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Staphylococcus hyicus is recognized as one of causative agents of porcine exudative epidermitis in piglets. However, research on clinical pathogenic S. hyicus remains limited. In this study, multidrug-resistant S. hyicus was isolated from a large-scale pig farm with cases of fatal exudative epidermitis in piglets. By characterizing the phenotypes and genotypes of S. hyicus isolates, we provide insights for clinical management of exudative epidermitis. Two 21-day-old piglets with clinical signs underwent necropsy and histopathological examination. 48 samples from lactating sows and suckling piglets were collected for pathogen identification. Antimicrobial and disinfectant susceptibility of the isolates was determined using broth microdilution, as well as whole-genome sequencing (WGS) was used to identify antimicrobial resistance genes. Moreover, comparative genomic analysis with public genomes in the Genbank database was performed. The virulence of mecA-carrying S. hyicus was evaluated using the Galleria mellonella infection model. Exudative epidermitis was first observed in 3-day-old piglets. Through necropsy, pathogen isolation, and other diagnostic approaches, S. hyicus was preliminarily identified as the primary causative agent of this episode, and 23 S. hyicus were isolated from samples. Antimicrobial susceptibility testing indicated most of isolated S. hyicus were susceptible to doxycycline, vancomycin and linezolid, while resistant to florfenicol, erythromycin, spectinomycin, amoxicillin, ceftiofur, enrofloxacin that are commonly used for pigs. Twelve resistance genes were identified by WGS, including aadD, ant(6)-Ia, aph(2'')-Ia, blaZ, erm(B), erm(C), fexA, lnu(B), lsa(E), mecA, tet(L), and tet(M). Compared with 39 GenBank genomes, mecA-carrying S. hyicus in our study carried more resistance genes and exhC islands closely related to previous Chinese strains. Based on our findings, we implemented a targeted treatment protocol that brought the outbreak under control and reduced piglet mortality to below 5%. This study successfully isolated pathogenic mecA-carrying S. hyicus responsible for high mortality in piglets, characterized its drug resistance phenotypes and genotypes, offering valuable insights for the prevention and control of this pathogen in piglets.

Although poly (ADP-ribose) polymerase inhibitors (PARPi) have been established to enhance ovarian cancer outcomes, the emergence of drug resistance poses considerable clinical challenges. In this study, we constructed a Hi-C atlas to systematically characterize the effect of olaparib on chromatin organization at multiple hierarchical scales, namely, chromosomes, A/B compartments, topologically associating domains, and chromatin loops. To investigate the effects of PARPi on expression of the cohesion subunit RAD21, we established olaparib-resistant ovarian cancer cell line. Furthermore, we examined the effects of RAD21 on the functions of ovarian cancer cells and spheroids based on cell proliferation, apoptosis, and comet assays. In addition, by performing integrated analyses using ChIP-seq datasets, ChIP-qPCR, and chromosome conformation capture assays, we assessed the influence of RAD21 on the enhancer-promoter interactions of a homologous recombination repair gene. Moreover, on the basis of our findings in previous studies using clinical samples, we further evaluated the clinical value of RAD21 in multiple databases. Genome-wide Hi-C heatmap analysis revealed that olaparib led to a reduction in the genome-wide contact frequency for long distance interactions, altered the degree of chromatin compartmentalization, and promoted compartment switching in ovarian cancer. Differences between the olaparib-treated and control cells with respect to topologically associating domain boundaries and chromatin loops were found to be associated with key cellular functions, such as DNA repair and transcriptional mis-regulation in cancer. Furthermore, PARPi treatment was observed to induce the expression of RAD21, whereas an upregulation of RAD21 promoted proliferation and inhibited apoptosis in ovarian cancer spheroids. Mechanistically, we obtained evidence to indicate that by maintaining enhancer-promoter interactions within chromatin conformation, RAD21 regulates the transcription of RAD51, thereby mediating olaparib resistance in ovarian cancer. The high expression of RAD21 was found to show a significant association with poor overall and progression-free survival in patients with ovarian cancer. Our findings in this study indicate that RAD21 could serve as a potential therapeutic target for overcoming olaparib resistance in ovarian cancer, and provide new insights into the mechanisms underlying the resistance to PARPi from the perspective of chromatin organization.

