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Although major advances in genomics have initiated an exciting new era of research, a lack of information regarding cis -regulatory elements has limited the genetic improvement or manipulation of pigs as a meat source and biomedical model. Here, we systematically characterize cis -regulatory elements and their functions in 12 diverse tissues from four pig breeds by adopting similar strategies as the ENCODE and Roadmap Epigenomics projects, which include RNA-seq, ATAC-seq, and ChIP-seq. In total, we generate 199 datasets and identify more than 220,000 cis -regulatory elements in the pig genome. Surprisingly, we find higher conservation of cis -regulatory elements between human and pig genomes than those between human and mouse genomes. Furthermore, the differences of topologically associating domains between the pig and human genomes are associated with morphological evolution of the head and face. Beyond generating a major new benchmark resource for pig epigenetics, our study provides basic comparative epigenetic data relevant to using pigs as models in human biomedical research. To date, little is known about the regulatory landscape of the pig genome. Here, the authors characterize cis -regulatory elements in the pig genome using RNA-seq, ChIP-Seq and ATAC-seq, finding a higher degree of usage conservation between pig and human than mouse and human.

Advances in high-throughput sequencing technologies have reduced the cost of genotyping dramatically and led to genomic prediction being widely used in animal and plant breeding, and increasingly in human genetics. Inspired by the efficient computing of linear mixed model and the accurate prediction of Bayesian methods, we propose a machine learning-based method incorporating cross-validation, multiple regression, grid search, and bisection algorithms named KAML that aims to combine the advantages of prediction accuracy with computing efficiency. KAML exhibits higher prediction accuracy than existing methods, and it is available at https://github.com/YinLiLin/KAML .

The lack of integrated analysis of genome-wide association studies (GWAS) and 3D epigenomics restricts a deep understanding of the genetic mechanisms of meat-related traits. With the application of techniques as ChIP-seq and Hi-C, the annotations of cis-regulatory elements in the pig genome have been established, which offers a new opportunity to elucidate the genetic mechanisms and identify major genetic variants and candidate genes that are significantly associated with important economic traits. Among these traits, loin muscle depth (LMD) is an important one as it impacts the lean meat content. In this study, we integrated cis-regulatory elements and genome-wide association studies (GWAS) to identify candidate genes and genetic variants regulating LMD. Five single nucleotide polymorphisms (SNPs) located on porcine chromosome 17 were significantly associated with LMD in Yorkshire pigs. A 10 kb quantitative trait locus (QTL) was identified as a candidate functional genomic region through the integration of linkage disequilibrium and linkage analysis (LDLA) and high-throughput chromosome conformation capture (Hi-C) analysis. The BMP2 gene was identified as a candidate gene for LMD based on the integrated results of GWAS, Hi-C meta-analysis, and cis-regulatory element data. The identified QTL region was further verified through target region sequencing. Furthermore, through using dual-luciferase assays and electrophoretic mobility shift assays (EMSA), two SNPs, including SNP rs321846600, located in the enhancer region, and SNP rs1111440035, located in the promoter region, were identified as candidate SNPs that may be functionally related to the LMD. Based on the results of GWAS, Hi-C, and cis-regulatory elements, the BMP2 gene was identified as an important candidate gene regulating variation in LMD. The SNPs rs321846600 and rs1111440035 were identified as candidate SNPs that are functionally related to the LMD of Yorkshire pigs. Our results shed light on the advantages of integrating GWAS with 3D epigenomics in identifying candidate genes for quantitative traits. This study is a pioneering work for the identification of candidate genes and related genetic variants regulating one key production trait (LMD) in pigs by integrating genome-wide association studies and 3D epigenomics.

Fresh coconut meat polysaccharides (FCMPs) are high-value natural active polysaccharides with both medicinal and edible uses, but their structural characteristics and potential biological activities have not been well studied. In this work, FFCMP was separated and purified by sequential application of water extraction and alcohol precipitation methods, the Sevag method, DEAE-52 cellulose column chromatography, and Sephadex G-100 gel column chromatography, yielding four components (FCMP 1-FCMP 4). High-performance liquid chromatography (HPLC) was used to determine their molecular weights as 343,016.9, 2279.4, 1363.2, and 2228.9 Da, respectively. Structural characterization and monosaccharide analysis revealed that the FCMP series primarily consists of mannose, glucose, galactose, arabinose, and rhamnose. Methylation experiments and nuclear magnetic resonance (NMR) indicated that FCMP 1 exhibits a complex topological structure with a β-1→4 main chain, β-1→6 branches, and an α-L-rhamnose terminal; FCMP 2 is a heteropolysaccharide with a β-(1→3)-mannan main chain containing β-(1→6)-galactose branches; the main chain of FCMP 3 consists of β-D-mannose and β-D -galactose, with side chains containing α-L-rhamnose and terminal α-L-arabinose and β-D-mannose; and FCMP 4 has a main chain primarily composed of glucose and mannose linked via 1→4 bonds, with some C6 positions exhibiting 1→6 branch structures. Molecular docking predictions suggest that the FCMP series of polysaccharides possess immunomodulatory, anti-inflammatory, and edema-treating properties, providing a theoretical basis for their application in pharmacology and food science research.

