Search Results (256)

Central chondrosarcoma is the second most common primary malignant bone tumour, and grade progression markedly worsens prognosis. The contributions of lipid metabolic reprogramming and epigenetic co-dysregulation to grade progression remain poorly characterised. We integrated a bulk RNA-seq discovery cohort of 53 graded central chondrosarcomas (GSE299759) with a single-cell analysis of eight chondrosarcomas (GSE184118). Because the atypical cartilaginous tumour (ACT) and dedifferentiated groups each comprised only three samples, the Grade 3 versus Grade 2 contrast was pre-specified as the primary comparison. Curated panels of 44 lipid metabolism genes and 50 epigenetic regulators were assessed by differential expression and a correlation-based connectivity ranking, evaluated by permutation testing. In the primary Grade 3 versus Grade 2 comparison, SQLE, ACACA, and FASN were upregulated (FDR < 0.05), indicating a grade-associated increase in de novo lipogenesis. In the exploratory Grade 3 versus ACT comparison, additional lipid genes (HMGCR, LDLRAP1) and the epigenetic regulators EHMT2 and SIRT2 showed altered expression, although the small ACT group limits these estimates. A connectivity ranking highlighted FASN, KMT2C, TET2, SETD5, and KDM5B; permutation testing confirmed this co-expression structure was non-random (p < 0.0001). Single-cell analysis showed FASN, SETD5, and KDM5B are expressed predominantly in malignant cells, whereas KMT2C and TET2 are not, indicating cell-type heterogeneity. De novo lipogenesis upregulation is the most consistent lipid alteration in high-grade central chondrosarcoma, nominating SQLE, ACACA, and FASN as candidates for experimental investigation. Full article

The ubiquitously transcribed tetratricopeptide repeat Y-linked gene (UTY/KDM6C), a catalytically impaired histone demethylase encoded on the Y chromosome, has garnered increasing attention for its emerging roles in tumorigenesis and cancer progression. Despite high sequence homology with its X-linked paralog UTX/KDM6A, UTY exhibits markedly reduced or absent H3K27me3 demethylase activity due to critical amino acid substitutions in its Jumonji C domain. Consequently, UTY primarily functions through non-enzymatic mechanisms, acting as a scaffold in chromatin-remodelling complexes like COMPASS and SWI/SNF, or mediating protein–protein interactions that regulate transcriptional programs independent of demethylation. This aligns with epigenetic dysregulation in cancers, where imbalances in repressive H3K27me3 and active H3K4me either drive tumour suppressor silencing or oncogene activation. Unlike frequently mutated UTX in cancers such as breast, renal cell carcinoma, and acute myeloid leukaemia, UTY’s contributions in cancer are less defined, constrained by male-specific expression. Emerging evidence suggests UTY as a context-dependent tumour suppressor in AML and squamous-like pancreatic ductal adenocarcinoma. While direct functional validation remains limited in several cancer types, UTY is increasingly implicated as a potential tumour suppressor in haematological malignancies and prostate cancer. Therapeutically targeting UTY’s scaffold functions shows promise for male-specific cancers and merits future investigation. Full article

Background and Objectives: Gastric cancer remains a leading cause of cancer-related mortality worldwide and develops through complex interactions between environmental factors, microbial dysbiosis, and host molecular pathways. Although Helicobacter pylori infection is a well-established risk factor, emerging evidence suggests that broader alterations in the gastric microbiome may also contribute to carcinogenesis. However, the associations between gastric cancer-associated microbial taxa and host gene expression profiles remain insufficiently characterized. This study aimed to identify host gene signatures associated with gastric cancer-related microbial taxa through a descriptive analysis integrating microbiome-derived taxa with transcriptome data. Materials and Methods: Microbial taxa associated with gastric cancer were systematically retrieved from the Disbiome database. Taxon set enrichment analysis (TSEA) was performed using the MicrobiomeAnalyst platform to identify host genes associated with gastric cancer-associated taxa. Importantly, TSEA relies on healthy reference data from the Human Microbiome Project and does not establish gastric cancer-specific interactions or causal relationships. Gene expression levels were subsequently evaluated using The Cancer Genome Atlas (TCGA) PanCancer stomach adenocarcinoma (STAD) dataset by comparing tumor and matched normal gastric tissues. Gene interaction network and transcription factor (TF) enrichment analyses were conducted to explore predicted regulatory relationships. Results: Among 64 microbial taxa associated with gastric cancer, 43 were reported as elevated. After removing overlapping taxa across studies, 37 elevated and 21 reduced taxa were retained for analysis. TSEA identified 11 host genes associated with gastric cancer-related microbial taxa. Transcriptomic analysis demonstrated significant downregulation of DPP6 and DLG2, while KDM4D, USP34, and VDR were significantly upregulated in gastric cancer tissues compared with normal controls. Network and TF enrichment analyses revealed predicted co-expression and co-localization patterns among these genes, suggesting their potential involvement in immune-related processes, epigenetic regulation, and cellular organization. Conclusions: This descriptive study identifies distinct host gene expression signatures associated with gastric cancer-associated microbial dysbiosis. This study is purely associative and hypothesis-generating; no causal or mechanistic inferences are made. TSEA used healthy reference data and therefore does not reflect gastric cancer-specific host–microbe interactions. The findings provide a basis for future hypothesis-driven research but require validation in independent cohorts. Full article