Getah virus (GETV) is a mosquito-borne zoonotic arbovirus, and clinical infections in animals have been reported with increasing frequency in recent years, posing a potential threat to animal health and public health. In this study, a Getah virus strain, designated GETV-HN2024, was isolated from a spleen sample collected from an aborted fetus in a swine herd in Anhui Province. Phylogenetic trees based on the complete genome and the E2 gene revealed that HN2024 belongs to GETV genotype GIII and is relatively distant from the original Malaysian prototype strain (MM2021), while exhibiting higher genetic homology with porcine-derived GETV strains. Amino acid sequence analysis of the E2 coding region further demonstrated that HN2024 shared 96.9% to 99.8% amino acid identity with reference strains deposited in GenBank. Using the field isolate, rabbit polyclonal antibodies targeting the GETV E1 protein were generated. Simultaneously, the full-length viral genome was cloned into the pBluescript SK(+) vector downstream of the T7 promoter, leading to the successful rescue of the recombinant virus rHN2024. The results showed that the rescued virus exhibited biological characteristics similar to those of the parental strain and maintained good genetic stability. In conclusion, we isolated a contemporary GETV strain, constructed a full-length infectious cDNA clone, and successfully rescued the recombinant GETV. This infectious clone provides a practical reverse genetics platform that will facilitate detailed studies on the virulence determinants, pathogenic mechanisms of GETV, as well as the development of novel vaccines and control strategies in veterinary preventive medicine.

UNC-89 is a giant modular protein located at the sarcomeric M-line of C. elegans striated muscle and is required for sarcomere organization and function. UNC-89 contains two protein kinase domains, PK1 and PK2, separated by 850 residues, that includes a 645-residue long intrinsically disordered sequence that acts like an elastic spring. Bioinformatic analysis suggests that PK2 is an active kinase whereas PK1 is a pseudokinase. We recently reported that a genome-edited worm, unc-89(sf22), that expresses UNC-89 carrying a kinase-inactivating point mutation in PK2 has an unusual phenotype with normally organized sarcomeres and SR, normal muscle function and yet fragmented mitochondria, increased ATP levels, increased glycolysis and alterations in electron transport chain complexes and respiration. Here, we show that a genome-edited worm unc-89(sf23), that expresses UNC-89 with an in-frame deletion of the C-lobe of PK1 has approximately the same phenotype as the PK2 catalytically dead mutant. The fact that mutations in two different regions of UNC-89 result in a mitochondrial phenotype is further evidence of communication between the sarcomere and mitochondria. We further demonstrate that in vitro PK2 interacts with full length PK1 and the C-lobe of PK1. The protein kinase domains of giant sarcomeric proteins are autoinhibited by parts of their own sequence, and this is also likely for PK2, but the mechanism by which PK2 would be activated is unknown. Our data is compatible with a model in which PK1 interacts with PK2 and thereby stimulates PK2 kinase activity.

Respiratory illness contributes to substantial global morbidity and mortality. In Madagascar, an island nation off the southeastern coast of the African continent, hospital-based public health surveillance for respiratory pathogens screens for common respiratory viruses. However, many cases remain undiagnosed. We conducted metagenomic Next Generation Sequencing (mNGS) to identify the pathogen profile of 102 undiagnosed febrile patients who presented to public hospitals with respiratory symptoms and screened negative on a 14-virus multiplex RT-qPCR. We analyzed the diversity of the respiratory microbiome of each patient from mNGS data and identified viral infections potentially linked to undiagnosed fever. We assembled whole genome consensus sequences of viruses with sufficient read depth and coverage, characterized each phylogenetically, and identified any discrepancies with the primers used in the multiplex RT-qPCR panel. Finally, we compared all whole genome sequences against publicly available global databases in a phylogenetic analysis. We identified evidence of infection by a wide range of known human viruses in approximately two thirds (64.7%) of study participants from nine different families of viruses and generated 30 complete or nearly complete consensus sequences of known respiratory viruses including orthopneumoviruses, metapneumoviruses, rhinoviruses, coronaviruses, parainfluenza virus, and bocaparvovirus. mNGS-attributed evidence of infection was predominantly due to orthopneumovirus (also called respiratory syncytial virus [RSV]; n = 24; n = 8 previously diagnosed) and rhinovirus (n = 18) detections, despite previous negative RT-qPCR results for the majority of these cases. Finally, phylogenetic analysis identified two distinct phylogenetic clusters of RSV subtype A, suggesting local transmission following distinct international introductions for this virus. mNGS provides a sensitive pan-pathogenic tool for virus detection. We demonstrate the diversity of viruses associated with undiagnosed respiratory fevers in Madagascar, emphasize the importance and relevance of the existing respiratory surveillance in the country, and highlight the interconnectedness of regional respiratory infection dynamics with global networks of respiratory pathogen transmission.

