Mortality Risk Profiling of Staphylococcus aureus Bacteremia by Multi-omic Serum Analysis Reveals Early Predictive and Pathogenic Signatures.

Staphylococcus aureus bacteremia (SaB) causes significant disease in humans, carrying mortality rates of ∼25%. The ability to rapidly predict SaB patient responses and guide personalized treatment regimens could reduce mortality. Here, we present a resource of SaB prognostic biomarkers. Integrating proteomic and metabolomic techniques enabled the identification of >10,000 features from >200 serum samples collected upon clinical presentation. We interrogated the complexity of serum using multiple computational strategies, which provided a comprehensive view of the early host response to infection. Our biomarkers exceed the predictive capabilities of those previously reported, particularly when used in combination. Last, we validated the biological contribution of mortality-associated pathways using a murine model of SaB. Our findings represent a starting point for the development of a prognostic test for identifying high-risk patients at a time early enough to trigger intensive monitoring and interventions.

Immunization with lytic polysaccharide monooxygenase CbpD induces protective immunity against Pseudomonas aeruginosa pneumonia.

Pseudomonas aeruginosa (PA) CbpD belongs to the lytic polysaccharide monooxygenases (LPMOs), a family of enzymes that cleave chitin or related polysaccharides. Here, we demonstrate a virulence role of CbpD in PA pneumonia linked to impairment of host complement function and opsonophagocytic clearance. Following intratracheal challenge, a PA ΔCbpD mutant was more easily cleared and produced less mortality than the wild-type parent strain. The x-ray crystal structure of the CbpD LPMO domain was solved to subatomic resolution (0.75Å) and its two additional domains modeled by small-angle X-ray scattering and Alphafold2 machine-learning algorithms, allowing structure-based immune epitope mapping. Immunization of naive mice with recombinant CbpD generated high IgG antibody titers that promoted human neutrophil opsonophagocytic killing, neutralized enzymatic activity, and protected against lethal PA pneumonia and sepsis. IgG antibodies generated against full-length CbpD or its noncatalytic M2+CBM73 domains were opsonic and protective, even in previously PA-exposed mice, while antibodies targeting the AA10 domain were not. Preexisting antibodies in PA-colonized cystic fibrosis patients primarily target the CbpD AA10 catalytic domain. Further exploration of LPMO family proteins, present across many clinically important and antibiotic-resistant human pathogens, may yield novel and effective vaccine antigens.

Assembly of a pangenome for global cattle reveals missing sequences and novel structural variations, providing new insights into their diversity and evolutionary history.

A cattle pangenome representation was created based on the genome sequences of 898 cattle representing 57 breeds. The pangenome identified 83 Mb of sequence not found in the cattle reference genome, representing 3.1% novel sequence compared with the 2.71-Gb reference. A catalog of structural variants developed from this cattle population identified 3.3 million deletions, 0.12 million inversions, and 0.18 million duplications. Estimates of breed ancestry and hybridization between cattle breeds using insertion/deletions as markers were similar to those produced by single nucleotide polymorphism-based analysis. Hundreds of deletions were observed to have stratification based on subspecies and breed. For example, an insertion of a Bov-tA1 repeat element was identified in the first intron of the APPL2 gene and correlated with cattle breed geographic distribution. This insertion falls within a segment overlapping predicted enhancer and promoter regions of the gene, and could affect important traits such as immune response, olfactory functions, cell proliferation, and glucose metabolism in muscle. The results indicate that pangenomes are a valuable resource for studying diversity and evolutionary history, and help to delineate how domestication, trait-based breeding, and adaptive introgression have shaped the cattle genome.

AAV-mediated hepatic LPL expression ameliorates severe hypertriglyceridemia and acute pancreatitis in Gpihbp1 deficient mice and rats.

