General Synthesis of meso-1,4-Dialdehydes and Their Application in Ir-Catalyzed Asymmetric Tishchenko Reactions.

A practical synthesis of meso-1,4-dialdehydes based on the oxidative cleavage of cyclobutanediol derivatives using polymer-supported periodate was developed. The meso-1,4-dialdehydes were obtained in up to >99% yield and subsequently employed in Ir-catalyzed asymmetric Tishchenko reactions to give the corresponding chiral lactones, which are versatile synthetic intermediates, in good yield with moderate enantiomeric excess. The catalytically active species was identified by means of cold-spray ionization mass spectrometry and 1H NMR spectroscopy.

A Million-Cow Validation of a Chromosome 14 Region Interacting with All Chromosomes for Fat Percentage in U.S. Holstein Cows.

A genome-wide association study (GWAS) of fat percentage (FPC) using 1,231,898 first lactation cows and 75,198 SNPs confirmed a previous result that a Chr14 region about 9.38 Mb in size (0.14-9.52 Mb) had significant inter-chromosome additive × additive (A×A) effects with all chromosomes and revealed many new such effects. This study divides this 9.38 Mb region into two sub-regions, Chr14a at 0.14-0.88 Mb (0.74 Mb in size) with 78% and Chr14b at 2.21-9.52 Mb (7.31 Mb in size) with 22% of the 2761 significant A×A effects. These two sub-regions were separated by a 1.3 Mb gap at 0.9-2.2 Mb without significant inter-chromosome A×A effects. The PPP1R16A-FOXH1-CYHR1-TONSL (PFCT) region of Chr14a (29 Kb in size) with four SNPs had the largest number of inter-chromosome A×A effects (1141 pairs) with all chromosomes, including the most significant inter-chromosome A×A effects. The SLC4A4-GC-NPFFR2 (SGN) region of Chr06, known to have highly significant additive effects for some production, fertility and health traits, specifically interacted with the PFCT region and a Chr14a region with CPSF1, ADCK5, SLC52A2, DGAT1, SMPD5 and PARP10 (CASDSP) known to have highly significant additive effects for milk production traits. The most significant effects were between an SNP in SGN and four SNPs in PFCT. The CASDSP region mostly interacted with the SGN region. In the Chr14b region, the 2.28-2.42 Mb region (138.46 Kb in size) lacking coding genes had the largest cluster of A×A effects, interacting with seventeen chromosomes. The results from this study provide high-confidence evidence towards the understanding of the genetic mechanism of FPC in Holstein cows.

[Degradation of Ciprofloxacin by Activating Peroxymonosulfate with Sludge Biochar].

Sludge biochar(BC), which was prepared by the pyrolysis of waste-activated sludge at 450℃, was applied for peroxymonosulfate(PMS) activation to construct a BC/PMS system for ciprofloxacin(CIP) degradation. The physical and chemical properties of BC were studied using scanning electron microscopy(SEM), an energy dispersive spectrometer(EDS), a Fourier transform infrared spectrometer(FTIR), X-ray diffraction(XRD), a Zeta potential analyzer, and electron paramagnetic resonance spectroscopy(EPR). The effects of BC dosage, PMS dosage, initial pH value, and inorganic anions on CIP removal in the BC/PMS system were investigated. Further, the degradation mechanism of the BC/PMS system was speculated through the free radical quenching experiment and X-ray photoelectron spectroscopy(XPS) analysis. The results showed that the CIP degradation rate was 49.09% at a BC dosage of 1.0 g·L-1, PMS of 3.0 mmol·L-1, CIP of 20 mg·L-1, and pH of 6.0 in 120 min. SO42- and NO3- had no obvious effect on the removal of CIP in the BC/PMS system, whereas HCO3- and Cl-could inhibit CIP degradation significantly. The CIP removal in the BC/PMS system was attributed to the common function of the radical pathway dominated by ·OH and SO4-· and the non-radical pathway dominated by 1O2. The CIP degradation pathway mainly included piperazine ring opening and hydroxylation reaction.

Comparison of the Accuracy of Epistasis and Haplotype Models for Genomic Prediction of Seven Human Phenotypes.

