, i.e., T24 bladder cancer cells, Jurkat lymphocytes, and HT-29 colon cancer cells respectively, which derived from the correspondent tissues that could interact with the respective corresponding body fluids in organism. Cell viability was determined by using MTT or trypan blue staining. Results The results showed that urine, serum, and feces extract of the rats exposed to chlorpyrifos displayed concentration- and time-dependent cytotoxicity to the cell lines. Furthermore, we found that the cytotoxicity of body fluids from the exposed animals was mainly due to the presence of 3, 4, 5-trichloropyrindinol, the major toxic metabolite of chlorpyrifos. Conclusions These findings indicated that urine, serum, and feces extraction, especially urine, combining with the corresponding tissue-derived cell lines as the in vitro cell models could be used to evaluate the animal exposure to pesticides even at the low dose with no apparent toxicological signs in the animals. Thus, this in vitro approach could be served as complementary methodology to the existing toolbox of biological monitoring of long-term and low-dose exposure to environmental pesticide residues in practice.

Psoriasis is characterized by keratinocyte proliferation and immune cell infiltration. M2 isoform of pyruvate kinase (PKM2) was reported to have an important role in cell proliferation, which is a rate-limiting enzyme that regulates the final step of glycolysis. However, how PKM2 regulates cell metabolism and proliferation in psoriatic keratinocytes is still poorly understood. Interestingly, we found that PKM2 was highly expressed in psoriatic epidermis from patients and mouse models. PKM2 overexpression promoted keratinocyte glycolytic metabolism while knockdown inhibited keratinocyte proliferation and glycolysis. Mice lacking PKM2 specifically in keratinocytes, pharmacological inhibition of PKM2 or glycolysis inhibited keratinocyte proliferation and showed obvious remission in an imiquimod-induced psoriatic mouse model. Moreover, the inhibitor of the EGF-receptor blocked EGF-stimulated PKM2 expression and glycolysis in keratinocytes. We identify PKM2 as an upregulated gene in psoriasis. PKM2 is essential in keratinocyte over-proliferation and may represent a therapeutic target for psoriasis.

Organophosphate-induced delayed neuropathy (OPIDN) is characterized by progressive axonal degeneration and demyelination of the spinal cord and sciatic nerves. The neuregulin 1/epidermal growth factor receptor (ErbB) signaling pathway is crucial for axonal myelination. In this study, we investigated whether the neuregulin 1/ErbB signaling pathway mediated the progression of OPIDN. Adult hens were given tri-o-cresyl phosphate (TOCP), a typical neuropathic organophosphorus compound, to induce OPIDN. The ErbB inhibitor lapatinib was administered to hens 4 h prior to and 4 days after TOCP exposure. The neuregulin 1/ErbB signaling pathway was examined for their role in maintaining spinal cord and sciatic nerve fiber integrity. Schwann cell line sNF96.2 was used as the in vitro cell model. The in vivo results showed that TOCP (750 mg/kg body weight, p.o.) induced prominent ataxia and significant axon degeneration in the spinal cord and sciatic nerves. Lapatinib (25 mg/kg body weight, p.o.) treatment attenuated OPIDN clinically and histopathlogically and partially prevented the TOCP-induced activation of neuregulin 1/ErbB signaling pathway. Lapatinib also prevented the TOCP-induced inhibition of neuropathy target esterase (NTE), a key enzyme during the development of OPIDN, and the disturbed metabolism of phosphatidylcholine in sciatic nerves. In addition, lapatinib was shown, in vitro, to protect sNF96.2 cells from TOCP-induced dedifferentiation through neuregulin 1/ErbB signaling. Our results suggest that neuregulin 1/ErbB, through regulation of NTE activity in the peripheral nervous system, mediates the progression of OPIDN. Thus, this signal may serve as a potential target for the treatment of OPIDN.

