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Chain-of-Authorization: Internalizing Authorization into Large Language Models via Reasoning Trajectories

arXiv:2603.22869v1 Announce Type: new Abstract: Large Language Models (LLMs) have become core cognitive components in modern artificial intelligence (AI) systems, combining internal knowledge with external context to perform complex tasks. However, LLMs typically treat all accessible data indiscriminately, lacking inherent awareness of knowledge ownership and access boundaries. This deficiency heightens risks of sensitive data leakage and adversarial manipulation, potentially enabling unauthorized system access and severe security crises. Existing protection strategies rely on rigid, uniform defense that prevent dynamic authorization. Structural isolation methods faces scalability bottlenecks, while prompt guidance methods struggle with fine-grained permissions distinctions. Here, we propose the Chain-of-Authorization (CoA) framework, a secure training and reasoning paradigm that internalizes authorization logic into LLMs' core capabilities. Unlike passive external defneses, CoA restructures the model's information flow: it embeds permission context at input and requires generating explicit authorization reasoning trajectory that includes resource review, identity resolution, and decision-making stages before final response. Through supervised fine-tuning on data covering various authorization status, CoA integrates policy execution with task responses, making authorization a causal prerequisite for substantive responses. Extensive evaluations show that CoA not only maintains comparable utility in authorized scenarios but also overcomes the cognitive confusion when permissions mismatches. It exhibits high rejection rates against various unauthorized and adversarial access. This mechanism leverages LLMs' reasoning capability to perform dynamic authorization, using natural language understanding as a proactive security mechanism for deploying reliable LLMs in modern AI systems.
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ESM1 drives cancer angiogenesis and bevacizumab resistance via trioleate synthesis

Neoplasia. 2026 May;75:101298. doi: 10.1016/j.neo.2026.101298. Epub 2026 Mar 20.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) exhibits high recurrence rates and limited therapeutic options. Endothelial cell-specific molecule 1 (ESM1) and angiopoietin-like 4 (ANGPTL4) are implicated in tumor progression, yet their synergistic role in HCC lipid metabolism and angiogenesis remains unexplored.

METHODS: We integrated multi-omics approaches, including RNA sequencing, metabolomics, and immunoprecipitation-mass spectrometry, in HCC cell lines and patient-derived xenograft models. Key experiments involved Co-IP, Western blotting, tube formation assays, and clinical tissue microarray analysis to validate the ESM1-ANGPTL4-FASN-trioleate axis.

RESULTS: ESM1 and ANGPTL4 formed a positive feedback loop, stabilizing fatty acid synthase (FASN) to promote trioleate synthesis. Trioleate activated the NF-ΞΊB/IL-17 pathway in HCC cells and upregulated CD99 in endothelial cells, driving angiogenesis. In vivo, ESM1/ANGPTL4 knockdown suppressed tumor growth, which was rescued by trioleate supplementation. Clinical data revealed elevated ESM1/ANGPTL4 expression in bevacizumab-resistant HCC, correlating with poor prognosis.

CONCLUSIONS: The ESM1-ANGPTL4-FASN-trioleate axis orchestrates metabolic reprogramming and endothelial activation, representing a promising therapeutic target. Future studies should explore combination therapies targeting this axis and overcoming bevacizumab resistance in HCC.

PMID:41864037 | PMC:PMC13019581 | DOI:10.1016/j.neo.2026.101298

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