Clostridioides difficile infection (CDI) is one of the leading infectious diarrhea worldwide. C. difficile pathogenicity is mediated by various virulence factors, including toxins and biofilm formation. This study included 313 C. difficile isolates that were previously collected from four medical centers. We aimed to investigate the prevalence, distribution, and associations of virulence factors in C. difficile strains from both healthcare-associated (HA)- and community-acquired (CA)-CDI patients across Israel from 2020 to 2022. Multi-locus sequence typing (MLST) and whole-genome sequencing (WGS) were performed for strain classification and virulence gene detection. Toxin and biofilm production were also characterized. Sequence type (ST) 42 (12.5%) and ST2 (11.5%) were the most prevalent strains. Toxin production patterns were significantly associated with setting of infection acquisition (p&#x2009;<&#x2009;0.0001). Isolates producing both toxin A and B were 2.5-fold more common among HA-CDI strains, while toxin-A-producers were more frequent in CA-CDI. Biofilm was produced by 96.9% of isolates, with strong biofilm-producing strains significantly more prevalent in hospitals (p&#x2009;<&#x2009;0.001). Furthermore, isolates producing both toxins A and B were predominantly moderate or strong biofilm producers (p&#x2009;<&#x2009;0.0001). agrD presence was significantly associated with ST, toxin production patterns and biofilm-production capacity (p&#x2009;<&#x2009;0.0001 for ST and biofilm, p&#x2009;=&#x2009;0.0016 for toxins). This study revealed a high diversity of C. difficile strains in Israel and demonstrated that virulence factor patterns differ significantly across STs and the acquisition setting. The differences between HA-CDI and CA-CDI isolates in some virulence factors underscores the importance of continuous epidemiological surveillance to guide tailored treatment and prevention strategies.

Temperature sensitivity remains a significant bottleneck in the industrial application of the oleaginous yeast Yarrowia lipolytica. While adaptive evolution and metabolic engineering have produced thermotolerant variants, the impact of thermal stress on the genomic integrity of this non-conventional yeast remains poorly understood. Here, we employed a mutation accumulation framework coupled with whole-genome sequencing to characterize the mutational landscape of Y. lipolytica at 37&#xb0;C. We observed a 29- and 68-fold increase in single-nucleotide variations and small insertions/deletions, respectively, compared to optimal growth conditions (30&#xb0;C). Mechanistic analysis revealed that this mutagenicity is independent of error-prone translesion and nonhomologous end joining pathways; instead, thermal stress overwhelms the replicative fidelity of DNA polymerases and the mismatch repair system. Furthermore, long-read sequencing identified severe telomere instability and large-scale chromosomal rearrangements, including the frequent formation of circular chromosomes and terminal fusions. Lastly, functional genomics revealed YALI1_B03404g to be a key negative regulator of heat resistance. Its deletion substantially enhances thermotolerance, a phenotype potentially mediated through the modulation of yeast-to-hypha transitions. Collectively, our findings enhance the understanding of genomic evolution in non-conventional yeasts under thermal stress and offer a valuable framework for developing robust industrial strains.