Background: There is conflicting evidence as to whether the femoral head should be preserved or replaced in elderly patients with displaced intracapsular femoral neck fractures. In this article, we performed a systematic review and meta-analysis to compare the short- and long-term effectiveness of arthroplasty (AR) and internal fixation (IF). Methods: PubMed, Embase, and the Cochrane Library were searched systematically up to January 2016. All randomized controlled trials directly comparing the effectiveness of AR and IF for displaced intracapsular fracture were retrieved with no limitation on language or publication year. Results: In total, eight prospective randomized studies involving 2206 patients were included. The results of our study showed that patients in the AR group reported significantly lower complication (risk ratio: 0.56, 95% confidence interval [CI] = 0.38–0.80), re-operation (risk ratio: 0.17, 95% CI = 0.13–0.22), revision rates (risk ratio: 0.11, 95% CI: 0.08–0.16), and better function compared with their IF counterparts, and they were less likely to suffer postoperative pain. No statistically significant differences for the rates of mortality, infection, and/or deep vein thrombosis between AR and IF were found. Conclusions: Based on our analysis, we recommend that AR should be used as the primary treatment for displaced intracapsular femoral neck fractures in the elderly. However, IF may be appropriate for those who are very frail.

During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What’s more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2.

Abstract Over the years, microbiome research has achieved tremendous advancements driven by culture‐independent meta‐omics approaches. Despite extensive research, our understanding of the functional roles and causal effects of the microbiome on phenotypes remains limited. In this study, we focused on the rumen metaproteome, combining it with metatranscriptome and metabolome data to accurately identify the active functional distributions of rumen microorganisms and specific functional groups that influence feed efficiency. By integrating host genetics data, we established the potentially causal relationships between microbes‐proteins/metabolites‐phenotype, and identified specific patterns in which functional groups of rumen microorganisms influence host feed efficiency. We found a causal link between Selenomonas bovis and rumen carbohydrate metabolism, potentially mediated by bacterial chemotaxis and a two‐component regulatory system, impacting feed utilization efficiency of dairy cows. Our study on the nutrient utilization functional groups in the rumen of high‐feed‐efficiency dairy cows, along with the identification of key microbiota functional proteins and their potentially causal relationships, will help move from correlation to causation in rumen microbiome research. This will ultimately enable precise regulation of the rumen microbiota for optimized ruminant production.

Rumen microbiota play a central role in the digestive process of ruminants. Their remarkable ability to break down complex plant fibers and proteins, converting them into essential organic compounds that provide animals with energy and nutrition. Research on rumen microbiota not only contributes to improving animal production performance and enhancing feed utilization efficiency but also holds the potential to reduce methane emissions and environmental impact. Nevertheless, studies on rumen microbiota face numerous challenges, including complexity, difficulties in cultivation, and obstacles in functional analysis. This review provides an overview of microbial species involved in the degradation of macromolecules, the fermentation processes, and methane production in the rumen, all based on cultivation methods. Additionally, the review introduces the applications, advantages, and limitations of emerging omics technologies such as metagenomics, metatranscriptomics, metaproteomics, and metabolomics, in investigating the functionality of rumen microbiota. Finally, the article offers a forward-looking perspective on the new horizons and technologies in the field of rumen microbiota functional research. These emerging technologies, with continuous refinement and mutual complementation, have deepened our understanding of rumen microbiota functionality, thereby enabling effective manipulation of the rumen microbial community.

