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Predicting Neuromodulation Outcome for Parkinson's Disease with Generative Virtual Brain Model
AGFT: Alignment-Guided Fine-Tuning for Zero-Shot Adversarial Robustness of Vision-Language Models
LaSM: Layer-wise Scaling Mechanism for Defending Pop-up Attack on GUI Agents
Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma
Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.
ABSTRACT
Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.
PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708
Dynamic Targetable Extracellular Vesicle Surface Proteins Monitor Depth of Response to CAR T Therapy
Res Sq [Preprint]. 2026 Mar 18:rs.3.rs-8913641. doi: 10.21203/rs.3.rs-8913641/v1.
ABSTRACT
Extracellular vesicles (EVs) represent a promising liquid biopsy platform in multiple myeloma (MM). We developed an MM EV Surface Protein Assay to quantify and dynamically monitor four MM EV subpopulations defined by targetable MM surface proteins (BCMA, CD38, GPRC5D, and CD319) across 336 serial blood samples from 45 relapsed/refractory MM (RRMM) patients treated with anti-BCMA chimeric antigen receptor (CAR) T-cell therapy. All four MM EV subpopulations significantly decreased in 43 patients with initial response, while BCMA+, GPRC5D+, and CD319+ MM EVs increased in 19 patients with progression, and antigen escape was detected by BCMA+ MM EVs. MM EV subpopulations differentiated minimal residual disease (MRD) status and complemented MRD for detecting early relapse before clinical progression. Notably, CD319+ MM EVs were early predictors of progression-free and overall survival in MRD-negative patients. This assay enables noninvasive monitoring of deep response, progression, and antigen escape, and stratifies survival in MRD-negative patients with RRMM.
PMID:41890853 | PMC:PMC13015583 | DOI:10.21203/rs.3.rs-8913641/v1
OmniDiT: Extending Diffusion Transformer to Omni-VTON Framework
Unraveling the Link Between Azathioprine and Acute Pancreatitis: Integrating Network Toxicology, Machine Learning, and Mendelian Randomization
CPT Pharmacometrics Syst Pharmacol. 2026 Mar;15(3):e70178. doi: 10.1002/psp4.70178.
ABSTRACT
Azathioprine (AZA), a widely used immunosuppressant, can induce acute pancreatitis (AP), yet the underlying molecular mechanisms remain unclear. This study employed an integrative multiomics strategy-combining network toxicology, machine learning, Mendelian randomization (MR), and molecular docking-to elucidate the biological basis of AZA-induced AP. AZA-associated genes were first identified through bioinformatics databases and analyzed using protein-protein interaction networks and GO/KEGG functional enrichment. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) were applied to prioritize key differentially expressed genes for diagnostic modeling. MR was then used to examine potential causal links between gene expression and AP risk, followed by molecular docking to assess AZA-protein interactions. Sixty-eight candidate genes related to AZA-induced AP were identified. Enrichment analyses indicated involvement in lipid metabolic regulation, inflammatory pathways, and energy homeostasis. Machine learning highlighted seven key genes-CES1, CTSK, JAK1, NR3C2, PLIN5, WEE1, and RORA-as central to AP development. MR analysis further demonstrated that decreased expression of CES1 and CTSK may mediate AZA-related AP susceptibility. Docking simulations revealed strong, specific binding between AZA and both CES1 and CTSK. Overall, this study identifies CES1 and CTSK as genetically protective factors and mechanistic mediators in AZA-triggered AP. These findings offer new molecular insights into the genomic and biochemical pathways underlying this adverse drug reaction.
PMID:41832938 | DOI:10.1002/psp4.70178
LINC-AC092535.5 regulates MICAL2 mRNA level to inhibit p53-mediated ferroptosis in nasopharyngeal carcinoma
Oncogene, Published online: 14 March 2026; doi:10.1038/s41388-026-03714-y
LINC-AC092535.5 regulates MICAL2 mRNA level to inhibit p53-mediated ferroptosis in nasopharyngeal carcinoma