Structural basis of long non-coding RNA PVT1 interactions with select mRNAs universal in pan-cancer system: A computational study.

Integration of multienvironment QTL mapping and GWAS revealed three candidate genes-ZmFum1, ZmDGAT1-1, and ZmLPAAT4-as potential key regulators of maize kernel oil content. With an exceptional energy density and high polyunsaturated fatty acid content, maize oil positions high-oil maize as multifunctional feedstocks. Exploring the genetic architecture of oil content (OC) in maize kernel is crucial for breeding high-oil maize varieties. Herein, a combination of genome-wide association study and linkage mapping was employed to explore the quantitative trait loci (QTL) and candidate genes underlying the OC in maize kernel under four environments. Linkage mapping identified 17 QTLs for the OC, among which three QTL were repeatedly detected under multiple environments. GWAS revealed 17 OC-associated SNPs, of which 12 SNPs had large phenotype contribution rates with one accounting for 17.2% of the phenotypic variance. By integrating three multienvironment QTL identified through linkage mapping with the 17 most significant SNPs detected by GWAS, a total of 1142 genes were identified as the candidate genes. Based on the functional annotations, expression profiling, and gene-based association analysis, three candidate genes were prioritized: Zm00001d029084, Zm00001d037760, and Zm00001d043267, which encode fumarate hydratase 1 (ZmFum1), diacylglycerol acyltransferase-type I2 (ZmDGAT1-1), and 1-acyl-sn-glycerol-3-phosphate acyltransferase 4 (ZmLPAAT4), respectively. The SNPs in the coding sequences of Zm00001d029084 and Zm00001d037760 were significantly associated with OC and result in amino acid substitutions, whereas the promoter and 3'UTR regions of Zm00001d043267 each harbor an SNP significantly associated with OC. These findings provide valuable insights into the genetic basis of OC and highlight potential targets for marker-assisted selection in high-oil maize breeding.

Avian leukosis virus (ALV) is a prototypical alpharetrovirus that can induce various tumors and cause serious immunosuppression, posing severe threats to the poultry industry. ALVs isolated from chickens are classified into seven subgroups (A to E, J, and K). In 2024, a novel ALV-K strain designated GD24LHB130 was isolated from Qingyuan Partridge chickens in Guangdong Province, China. Whole-genome sequencing revealed that GD24LHB130 is a recombinant ALV-K strain harboring the LTR, pol, and 3'UTR regions of ALV-J. In vitro infection assays and LTR promoter activity analysis demonstrated that GD24LHB130 exhibits significantly enhanced replicative capacity compared to classical ALV-K strains, with the recombination of the ALV-J LTR region strongly associated with this replication advantage. In vivo pathogenicity experiments confirmed that GD24LHB130 causes significant growth retardation, immune organ damage, persistent viremia and viral shedding, and hemangioma-like lesion formation in infected chickens. This is the first report of a recombinant ALV-K strain capable of inducing hemangioma-like lesions, which exhibits enhanced replication capacity and pathogenic potential. These findings not only expand the epidemiological knowledge of ALV but also provide critical insights into the molecular mechanisms underlying ALV-K pathogenesis.

Glucocorticoid receptor (GR, encoded by NR3C1) and mineralocorticoid receptor (MR, encoded by NR3C2) are critical regulators of the hypothalamic-pituitary-adrenal (HPA) axis and stress response, both of which are closely related to the pathogenesis of schizophrenia. This study aimed to investigate the genetic associations and gene-gene interactions of NR3C1 and NR3C2 polymorphisms with schizophrenia. A total of 527 participants (162 schizophrenia patients and 365 healthy controls) were initially enrolled. Given the insufficient sample size of female subjects, additional participants were recruited using identical diagnostic and enrolment criteria, yielding a final expanded cohort of 279 patients and 502 healthy controls (n = 781) for validation of the NR3C1 rs6191 locus. Five single nucleotide polymorphisms (SNPs) of NR3C1 (rs6191, rs6198, rs6190, rs56149945 and rs41423247) and four SNPs of NR3C2 (rs2871, rs5522, rs5525 and rs2070951) were genotyped via an improved multiplex ligation detection reaction (iMLDR) assay. In the expanded sample, the NR3C1 rs6191 polymorphism was significantly associated with schizophrenia in females. Females harbouring the CC genotype at rs6191 exhibited a higher risk of schizophrenia than those carrying the AA or AC genotypes. No significant between-group differences were observed in the allele or genotype frequencies of the four NR3C2 SNPs. Notably, significant gene-gene interactions were detected between NR3C1 and NR3C2 loci, with the rs6191/rs5522/rs2871 combination identified as the optimal model (cross-validation consistency = 10/10). Our findings support NR3C1 as a candidate susceptibility gene for schizophrenia. The NR3C1 rs6191 polymorphism (3'-UTR region) is associated with schizophrenia in the female population, and the CC genotype at this locus confers an elevated risk of schizophrenia. Whereas NR3C2 polymorphisms are not independently associated with schizophrenia, significant gene-gene interactions exist between NR3C1 and NR3C2 loci.