Abstract Background As the global population continues to grow, competition for resources between humans and livestock has been intensifying. Increasing milk protein production and improving feed efficiency are becoming increasingly important to meet the demand for high-quality dairy protein. In a previous study, we found that milk protein yield in dairy cows was associated with the rumen microbiome. The objective of this study was to elucidate the potential microbial features that underpins feed efficiency in dairy cows using metagenomics, metatranscriptomics, and metabolomics. Results Comparison of metagenomic and metatranscriptomic data revealed that the latter was a better approach to uncover the associations between rumen microbial functions and host performance. Co-occurrence network analysis of the rumen microbiome revealed differential microbial interaction patterns between the animals with different feed efficiency, with high-efficiency animals having more and stronger associations than low-efficiency animals. In the rumen of high-efficiency animals, Selenomonas and members of the Succinivibrionaceae family positively interacted with each other, functioning as keystone members due to their essential ecological functions and active carbohydrate metabolic functions. At the metabolic level, analysis using random forest machine learning suggested that six ruminal metabolites (all derived from carbohydrates) could be used as metabolic markers that can potentially differentiate efficient and inefficient microbiomes, with an accuracy of prediction of 95.06%. Conclusions The results of the current study provided new insights into the new ruminal microbial features associated with feed efficiency in dairy cows, which may improve the ability to select animals for better performance in the dairy industry. The fundamental knowledge will also inform future interventions to improve feed efficiency in dairy cows. Video Abstract.

Abstract Background Dairy cows utilize human-inedible, low-value plant biomass to produce milk, a low-cost product with rich nutrients and high proteins. This process largely relies on rumen microbes that ferment lignocellulose and cellulose to produce volatile fatty acids (VFAs). The VFAs are absorbed and partly metabolized by the stratified squamous rumen epithelium, which is mediated by diverse cell types. Here, we applied a metagenomic binning approach to explore the individual microbes involved in fiber digestion and performed single-cell RNA sequencing on rumen epithelial cells to investigate the cell subtypes contributing to VFA absorption and metabolism. Results The 52 mid-lactating dairy cows in our study (parity = 2.62 ± 0.91) had milk yield of 33.10 ± 6.72 kg. We determined the fiber digestion and fermentation capacities of 186 bacterial genomes using metagenomic binning and identified specific bacterial genomes with strong cellulose/xylan/pectin degradation capabilities that were highly associated with the biosynthesis of VFAs. Furthermore, we constructed a rumen epithelial single-cell map consisting of 18 rumen epithelial cell subtypes based on the transcriptome of 20,728 individual epithelial cells. A systematic survey of the expression profiles of genes encoding candidates for VFA transporters revealed that IGFBP5 + cg-like spinous cells uniquely highly expressed SLC16A1 and SLC4A9, suggesting that this cell type may play important roles in VFA absorption. Potential cross-talk between the microbiome and host cells and their roles in modulating the expression of key genes in the key rumen epithelial cell subtypes were also identified. Conclusions We discovered the key individual microbial genomes and epithelial cell subtypes involved in fiber digestion, VFA uptake and metabolism, respectively, in the rumen. The integration of these data enables us to link microbial genomes and epithelial single cells to the trophic system. Video abstract

ABSTRACT Recent studies have reported that some rumen microbes are heritable. However, it is necessary to clarify the functions and specific contributions of the heritable rumen microbes to cattle phenotypes (microbiability) in comparison with those that are nonheritable. This study aimed to identify the distribution and predicted functions of heritable and nonheritable bacterial taxa at species level in the rumen of dairy cows and their respective contributions to energy-corrected milk yield, protein content and yield, and fat content and yield in milk. Thirty-two heritable and 674 nonheritable bacterial taxa were identified at species level, and the functional analysis revealed that predicted microbial functions for both groups were mainly enriched for energy, amino acid, and ribonucleotide metabolism. The mean microbiability (to reflect a single taxon’s contribution) of heritable bacteria was found to range from 0.16% to 0.33% for the different milk traits, whereas the range for nonheritable bacteria was 0.03% to 0.06%. These findings suggest a strong contribution by host genetics in shaping the rumen microbiota, which contribute significantly to milk production traits. Therefore, there is an opportunity to further improve milk production traits through attention to host genetics and the interaction with the rumen microbiota. IMPORTANCE Rumen bacteria produce volatile fatty acids which exert a far-reaching influence on hepatic metabolism, mammary gland metabolism, and animal production. In the current study, 32 heritable and 674 nonheritable bacterial taxa at species level were identified, and shown to have different microbiability (overall community contribution) and mean microbiability (the average of a single taxon’s contribution) for lactation performance. The predicted functions of heritable and nonheritable bacterial taxa also differed, suggesting that targeted nutritional and genetic breeding approaches could be used to manipulate them to improve dairy cow performance.