GPIHBP1 plays an important role in the hydrolysis of triglyceride (TG) lipoproteins by lipoprotein lipases (LPLs). However, Gpihbp1 knockout mice did not develop hypertriglyceridemia (HTG) during the suckling period but developed severe HTG after weaning on a chow diet. It has been postulated that LPL expression in the liver of suckling mice may be involved. To determine whether hepatic LPL expression could correct severe HTG in Gpihbp1 deficiency, liver-targeted LPL expression was achieved via intravenous administration of the adeno-associated virus (AAV)-human LPL gene, and the effects of AAV-LPL on HTG and HTG-related acute pancreatitis (HTG-AP) were observed. Suckling Gpihbp1-/- mice with high hepatic LPL expression did not develop HTG, whereas Gpihbp1-/- rat pups without hepatic LPL expression developed severe HTG. AAV-mediated liver-targeted LPL expression dose-dependently decreased plasma TG levels in Gpihbp1-/- mice and rats, increased post-heparin plasma LPL mass and activity, decreased mortality in Gpihbp1-/- rat pups, and reduced the susceptibility and severity of both Gpihbp1-/- animals to HTG-AP. However, the muscle expression of AAV-LPL had no significant effect on HTG. Targeted expression of LPL in the liver showed no obvious adverse reactions. Thus, liver-targeted LPL expression may be a new therapeutic approach for HTG-AP caused by GPIHBP1 deficiency.

Comparative transcriptome analysis of acne vulgaris, rosacea, and hidradenitis suppurativa supports high-dose dietary zinc as a therapeutic agent.

Acne vulgaris, rosacea, and hidradenitis suppurativa are enduring inflammatory skin conditions that frequently manifest with akin clinical attributes, posing a considerable challenge for their distinctive diagnosis. While these conditions do exhibit certain resemblances, they also demonstrate distinct underlying pathophysiological mechanisms and treatment modalities. Delving into both the molecular parallels and disparities among these three disorders can yield invaluable insights for refined diagnostics, effective management, and targeted therapeutic interventions. In this report, we present a comparative analysis of transcriptomic data across these three diseases, elucidating differentially expressed genes and enriched pathways specific to each ailment, as well as those shared among them. Specifically, we identified multiple zinc-binding proteins (SERPINA1, S100A7, S100A8, S100A9 and KRT16) as consistently highly upregulated genes across all three diseases. Our hypothesis suggests that these proteins could bind and sequester zinc, potentially leading to localized zinc deficiency and heightened inflammation. We identified high-dose dietary zinc as a promising therapeutic approach and confirmed its effectiveness through validation in an acne mouse model.

Retrospective Evaluation of Ultrasound Guided Percutaneous Plantar Fasciotomy With and Without Platelet Rich Plasma.

Plantar fasciitis is one of the most common foot conditions presenting to a foot and ankle specialist. Surgical treatment outcomes following plantar fasciotomy vary but short-term studies have reported excellent early pain relief and significant improvements in symptoms. This study evaluates patient reported pain scores collected pre- and post-op for patients who underwent percutaneous ultrasonic microtenotomy (PUT) plantar fasciotomy with PRP injection vs without the use of PRP. We compared pain visual analog scale (VAS) scores, for patients treated surgically by Orthopedic Surgery department of foot and ankle faculty members between December 2007 and December 2022. A total of 30 patients were identified that met inclusion and exclusion criteria. Our results showed that there was a significant decrease in pain VAS scores from pre-op visit (at least 1 month prior to operation) to post-op visit (at least 1 month following operation) for both groups, with a paired t test (p value <.0001). However, patients who received PRP had a statistically significant decrease in pain level compared to the group who did not receive PRP. Statistical analysis completed with a 2-sample t test (p-value <.0325). Our results found the mean time between the initial pre-op visit and last post-op follow-up visit was 19 months. The mean for time following surgical intervention was 10 months. The findings of our study suggest that the dual use of PUT and PRP to treat plantar fasciitis, could potentially lead to an improvement in pain reduction and longevity of pain relief.

