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FEAT: A Linear-Complexity Foundation Model for Extremely Large Structured Data
Unveiling the Diagnostic Value and Potential Therapeutic Targets of Phenylalanine Metabolism in Pancreatic Cancer via Integrated Multi-Omics and Machine Learning
FASEB J. 2026 Sep 30;40(18):e72296. doi: 10.1096/fj.202603069R.
ABSTRACT
Pancreatic cancer (PC) presents a significant global health challenge because of its high mortality rate, highlighting the urgent requirement for effective early diagnostic and therapeutic strategies. This study examined the function of phenylalanine metabolism in PC and developed a high-accuracy diagnostic model by integrating metabolomics, Mendelian randomization (MR), and machine learning (ML) algorithms. Initially, MR analysis was conducted on 55 plasma metabolites, revealing a significant causal link between phenylalanine and PC. Utilizing GeneCards and public transcriptomic databases, we determined eight differentially expressed genes (DEGs) in PC associated with phenylalanine. Based on these genes, we utilized 12 ML algorithms, totaling 113 combinations, to select the optimal diagnostic model. We applied Shapley Additive exPlanations (SHAP) for feature interpretation and constructed a prognostic nomogram with strong predictive performance by incorporating clinical variables. Furthermore, immune infiltration analysis demonstrated strong connections between these key genes and specific immune cell populations. Based on the SHAP value, we conducted single-cell RNA sequencing (scRNA-seq) data and simulated gene knockout analyses using SLC6A14 as the key gene. Drug target prediction-guided molecular docking and molecular dynamics simulations, focusing on the core gene SLC6A14, confirmed the high binding stability of candidate compounds. Finally, in vitro cell experiments quantitative real-time PCR (RT-qPCR) verified the expression trends of the key genes in PC cell lines. In conclusion, this study successfully developed an ML diagnostic model with high biological interpretability. This analysis aims to identify biomarkers related to phenylalanine metabolism and potential therapeutic drugs for PC, offering new strategies for personalized targeted therapy of PC.
PMID:42730913 | PMC:PMC13570651 | DOI:10.1096/fj.202603069R
Deep learning combined habitat radiomics analysis of central lymph node metastasis in papillary thyroid carcinoma
npj Digital Medicine, Published online: 12 September 2026; doi:10.1038/s41746-026-03203-2
Deep learning combined habitat radiomics analysis of central lymph node metastasis in papillary thyroid carcinomaXAI-Refine: An Automated Explanation-Knowledge Loop for Brain-Age Prediction
Can AI Agents Detect and Repair Artifact Drift in Network Experiments?
Can AI Agents Deliver Verifiable Network-Wide Outcomes Across Authority Boundaries?
FrontierOR: Benchmarking LLMs' Capacity for Efficient Algorithm Design in Large-Scale Optimization
Don't Retrain, Just Reuse: Recovering Dual-Target Molecules from Single-Target Diffusion Models
Generative structure search for efficient and diverse discovery of molecular and crystal structures
Transplantation of encapsulated mitochondria alleviates dysfunction in mitochondrial and Parkinson’s disease models
Memory Intelligence Agent
SkillX: Automatically Constructing Skill Knowledge Bases for Agents
RIFT: A RubrIc Failure Mode Taxonomy and Automated Diagnostics
Energy-Aware Reinforcement Learning for Robotic Manipulation of Articulated Components in Infrastructure Operation and Maintenance
Remembrance of inflammations past
Nature, Published online: 25 March 2026; doi:10.1038/d41586-026-00639-0
Chronic inflammation increases the risk of colon cancer. This inflammation drives epigenetic changes in the nucleus of stem cells that promote tumour formation.PAK4 functions as an immune suppressor by reprogramming the phosphatidylcholine metabolism of CD8 + T cells within the glioblastoma tumor microenvironment
Oncogene, Published online: 23 March 2026; doi:10.1038/s41388-026-03734-8
PAK4 functions as an immune suppressor by reprogramming the phosphatidylcholine metabolism of CD8 + T cells within the glioblastoma tumor microenvironmentMechanisms of Xinwei Tang in stress-induced gastric dysmotility: evidence from rat and In Vitro models
In Vitro Cell Dev Biol Anim. 2026 Mar 18. doi: 10.1007/s11626-026-01151-5. Online ahead of print.
ABSTRACT
Stress is a key trigger of gastric dysmotility, partly via mitochondrial dysfunction and disordered gut-brain hormonal signaling. Xinwei Tang (XWT) is a multi-herb formula used empirically for upper gastrointestinal symptoms, but its mechanisms remain unclear. This study aimed to determine whether XWT alleviates water-immersion restraint stress (WIRS)-induced gastric dysmotility and to delineate underlying mitochondrial and metabolic pathways using integrated in vivo, in vitro and multi-omics approaches. Male rats underwent 7-d WIRS and received vehicle, domperidone (3 mg/kg) or XWT (3, 6, 12 g/kg). Gastric emptying, serum motilin/gastrin, oxidative stress indices and PINK1/Parkin-LC3/p62 proteins were assessed, and H₂O₂-injured GES-1 cells were treated with XWT-medicated serum. Gastric antra from MOD and XWT-H rats were analyzed by RNA-seq and DIA proteomics (n = 3/group). WIRS reduced gastric emptying by roughly half and lowered motilin/gastrin, increased ROS/MDA and disrupted PINK1/Parkin-LC3/p62 profiles; XWT dose-dependently reversed these changes, with XWT-H approximating domperidone. Omics revealed XWT-associated downregulation of inflammatory/protease and acute-phase genes/proteins and enrichment of oxidative phosphorylation, tricarboxylic-acid cycle and other metabolic pathways, without global activation of canonical autophagy/mitophagy gene sets. These preclinical data indicate that XWT ameliorates stress-induced gastric dysmotility via mitochondria- and metabolism-centred protection with selective tuning of mitophagy-related proteins.
PMID:41851413 | DOI:10.1007/s11626-026-01151-5