The accuracy of predicting seven human phenotypes of 3657-7564 individuals using global epistasis effects was evaluated and compared to the accuracy of haplotype genomic prediction using 380,705 SNPs and 10-fold cross-validation studies. The seven human phenotypes were the normality transformed high density lipoproteins (HDL), low density lipoproteins (LDL), total cholesterol (TC), triglycerides (TG), weight (WT), and the original phenotypic observations of height (HTo) and body mass index (BMIo). Fourth-order epistasis effects virtually had no contribution to the phenotypic variances, and third-order epistasis effects did not affect the prediction accuracy. Without haplotype effects in the prediction model, pairwise epistasis effects improved the prediction accuracy over the SNP models for six traits, with accuracy increases of 2.41%, 3.85%, 0.70%, 0.97%, 0.62% and 0.93% for HDL, LDL, TC, HTo, WT and BMIo respectively. However, none of the epistasis models had higher prediction accuracy than the haplotype models we previously reported. The epistasis model for TG decreased the prediction accuracy by 2.35% relative to the accuracy of the SNP model. The integrated models with epistasis and haplotype effects had slightly higher prediction accuracy than the haplotype models for two traits, HDL and BMIo. These two traits were the only traits where additive × dominance effects increased the prediction accuracy. These results indicated that haplotype effects containing local high-order epistasis effects had a tendency to be more important than global pairwise epistasis effects for the seven human phenotypes, and that the genetic mechanism of HDL and BMIo was more complex than that of the other traits.

Accumulation of squalene in filamentous fungi Trichoderma virens PS1-7 in the presence of butenafine hydrochloride, squalene epoxidase inhibitor: biosynthesis of 13C-enriched squalene.

Squalene is a triterpenoid compound and widely used in various industries such as medicine and cosmetics due to its strong antioxidant and anticancer properties. The purpose of this study is to increase the accumulation of squalene in filamentous fungi using exogeneous butenafine hydrochloride, which is an inhibitor for squalene epoxidase. The detailed settings achieved that the filamentous fungi, Trichoderma virens PS1-7, produced squalene up to 429.93 ± 51.60 mg/L after culturing for 7 days in the medium consisting of potato infusion with glucose at pH 4.0, in the presence of 200 µm butenafine. On the other hand, no squalene accumulation was observed without butenafine. This result indicated that squalene was biosynthesized in the filamentous fungi PS1-7, which can be used as a novel source of squalene. In addition, we successfully obtained highly 13C-enriched squalene by using [U-13C6]-glucose as a carbon source replacing normal glucose.

A Million-Cow Genome-Wide Association Study of Three Fertility Traits in U.S. Holstein Cows.

A genome-wide association study (GWAS) of the daughter pregnancy rate (DPR), cow conception rate (CCR), and heifer conception rate (HCR) using 1,001,374-1,194,736 first-lactation Holstein cows and 75,140-75,295 SNPs identified 7567, 3798, and 726 additive effects, as well as 22, 27, and 25 dominance effects for DPR, CCR, and HCR, respectively, with log10(1/p) > 8. Most of these effects were new effects, and some new effects were in or near genes known to affect reproduction including GNRHR, SHBG, and ESR1, and a gene cluster of pregnancy-associated glycoproteins. The confirmed effects included those in or near the SLC4A4-GC-NPFFR2 and AFF1 regions of Chr06 and the KALRN region of Chr01. Eleven SNPs in the CEBPG-PEPD-CHST8 region of Chr18, the AFF1-KLHL8 region of Chr06, and the CCDC14-KALRN region of Chr01 with sharply negative allelic effects and dominance values for the recessive homozygous genotypes were recommended for heifer culling. Two SNPs in and near the AGMO region of Chr04 that were sharply negative for HCR and age at first calving, but slightly positive for the yield traits could also be considered for heifer culling. The results from this study provided new evidence and understanding about the genetic variants and genome regions affecting the three fertility traits in U.S. Holstein cows.

Genome-Wide Association Study of Age at First Calving in U.S. Holstein Cows.

A genome-wide association study (GWAS) of age at first calving (AFC) using 813,114 first lactation Holstein cows and 75,524 SNPs identified 2063 additive effects and 29 dominance effects with p-values < 10-8. Three chromosomes had highly significant additive effects in the regions of 7.86-8.12 Mb of Chr15, 27.07-27.48 Mb and 31.25-32.11 Mb of Chr19, and 26.92-32.60 Mb of Chr23. Two of the genes in those regions were reproductive hormone genes with known biological functions that should be relevant to AFC, the sex hormone binding globulin (SHBG) gene, and the progesterone receptor (PGR) gene. The most significant dominance effects were near or in EIF4B and AAAS of Chr05 and AFF1 and KLHL8 of Chr06. All dominance effects were positive overdominance effects where the heterozygous genotype had an advantage, and the homozygous recessive genotype of each SNP had a very negative dominance value. Results from this study provided new evidence and understanding about the genetic variants and genome regions affecting AFC in U.S. Holstein cows.

