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Proteomic and lipidomic analyses reveal molecular subtypes and potential targets in early-stage lung adenocarcinoma among non-smokers

29 April 2026 at 18:00

Cell Rep. 2026 May 26;45(5):117215. doi: 10.1016/j.celrep.2026.117215. Epub 2026 Apr 28.

ABSTRACT

Early-stage lung adenocarcinoma (LUAD) in never smokers exhibits distinct biological features, yet the metabolic programs driving early invasion remain unclear. We integrate proteomic and lipidomic profiling of primary LUAD tumors from never smokers, matched normal adjacent tissues (NATs), and benign pulmonary nodules (BPNs). Integrated multi-omics analysis reveals coordinated dysregulation of lipid metabolism and immune signaling in early LUAD. Proteome-based network fusion stratifies invasive LUAD into immune-metabolic synergistic (IMS) and metabolic-stress-driven (MSD) subtypes. IMS tumors retain apolipoprotein-associated lipid modules and favorable immune features, whereas MSD tumors exhibit stress-response programs. Mechanistically, APOA1 and APOC1 emerge as key nodes linking lipid homeostasis to invasion, and their depletion promotes LUAD cell migration and invasion. We establish a two-protein, four-lipid diagnostic panel demonstrating robust performance across tissue and plasma cohorts. These findings provide a molecular basis for early detection and risk stratification in never smokers.

PMID:42054209 | DOI:10.1016/j.celrep.2026.117215

Hierarchical Memory Orchestration for Personalized Persistent Agents

arXiv:2604.01670v1 Announce Type: new Abstract: While long-term memory is essential for intelligent agents to maintain consistent historical awareness, the accumulation of extensive interaction data often leads to performance bottlenecks. Naive storage expansion increases retrieval noise and computational latency, overwhelming the reasoning capacity of models deployed on constrained personal devices. To address this, we propose Hierarchical Memory Orchestration (HMO), a framework that organizes interaction history into a three-tiered directory driven by user-centric contextual relevance. Our system maintains a compact primary cache, coupling recent and pivotal memories with an evolving user profile to ensure agent reasoning remains aligned with individual behavioral traits. This primary cache is complemented by a high-priority secondary layer, both of which are managed within a global archive of the full interaction history. Crucially, the user persona dictates memory redistribution across this hierarchy, promoting records mapped to long-term patterns toward more active tiers while relegating less relevant information. This targeted orchestration surfaces historical knowledge precisely when needed while maintaining a lean and efficient active search space. Evaluations on multiple benchmarks achieve state-of-the-art performance. Real-world deployments in ecosystems like OpenClaw demonstrate that HMO significantly enhances agent fluidity and personalization.
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