Colorectal cancer (CRC) shows consistent sex-related differences in incidence, anatomic distribution, molecular subtype, immune context, and clinical outcome. However, these differences are often discussed through broad parallel themes such as hormones, genetics, or the microbiome, rather than through the biological settings in which sex meaningfully modifies tumor behavior. This review argues that sex is most informative in CRC when treated as a contextual modifier whose relevance emerges only after integrating tumor sidedness, mismatch repair status, oncogenic background, immune ecology, and age at onset. The clearest signals arise from interaction-based contexts, particularly when sex is interpreted together with tumor sidedness and dMMR/MSI-H or BRAF-linked disease states. Current evidence indicates that women are enriched for proximal or right-sided, microsatellite instability-high, mismatch repair-deficient, CpG island methylator phenotype-high, and BRAF-associated CRC, whereas men more often present with distal disease and a higher overall burden. Mechanistic studies further show that sex-related differences extend beyond hormone exposure to include KRAS–STAT4–KDM5D signaling, site-specific immune-checkpoint programs, metabolic phenotypes, epigenetic biomarker variation, and microbiota–hormone crosstalk. These effects are most evident in defined clinical niches, particularly right-sided CRC, mismatch repair-deficient disease, BRAF-mutated metastatic CRC, and early-onset CRC. A sex-aware, subtype-aware, and location-aware framework therefore offers a more clinically useful interpretation of CRC heterogeneity than descriptive male-versus-female comparisons alone. Full article

To address the challenges of steel surface defect detection—characterized by fine-grained textures, substantial scale variations, and complex background interference—conventional lightweight detectors often struggle to balance real-time navigation requirements with high-precision spatial localization on mobile inspection platforms. In this work, we propose KDM-YOLO, a lightweight visual localization and detection method built upon YOLOv10n, designed to provide an efficient perception engine for autonomous inspection robots. The proposed approach enhances the baseline through three key perspectives: feature extraction, context modeling, and multi-scale fusion. Specifically, KWConv is introduced to strengthen the representation of fine-grained texture and edge cues; C2f-DRB is employed to enlarge the effective receptive field and improve long-range dependency perception to reduce missed detections; and a multi-scale attention fusion (MSAF) module is inserted before the detection head to adaptively integrate spatial details with semantic context while suppressing redundant background responses. Ablation studies confirm that each module contributes to performance gains, and their combination yields the best overall results. Comparative experiments further demonstrate that KDM-YOLO significantly improves detection performance while retaining a compact model size and high inference speed. Compared with the YOLOv10n baseline, Precision, Recall and mAP@50 are increased to 91.0%, 93.9%, and 95.4%, respectively, with a parameter count of 3.29 M and an inference speed of 155.6 f/s. These results indicate that KDM-YOLO achieves an ideal balance between the accuracy and computational efficiency required for embedded navigation platforms, providing an effective solution for online autonomous inspection and real-time localization of steel surface defects. Full article

Drought stress is a major abiotic factor limiting maize yield and stability. Although Jumonji C (JMJ) histone demethylases are known to regulate plant growth, development, and stress responses, their systematic characterization in maize has remained limited. Here, 27 ZmJMJ genes were identified in the maize genome through BLAST and conserved-domain analyses and classified into five subfamilies: JMJD6, KDM3/JHDM2, KDM4/JHDM3, KDM5/JARID1, and JmjC domain-only. Members within the same subfamily showed similar physicochemical properties, domain composition, and motif distribution, whereas clear divergence was observed among subfamilies. Chromosomal mapping revealed that ZmJMJ genes were unevenly distributed across nine chromosomes, with two interchromosomal homologous gene pairs, suggesting roles for segmental and/or whole-genome duplication in family expansion. Promoter analysis indicated widespread enrichment of elements related to light responsiveness, growth and development, and hormone and stress responses. Expression profiling showed that most ZmJMJ genes were highly expressed in leaves, while several displayed tissue specificity. Under drought stress, ZmJMJ17a, ZmJMJ17b, ZmJMJ28, and ZmJMJ32 were significantly induced, highlighting them as promising candidates for functional studies and molecular breeding for drought tolerance in maize. This study provides a foundation for elucidating the evolution and functions of the ZmJMJ family and identifies candidate genes for drought-related functional validation and molecular breeding. Full article

