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Lipotoxicity-induced ER-mitochondrial hypercoupling activates the mtDNA-cGAS-STING-NF-κB axis to drive follicular arrest in metabolically compromised PCOS
Cell Death Discovery, Published online: 08 September 2026; doi:10.1038/s41420-026-03339-w
Lipotoxicity-induced ER-mitochondrial hypercoupling activates the mtDNA-cGAS-STING-NF-κB axis to drive follicular arrest in metabolically compromised PCOSAn explainable detection framework for health insurance fraud via temporal capture and confidence assurance
npj Digital Medicine, Published online: 08 September 2026; doi:10.1038/s41746-026-03200-5
An explainable detection framework for health insurance fraud via temporal capture and confidence assuranceMultiomic characterization of malignant pulmonary nodules and development of a methylation-based diagnostic Model
J Transl Med. 2026 Jun 8;24(1):776. doi: 10.1186/s12967-026-08382-w.
ABSTRACT
BACKGROUND: The molecular distinction between benign and malignant pulmonary nodules remains a significant diagnostic challenge. While genomic drivers are well studied, multiomic integration of the epigenetic-transcriptional landscape and its translation into noninvasive tools are lacking.
METHODS: We performed a multiomic characterization (genomic, epigenomic, and transcriptomic) of 158 pulmonary nodules. Unsupervised factor analysis integrated these layers to identify core regulatory axes. A 9-gene cell-free DNA (cfDNA) methylation classifier was developed and validated in blood and tissue cohorts.
RESULTS: Genomic profiling revealed EGFR mutations (exclusive to malignant nodules) and MYC amplification as fundamental initiators of malignancy. Multiomic factor analysis (Factor 1) revealed profound genetic‒epigenetic synergy, in which these alterations dictate a permissive methylome, leading to aberrant epigenetic programming of chromatin accessibility, as well as epigenetic-transcriptional effects: hypomethylation at the promoters of cell cycle genes that augments their expression, and hypermethylation at immune related pathways gene loci that silences their transcription. This effect orchestrates formation of proproliferative (E2F target/G2M checkpoint) and "immune-cold" malignant phenotype, characterized by elevated Treg/CD8+ ratios and fibroblast recruitment. Notably, we observed a gradual accumulation of methylation aberrations along the premalignant-to-invasive continuum (adenocarcinoma in situ [AIS]→minimally invasive adenocarcinoma [MIA]→adenocarcinoma [ADC]), identifying progressive epigenetic dysregulation as a hallmark of tumor aggressiveness. Global methylome remodeling drives ADC progression through hypermethylation-mediated silencing of tumor suppressors (RASA3 and PPARG) and hypomethylation-activated oncogenic axes, specifically the GDF15 axis, which independently predict poor survival in patients with lung ADC in the TCGA cohort. We translated these tissue-derived insights into a 9-gene cfDNA methylation classifier, which achieved exceptional diagnostic accuracy across independent cohorts (training AUC = 1.00; test AUC = 0.93; tissue AUC = 0.96). Rooted in the biological "ground truth" of tissue dysregulation, this classifier functions specifically as a functional readout of the core cell cycle and proliferative pathways, offering a robust, noninvasive tool for the biology-informed risk assessment of pulmonary nodules.
CONCLUSIONS: This study delineates an epigenetic-transcriptional regulatory network that drives nodule malignancy. Our findings provide a robust theoretical foundation and a high-performance liquid biopsy tool for the precise, noninvasive diagnosis of pulmonary nodules.
PMID:42260586 | PMC:PMC13274191 | DOI:10.1186/s12967-026-08382-w
Sirt1 sustains Sonic hedgehog signaling to promote medulloblastoma progression through regulating Gli3 processing
Oncogene, Published online: 18 April 2026; doi:10.1038/s41388-026-03781-1
Sirt1 sustains Sonic hedgehog signaling to promote medulloblastoma progression through regulating Gli3 processingComparative reversal learning reveals rigid adaptation in LLMs under non-stationary uncertainty
Genetically encoded fluorescent reporters to visualize α-synuclein pathology in live brain
Diverse genomic and transcriptomic heterogeneity in EGFR-mutant lung adenocarcinoma between exon 19 del and exon 21 L858R
Cell Commun Signal. 2026 Mar 14. doi: 10.1186/s12964-026-02793-4. Online ahead of print.
NO ABSTRACT
PMID:41826981 | DOI:10.1186/s12964-026-02793-4
METTL16 enhances proteasome inhibitor resistance in multiple myeloma by inhibiting eIF2α-PERK interaction and promoting PSMB5 translation
Oncogene, Published online: 13 March 2026; doi:10.1038/s41388-026-03706-y
METTL16 enhances proteasome inhibitor resistance in multiple myeloma by inhibiting eIF2α-PERK interaction and promoting PSMB5 translation