RNA granules are essential regulators of post-transcriptional gene expression, enabling mRNA transport, localization, and local translation in neurons. The localized transcriptome is diverse; however, how different mRNAs are organized into granules for efficient localization and translation remains unknown. Here, we combine real-time endogenous single RNA imaging with protein and RNA proximity labeling to investigate two distinct endogenous neuronal mRNA granule populations, Actb and Arc , in stimulated primary hippocampal neurons. Using orthogonal RNA labeling systems in a dual knock-in mouse model, we show that Actb and Arc mRNAs are packaged into spatially segregated granules with distinct trafficking dynamics, localization kinetics, and responses to synaptic stimulation. Actb granules displayed rapid and sustained localization, whereas Arc granules showed delayed, transient recruitment, consistent with their respective roles in structural and activity-dependent plasticity. Proximity labeling reveals that these granules are distinct in their mRNA composition, despite sharing core RNA-binding proteins, suggesting that shared cis-regulatory elements within mRNA 3'UTR regions drive selective co-packaging of mRNAs into unique granules. Together, these findings demonstrate that neuronal mRNAs are differentially sorted into molecularly and functionally distinct granules, providing a framework for understanding how precise spatio-temporal control of mRNA localization and translation is achieved across complex neuronal arbors.

ABSTRACT Triple-negative breast cancer (TNBC) represents a particularly aggressive form of breast tumors. Mitochondrial dysfunction represses the proliferation of TNBC cells. Ubiquitin-specific proteases 34 (USP34) has been predicted to be abnormally overexpressed in TNBC. This research examined the role of USP34 in the mitochondrial function modulation of TNBC. Herein, cell proliferation was evaluated by the 5-ethynyl-2’-deoxyuridine assay. Mitochondrial membrane potential was detected employing the JC-1 assay. Mitochondrial superoxide was measured utilizing MitoSOX Red assay. Mito‑Tracker Red CMXRos staining was selected to monitor mitochondrial network structure. The relationship among USP34, eukaryotic translation initiation factor 3 m (eIF3m), and mitochondrial carrier homolog 2 (MTCH2) was validated by co-immunoprecipitation, GST-pull down, RNA immunoprecipitation and RNA-pull down analysis. We found that USP34 silencing inhibited cell proliferation by inducing mitochondrial dysfunction in TNBC cells. USP34 maintained the stability of the eIF3m protein through deubiquitination. Overexpression of eIF3m countered the mitochondrial dysfunction induced by USP34 silencing. Furthermore, eIF3m upregulated the MTCH2 level by directly binding to its 5’UTR region. MTCH2 overexpression reversed the damaging effect of eIF3m silencing on mitochondrial function. Collectively, USP34 maintained the stability of eIF3m protein through deubiquitination; the upregulated eIF3m bound to the 5’UTR of MTCH2 mRNA to promote MTCH2 expression, thereby maintaining mitochondrial function and promoting the malignant progression of TNBC.