Biodiversity is at increasing risk, and amphibians are the most threatened vertebrate class, with 40.7% of species globally at risk. For amphibians, the primary cause for their decline is habitat loss. The scale of this global issue becomes most evident in so-called deforestation hotspots, such as the Chiquitano Dry Forest in Bolivia, which harbours a highly diverse fauna and flora with many species still awaiting formal description. Only recently, the frog Oreobates chiquitanus has been described from a single location within this forest. Since then, it was discovered at only two additional sites. An ongoing logging initiative at the type locality led to the deforestation of the sampling site, even before the species was formally described. Ongoing logging activities in the vicinity of all known sites raise questions about the species' fate. Here, we provide a comprehensive genetic definition of the species and try to assess the genetic diversity and conservation value of the type population. We sequenced all available type specimens of Oreobates chiquitanus, providing a reference genome from one of the paratopotypes and mitochondrial assemblies for all type specimens. We further show that all known populations of this species are near recent logging initiatives. The reconstruction of the demographic history indicates that the population was recovering from a dip roughly 300kya. The estimates of relatedness and heterozygosity imply a genetically vital population. This study exemplifies the importance of collaboration of natural history collections and genomic initiatives like TBG (Translational Biodiversity Genomics) for a better understanding of the anthropogenic impacts in times of global change, to identify and describe biodiversity, to raise awareness, and inform potential conservation measures. We not only provide a comprehensive and permanent molecular definition for O. chiquitanus but also assess the genetic diversity of the population. Therefore, this study provides an important baseline for future studies of genetic erosion in this species. Furthermore, it illustrates the risk of biodiversity loss in the Chiquitano Dry Forest and signifies the need for conservation efforts.

The Irish Wolfhound (IW) is a dog breed characterised by a complex demographic history and reduced population size. In this study, we combined multiple population genomic approaches to characterise the genetic structure of 96 dogs collected from 23 countries worldwide, genotyped using the Illumina CanineHD BeadChip. Analyses of effective population size (Ne), linkage disequilibrium (LD) decay, heterozygosity and principal component analysis (PCA) consistently revealed limited genetic diversity. Complementary analyses of runs of homozygosity (ROH) and integrated haplotype score (iHS) identified extended homozygous segments and signatures of selection across the genome. ROH were predominantly short in length, and 40 samples showed ROH longer than 8&#xa0;Mb. No ROH exceeding 16&#xa0;Mb were detected, suggesting that these patterns reflect long-term demographic processes and historical selection rather than exclusively recent inbreeding. Particularly, 26 ROH islands were shared by at least 85% of the analysed individuals, with 3 ROHs shared by 100% of the population. Several ROH islands overlapped with regions previously reported in other hunting dog breeds and harboured genes associated with morphology, behaviour and diseases of major relevance to IWs, including osteosarcoma. Genomic regions identified by iHS also include genes involved in cancer and immune response. Compared with a previous IW population with publicly available genotypes, the dogs analysed here represent a more homogeneous subgroup. Overall, all approaches converged on a coherent genomic scenario, which highlights the combined effects of demographic history and selection in shaping the current genetic architecture of the IWs.

Spontaneous coronary artery dissection (SCAD) is a major cause of myocardial infarction in young women without traditional cardiovascular risk factors (Hayes et al., 2018; Adlam et al., 2018 [1, 2]). Despite growing awareness, its biological underpinnings remain incompletely understood, and clinical management is largely based on observational evidence rather than mechanistic insight (Saw et al., 2014; Lettieri et al., 2015; Steg et al., 2024 [3-5]). To systematically integrate genomic, epitranscriptomic, proteomic, and metabolomic data in order to characterize the multi-omic architecture of SCAD and identify potential biomarkers and therapeutic targets. A systematic review was conducted in accordance with the PRISMA 2020 statement (Arbelo et al., 2023 [6]). PubMed/MEDLINE was searched for original studies investigating genomic and multi-omic features of SCAD. Data were extracted on study design, patient characteristics, identified variants, circulating biomarkers, and implicated biological pathways. Functional enrichment analysis was performed using the DAVID bioinformatics resource (Page et al., 2021 [7]). A total of 16 studies were included. Genome-wide association studies consistently identified susceptibility loci related to arterial structure and extracellular matrix integrity, including ADAMTSL4, PHACTR1/EDN1, LRP1, and FBN1 (Huang et al., 2009; Saw et al., 2020; Turley et al., 2020 [8-10]). Rare variant analyses further supported the role of genes involved in extracellular matrix remodeling and vascular smooth muscle cell function, including COL3A1, COL4A1/2, SMAD3, and TLN1 (Adlam et al., 2023; Turley et al., 2021, 2019; Carss et al., 2020; Zekavat et al., 2022; Wang et al., 2022 [11-16]), while ancestry-specific signals such as TSR1 variants were observed in distinct populations (Turley et al., 2023 [17]). Proteogenomic approaches linked genetic susceptibility loci to circulating proteins involved in matrix remodeling and inflammation, including cathepsin B and ECM1 (Maioli et al., 2010 [18]). Epitranscriptomic analyses identified differential microRNA expression profiles associated with vascular injury and repair pathways (Sun et al., 2019 [19]). SCAD is characterized by a complex, multi-layered biological architecture involving genetic susceptibility, extracellular matrix dysregulation, and vascular signaling pathways. Integration of multi-omic data provides novel insights into disease mechanisms and highlights potential biomarkers and targets for precision medicine approaches in SCAD.