Towards a Genetic Linkage Map of the California Condor, an Endangered New World Vulture Species.

The development of a linkage map is an important component for promoting genetic and genomic studies in California condors, an endangered New World vulture species. Using a set of designed anonymous microsatellite markers, we genotyped a reference condor population involving 121 individuals. After marker validation and genotype filtering, the genetic linkage analysis was performed using 123 microsatellite loci. This resulted in the identification of 15 linkage groups/subgroups that formed a first-generation condor genetic map, while no markers linked to a lethal chondrodystrophy mutation were found. A panel of polymorphic markers that is instrumental in molecular parentage diagnostics and other genetic studies in the California condor was selected. Further condor conservation genomics research will be focused on updating the linkage map and integrating it with cytogenetic and BAC-based physical maps and ultimately with the genome sequence assembly.

Impact of epistasis effects on the accuracy of predicting phenotypic values of residual feed intake in U. S Holstein cows.

The impact of genomic epistasis effects on the accuracy of predicting the phenotypic values of residual feed intake (RFI) in U.S. Holstein cows was evaluated using 6215 Holstein cows and 78,964 SNPs. Two SNP models and seven epistasis models were initially evaluated. Heritability estimates and the accuracy of predicting the RFI phenotypic values from 10-fold cross-validation studies identified the model with SNP additive effects and additive × additive (A×A) epistasis effects (A + A×A model) to be the best prediction model. Under the A + A×A model, additive heritability was 0.141, and A×A heritability was 0.263 that consisted of 0.260 inter-chromosome A×A heritability and 0.003 intra-chromosome A×A heritability, showing that inter-chromosome A×A effects were responsible for the accuracy increases due to A×A. Under the SNP additive model (A-only model), the additive heritability was 0.171. In the 10 validation populations, the average accuracy for predicting the RFI phenotypic values was 0.246 (with range 0.197-0.333) under A + A×A model and was 0.231 (with range of 0.188-0.319) under the A-only model. The average increase in the accuracy of predicting the RFI phenotypic values by the A + A×A model over the A-only model was 6.49% (with range of 3.02-14.29%). Results in this study showed A×A epistasis effects had a positive impact on the accuracy of predicting the RFI phenotypic values when combined with additive effects in the prediction model.

Potential therapeutic use of plant flavonoids in AD and PD.

Background: Millions of people suffer from Alzheimer's disease (AD) and Parkinson's disease (PD) worldwide. Due to their complex pathology, no effective pharmacological treatment has been found to date, despite extensive research. Developing new, effective therapeutic agents to cure these disease remains a major challenge. Although the cause of AD and PD remains illusive, numerous studies indicates that oxidative stress and neuro-inflammation lead to neurodegeneration in the central nervous system and play vital role in AD and PD morbidity and progression. Flavonoids, which are found widely in nature, exhibit anti-oxidative, anti-inflammatory, anti-mutative, anti-microbial, and neuroprotective properties, so have potential to treat these two kinds of diseases. Methods: In this review, we focus on the anti-oxidative and neuroprotective action of flavonoids in attenuating Alzheimer's and Parkinson's disease, and how they might be harnessed in the development of new pharmacological agents to treat these two diseases. Result: Some flavonoid compounds, like hesperidin, naringin, naringenin, tangeretin, nobiletin, silibinin, Epigallocatechin-3-gallate, displayed to be effective in both AD and PD. Conclusion: Considerable studies have demonstrated the anti-AD and anti-PD effects of flavonoids through various in vitro and in vivo models. However, more rigorous studies are needed to be done for flavonoids to develop into effective drugs and apply them to clinical practice.

Multifactorial methods integrating haplotype and epistasis effects for genomic estimation and prediction of quantitative traits.