Background: Pathogenic variants in KDM3B have been implicated as the cause of Diets-Jongmans syndrome (DIJOS), an autosomal-dominant disorder characterized by growth retardation, intellectual disability, facial dysmorphism and autism-spectrum disorder. However, only a limited number of cases have been reported. Methods: The general characteristics of four patients were recorded, including clinical features, child development, neuropsychological assessment and therapeutic interventions. Whole exome sequencing (WES) was performed for potential genetic causes and interpretation of variants was performed in accordance with ACMG guidelines. Results: All patients carried de novo variants in the KDM3B gene, namely, c.2832-3C>G, c.1188del p.(Glu397Argfs*21), c.4580T>C p.(Leu1527Pro), and c.3220dup p.(Glu1074Glyfs*48). Unlike other patients with DIJOS who presented with growth retardation, mild to moderate intellectual developmental disorder and facial dysmorphism, our patients mainly presented with growth retardation, while their neurodevelopment was either normal or mildly impaired. In addition, our patients received primarily supportive care. One patient treated with recombinant human growth hormone (rhGH) showed improvement in growth. Conclusions: Our results broaden the mutational spectrum of KDM3B-related disorder and highlight the inter-patient variability of the clinical phenotype. For the first time, we demonstrate that rhGH therapy can partially promote growth, providing novel evidence for genetic counseling. Full article

This work conducted a transcriptome analysis of canine intestinal epithelial cells (cIECs) treated with nicotinamide mononucleotide (NMN), a physiologically active nucleotide with a pyridine base known for its anti-aging and anti-inflammatory effects. In our experiment, cIECs were cultured and segregated into a control group (Ctrl) and an NMN-treated group. The finding demonstrated that NMN significantly affects cell proliferation in cIECs in comparison to the Ctrl. The transcriptome analysis indicated a high enrichment of genes associated with the cell cycle, proliferation, cellular senescence, and inflammatory pathways in NMN-treated cIECs, showing that NMN has the capacity to modify these biological processes. Compared to the Ctrl group, NMN treatment significantly increased ATP, SOD, CAT and GSH levels and decreased the activities of ROS and MDA. NMN treatment also significantly increased the activity of the relative complex I, III and V enzymes compared to the Ctrl group. Furthermore, the expression of MAPK13, EDN1, TNFAIP6, TNFSF15 and SLC7A11 were decreased significantly, while ACOX2, CPT1C, CCNA1 and CCNE1 were increased significantly in NMN-5μM treatment compared to Ctrl. NMN-treated significantly decreased the expression of Hdac2, Hdac6 and Hdac8, while increasing the expression of Kdm5a, Kdm5b and Kdm5c compared to the Ctrl group. Additionally, ChIP-qPCR use discovered that NMN-treatment significantly downregulated the enrichment of EDN-1 at target loci of NR4A1, SRC1, P300, Pol II and Ser5- Pol II compared to the Ctrl group. Expression of the NR4A1 gene suggests that its exert in biological activities by inhibiting inflammatory responses and anti-aging pathways. Then, we detected the transcriptional activation linked histone markers and found that H3K23ac and H3K27ac were significantly downregulated, while H3K27me3 was significantly upregulated in the NMN-treatment compared to the Ctrl group. We conclude that NMN regulates EDN-1 expression in cIECs through mechanisms involving NR4A1 and histone modifications, highlighting its potential role in canine intestinal health. Full article