Abstract Background Antimicrobial resistance poses super challenges in both human health and livestock production. Rumen microbiota is a large reservoir of antibiotic resistance genes (ARGs), which show significant varations in different host species and lifestyles. To compare the microbiome and resistome between dairy cows and dairy buffaloes, the microbial composition, functions and harbored ARGs of rumen microbiota were explored between 16 dairy cows (3.93 ± 1.34 years old) and 15 dairy buffaloes (4.80 ± 3.49 years old) using metagenomics. Results Dairy buffaloes showed significantly different bacterial species (LDA > 3.5 & P 2) in the rumen compared with dairy cows. Distinct resistive profiles were identified between dairy cows and dairy buffaloes. Among the total 505 ARGs discovered in the resistome of dairy cows and dairy buffaloes, 18 ARGs conferring resistance to 16 antibiotic classes were uniquely detected in dairy buffaloes. Gene tcmA (resistance to tetracenomycin C) presented high prevalence and age effect in dairy buffaloes, and was also highly positively correlated with 93 co-expressed ARGs in the rumen (R = 0.98 & P = 5E-11). In addition, 44 bacterial species under Lactobacillus genus were found to be associated with tcmA (R > 0.95 & P

Abstract Background Antimicrobial resistance is one of the most urgent threat to global public health, as it can lead to high morbidity, mortality, and medical costs for humans and livestock animals. In ruminants, the rumen microbiome carries a large number of antimicrobial resistance genes (ARGs), which could disseminate to the environment through saliva, or through the flow of rumen microbial biomass to the hindgut and released through feces. The occurrence and distribution of ARGs in rumen microbes has been reported, revealing the effects of external stimuli (e.g., antimicrobial administrations and diet ingredients) on the antimicrobial resistance in the rumen. However, the host effect on the ruminal resistome and their interactions remain largely unknown. Here, we investigated the ruminal resistome and its relationship with host feed intake and milk protein yield using metagenomic sequencing. Results The ruminal resistome conferred resistance to 26 classes of antimicrobials, with genes encoding resistance to tetracycline being the most predominant. The ARG-containing contigs were assigned to bacterial taxonomy, and the majority of highly abundant bacterial genera were resistant to at least one antimicrobial, while the abundances of ARG-containing bacterial genera showed distinct variations. Although the ruminal resistome is not co-varied with host feed intake, it could be potentially linked to milk protein yield in dairy cows. Results showed that host feed intake did not affect the alpha or beta diversity of the ruminal resistome or the abundances of ARGs, while the Shannon index (R 2 = 0.63, P

Abstract Background Recently, we reported that some dairy cows could produce high amounts of milk with high amounts of protein (defined as milk protein yield [MPY]) when a population was raised under the same nutritional and management condition, a potential new trait that can be used to increase high-quality milk production. It is unknown to what extent the rumen microbiome and its metabolites, as well as the host metabolism, contribute to MPY. Here, analysis of rumen metagenomics and metabolomics, together with serum metabolomics was performed to identify potential regulatory mechanisms of MPY at both the rumen microbiome and host levels. Results Metagenomics analysis revealed that several Prevotella species were significantly more abundant in the rumen of high-MPY cows, contributing to improved functions related to branched-chain amino acid biosynthesis. In addition, the rumen microbiome of high-MPY cows had lower relative abundances of organisms with methanogen and methanogenesis functions, suggesting that these cows may produce less methane. Metabolomics analysis revealed that the relative concentrations of rumen microbial metabolites (mainly amino acids, carboxylic acids, and fatty acids) and the absolute concentrations of volatile fatty acids were higher in the high-MPY cows. By associating the rumen microbiome with the rumen metabolome, we found that specific microbial taxa (mainly Prevotella species) were positively correlated with ruminal microbial metabolites, including the amino acids and carbohydrates involved in glutathione, phenylalanine, starch, sucrose, and galactose metabolism. To detect the interactions between the rumen microbiome and host metabolism, we associated the rumen microbiome with the host serum metabolome and found that Prevotella species may affect the host’s metabolism of amino acids (including glycine, serine, threonine, alanine, aspartate, glutamate, cysteine, and methionine). Further analysis using the linear mixed effect model estimated contributions to the variation in MPY based on different omics and revealed that the rumen microbial composition, functions, and metabolites, and the serum metabolites contributed 17.81, 21.56, 29.76, and 26.78%, respectively, to the host MPY. Conclusions These findings provide a fundamental understanding of how the microbiome-dependent and host-dependent mechanisms contribute to varied individualized performance in the milk production quality of dairy cows under the same management condition. This fundamental information is vital for the development of potential manipulation strategies to improve milk quality and production through precision feeding. Video Abstract