We reported stepwise evolution of a Methicillin-Resistant Staphylococcus epidermidis (MRSE) with reduced susceptibility to dalbavancin in a patient with recurrent episode of bloodstream infections (BSIs). (Single nucleotide polymorphism) SNPs and insert/deletions analysis between genomes of dalbavancin -susceptible and -non-susceptible strains was performed. Dalbavancin exposure and PK/PD target attainment was determined by TDM. In vitro synergy testing was performed by evaluating the fractional inhibitory concentration indices. Four clonally related MRSE isolates belonging to ST23 were recovered during recurrent bacteraemic episodes in a single patient treated with dalbavancin-based therapy over a 3-year period. Progressive increases of the dalbavancin MIC was observed and resistome analysis showed a conserved antimicrobial resistance genes among isolates. First dalbavancin non-susceptible strain carried an A414T substitution within walK, whereas the second non-susceptible MRSE strain harboured L957F and G470D mutations in rpoB and vraG, respectively. TDM analysis indicated optimal plasma exposure and prolonged PK/PD target attainment by considering clinical breakpoint and MIC of dalbavancin of the susceptible MRSE strains. Synergy testing demonstrated that dalbavancin combined with fosfomycin exhibited synergistic activity against 75% of isolates, whereas combinations with &#x3b2;-lactams were mostly indifferent. We described in vivo evolution of dalbavancin reduced susceptibility in MRSE during long-term dalbavancin therapy highlighting multiple genetic trajectories involving different genetic determinants. These findings underscore the risk of resistance selection despite adequate systemic exposure and support the need for optimized dosing strategies, source control in preventing recurrence in prosthetic infections, and combination regimens to prevent resistance during dalbavancin treatment of MRSE infections.

Napham, traditional fermented food of the Bodo community in Assam, is produced from tender shoots of Colocasia esculenta and dried fish, and was recently granted Geographical Indication (GI) status. Despite its cultural and nutritional significance, its beneficial microbiota remains insufficiently characterized. This study aimed to identify multifunctional bacterial isolates with both functional and flavor-enhancing properties for use as starter cultures. Forty-eight isolates were screened for Gram reaction, enzymatic activities (protease, lipase, carbohydrate fermentation), and biosafety traits. Four isolates (NAP/1, NAP/2, NAP/3, NAP/4) exhibiting a preliminary phenotypic safety profile based on in vitro screening were evaluated for gastrointestinal stress tolerance traits, including tolerance to acid (pH 2.0), phenol (0.4%), salt (8% NaCl), as well as auto-aggregation capacity and adhesion to chicken crop epithelial cells. Among them, isolate NAP/4 exhibited comparatively higher tolerance, strong adhesion, and high auto-aggregation, and demonstrated a favorable in vitro safety profile, including &#x3b3;-hemolysis and broad antibiotic susceptibility. In curd and rice beverage models, NAP/4 enhanced sensory qualities and produced diverse flavor volatiles, supporting its candidacy as a multifunctional food-fermenting isolate prior to genomic validation. 16S rRNA sequencing revealed NAP/4 as Staphylococcus sp. (GenBank accession: PQ471484.1). Collectively, these findings highlight NAP/4 as a promising candidate for further genomic evaluation toward potential application in controlled fermentation systems and clean-label formulations. However, whole-genome sequencing and in vivo validation remain essential next steps to confirm safety and functional efficacy at the molecular level.