The rapid growth in genomic selection data provides unprecedented opportunities to discover and utilize complex genetic effects for improving phenotypes, but the methodology is lacking. Epistasis effects are interaction effects, and haplotype effects may contain local high-order epistasis effects. Multifactorial methods with SNP, haplotype, and epistasis effects up to the third-order are developed to investigate the contributions of global low-order and local high-order epistasis effects to the phenotypic variance and the accuracy of genomic prediction of quantitative traits. These methods include genomic best linear unbiased prediction (GBLUP) with associated reliability for individuals with and without phenotypic observations, including a computationally efficient GBLUP method for large validation populations, and genomic restricted maximum estimation (GREML) of the variance and associated heritability using a combination of EM-REML and AI-REML iterative algorithms. These methods were developed for two models, Model-I with 10 effect types and Model-II with 13 effect types, including intra- and inter-chromosome pairwise epistasis effects that replace the pairwise epistasis effects of Model-I. GREML heritability estimate and GBLUP effect estimate for each effect of an effect type are derived, except for third-order epistasis effects. The multifactorial models evaluate each effect type based on the phenotypic values adjusted for the remaining effect types and can use more effect types than separate models of SNP, haplotype, and epistasis effects, providing a methodology capability to evaluate the contributions of complex genetic effects to the phenotypic variance and prediction accuracy and to discover and utilize complex genetic effects for improving the phenotypes of quantitative traits.

Bioresorbable scaffolds vs. drug-eluting stents on short- and mid-term target lesion outcomes in patients after PCI: A systematic review and meta-analysis.

Background: While current concerns about bioresorbable scaffolds (BRS) are centered on late or very late scaffold thrombosis, less attention had been paid to short- and mid-term clinical outcomes. This review aimed to compare the short- and mid-term outcomes between BRS and drug-eluting stents (DES). Methods: A systematic review of randomized controlled trials (RCTs) that compared BRS vs. DES was conducted by searching PubMed, Cochrane Library, Web of Science, CNKI, WanFang, and VIP databases from inception until 19 April 2022 (language limited to English or Chinese). The primary outcome was target lesion failure (TLF) within 12 months, defined as a composite of target lesion revascularization (TLR), target vessel myocardial infarction (TVMI), and cardiac death. The secondary outcomes were in-stent diameter stenosis (DS%) provided by intraluminal imaging. Results: A total of 13 studies were eligible and were included in this review (N = 9,702 patients). The follow-up duration ranged from 6 months to 1 year. A significantly higher rate of TLF [RR, 1.22, 95% CI (1.03, 1.44)] driven by the higher rate of TVMI [RR, 1.39, 95% CI (1.09, 1.76)] was observed in the BRS group than in the DES group. The risk of TLR and cardiac death was similar between the groups. Also, compared with the DES group, the BRS group had a significantly higher in-stent DS% within 1 year [MD = 5.23, 95%CI (3.43, 7.04); I2 = 97%; p < 0.00001]. Conclusion: Bioresorbable scaffolds were associated with an increased risk of target lesion failure within 1 year as compared with DES, driven by the increased rates of target vessel myocardial infarction. Also, the in-stent DS% seemed to be higher with BRS. Therefore, BRS was inferior to DES in terms of target lesion outcomes at short- or mid-term follow-up. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=327966, PROSPERO (CRD42022327966).

Respiratory exposure to graphene oxide induces pulmonary fibrosis and organ damages in rats involving caspase-1/p38MAPK/TGF-ß1 signaling pathways.

Numerous studies have shown that graphene oxide (GO) respiratory exposure led to severe lung injury, but whether pulmonary fibrosis caused by GO respiratory exposure is related to the activation of the caspase-1/p38MAPK/TGF-ß1 remains unclear. In this study, rats were administrated GO by intratracheal instillation and fed for three months, and the molecular mechanisms of GO on the pulmonary fibrosis and other organ damage caused by GO respiratory exposure were examined. The results showed that the expression of caspase-1/p38MAPK/TGF-ß1 pathway-related factors were significantly elevated with the increase of exposure concentrations of GO. Those data proved that the caspase-1/p38MAPK/TGF-ß1 signaling pathway was involved in the pulmonary fibrosis caused by GO respiratory exposure. The trends of related factors also proved that the caspase-1/p38MAPK/TGF-ß1 pathway was likely to play a dominant role in the sub-acute and sub-chronic stages. The other organ damage examination found that the liver and spleen were damaged initially by the GO respiratory exposure. Meanwhile for the testicle, although the acute injury was severe, signs of recovery were found during the three-month trial period.