Cadmium(Cd) and chlorpyrifos (CPF) are widespread harmful environmentalpollutants with neurotoxicity to mammals. Although the exposure toCd and CPF at the same time may pose a significant risk to human health,the subchronic combined neurotoxicity of these two chemicals at lowlevels in the brain is poorly understood. In this study, we treatedrats with three doses (low, middle, and high) of Cd, CPF, or theirmixture for 90 days. No obvious symptom was observed in the treatedanimals except those treated with high-dose CPF. Histological resultsshowed that middle and high doses of the chemicals caused neuronalcell damage in brains. GC–MS-based metabonomics analysis revealedthat energy and amino acid metabolism were disturbed in the brainsof rats exposed to the two chemicals and their combinations even atlow doses. We further identified the unique brain metabolite biomarkersfor rats treated with Cd, CPF, or both. Two amino acids, tyrosineand l-leucine, were identified as the biomarkers for Cd andCPF treatment, respectively. In addition, a set of five unique biomarkers(1,2-propanediol-1-phosphate, d-gluconic acid, 9H-purine, serine, and 2-ketoisovaleric acid) was identified for themixtures of Cd and CPF. Therefore, the metabolomics analysis is moresensitive than regular clinical observation and pathological examinationfor detecting the neurotoxicity of the individual and combined Cdand CPF at low levels. Overall, these results identified the uniquebiomarkers for Cd and CPF exposure, which provide new insights intothe mechanism of their joint toxicity. [ABSTRACT FROM AUTHOR]

Age is an important factor in shaping the gut microbiome. However, the age effect on the rumen microbial community for dairy buffaloes remains less explored. Using metagenomics, we examined the microbial composition and functions of rumen microbiota in dairy Murrah buffaloes of different ages: Y (1 year old), M (3–5 years old), E (6–8 years old), and O (>9 years old). We found that Bacteroidetes and Firmicutes were the predominant phyla, with Prevotella accounting for the highest abundance at the genus level. The proportion of Bacteroides and Methanobrevibacter significantly increased with age, while the abundance of genus Lactobacillus significantly decreased with age (LDA > 3, p < 0.05). Most differed COG and KEGG pathways were enriched in Y with carbohydrate metabolism, while older buffaloes enriched more functions of protein metabolism and the processing of replication and repair (LDA > 2, p < 0.05). Additionally, the functional contribution analysis revealed that the genera Prevotella and Lactobacillus of Y with more functions of CAZymes encoded genes of glycoside hydrolases and carbohydrate esterases for their roles of capable of metabolizing starch and sucrose-associated oligosaccharide enzyme, hemicellulase, and cellulase activities than the other three groups (LDA > 2, p < 0.05), thus affecting the 1-year-old dairy buffalo rumen carbohydrate metabolism. This study provides comprehensive dairy buffalo rumen metagenome data and assists in manipulating the rumen microbiome for improved dairy buffalo production.