Correlation Between Traditional Anteroposterior Radiographic Measurements With Lateral Radiographic Measurements Following Triplanar Correction of Hallux Valgus and With Patient-Reported Outcomes From a Prospective Multicenter Trial.

Hallux valgus (HV) is a common condition in which the first ray is deformed, leading to pain and altered joint mechanics. A variety of radiographic measurements are used to evaluate HV. Little is known about measurements used in the assessment of HV on lateral radiographs compared to anteroposterior (AP) radiographs. The primary aim of this study was to correlate lateral measurements with AP measurements pre and postoperatively. The secondary aim was to correlate lateral measurements with patient-reported outcome measures (PROMs) pre and postoperatively. One hundred eighty-three patients were initially enrolled in the study. Two fellowship-trained musculoskeletal radiologists independently performed all measurements. On AP radiographs, hallux valgus angle (HVA) and intermetatarsal angle (IMA) were measured. On lateral radiographs, sagittal IMA, Meary's angle, and sagittal first ray length were measured. Measurements were recorded at baseline and 6, 12, and 24 months postoperatively. Intraclass correlation coefficients (ICCs) were used for inter-reader analysis. ICCs were moderate to very strong among readers. There were significant but weak correlations between lateral measurements and AP measurements. For at least 1 timepoint, IMA correlated with sagittal IMA, sagittal first ray length, and Meary's angle. HVA only correlated with sagittal first ray length. These correlations were all weak in magnitude. There were a few significant but weak correlations between the measurements in the study and PROMs. This study showed that sagittal IMA, sagittal first ray length, and Meary's angle are not predictive of AP measurements or patient outcomes and are not useful in preoperative assessment of HV.

Genome-wide association analysis of heifer livability and early first calving in Holstein cattle.

BACKGROUND: The survival and fertility of heifers are critical factors for the success of dairy farms. The mortality of heifers poses a significant challenge to the management and profitability of the dairy industry. In dairy farming, achieving early first calving of heifers is also essential for optimal productivity and sustainability. Recently, Council on Dairy Cattle Breeding (CDCB) and USDA have developed new evaluations of heifer health and fertility traits. However, the genetic basis of these traits has yet to be thoroughly studied. RESULTS: Leveraging the extensive U.S dairy genomic database maintained at CDCB, we conducted large-scale GWAS analyses of two heifer traits, livability and early first calving. Despite the large sample size, we found no major QTL for heifer livability. However, we identified a major QTL in the bovine MHC region associated with early first calving. Our GO analysis based on nearby genes detected 91 significant GO terms with a large proportion related to the immune system. This QTL in the MHC region was also confirmed in the analysis of 27 K bull with imputed sequence variants. Since these traits have few major QTL, we evaluated the genome-wide distribution of GWAS signals across different functional genomics categories. For heifer livability, we observed significant enrichment in promotor and enhancer-related regions. For early calving, we found more associations in active TSS, active Elements, and Insulator. We also identified significant enrichment of CDS and conserved variants in the GWAS results of both traits. By linking GWAS results and transcriptome data from the CattleGTEx project via TWAS, we detected four and 23 significant gene-trait association pairs for heifer livability and early calving, respectively. Interestingly, we discovered six genes for early calving in the Bovine MHC region, including two genes in lymph node tissue and one gene each in blood, adipose, hypothalamus, and leukocyte. CONCLUSION: Our large-scale GWAS analyses of two heifer traits identified a major QTL in the bovine MHC region for early first calving. Additional functional enrichment and TWAS analyses confirmed the MHC QTL with relevant biological evidence. Our results revealed the complex genetic basis of heifer health and fertility traits and indicated a potential connection between the immune system and reproduction in cattle.

Comprehensive analyses of 723 transcriptomes enhance genetic and biological interpretations for complex traits in cattle.