Laboratory genetic counselors (GCs) in cytogenetics oversee a laboratory stewardship (LS) program to review the appropriateness of incoming test orders, which saves both time and healthcare resources. This is especially important for familial cytogenetic testing performed after proband genomic testing, since appropriate testing methodology may vary between families and among family members. We describe three inappropriate orders for familial cytogenetic testing performed after proband genomic testing that were identified and corrected because of the LS process at ARUP Laboratories. Review of familial testing using an LS program avoids false-negative results in at-risk relatives and shortens the time to provide accurate results, enabling relatives to make informed clinical management decisions. This series highlights the importance of seeking genetic advice prior to submitting familial testing samples and including the proband's test results to help the laboratory confirm the appropriateness of test orders. Structural variants (SVs) are identified by proband chromosome analysis, genomic microarray (GMA), and genome sequencing. Healthcare providers without specialized genetics expertise may not realize that SVs can be cryptic by karyotype or undetectable by GMA (when balanced), and that standard FISH probes may fail to detect SVs due to FISH probe localization not spanning the abnormality, even when the FISH probe is designed to target the patient's condition. This series illustrates the benefits of a routine laboratory LS program for familial cytogenetic testing, particularly when cryptic SVs are involved.

Extensive research has shown that the microRNA-122 (miR-122) plays an important role in liver homeostasis, and its dysregulation has been implicated in various liver pathologies such as liver cancer and non-alcoholic fatty liver disease. The primary transcript for miR-122, long non-coding RNA 122 (lnc122) has traditionally only been considered an intermediate product for mature miR-122. We used CRISPRi to inhibit lnc122 RNA expression in hepatoma cells and mouse livers with and without expression of mature miR-122 RNA to determine if a lnc122 RNA has a separate function. These models were used in combination of RNAseq, Gene Set Enrichment Analysis, RNA pulldown-mass spectrometry, and a CRSIRPi/CRISPRa mediated liver tumor model to establish the specific role of lnc122 in hepatic homeostasis. We demonstrate that lnc122 RNA has a distinct tumor suppressive role that is separate from the anti-proliferative function of miR-122. Specifically, lnc122 RNA promotes MYC protein degradation by stabilizing the MYC-UBR5 E3 ubiquitin ligase protein complex. Unlike other E3 ubiquitin ligases for MYC, UBR5 is co-amplified with MYC in >40% of human cancers due to their close location on the human genome and lnc122 is indispensable for efficient MYC degradation by UBR5. Paired patient liver and tumor samples showed decreased concentrations of lnc122 RNA in tumors. Furthermore, reducing the lnc122 RNA transcripts in mouse liver exacerbated MYC-driven liver tumorigenesis. Although lnc122 expression is restricted to the liver, exogenous expression of lnc122 in non-hepatic transformed cells also destabilized MYC protein. Our findings indicate that lnc122 RNA has a synergistic role with miR-122 in the surveillance and prevention of liver tumorigenesis and may represent a new target for treating MYC-driven human cancers. The study demonstrates that lnc122 RNA not only is a precursor for miR-122 but functions in forming a ubiquitination complex via UBR5, and responsible for limiting the half-life of MYC protein. Loss of lnc122 RNA expression promotes liver cancer perhaps categorizing it as tumor-suppressor gene. Further studies to develop agents to enhance the activity of this complex may offer a new therapeutic approach to treat hepatocellular carcinoma.

This study aims to identify macrophage polarization (MP)-related genes implicated in esophageal cancer (EC) by integrating methylation quantitative trait loci (mQTL), expression QTL (eQTL), and protein QTL (pQTL) data with EC genome-wide association study (GWAS) data. GWAS data were obtained from the UK Biobank for discovery and the FinnGen R10 release for validation. Blood-based mQTL, eQTL, and pQTL summary data were sourced from large European cohorts. Summary Data-based Mendelian Randomization (SMR) analysis assessed the associations between MP-related gene methylation, expression, protein abundance, and EC risk. Colocalization analysis identified shared causal variants. SMR and colocalization analysis identified 54 methylation loci, seven genes, and one protein associated with EC risk. Based on multi-omics integration and tiered evidence, LEP was classified as tier 1 due to its significant negative association in integrated mQTL-eQTL data. LEP (cg13454199) methylation showed a positive association with EC risk, while LEP expression was negatively associated, indicating that increased LEP methylation may downregulate its expression, potentially raising EC risk. INPP5D and PGF were tier 2 genes due to their associations with EC risk at both methylation and expression levels, with strong colocalization (PPH4&#x2009;>&#x2009;0.5). Tier 3 genes SPP1 and USP18 were associated with EC risk at single regulatory levels (protein and methylation, respectively) in the discovery cohort, with colocalization evidence and validation in an independent dataset, respectively. We identified LEP, INPP5D, PGF, SPP1, and USP18 as key MP-related genes associated with EC risk, providing potential therapeutic targets for EC. Not applicable.