Abstract Background Lactation is extremely important for dairy cows; however, the understanding of the underlying metabolic mechanisms is very limited. This study was conducted to investigate the inherent metabolic patterns during lactation using the overall biofluid metabolomics and the metabolic differences from non-lactation periods, as determined using partial tissue-metabolomics. We analyzed the metabolomic profiles of four biofluids (rumen fluid, serum, milk and urine) and their relationships in six mid-lactation Holstein cows and compared their mammary gland (MG) metabolomic profiles with those of six non-lactating cows by using gas chromatography-time of flight/mass spectrometry. Results In total, 33 metabolites were shared among the four biofluids, and 274 metabolites were identified in the MG tissues. The sub-clusters of the hierarchical clustering analysis revealed that the rumen fluid and serum metabolomics profiles were grouped together and highly correlated but were separate from those for milk. Urine had the most different profile compared to the other three biofluids. Creatine was identified as the most different metabolite among the four biofluids (VIP = 1.537). Five metabolic pathways, including gluconeogenesis, pyruvate metabolism, the tricarboxylic acid cycle (TCA cycle), glycerolipid metabolism, and aspartate metabolism, showed the most functional enrichment among the four biofluids (false discovery rate 2). Clear discriminations were observed in the MG metabolomics profiles between the lactating and non-lactating cows, with 54 metabolites having a significantly higher abundance (P 1) in the lactation group. Lactobionic acid, citric acid, orotic acid and oxamide were extracted by the S-plot as potential biomarkers of the metabolic difference between lactation and non-lactation. The TCA cycle, glyoxylate and dicarboxylate metabolism, glutamate metabolism and glycine metabolism were determined to be pathways that were significantly impacted (P 0.1) in the lactation group. Among them, the TCA cycle was the most up-regulated pathway (P

Mastitis is one of the major problems for the productivity of dairy cows and its classifications have usually been based on milk somatic cell counts (SCCs). In this study, we investigated the differences in milk production, rumen fermentation parameters, and diversity and composition of rumen and hindgut bacteria in cows with similar SCCs with the aim to identify whether they can be potential microbial biomarkers to improve the diagnostics of mastitis. A total of 20 dairy cows with SCCs over 500 × 103 cells/mL in milk but without clinical symptoms of mastitis were selected in this study. Random forest modeling revealed that Erysipelotrichaceae UCG 004 and the [Eubacterium] xylanophilum group in the rumen, as well as the Family XIII AD3011 group and Bacteroides in the hindgut, were the most influential candidates as key bacterial markers for differentiating “true” mastitis from cows with high SCCs. Mastitis statuses of 334 dairy cows were evaluated, and 96 in 101 cows with high SCCs were defined as healthy rather than mastitis according to the rumen bacteria. Our findings suggested that bacteria in the rumen and hindgut can be a new approach and provide an opportunity to reduce common errors in the detection of mastitis.

Pesticides and heavy metals can be easily biomagnified in food chains and bioaccumulated in individuals, thus pose significant threat to human health. However, their joint toxicity for long-term exposure at low dose has not been thoroughly investigated. In the present study, we investigated the oxidative damages in brain of rats exposed subchronically to organophosphorus pesticide chlorpyrifos (CPF) and heavy metal cadmium (Cd), and their mixtures at the environmentally relevant doses. Rats were given different doses of CPF and Cd by oral gavage for three months. After treatment, brain tissues were subjected for biochemical analysis. Mitochondrial damage and reactive oxidative species were also measured in neuroblastoma SH-SY5Y cells treated with CPF, Cd and their mixtures. The results showed that CPF and Cd generated protein and lipid peroxidation, disturbed the total antioxidant capability, and altered mitochondria ultrastructure in the brain. Lipids and proteins were sensitive to the oxidative damage induced by CPF and Cd. CPF and Cd decreased mitochondrial potential and induced reactive oxygen species in SH-SY5Y cells. However, the mixture did not display higher toxicity than the sum of that of the individual treatments. Thus, CPF and Cd could have a potential antagonistic interaction on the induction of oxidative stress. [ABSTRACT FROM AUTHOR]