Using α- and ß-Epimerizations of cis-2,3-Bis(hydroxymethyl)-γ-butyrolactone for the Synthesis of Both Enantiomers of Enterolactone.

In the context of asymmetric synthesis, epimerization is usually problematic. Here, we describe the use of the epimerization of cis-2,3-bis(hydroxymethyl)-γ-butyrolactone for the synthesis of enterolactones with anti-carcinogenic, anti-inflammatory, anti-angiogenic, and antioxidant activity. Selective α- or ß-epimerization of a γ-butyrolactone was used to selectively synthesize both enantiomers of enterolactone. Theoretical and kinetic studies were performed to elucidate the epimerization mechanism.

Liver involvement in patients with erythropoietic protoporphyria: retrospective analysis of clinicopathological features of 5 cases.

Erythropoietic protoporphyria (EPP) is a rare inherited disease whose morbidity is about 1:75,000 to 1:200,000. It is caused by the deficiency of porphyrin ferrochelatase (FECH). Liver involvement in EPP is even rarer. The diagnosis of EPP with liver involvement mainly relies on clinical manifestations, laboratory examinations, histopathological examinations and genetic testing, which is still a huge challenge for both clinicians and pathologists. Here, 5 cases of EPP with liver injury were collected, and the clinicopathological features of these patients were analyzed. The clinical manifestations and laboratory examinations varied from person to person, whereas the liver biopsies showed that there were dark brown deposits within the hepatocytes, Kupffer cells, bile canaliculi and the lumen of bile ducts, which was a constant finding by histopathological examination. Gene tests were conducted in two of the five cases, and the results confirmed the diagnosis. Fully understanding of the diseases can help us reduce the rate of missed diagnosis and provide proper treatment as early as possible.

Early Biomarkers and Hearing Impairments in Patients with Neonatal Hypoxic-Ischemic Encephalopathy.

Identifying biomarkers for hearing impairments (HIs) in patients with neonatal hypoxic-ischemic encephalopathy (HIE), to initialize early hearing habilitation, is crucial. Seventy-eight neonates with HIE were divided into the following two groups: those with HIs and those without HIs. We compared those patients with 11,837 newborns without HIE, and analyzed the risk factors of HIs among neonatal HIE. Of the 78 patients, 11 were confirmed to have an HI, which is a substantially higher percentage than in the 11,837 newborns without HIE (14.1% vs. 0.87%; p < 0.001). More patients with moderate-to-severe HIE had confirmed HIs (p = 0.020; odds ratio, 8.61) than those with mild HIE. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE. The patients who exhibited HIs had significantly higher lactate (104.8 ± 51.0 vs. 71.4 ± 48.4; U = 181, p = 0.032) and serum glucose (159.5 ± 86.1 vs. 112.1 ± 62.3; U = 166, p = 0.036) levels than those without HIs. A higher prevalence of HIs was noted in the patients with stage III HIE than those with stage II HIE (43.8% vs. 10%; p = 0.008). The degree of HI correlated with brain anomalies and neurodevelopmental outcomes at 1 year of age. Clinical staging, and blood lactate and glucose levels could be predictive factors for HIs among patients with HIE.

Haplotype genomic prediction of phenotypic values based on chromosome distance and gene boundaries using low-coverage sequencing in Duroc pigs.

