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LifeFuse-Mem: Lifecycle-Aware State Fusion Against Temporary Overwriting for Long-Term Memory

arXiv:2609.12436v1 Announce Type: new Abstract: Long-running LLM agents require memory mechanisms that maintain coherent internal states across interactions. We study a lifecycle-labeled memory setting in which write episodes provide lifecycle metadata during training, and phase-aware readout is used during evaluation. This setting reflects the need to distinguish information that should remain influential across future interactions from information that should affect only the current context. A mismatch between these lifecycles can cause temporary information to overwrite durable knowledge, leading to behavioral drift in persistent agents. Within this setting, we introduce \textbf{LifeFuse-Mem}, a lifecycle-aware neural memory framework that separates information according to its temporal commitment. LifeFuse-Mem uses dedicated memory components and lifecycle-aware updates to allow stable and transient knowledge to evolve locally without converting temporary context into durable state. On the controlled anti-overwrite benchmark, LifeFuse-Mem improves acquisition-controlled retention and reduces temporary overwrite; on two public long-memory benchmarks, it remains broadly competitive. These results suggest that explicit lifecycle signals can help diagnose and mitigate overwrite in compact online memory.

Deciphering lung adenocarcinoma heterogeneity: a multi-omics approach reveals nuclear division fibroblasts as prognosticators and therapeutic targets

J Transl Med. 2026 Mar 20. doi: 10.1186/s12967-026-08022-3. Online ahead of print.

ABSTRACT

BACKGROUND: Lung adenocarcinoma (LUAD) is a predominant contributor to cancer‑related mortality globally. Lung‑associated fibroblasts (LAFs) are intricately linked to tumorigenesis and the tumor microenvironment (TME), but their heterogeneity and prognostic relevance in LUAD remain incompletely understood. This study aimed to systematically characterize LAF subsets across the spectrum of pulmonary disease, identify LAF subpopulations associated with LUAD prognosis, and construct a robust LAF‑based prognostic signature.

METHODS: We employed a multi-omics approach, leveraging bulk RNA data of 2719 patients from 19 LUAD cohorts, single-cell RNA (scRNA) sequencing data of 368,904 cells from 93 samples, and spatial transcriptomics data of 15,673 spots from 6 samples to characterize the landscape of LAFs across various stages of pulmonary disease. We employed multiple advanced machine learning algorithms to construct and validate a robust nuclear division LAFs (nLAFs) risk score (nLRS) prediction model.

RESULTS: We observed a dynamic and gradual increase in the proportion of LAFs during the progression of LUAD. Throughout this process, we identified nine LAFs subtypes and found nLAFs are significantly associated with the prognosis of LUAD. Utilizing 100 machine learning algorithm combinations and integrating nLAFs marker genes, we developed a five gene based nLRS model, which demonstrated superior performance than other 49 published models in predicting clinical outcomes for LUAD. Additionally, we observed distinct biological functions and immune cell infiltration in the TME between high and low nLRS groups. Exploratory analysis of pan-cancer immunotherapy cohorts suggested that patients with high nLRS scores may exhibit resistance to immunotherapy in some cancer types, but prospective validation in LUAD-specific cohorts is required. Conversely, high nLRS patients displayed increased sensitivity to chemotherapeutic and targeted therapies in preclinical models.

CONCLUSION: Our study introduces a candidate five-gene signature derived from nLAFs that may serve as a robust prognostic biomarker pending prospective validation, offering insights into personalized therapeutic strategies for LUAD patients.

PMID:41862916 | DOI:10.1186/s12967-026-08022-3

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