Background Lysine crotonylation has been implicated in the pathogenesis of preeclampsia (PE). However, the underlying mechanisms remain unclear. This study aimed to identify crotonylation-related biomarkers in PE through bioinformatics analysis. Methods Publicly available datasets, including GSE48424 and GSE149440, were utilized in this study. Candidate biomarkers were identified by intersecting differentially expressed genes (DEGs) from differential expression analysis with key module genes obtained through weighted gene co-expression network analysis (WGCNA). Biomarkers were further refined using expression analysis and machine learning techniques. Functional analysis, immune infiltration analysis, methylation modifications, and construction of molecular regulatory networks were employed to explore the potential mechanisms underlying the involvement of candidate biomarkers in PE pathogenesis. Additionally, associations between the biomarkers and common clinical predictive molecules were examined, and their diagnostic performance for PE was evaluated. Results A total of 323 candidate genes were identified by intersecting 3,353 DEGs with 402 key module genes. Expression analysis and machine learning algorithms pinpointed DPYD and PRDX3 as biomarkers. DPYD and PRDX3 were identified as lysine crotonylation-related biomarkers in PE. These genes were significantly downregulated in PE and associated with pathways such as olfactory signaling, neutrophil degranulation, and immune microenvironment dysregulation. Both biomarkers demonstrated excellent diagnostic efficacy (AUC > 0.85), outperforming traditional markers like VEGFA. Additionally, DPYD and PRDX3 are associated with oxidative stress and immune dysregulation, which may be the key mechanisms for the development of PE. Conclusion This study identified DPYD and PRDX3 as lysine crotonylation-related biomarkers in PE, providing new insights for the diagnosis and management of the condition.

The liver plays an important role in lipid and glucose metabolism. Here, we show the role of human antigen R (HuR), an RNA regulator protein, in hepatocyte steatosis and glucose metabolism. We investigated the level of HuR in the liver of mice fed a normal chow diet (NCD) and a high-fat diet (HFD). HuR was downregulated in the livers of HFD-fed mice. Liver-specific HuR knockout (HuR LKO ) mice showed exacerbated HFD-induced hepatic steatosis along with enhanced glucose tolerance as compared with control mice. Mechanistically, HuR could bind to the adenylate uridylate-rich elements of phosphatase and tensin homolog deleted on the chromosome 10 (PTEN) mRNA 3′ untranslated region, resulting in the increased stability of Pten mRNA; genetic knockdown of HuR decreased the expression of PTEN. Finally, lentiviral overexpression of PTEN alleviated the development of hepatic steatosis in HuR LKO mice in vivo. Overall, HuR regulates lipid and glucose metabolism by targeting PTEN.

Japanese encephalitis virus (JEV) is a mosquito-borne zoonotic flavivirus that causes encephalitis and reproductive disorders in mammalian species. However, the host factors critical for its entry, replication, and assembly are poorly understood. Here, we design a porcine genome-scale CRISPR/Cas9 knockout (PigGeCKO) library containing 85,674 single guide RNAs targeting 17,743 protein-coding genes, 11,053 long ncRNAs, and 551 microRNAs. Subsequently, we use the PigGeCKO library to identify key host factors facilitating JEV infection in porcine cells. Several previously unreported genes required for JEV infection are highly enriched post-JEV selection. We conduct follow-up studies to verify the dependency of JEV on these genes, and identify functional contributions for six of the many candidate JEV-related host genes, including EMC3 and CALR . Additionally, we identify that four genes associated with heparan sulfate proteoglycans (HSPGs) metabolism, specifically those responsible for HSPGs sulfurylation, facilitate JEV entry into porcine cells. Thus, beyond our development of the largest CRISPR-based functional genomic screening platform for pig research to date, this study identifies multiple potentially vulnerable targets for the development of medical and breeding technologies to treat and prevent diseases caused by JEV. Here the authors report the construction of a genome-scale porcine CRISPR/Cas9 library, called PigGeCKO, for screening and analyses of host resistance genes and factors associated with Japanese encephalitis virus replication.