By uniformly analyzing 723 RNA-seq data from 91 tissues and cell types, we built a comprehensive gene atlas and studied tissue specificity of genes in cattle. We demonstrated that tissue-specific genes significantly reflected the tissue-relevant biology, showing distinct promoter methylation and evolution patterns (e.g., brain-specific genes evolve slowest, whereas testis-specific genes evolve fastest). Through integrative analyses of those tissue-specific genes with large-scale genome-wide association studies, we detected relevant tissues/cell types and candidate genes for 45 economically important traits in cattle, including blood/immune system (e.g., CCDC88C) for male fertility, brain (e.g., TRIM46 and RAB6A) for milk production, and multiple growth-related tissues (e.g., FGF6 and CCND2) for body conformation. We validated these findings by using epigenomic data across major somatic tissues and sperm. Collectively, our findings provided novel insights into the genetic and biological mechanisms underlying complex traits in cattle, and our transcriptome atlas can serve as a primary source for biological interpretation, functional validation, studies of adaptive evolution, and genomic improvement in livestock.

Smooth Muscle Overexpression of PGC1α Attenuates Atherosclerosis in Rabbits.

[Figure: see text].

Taming transposable elements in livestock and poultry: a review of their roles and applications.

Livestock and poultry play a significant role in human nutrition by converting agricultural by-products into high-quality proteins. To meet the growing demand for safe animal protein, genetic improvement of livestock must be done sustainably while minimizing negative environmental impacts. Transposable elements (TE) are important components of livestock and poultry genomes, contributing to their genetic diversity, chromatin states, gene regulatory networks, and complex traits of economic value. However, compared to other species, research on TE in livestock and poultry is still in its early stages. In this review, we analyze 72 studies published in the past 20 years, summarize the TE composition in livestock and poultry genomes, and focus on their potential roles in functional genomics. We also discuss bioinformatic tools and strategies for integrating multi-omics data with TE, and explore future directions, feasibility, and challenges of TE research in livestock and poultry. In addition, we suggest strategies to apply TE in basic biological research and animal breeding. Our goal is to provide a new perspective on the importance of TE in livestock and poultry genomes.

Extracellular vesicles carrying proinflammatory factors may spread atherosclerosis to remote locations.

Most cells involved in atherosclerosis release extracellular vesicles (EVs), which can carry bioactive substances to downstream tissues via circulation. We hypothesized that EVs derived from atherosclerotic plaques could promote atherogenesis in remote locations, a mechanism that mimics the blood metastasis of cancer. Ldlr gene knockout (Ldlr KO) rats were fed on a high cholesterol diet and underwent partial carotid ligation to induce local atherosclerosis. EVs were separated from carotid artery tissues and downstream blood of carotid ligation by centrifugation. MiRNA sequencing and qPCR were then performed to detect miRNA differences in EVs from rats with and without induced carotid atherosclerosis. Biochemical analyses demonstrated that EVs derived from atherosclerosis could increase the expression of ICAM-1, VCAM-1, and E-selectin in endothelial cells in vitro. EVs derived from atherosclerosis contained a higher level of miR-23a-3p than those derived from controls. MiR-23a-3p could promote endothelial inflammation by targeting Dusp5 and maintaining ERK1/2 phosphorylation in vitro. Inhibiting EV release could attenuate atherogenesis and reduce macrophage infiltration in vivo. Intravenously administrating atherosclerotic plaque-derived EVs could induce intimal inflammation, arterial wall thickening and lumen narrowing in the carotids of Ldlr KO rats, while simultaneous injection of miR-23a-3p antagomir could reverse this reaction. The results suggested that EVs may transfer atherosclerosis to remote locations by carrying proinflammatory factors, particularly miR-23a-3p.

Distribution of DGAT1 copy number variation in Chinese goats and its associations with milk production traits.