Molecular sex determination in Syrian hamsters (Mesocricetus auratus) has been limited by the incomplete annotation of Y-linked loci in currently available genome assemblies. Here, we evaluate the Y-linked gene PRSSLY, which encodes a testis-specific serine protease-like protein, as a molecular marker for genetic sexing of Syrian hamster embryonic and placental tissues. Primers flanking a conserved PRSSLY coding region produced a male-specific amplicon showing 100% concordance with results from the established KDM5C/KDM5D PCR assay in E15.5 tail biopsies. SYBR Green–based qPCR enables the accurate detection of PRSSLY, characterized by a unique melt-curve profile, exclusively in male samples, allowing for efficient and sensitive mid-throughput analysis. Application of the PRSSLY assay to 417 placental samples from 39 dams demonstrated its suitability for large-scale sex genotyping, enabling sex assignment in the majority of samples despite the intrinsic complexity of placental tissue containing both maternal and embryonic genetic material. This assay provides a robust and reproducible approach for accurate sex genotyping in developmental and reproductive studies using Syrian hamsters. Full article

Desmoplastic small round cell tumor (DSRCT) is a rare but aggressive soft tissue sarcoma of the abdomen. With an asymptomatic course and rapid dissemination, DSRCT’s prognosis is poor at diagnosis. This study characterizes the demographic variation and genomic profile of DSRCT to guide studies into diagnosis and treatment. The AACR GENIE database was utilized to identify genetic alterations in DSRCT. Data was queried to identify disease prevalence by different demographic variables. Information was collected on frequency of somatic mutations and copy number alterations, rates of mutation co-occurrence, and mutations seen in primary and metastatic samples. ARID1A, TP53, ATM, TERT, and FGFR4 were the most frequently identified somatic mutations. Copy number alterations seen in DSRCT were commonly homozygous deletions in tumor suppressor genes. Independent of sex, WT1 mutations were most common. Non-White patients saw single occurrences of many mutations but recurrent ones in ANKRD11 and KMT2C. Co-occurrence was found between FGFR4 and EP300. Moreover, primary tumor samples had exclusive mutations in AKAP9, KDM2B, MAGED1, MKI67, PCLO, and TRAF1. Metastatic samples had exclusive mutations in FIP1L1 and NRIP1. Our data highlights mutational variation across demographic cohorts. These patterns are vital to future studies into identifying diagnostic markers or therapeutic targets. Full article

Chromatin architecture is highly dynamic, undergoing nanoscale rearrangements throughout the cell cycle and in response to environmental cues. In this study, we employed high-resolution stochastic optical reconstruction microscopy (STORM) to visualize chromatin organization and cellular plasticity at the nanoscale in two osteosarcoma cell lines, U2OS and MG63. To promote a tumor-suppressive bone microenvironment, we applied three biophysical modalities, namely mechanical vibration, electrical stimulation, and optical pulses, each previously linked to altered tumor behavior by reprogramming cells and generating induced tumor-suppressing (iTS) cells. These stimuli enlarged nuclear size and disrupted nuclear envelope integrity, as revealed by increased surface roughness. Critically, all three modalities transiently scattered nucleosome clusters, indicating chromatin decondensation as a hallmark of iTS cell generation. iTS cells exhibited elevated expression of histone demethylases lysine demethylase 3A (KDM3A) and lysine demethylase 4 (KDM4), accompanied by reduced levels of trimethylated histone H3 lysine 9 (H3K9me3). Consistently, pharmacological agents—Trichostatin A as a histone deacetylase inhibitor and chaetocin as a histone methyltransferase inhibitor—induced nucleosome scattering and converted U2OS cells into iTS cells, whose conditioned media exerted tumor-suppressive effects. Our findings highlight nucleosome clustering as a key epigenetic feature responsive to both biophysical and chemical cues, underscoring its role in microscale chromatin remodeling and reprogramming of the tumor microenvironment. Full article

Bladder and urothelial carcinoma are marked by profound genomic diversity. Using a large, multi-institutional dataset, we performed comprehensive genomic profiling of 4631 tumor samples from 4050 individuals. A retrospective analysis of bladder and urothelial cancer was performed using the AACR Project GENIE database. Demographic associations, mutation frequencies, copy number changes, and survival correlations were analyzed with a p-value < 0.05. Frequent mutations were identified in TP53, TERT, KDM6A, KMT2D, ARID1A, and FGFR3. Mutation frequencies varied by sex and race, with specific alterations enriched in female and Asian patients. Distinct patterns of co-occurrence, including TP53 with RB1, and mutual exclusivity, including TP53 with FGFR3 or KDM6A, revealed distinct molecular subtypes. This study highlights the extensive heterogeneity of bladder cancer, and our findings emphasize the clinical importance of molecular stratification and support the need for further mechanistic and prospective studies to inform the development of targeted therapies. Full article

