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MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy

Nature Cancer, Published online: 11 September 2026; doi:10.1038/s43018-026-01236-w

Zheng et al. describe how hypoxia-induced methylmalonate semialdehyde dehydrogenase lactylation promotes acyl-CoA synthetase long-chain family member 4 propionylation and degradation, thereby suppressing ferroptosis induced by chemotherapy, and develop a blocking peptide that increased chemotherapy efficacy in pancreatic ductal adenocarcinoma.
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SafeCtrl-RL: Inference-Time Adaptive Behaviour Control for LLM Dialogue via RL-Driven Prompt Optimisation

arXiv:2605.25984v1 Announce Type: cross Abstract: Ensuring safe and contextually appropriate behaviour in Large Language Models (LLMs) remains a critical challenge for real-world deployment. We present \textbf{SafeCtrl-RL}, an inference-time behavioural control framework that enables adaptive safety regulation without model retraining or parameter modification. The method formulates dialogue generation as a sequential decision process, where a reinforcement learning agent dynamically selects prompt adjustment strategies based on contextual feedback. This allows unsafe behaviours to be suppressed through iterative refinement, which we conceptualise as inference-time behavioural unlearning. Evaluated across multiple LLMs and unsafe dialogue scenarios, SafeCtrl-RL consistently improves safety and response quality, outperforms existing prompt-based optimisation methods, and achieves favourable performance--efficiency trade-offs. **Warning: This paper may contain examples of harmful language, and reader discretion is recommended.
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