Goat is an important sector for meat and dairy products. Diacylglycerol O-acyltransferase 1 (DGAT1), which is a key gene in milk production, has been recently detected to overlap with a novel copy number variation (CNV) in goats. CNVs could be genetic markers providing new insights into the genetic basis of phenotypic variation. Up to now, there are no reports on the DGAT1-related CNV (DGAT1 CNV) in Chinese goats. This study first detected the distribution of the DGAT1 CNV in Chinese seven goat breeds, finding substantial differences among dairy, meat, and fiber goats (P < 0.01). The association analysis between the DGAT1 CNV and milk production traits revealed significant associations: Xinong Sannen (XS) dairy goat with copy number loss type had higher freezing point depression (FPD) (P < 0.01) and milk solids-not-fat (SNF) content (P < 0.05). Overall, our study unraveled the distribution of DGAT1 CNV in Chinese goats for the first time and found the potential role of this CNV in the marker-assisted selection of dairy goat breeding.

Transcriptional atlas analysis from multiple tissues reveals the expression specificity patterns in beef cattle.

BACKGROUND: A comprehensive analysis of gene expression profiling across tissues can provide necessary information for an in-depth understanding of their biological functions. We performed a large-scale gene expression analysis and generated a high-resolution atlas of the transcriptome in beef cattle. RESULTS: Our transcriptome atlas was generated from 135 bovine tissues in adult beef cattle, covering 51 tissue types of major organ systems (e.g., muscular system, digestive system, immune system, reproductive system). Approximately 94.76% of sequencing reads were successfully mapped to the reference genome assembly ARS-UCD1.2. We detected a total of 60,488 transcripts, and 32% of them were not reported before. We identified 2654 housekeeping genes (HKGs) and 477 tissue-specific genes (TSGs) across tissues. Using weighted gene co-expression network analysis, we obtained 24 modules with 237 hub genes (HUBGs). Functional enrichment analysis showed that HKGs mainly maintain the basic biological activities of cells, while TSGs were involved in tissue differentiation and specific physiological processes. HKGs in bovine tissues were more conserved in terms of expression pattern as compared to TSGs and HUBGs among multiple species. Finally, we obtained a subset of tissue-specific differentially expressed genes (DEGs) between beef and dairy cattle and several functional pathways, which may be involved in production and health traits. CONCLUSIONS: We generated a large-scale gene expression atlas across the major tissues in beef cattle, providing valuable information for enhancing genome assembly and annotation. HKGs, TSGs, and HUBGs further contribute to better understanding the biology and evolution of multiple tissues in cattle. DEGs between beef and dairy cattle also fill in the knowledge gaps about differential transcriptome regulation of bovine tissues underlying economically important traits.

Functional annotation of regulatory elements in cattle genome reveals the roles of extracellular interaction and dynamic change of chromatin states in rumen development during weaning.

We profiled landscapes of bovine regulatory elements and explored dynamic changes of chromatin states in rumen development during weaning. The regulatory elements (15 chromatin states) and their coordinated activities in cattle were defined through genome-wide profiling of four histone modifications, CTCF-binding, DNA accessibility, DNA methylation, and transcriptome in rumen epithelial tissues. Each chromatin state presented specific enrichment for sequence ontology, methylation, trait-associated variants, transcription, gene expression-associated variants, selection signatures, and evolutionarily conserved elements. During weaning, weak enhancers and flanking active transcriptional start sites (TSS) were the most dynamic chromatin states and occurred in tandem with significant variations in gene expression and DNA methylation, significantly associated with stature, production, and reproduction economic traits. By comparing with in vitro cultured epithelial cells and in vivo rumen tissues, we showed the commonness and uniqueness of these results, especially the roles of cell interactions and mitochondrial activities in tissue development.

IL-10 Deficiency Protects Hamsters from Leptospira Infection.

