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Think Before You Drive: World Model-Inspired Multimodal Grounding for Autonomous Vehicles

arXiv:2512.03454v3 Announce Type: replace-cross Abstract: Interpreting natural-language commands to localize target objects is critical for autonomous driving (AD). Existing visual grounding (VG) methods for autonomous vehicles (AVs) typically struggle with ambiguous, context-dependent instructions, as they lack reasoning over 3D spatial relations and anticipated scene evolution. Grounded in the principles of world models, we propose ThinkDeeper, a framework that reasons about future spatial states before making grounding decisions. At its core is a Spatial-Aware World Model (SA-WM) that learns to reason ahead by distilling the current scene into a command-aware latent state and rolling out a sequence of future latent states, providing forward-looking cues for disambiguation. Complementing this, a hypergraph-guided decoder then hierarchically fuses these states with the multimodal input, capturing higher-order spatial dependencies for robust localization. In addition, we present DrivePilot, a multi-source VG dataset in AD, featuring semantic annotations generated by a Retrieval-Augmented Generation (RAG) and Chain-of-Thought (CoT)-prompted LLM pipeline. Extensive evaluations on six benchmarks, ThinkDeeper ranks #1 on the Talk2Car leaderboard and surpasses state-of-the-art baselines on DrivePilot, MoCAD, and RefCOCO/+/g benchmarks. Notably, it shows strong robustness and efficiency in challenging scenes (long-text, multi-agent, ambiguity) and retains superior performance even when trained on 50% of the data.
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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.

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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