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cs.AI, q-bio.NC updates on arXiv.org
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ImplicitRM: Unbiased Reward Modeling from Implicit Preference Data for LLM alignment
arXiv:2603.23184v1 Announce Type: cross Abstract: Reward modeling represents a long-standing challenge in reinforcement learning from human feedback (RLHF) for aligning language models. Current reward modeling is heavily contingent upon experimental feedback data with high collection costs. In this work, we study \textit{implicit reward modeling} -- learning reward models from implicit human feedback (e.g., clicks and copies) -- as a cost-effective alternative. We identify two fundamental chall
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Omics in Hepatocellular
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SIRT3 deacetylates STEAP4 to modulate cuproptosis sensitivity via mitochondrial metabolic reprogramming in HBV-related HCC
Cell Death Differ. 2026 Mar 16. doi: 10.1038/s41418-026-01713-w. Online ahead of print.ABSTRACTHepatitis B virus (HBV) infection remains a leading etiological driver of hepatocellular carcinoma (HCC). Cuproptosis is a recently defined copper-dependent form of regulated cell death that selectively eliminates mitochondria-dependent cells; whether HBV rewires this vulnerability remains unknown. Here we unveil a novel HBV X protein (HBx)-driven mechanism of cuproptosis evasion. Integrative analysis
SIRT3 deacetylates STEAP4 to modulate cuproptosis sensitivity via mitochondrial metabolic reprogramming in HBV-related HCC
Cell Death Differ. 2026 Mar 16. doi: 10.1038/s41418-026-01713-w. Online ahead of print.
ABSTRACT
Hepatitis B virus (HBV) infection remains a leading etiological driver of hepatocellular carcinoma (HCC). Cuproptosis is a recently defined copper-dependent form of regulated cell death that selectively eliminates mitochondria-dependent cells; whether HBV rewires this vulnerability remains unknown. Here we unveil a novel HBV X protein (HBx)-driven mechanism of cuproptosis evasion. Integrative analysis of clinical specimens, HBx-transgenic (HBx-Tg) mice, and multi-omics datasets revealed marked downregulation of STEAP4 (six-transmembrane epithelial antigen of prostate 4), a metalloreductase essential for cuproptosis sensitivity, in HBV-positive HCC. Mechanistically, HBx attenuates sirtuin 3 (SIRT3), impairing deacetylation of STEAP4 at lysine 404 and abolishing its mitochondrial targeting. Consequently, cells switch from the tricarboxylic acid (TCA) cycle respiration to glycolysis, reducing sensitivity to the copper ionophore elesclomol (ES). Restoring STEAP4 expression or pharmacological activation of SIRT3 with honokiol (HKL) re-instated mitochondrial STEAP4 localization and re-sensitized HBV-related HCC cells to cuproptosis; combination with ES produced synergistic tumor suppression in vitro and in orthotopic models. Collectively, our findings establish the SIRT3-STEAP4 axis as a novel regulator of cuproptosis resistance in HBV-related HCC. HBx-mediated repression of SIRT3 disrupts STEAP4 deacetylation and mitochondrial targeting, fostering metabolic reprogramming and evasion of copper-induced cell death. The results provide a pre-clinical rationale for copper-directed combination strategies in HBV-associated HCC.
PMID:41840161 | DOI:10.1038/s41418-026-01713-w
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cs.AI, q-bio.NC updates on arXiv.org
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Improving Diffusion Planners by Self-Supervised Action Gating with Energies
arXiv:2603.02650v1 Announce Type: cross Abstract: Diffusion planners are a strong approach for offline reinforcement learning, but they can fail when value-guided selection favours trajectories that score well yet are locally inconsistent with the environment dynamics, resulting in brittle execution. We propose Self-supervised Action Gating with Energies (SAGE), an inference-time re-ranking method that penalises dynamically inconsistent plans using a latent consistency signal. SAGE trains a Joi
Improving Diffusion Planners by Self-Supervised Action Gating with Energies
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cs.AI, q-bio.NC updates on arXiv.org
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CellINR: Implicitly Overcoming Photo-induced Artifacts in 4D Live Fluorescence Microscopy
arXiv:2508.19300v2 Announce Type: replace-cross Abstract: 4D live fluorescence microscopy is often compromised by prolonged high intensity illumination which induces photobleaching and phototoxic effects that generate photo-induced artifacts and severely impair image continuity and detail recovery. To address this challenge, we propose the CellINR framework, a case-specific optimization approach based on implicit neural representation. The method employs blind convolution and structure amplific