Leptospirosis is a global zoonotic disease with outcomes ranging from subclinical infection to fatal Weil's syndrome. In addition to antibiotics, some immune activators have shown protective effects against leptospirosis. However, the unclear relationship between Leptospira and cytokines has limited the development of antileptospiral immunomodulators. In this study, the particular role of interleukin-10 (IL-10) in leptospirosis was explored by using IL-10-defective (IL-10-/-) hamsters. After Leptospira infection, an improved survival rate, reduced leptospiral burden, and alleviation of organ lesions were found in IL-10-/- hamsters compared with wild-type (WT) hamsters. In addition, the levels of expression of the IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) genes and the level of nitric oxide (NO) were higher in IL-10-/- hamsters than in WT hamsters. Our results indicate that IL-10 deficiency protects hamsters from Leptospira infection.

Investigation of rumen long noncoding RNA before and after weaning in cattle.

BACKGROUND: This study aimed to identify long non-coding RNA (lncRNA) from the rumen tissue in dairy cattle, explore their features including expression and conservation levels, and reveal potential links between lncRNA and complex traits that may indicate important functional impacts of rumen lncRNA during the transition to the weaning period. RESULTS: A total of six cattle rumen samples were taken with three replicates from before and after weaning periods, respectively. Total RNAs were extracted and sequenced with lncRNA discovered based on size, coding potential, sequence homology, and known protein domains. As a result, 404 and 234 rumen lncRNAs were identified before and after weaning, respectively. However, only nine of them were shared under two conditions, with 395 lncRNAs found only in pre-weaning tissues and 225 only in post-weaning samples. Interestingly, none of the nine common lncRNAs were differentially expressed between the two weaning conditions. LncRNA averaged shorter length, lower expression, and lower conservation scores than the genome overall, which is consistent with general lncRNA characteristics. By integrating rumen lncRNA before and after weaning with large-scale GWAS results in cattle, we reported significant enrichment of both pre- and after-weaning lncRNA with traits of economic importance including production, reproduction, health, and body conformation phenotypes. CONCLUSIONS: The majority of rumen lncRNAs are uniquely expressed in one of the two weaning conditions, indicating a functional role of lncRNA in rumen development and transition of weaning. Notably, both pre- and post-weaning lncRNA showed significant enrichment with a variety of complex traits in dairy cattle, suggesting the importance of rumen lncRNA for cattle performance in the adult stage. These relationships should be further investigated to better understand the specific roles lncRNAs are playing in rumen development and cow performance.

A 13.42-kb tandem duplication at the ASIP locus is strongly associated with the depigmentation phenotype of non-classic Swiss markings in goats.

BACKGROUND: The pigmentation phenotype diversity is rich in domestic goats, and identification of the genetic loci affecting coat color in goats has long been of interest. Via the detections of selection signatures, a duplication upstream ASIP was previously reported to be a variant affecting the Swiss markings depigmentation phenotype in goats. RESULTS: We conducted a genome-wide association study using whole-genome sequencing (WGS) data to identify the genetic loci and causal variants affecting the pigmentation phenotype in 65 Jintang black (JT) goats (i.e., 48 solid black vs. 17 non-classic Swiss markings). Although a single association peak harboring the ASIP gene at 52,619,845-72,176,538 bp on chromosome 13 was obtained using a linear mixed model approach, all the SNPs and indels in this region were excluded as causal variants for the pigmentation phenotype. We then found that all 17 individuals with non-classic Swiss markings carried a 13,420-bp duplication (CHI13:63,129,198-63,142,617 bp) nearly 101 kb upstream of ASIP, and this variant was strongly associated (P = 1.48 × 10- 12) with the coat color in the 65 JT goats. The copy numbers obtained from the WGS data also showed that the duplication was present in all 53 goats from three European breeds with Swiss markings and absent in 45 of 51 non-Swiss markings goats from four other breeds and 21 Bezoars, which was further validated in 314 samples from seven populations based on PCR amplification. The copy numbers of the duplication vary in different goat breeds with Swiss markings, indicating a threshold effect instead of a dose-response effect at the molecular level. Furthermore, breakpoint flanking repeat analysis revealed that the duplication was likely to be a result of the Bov-B-mediated nonallelic homologous recombination. CONCLUSION: We confirmed that a genomic region harboring the ASIP gene is a major locus affecting the coat color phenotype of Swiss markings in goats. Although the molecular genetic mechanisms remain unsolved, the 13,420-bp duplication upstream of ASIP is a necessary but not sufficient condition for this phenotype in goats. Moreover, the variations in the copy number of the duplication across different goat breeds do not lead to phenotypic heterogeneity.