Bovine viral diarrhea virus (BVDV) is a major cattle pathogen associated with significant economic losses worldwide. In Brazil, the high genetic diversity of circulating strains represents an additional challenge for disease control. To update the molecular epidemiology of BVDV in southern Brazil, 16,198 bovine serum samples collected in 2020 through a national surveillance program were screened for pestivirus RNA by RT-qPCR. Forty-nine samples (0.36%) were positive and subjected to partial sequencing of the 5′UTR and Npro regions. Phylogenetic analysis identified BVDV-1a (25/49; 51%), BVDV-1b (1/49; 2%), BVDV-1d (7/49; 14%), and BVDV-2b (16/49; 33%), with no detection of HoBiPeV. When compared descriptively with data from 2010 in the same region, BVDV-1a remained the most frequent subgenotype, while BVDV-2b also represented a substantial proportion of detections, contrasting with other regions worldwide. Although the two datasets are not directly comparable, and no statistically significant differences were observed, these findings provide an updated overview of circulating BVDV subgenotypes in Rio Grande do Sul. The absence of HoBiPeV contrasts with reports from other regions of Brazil and suggests a distinct regional pattern of pestivirus circulation. Overall, the results reinforce the importance of continuous genomic surveillance to monitor changes in viral diversity and support control strategies in cattle populations.

Background: Breast cancer (BC) is a leading cause of cancer-related mortality worldwide and a major public health concern in Mexico. Regulatory variants in KRAS, particularly within the 3'UTR and intronic regions, may influence gene expression through microRNA binding and transcriptional regulation. Methods: Five regulatory single-nucleotide variants (SNVs) in KRAS (rs12228277, rs1137196, rs8720, rs12587, and rs12245) were genotyped in BC patients and cancer-free controls. Associations were evaluated using odds ratios (ORs) with 95% confidence intervals (CIs), adjusting for age, alcohol, and tobacco use. Multiple testing was corrected using the Benjamini-Hochberg false discovery rate (FDR). Linkage disequilibrium (LD), multilocus combinations, and in silico functional analyses were also performed. Results: Variants rs12228277, rs1137196, rs8720, and rs12245 showed significant genotype-level associations with BC susceptibility, all remaining significant after FDR correction (pFDR < 0.05). No clinicopathological associations remained significant after correction in single-variant analyses. Multilocus analysis identified specific high-risk combinations (e.g., involving rs12228277, rs1137196, and rs8720) associated with increased BC susceptibility. At the nominal level, these combinations showed associations with clinicopathological features, including hormone receptor-positive status (PR and ER), proliferation markers, and Luminal B subtype; however, none remained significant after FDR correction. LD analysis indicated weak linkage among variants. In silico analyses suggested potential regulatory effects on microRNA binding and KRAS expression. Conclusions: Regulatory variants in KRAS are associated with BC susceptibility through independent effects and potential combinatorial patterns. These findings support the relevance of non-coding variation in cancer risk and warrant further functional and replication studies.

The incidence of esophageal squamous cell carcinoma is geographically heterogeneous and exhibits complex genomic features. We aimed to preliminarily analyze noncoding mutations identified through whole-exome sequencing. Agilent SureSelect XT Human All Exon V6+UTR was used to capture the exome library from 10 African American ESCC patients. After calling variants, we analyzed noncoding mutations using Variant Effect Predictor, CScape-somatic, HumanBase modules and Opencravat. Pathway enrichment analysis was performed using the SIGNOR database via the NDEx IQuery web tool. Our results identified noncoding variants in the 3'UTR, 5'UTR, splice site, and promoter regions. We also observed a nominal enrichment of germline variations in DNA damage repair genes among patients with ESCC.

Bovine viral diarrhea virus (BVDV) is globally endemic, with the ability to establish persistent infection (PI) being central to its complex epidemiology. Currently the genetic variability of BVDV in Bangladesh remains poorly understood. This study involved a survey in commercial dairy herds in the south-eastern part of Bangladesh in 2024/2025. A total of 373 blood samples were collected from cattle in 24 dairy herds. Serum and buffy coat samples were analyzed using antibody-ELISA and RT-qPCR targeting the 5'-UTR region, followed by sequencing. The MDBK cell line was used for virus isolation and biotyping. Herd and animal-level seroprevalences were 83.3% and 15.3%, respectively, while the corresponding viremic rates were 79.2% and 11.0%. Analysis of 41 sequences identified nine distinct BVDV-1 subgenotypes (1a, 1b, 1c, 1d, 1e, 1k, 1p, 1o, and 1v), with BVDV-1b (41.5%) and BVDV-2a (14.6%) predominating. Additionally, five HoBiPeV-a pestiviruses were detected. Among antigen-positive cattle, 38 (92.68%) were identified as transiently infected and 3 (7.3%) were confirmed as PI. Six (14.6%) and 27 (65.9%) were identified as cytopathic and non-cytopathic biotypes, respectively. Risk factors for BVDV seropositivity included: female sex (OR: 3.0), clinical disease in the past three months (OR: 2.4), crowding (OR: 2.9), and lack of dedicated clothing for farm workers (OR: 5.7). Active infection was associated with calves (OR: 6.2), heifers (OR: 2.3), stunted growth (OR: 3.0), technician-performed artificial insemination (OR: 10.4), and frequent neighboring farm visits (OR: 3.1). This study has provided data crucial for formulating prevention and control strategies against BVDV to safeguard the Bangladeshi dairy industry.