Quorum sensing (QS) is a phenomenon of intercellular communication discovered mainly in bacteria. A QS system consisting of QS signal molecules and regulatory protein components could control physiological behaviors and virulence gene expression of bacterial pathogens. Therefore, QS inhibition could be a novel strategy to combat pathogens and related diseases. QS inhibitors (QSIs), mainly categorized into small chemical molecules and quorum quenching enzymes, could be extracted from diverse sources in marine environment and terrestrial environment. With the focus on the exploitation of marine resources in recent years, more and more QSIs from the marine environment have been investigated. In this article, we present a comprehensive review of QSIs from marine bacteria. Firstly, screening work of marine bacteria with potential QSIs was concluded and these marine bacteria were classified. Afterwards, two categories of marine bacteria-derived QSIs were summarized from the aspects of sources, structures, QS inhibition mechanisms, environmental tolerance, effects/applications, etc. Next, structural modification of natural small molecule QSIs for future drug development was discussed. Finally, potential applications of QSIs from marine bacteria in human healthcare, aquaculture, crop cultivation, etc. were elucidated, indicating promising and extensive application perspectives of QS disruption as a novel antimicrobial strategy.

Chemotherapy-induced intestinal mucositis (CIM) is a common adverse reaction to antineoplastic treatment with few appropriate, specific interventions. We aimed to identify the role of the G protein coupled estrogen receptor (GPER) in CIM and its mechanism. Adult male C57BL/6 mice were intraperitoneally injected with 5-fluorouracil to establish the CIM model. The selective GPER agonist G-1 significantly inhibited weight loss and histological damage in CIM mice and restored mucosal barrier dysfunction, including improving the expression of ZO-1, increasing the number of goblet cells, and decreasing mucosal permeability. Moreover, G-1 treatment did not alter the antitumor effect of 5-fluorouracil. In the CIM model, G-1 therapy reduced the expression of proapoptotic protein and cyclin D1 and cyclin B1, reversed the changes in the number of TUNEL + cells, Ki67 + and bromodeoxyuridine + cells in crypts. The selective GPER antagonist G15 eliminated all of the above effects caused by G-1 on CIM, and application of G15 alone increased the severity of CIM. GPER was predominantly expressed in ileal crypts, and G-1 inhibited the DNA damage induced by 5-fluorouracil in vivo and vitro, as confirmed by the decrease in the number of γH2AX + cells in the crypts and the comet assay results. Referring to the data from GEO dataset we verified GPER activation restored ERK1/2 activity in CIM and 5-fluorouracil-treated IEC-6 cells. Once the effects of G-1 on ERK1/2 activity were abolished with the ERK1/2 inhibitor PD0325901, the effects of G-1 on DNA damage both in vivo and in vitro were eliminated. Correspondingly, all of the manifestations of G-1 protection against CIM were inhibited by PD0325901, such as body weight and histological changes, the mucosal barrier, the apoptosis and proliferation of crypt cells. In conclusion, GPER activation prevents CIM by inhibiting crypt cell DNA damage in an ERK1/2-dependent manner, suggesting GPER might be a target preventing CIM.

ABSTRACT Background Post‐stroke cognitive impairment (PSCI) is a common complication following stroke, with limited effective treatments. This randomized controlled trial aims to evaluate the efficacy of two non‐pharmacological interventions—electroacupuncture therapy (EA) and herbal olfactory therapy (HOT)—in improving cognitive function in PSCI patients, both as standalone treatments and in combination. Methods This parallel‐group, assessor‐blinded, randomized controlled trial will recruit 210 PSCI patients, randomly assigned to one of six groups: control, EA, HOT, combination therapy, sham therapy, or the healthy (ratio 1:1:1:1:1:1). All participants will receive standard cognitive training and basic medical care. The EA group will receive 4 weeks of electro‐acupuncture at specific acupoints. The HOT group will receive 4 weeks of aromatic inhalation therapy using Acorus tatarinowii volatile oil. The combination group will receive both interventions. The primary outcome measure is cognitive function, assessed using the Montreal cognitive assessment (MoCA) at baseline, week 4, and week 8. Secondary outcomes include the mini‐mental state examination (MMSE), functional magnetic resonance imaging (fMRI), near‐infrared spectroscopy (fNIRS), and anxiety assessment using the state‐trait anxiety inventory (STAI) at baseline and week 4. Data analysis will be conducted using a modified intention‐to‐treat approach. Aims This study aims to evaluate the clinical efficacy of EA at cervical acupoints combined with HOT for PSCI, with a specific focus on determining the therapeutic superiority of this combined approach over monotherapy interventions. Conceptual schematic illustrating the trial design and mechanisms. Electroacupuncture (EA) targets cervical acupoints (GB20/Gongxue) to improve cerebral blood flow and neural connectivity. HOT (herbal olfactory therapy) delivers Acorus Tatarinowii volatile oil via inhalation to penetrate the blood‐brain barrier, reduce neuroinflammation, and enhance synaptic plasticity. Combined therapy synergistically modulates LRPs/ARF1 signaling, promotes mitochondrial function, and clears Aβ plaques. Outcomes are assessed via MoCA/MMSE (cognition), fMRI/fNIRS (brain activity), and STAI (anxiety). Healthy controls provide normative brain function baselines.