Comparative transcriptomic analysis reveals region-specific expression patterns in different beef cuts.

BACKGROUND: Beef cuts in different regions of the carcass have different meat quality due to their distinct physiological function. The objective of this study was to characterize the region-specific expression differences using comparative transcriptomics analysis among five representative beef cuts (tenderloin, longissimus lumborum, rump, neck, chuck). RESULTS: We obtained 15,701 expressed genes in 30 muscle samples across five regions from carcass meat. We identified a total of 80 region-specific genes (RSGs), ranging from three (identified in the rump cut) to thirty (identified in the longissimus lumborum cut), and detected 25 transcription factors (TFs) for RSGs. Using a co-expression network analysis, we detected seven region-specific modules, including three positively correlated modules and four negatively correlated modules. We finally obtained 91 candidate genes related to meat quality, and the functional enrichment analyses showed that these genes were mainly involved in muscle fiber structure (e.g., TNNI1, TNNT1), fatty acids (e.g., SCD, LPL), amino acids (ALDH2, IVD, ACADS), ion channel binding (PHPT1, SNTA1, SUMO1, CNBP), protein processing (e.g., CDC37, GAPDH, NRBP1), as well as energy production and conversion (e.g., ATP8, COX8B, NDUFB6). Moreover, four candidate genes (ALDH2, CANX, IVD, PHPT1) were validated using RT-qPCR analyses which further supported our RNA-seq results. CONCLUSIONS: Our results provide valuable insights into understanding the transcriptome regulation of meat quality in different beef cuts, and these findings may further help to improve the selection for health-beneficial meat in beef cattle.

Single-cell transcriptomic and chromatin accessibility analyses of dairy cattle peripheral blood mononuclear cells and their responses to lipopolysaccharide.

BACKGROUND: Gram-negative bacteria are important pathogens in cattle, causing severe infectious diseases, including mastitis. Lipopolysaccharides (LPS) are components of the outer membrane of Gram-negative bacteria and crucial mediators of chronic inflammation in cattle. LPS modulations of bovine immune responses have been studied before. However, the single-cell transcriptomic and chromatin accessibility analyses of bovine peripheral blood mononuclear cells (PBMCs) and their responses to LPS stimulation were never reported. RESULTS: We performed single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) in bovine PBMCs before and after LPS treatment and demonstrated that seven major cell types, which included CD4 T cells, CD8 T cells, and B cells, monocytes, natural killer cells, innate lymphoid cells, and dendritic cells. Bioinformatic analyses indicated that LPS could increase PBMC cell cycle progression, cellular differentiation, and chromatin accessibility. Gene analyses further showed significant changes in differential expression, transcription factor binding site, gene ontology, and regulatory interactions during the PBMC responses to LPS. Consistent with the findings of previous studies, LPS induced activation of monocytes and dendritic cells, likely through their upregulated TLR4 receptor. NF-κB was observed to be activated by LPS and an increased transcription of an array of pro-inflammatory cytokines, in agreement that NF-κB is an LPS-responsive regulator of innate immune responses. In addition, by integrating LPS-induced differentially expressed genes (DEGs) with large-scale GWAS of 45 complex traits in Holstein, we detected trait-relevant cell types. We found that selected DEGs were significantly associated with immune-relevant health, milk production, and body conformation traits. CONCLUSION: This study provided the first scRNAseq and scATAC-seq data for cattle PBMCs and their responses to the LPS stimulation to the best of our knowledge. These results should also serve as valuable resources for the future study of the bovine immune system and open the door for discoveries about immune cell roles in complex traits like mastitis at single-cell resolution.