Establishment of severe in vitro and in vivo infection models for coxsackievirus B4 and their application in identifying viral virulence determinants.

Objective MicroRNAs (miRNAs) are small endogenous single-stranded non-coding RNAs, approximately 20-25 nucleotides in length, that regulate the expression of potential target mRNAs at the post-transcriptional level. miRNAs are abnormally expressed in many malignant tumors, and are closely associated with tumorigenesis and development, functioning either as proto-oncogenes or oncogenes. Studies have revealed that microRNA-21 (miR-21) is one of the most common oncogenes across various cancer types. However, the function of miR-21 in osteosarcoma has not been fully elucidated. This study aims to investigate the effect of miR-21 on the proliferation, invasion and apoptosis of osteosarcoma cell line MG63 and its underlying mechanisms. Methods Bioinformatics was used to predict the potential target genes of miR-21. The expression levels of miR-21 and programmed cell death 4 (PDCD4) in osteosarcoma cell line MG63 were measured by qRT-PCR and Western blot, respectively. After the expression of miR-21 was regulated (either up-regulated or inhibited), its biological effects on cell viability, cell cycle progression and apoptosis were assessed. The targeting relationship between miR-21 and PDCD4 was verified by using dual-luciferase reporter gene assay. Results Bioinformatics prediction showed that the 3'-UTR region of human PDCD4 gene contained multiple potential miRNA target sites. qRT-PCR results showed that the expression level of miR-21 in the pcDNA3.1-miR-21 group was significantly higher than that in the pcDNA3.1 group and the blank group. Compared with the blank group, up-regulation of miR-21 significantly promoted the proliferation and invasion of osteosarcoma MG63 cells, while inhibiting cell apoptosis. Luciferase reporter gene assay confirmed that PDCD4 was a direct target gene of miR-21, and there was a negative correlation between miR-21 and PDCD4. Conclusion Up-regulation of miR-21 expression promotes proliferation and invasion while inhibiting apoptosis of osteosarcoma cell line MG63 by suppressing the level of endogenous PDCD4. In contrast, down-regulation of miR-21 expression inhibits proliferation and invasion while promoting apoptosis of osteosarcoma cell line MG63. Therefore, miR-21 functions as an oncogene in the development of osteosarcoma and could be a potential therapeutic target.

Non-linear age-related change in human Interleukin-11 and the receptor subunit alpha DNA methylation

DDX3X is a multifunctional DEAD-box RNA helicase with important roles in translation initiation and antiviral innate immune signaling, yet it is currently unknown whether viral infection affects its interactions with host RNAs. Here, we define the transcriptome-wide binding landscape of endogenous DDX3X in Sendai virus-infected human cells using PAR-CLIP. We show that DDX3X maintains its preference for GC-rich, highly structured 5′UTR regions during infection, but acquires a distinct set of infection-induced targets, including IFNB1 and multiple interferon-stimulated genes. We demonstrate that DDX3X directly binds the IFNB1 5′UTR and promotes its translation, establishing a previously unrecognized post-transcriptional mechanism contributing to DDX3X-dependent IFN-β production. We also evaluated DDX3X’s binding to SeV RNAs and concluded that DDX3X is likely not actively recruited by SeV or has a significant effect on its viral life cycle. Our findings add a novel dimension to DDX3X’s involvement in anti-viral immunity with implications for further therapeutic development of DDX3X inhibitors.