Pancreatic Ductal Adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies, driven by late diagnosis, limited therapeutic options, and high metastatic potential. Beyond their canonical roles in hemostasis, platelets have emerged as active modulators of tumor progression and promising noninvasive biomarkers. Among platelet-associated molecules, α-defensins, particularly Defensin Alpha 1/3 (DEFA1/3), have been implicated in inflammation and immunity; however, their contribution to PDAC pathogenesis remains unclear. We combined bioinformatic analysis of platelet transcriptomes with functional and in vivo zebrafish xenograft validation to investigate the impact of DEFA1/3 on PDAC aggressiveness. DEFA1/3 was significantly upregulated in PDAC-derived platelets. Defensin-enriched platelet-like particles (defensin-rich platelets, DRPs) and recombinant DEFA1/3 enhanced pancreatic cancer cell proliferation, migration, and three-dimensional growth in vitro and promoted tumor dissemination in zebrafish xenografts. Transcriptomic profiling revealed the upregulation of SPARC, KDM6A, and GATA6, whereas clinical data from The Cancer Genome Atlas (TCGA)-PDAC linked high DEFA1/3 expression to poor survival, increased immune infiltration, and activation of epithelial–mesenchymal transition (EMT). Platelet-derived DEFA1/3 acts as a functional modulator of PDAC progression, linking platelet granule content to tumor aggressiveness and highlighting a potential biomarker and therapeutic target within the platelet–tumor axis. Full article

Background: Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy characterized by impaired differentiation, apoptosis resistance, and metabolic reprogramming, which collectively contribute to therapeutic resistance and poor clinical outcomes. While targeted agents—such as LSD1 inhibitors, the BCL-2 inhibitor venetoclax, and IDH1 inhibitors—have provided clinical benefit, their efficacy is often limited by compensatory signaling and clonal evolution. This study aimed to identify FDA-approved compounds with multitarget potential to simultaneously modulate key epigenetic, apoptotic, and metabolic pathways in AML. Methods: Structure-based virtual screening of 3957 FDA-approved molecules was performed against three AML-relevant targets: lysine-specific demethylase 1 (LSD1), BCL-2, and mutant IDH1 (R132H). Top-ranked hits were evaluated using ADMET prediction and molecular dynamics (MD) simulations to assess pharmacokinetic properties, toxicity, and ligand–protein complex stability over 100 ns trajectories. Results: Three compounds—DB16703, DB08512, and DB16047—exhibited high binding affinities across all three targets with favorable pharmacokinetic and safety profiles. MD simulations confirmed the structural stability of the ligand–protein complexes, revealing persistent hydrogen bonding and minimal conformational deviation. These findings suggest that these repurposed drugs possess a promising multitarget profile capable of addressing AML’s multifactorial pathophysiology. Conclusions: This computational study supports the feasibility of a polypharmacology-based strategy for AML therapy by integrating epigenetic modulation, apoptotic reactivation, and metabolic correction within single molecular scaffolds. However, the identified compounds (Belumosudil, DB08512, and Elraglusib) have not yet demonstrated efficacy in AML models; further preclinical validation is warranted to substantiate these predictions and advance translational development. Full article

The malate–aspartate shuttle (MAS) is an NADH shuttle that transports cytoplasmic reducing equivalents to the mitochondria for producing energy. We previously demonstrated that K-demethylase 2A (KDM2A), a jmjC-type histone demethylase, decreases ribosomal RNA (rRNA) transcription via demethylation of H3K36me2 in the rRNA gene promoter region in response to energy reduction in MCF-7 cells. However, whether MAS inhibition is involved in KDM2A activity has not been investigated. In this study, we demonstrate that aminooxyacetic acid (AOA), which inhibits aspartate transaminase (AST/GOT) in MAS, decreased intracellular ATP levels and reduced rRNA transcription via KDM2A-dependent reduction in H3K36me2 levels in the rRNA gene promoter in MCF-7 cells. On the other hand, N-phenylmaleimide (NPM), which inhibits the mitochondrial αKG/malate carrier SLC25A11 in MAS, also decreased intracellular ATP levels but did not induce KDM2A activity. Additionally, NPM pretreatment or knockdown of SLC25A11 inhibited AOA-induced KDM2A activity. Dimethyl αKG, a cell-permeable αKG, restored KDM2A activity inhibited by NPM-pretreatment in AOA-treated cells. These results demonstrate that AOA and NPM have different abilities to induce a decrease in rRNA transcription via KDM2A. Furthermore, the αKG/malate carrier SLC25A11 is associated with KDM2A-dependent reduction in rRNA transcription via demethylation under MAS inhibition. Full article