BACKGROUND: Genomic selection using single nucleotide polymorphism (SNP) markers has been widely used for genetic improvement of livestock, but most current methods of genomic selection are based on SNP models. In this study, we investigated the prediction accuracies of haplotype models based on fixed chromosome distances and gene boundaries compared to those of SNP models for genomic prediction of phenotypic values. We also examined the reasons for the successes and failures of haplotype genomic prediction. METHODS: We analyzed a swine population of 3195 Duroc boars with records on eight traits: body judging score (BJS), teat number (TN), age (AGW), loin muscle area (LMA), loin muscle depth (LMD) and back fat thickness (BF) at 100 kg live weight, and average daily gain (ADG) and feed conversion rate (FCR) from 30 to100 kg live weight. Ten-fold validation was used to evaluate the prediction accuracy of each SNP model and each multi-allelic haplotype model based on 488,124 autosomal SNPs from low-coverage sequencing. Haplotype blocks were defined using fixed chromosome distances or gene boundaries. RESULTS: Compared to the best SNP model, the accuracy of predicting phenotypic values using a haplotype model was greater by 7.4% for BJS, 7.1% for AGW, 6.6% for ADG, 4.9% for FCR, 2.7% for LMA, 1.9% for LMD, 1.4% for BF, and 0.3% for TN. The use of gene-based haplotype blocks resulted in the best prediction accuracy for LMA, LMD, and TN. Compared to estimates of SNP additive heritability, estimates of haplotype epistasis heritability were strongly correlated with the increase in prediction accuracy by haplotype models. The increase in prediction accuracy was largest for BJS, AGW, ADG, and FCR, which also had the largest estimates of haplotype epistasis heritability, 24.4% for BJS, 14.3% for AGW, 14.5% for ADG, and 17.7% for FCR. SNP and haplotype heritability profiles across the genome identified several genes with large genetic contributions to phenotypes: NUDT3 for LMA, LMD and BF, VRTN for TN, COL5A2 for BJS, BSND for ADG, and CARTPT for FCR. CONCLUSIONS: Haplotype prediction models improved the accuracy for genomic prediction of phenotypes in Duroc pigs. For some traits, the best prediction accuracy was obtained with haplotypes defined using gene regions, which provides evidence that functional genomic information can improve the accuracy of haplotype genomic prediction for certain traits.

Dynamic Measurement and Structural Decomposition of Deep Poverty in Contiguous Destitute Areas.

Based on the sample data from 2005 to 2019, this paper calculates the poverty nature of contiguous destitute areas through FGT index and its decomposition and systematically analyzes the impact of economic growth, inequality, and population change on poverty change. From the decomposition results of poverty change, we can see that, first, economic growth, inequality, and population change have different impacts on poverty change in counties and rural areas, and inequality and population mobility have widened the gap between them; second, population factor has always played a key role in the change of poverty, and the deceleration of population growth has a more significant impact on poverty change; third, the impact of the mobility on the poverty change of the counties is different from that of the rural areas. Accordingly, the paper puts forward some countermeasures and suggestions, such as promoting the organic connection between rural revitalization and poverty alleviation, speeding up rural governance, and promoting the process of urbanization.

Dynamical Analysis of Universal Masking on the Pandemic.

We investigate the impact of the delay in compulsory mask wearing on the spread of COVID-19 in the community, set in the Singapore context. By using modified SEIR-based compartmental models, we focus on macroscopic population-level analysis of the relationships between the delay in compulsory mask wearing and the maximum infection, through a series of scenario-based analysis. Our analysis suggests that collective masking can meaningfully reduce the transmission of COVID-19 in the community, but only if implemented within a critical time window of approximately before 80-100 days delay after the first infection is detected, coupled with strict enforcement to ensure compliance throughout the duration. We also identify a delay threshold of about 100 days that results in masking enforcement having little significant impact on the Maximum Infected Values. The results therefore highlight the necessity for rapid implementation of compulsory mask wearing to curb the spread of the pandemic.

A Large-Scale Genome-Wide Association Study of Epistasis Effects of Production Traits and Daughter Pregnancy Rate in U.S. Holstein Cattle.

Epistasis is widely considered important, but epistasis studies lag those of SNP effects. Genome-wide association study (GWAS) using 76,109 SNPs and 294,079 first-lactation Holstein cows was conducted for testing pairwise epistasis effects of five production traits and three fertility traits: milk yield (MY), fat yield (FY), protein yield (PY), fat percentage (FPC), protein percentage (PPC), and daughter pregnancy rate (DPR). Among the top 50,000 pairwise epistasis effects of each trait, the five production traits had large chromosome regions with intra-chromosome epistasis. The percentage of inter-chromosome epistasis effects was 1.9% for FPC, 1.6% for PPC, 10.6% for MY, 29.9% for FY, 39.3% for PY, and 84.2% for DPR. Of the 50,000 epistasis effects, the number of significant effects with log10(1/p) ≥ 12 was 50,000 for FPC and PPC, and 10,508, 4763, 4637 and 1 for MY, FY, PY and DPR, respectively, and A × A effects were the most frequent epistasis effects for all traits. Majority of the inter-chromosome epistasis effects of FPC across all chromosomes involved a Chr14 region containing DGAT1, indicating a potential regulatory role of this Chr14 region affecting all chromosomes for FPC. The epistasis results provided new understanding about the genetic mechanism underlying quantitative traits in Holstein cattle.