Tongue gangrene is a rare but serious condition in buffaloes. Despite its clinical and economic importance, it remains poorly documented in Egypt. This retrospective study evaluated the clinical presentation, etiological factors, histopathological findings, and surgical outcomes of tongue gangrene in Egyptian buffaloes. Forty-four buffaloes examined between January 2022 and November 2025 were classified based on the extent of tongue loss, as determined by the length (cm) of the excised gangrenous segment. Microbiological analyses included culture of deep tissue samples from the demarcation zone and rice straw samples taken from the batches fed to affected buffaloes on their farms of origin. Viral RNA was extracted from affected tongue tissues, and FMDV detection and serotyping were performed using RT-PCR targeting the 5′UTR and VP1 regions. Sequenced PCR products were analyzed using BLAST and phylogenetic reconstruction. Partial glossectomy was performed in all cases, and recovery was monitored for up to 24 weeks based on medical records. The buffaloes showed systemic illness with fever and dehydration, along with characteristic dry tongue gangrene (discoloration, foul odor, loss of sensation, and a clear demarcation line). Most cases (31/44) had a recent history suggestive of FMD; the remaining cases were classified as suspected traumatic tongue injury (9/44) or no identified predisposing factor (4/44). Deep tongue tissue cultures yielded bacterial growth in 24/44 and fungal growth in 3/44 cases (presumptive identification), while rice straw samples yielded Fusarium-like fungi (12/44) and clostridia-like organisms (28/44). Histopathology confirmed coagulative necrosis with vascular congestion, bacterial colonization, and neutrophilic infiltration. FMDV serotype O was detected, showing ~ 98% identity by BLAST and clustering within the ME-SA topotype near Egy/Qalyubia/2021. Recovery time correlated significantly with the extent of tongue loss (p < 0.05): the shortest recovery was observed after ~ 5 cm loss, intermediate recovery after ~ 8 cm loss, and the longest recovery among survivors after ~ 10 cm loss. Tongue gangrene in the studied Egyptian buffaloes was most likely associated with recent FMD infection and/or traumatic tongue injuries, which may predispose to microlesions and subsequent microbial invasion. Clostridia-like organisms and Fusarium-like fungi were cultured from deep tongue tissue and from rice straw offered to the affected animals. Early diagnosis and prompt surgical intervention remain essential for successful outcomes and improved survival.

Impact of SNAP-25 MnlI polymorphism on brain activity patterns in children with ADHD: Insights from fractional amplitude of low-frequency fluctuation analysis.

Detection of CH25H gene polymorphism associated with growth traits of Yuexi frizzled chicken.

Circular RNAs (circRNAs) act as novel biomarkers associated with drug resistance in triple-negative breast cancer (TNBC). Our previous study has demonstrated that the Wnt/β-catenin pathway mediates TNBC chemoresistance, and the present study further investigates its upstream regulatory mechanisms. Gene chip analysis was used to screen for circRNAs in drug-resistant cells. The expression levels of circPTK2 in cells and tissues were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8), Transwell, flow cytometry, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL), three-dimensional (3D) multicellular tumor spheroid culture model, 5-ethynyl-2'-deoxyuridine (EdU) proliferation staining, western blot and immunofluorescence were used to detect the influence of circPTK2 on the drug sensitivity, cell invasion, proliferation, apoptosis and DNA damage repair of TNBC cells. The pull-down and dual-luciferase reporter gene assays were used to determine the interaction between circPTK2 and miR-495. Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) experiment verified the binding of miR-495 to β-catenin. A transplanted tumor model was established in nude mice to determine circPTK2 effects on the chemosensitivity of drug-resistant cells to cisplatin (DDP). Methylated RNA immunoprecipitation (MeRIP) and RNA electrophoretic mobility shift assay (RNA-EMSA) verified the enrichment of the N6-methyladenosine (m6A) methylated region of circPTK2. The m6A quantitative kit was used to detect the level of m6A modification. MeRIP-PCR was used to detect the enrichment amount of m6A-modified circPTK2 (m6A+ circPTK2). qRT-PCR results indicated that the expression level of circPTK2 in drug-resistant cells was higher than that in parental cells. The expression level of circPTK2 in DDP-resistant tissues was significantly higher than that in DDP-sensitive tissues. circPTK2 has the characteristics of resisting Rnase R digestion and having stronger stability than linear RNA. Knocking down of circPTK2 can reduce the viability and invasion ability of TNBC DDP-resistant cells, promote the DNA damage induced by DDP, and enhance the sensitivity of TNBC cells to DDP. RNA fluorescence in situ hybridization (RNA FISH) results showed that circPTK2 and miR-495 were co-localized in the cytoplasm. The dual luciferase reporter gene activity assay showed the targeted binding of miR-495 to the 3'UTR region of β-catenin. The RNA immunoprecipitation-polymerase chain reaction (RIP-PCR) experiment confirmed that YTH domain-containing protein 1 (YTHDC1) could bind to circPTK2. m6A quantitative kit showed that the m6A modification in the resistant cells was higher than that in the parental cells. qRT-PCR and Western blot results showed that the mRNA and protein expression level of YTHDC1 in the DDP resistant cells was higher than that in the parental cells. The m6A methylation reader YTHDC1 mediates the regulation of DDP resistance by circPTK2 in TNBC, and circPTK2 may serve as a non-invasive biomarker for clinical detection of DDP resistance in TNBC.

Chikungunya virus (CHIKV) and Dengue virus (DENV) infections present with highly similar clinical symptoms but require distinct management strategies, highlighting an urgent need for rapid and accurate differential diagnostic methods. The current gold standard, reverse transcription quantitative real-time PCR (RT-qPCR), has significant limitations: it relies on expensive thermal cyclers, complex laboratory infrastructure, and specialized personnel, making it difficult to implement in resource-limited settings and for on-site screening. To address this technological bottleneck, this study developed a portable, instrument-independent rapid detection technology based on the CRISPR-Cas12a/Cas13a dual-enzyme cleavage system. By precisely designing specific crRNAs targeting the CHIKV E1 gene and the DENV 3′-UTR region, and integrating them with reverse transcription recombinase-aided amplification (RT-RAA) technology, we established an integrated reaction system that performs nucleic acid amplification and detection under isothermal conditions. The core mechanism of the technology is as follows: upon recognition of the corresponding viral targets, Cas12a (targeting CHIKV) and Cas13a (targeting DENV) become activated and cleave fluorescent reporters or lateral flow strip reporter probes, enabling visual detection. Gradient-diluted viral nucleic acid tests indicated that the lowest detectable concentration that generated a signal reached 10² copies/mL, which is comparable to qPCR. Clinical simulated sample validation showed 100% overall agreement with qPCR, and the system accurately distinguished single infections from co-infections.The CRISPR dual-enzyme cleavage technology established in this study effectively circumvents the reliance of qPCR on sophisticated equipment, providing a rapid, simple, and low-cost solution for CHIKV/DENV differential diagnosis. It holds significant practical value for the early prevention and control of arboviral diseases.

Cholangiocarcinoma (CCA) is a primary malignant neoplasm with an extremely poor prognosis. While combined chemoradiotherapy has been demonstrated to delay CCA progression to a certain extent, the absence of specific molecular biomarkers or targets significantly hinders the diagnosis and treatment of CCA. Through cross-analysis of proteomics and ADMA modificationomics, we identified DDX1 overexpressed in CCA with elevated R602-ADMA modifications. HPLC-MS/MS identified PRMT1 as the methyltransferase and USP10 as the deubiquitinating enzyme for DDX1. Immunofluorescence and nuclear-cytoplasmic partitioning experiments confirmed DDX1's nuclear localization. GO and KEGG analyses clarify the biological functions of DDX1 in response to hypoxia. RNA-seq transcriptomics analyzed key pathways influenced by DDX1. A hydrodynamic in situ CCA mouse model was established to validate the chemopreventive effects of the PRMT1-specific inhibitor GSK715 on CCA development. DDX1 promotes CCA progression both in vivo and in vitro and can be inhibited by GSK715. Mechanistically, PRMT1 mediates ADMA modification at position R602 of DDX1. This modification promotes DDX1 nuclear localization by recruiting USP10 to deubiquitinate DDX1, while simultaneously inhibiting PRMT1 degradation. DDX1 promotes the transcription of PRMT1 and USP10 by binding to the mRNA 3'UTR region, establishing a positive feedback regulatory pathway. This mechanism promotes the occurrence and development of CCA and can serve as a target for the inhibitor GSK715 to suppress CCA progression. Our study identified DDX1-R602-ADMA modification as a novel ADMA modification in CCA. It further confirmed its pivotal role in CCA progression. Targeting the USP10-PRMT1-DDX1 axis may represent a significant therapeutic approach for CCA.