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cs.AI, q-bio.NC updates on arXiv.org
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VBVR-Pro: A Scalable and Verifiable Suite for Native Visual Reasoning
arXiv:2608.26105v2 Announce Type: replace-cross Abstract: Native visual reasoning treats visual generation as the medium of reasoning itself: visual states (i.e. images and videos) are not merely inputs to be understood or outputs to be rendered, but first-class substrates for problem solving beyond language. Yet progress remains bottlenecked by the lack of scalable training tasks, reliable feedback, and controlled comparisons across generative substrates. In this work, we introduce VBVR-Pro, a
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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NBR1-Mediated Autophagic Degradation of YTHDF1 Curtails <em>FDX1</em> Translation to Drive Concurrent Multikinase Inhibitor Resistance and Cuproptosis Tolerance
Cancer Commun (Lond). 2026 Sep 11;46:0048. doi: 10.34133/cancomm.0048. eCollection 2026.ABSTRACTBackground: Cancer cells frequently acquire adaptive resistance to targeted therapies; however, strategies capable of concurrently overcoming treatment tolerance and reactivating cell death pathways are currently lacking. Here, we investigated the dual role of ferredoxin 1 (FDX1) in modulating both multikinase inhibitor (MKI) sensitivity and cuproptosis susceptibility in hepatocellular carcinoma (HCC)
NBR1-Mediated Autophagic Degradation of YTHDF1 Curtails <em>FDX1</em> Translation to Drive Concurrent Multikinase Inhibitor Resistance and Cuproptosis Tolerance
Cancer Commun (Lond). 2026 Sep 11;46:0048. doi: 10.34133/cancomm.0048. eCollection 2026.
ABSTRACT
Background: Cancer cells frequently acquire adaptive resistance to targeted therapies; however, strategies capable of concurrently overcoming treatment tolerance and reactivating cell death pathways are currently lacking. Here, we investigated the dual role of ferredoxin 1 (FDX1) in modulating both multikinase inhibitor (MKI) sensitivity and cuproptosis susceptibility in hepatocellular carcinoma (HCC), and sought to develop a therapeutic approach for reversing resistance. Methods: HCC models, both in vitro and in vivo, were employed to investigate the role of FDX1 in MKI resistance and cuproptosis evasion. Polysome profiling, SunTag translation reporters, CRISPR-Cas9 mutagenesis, and mass spectrometry were employed to delineate the underlying mechanisms. A codelivery nanoliposome system was engineered and tested in orthotopic HCC models. Results: Prolonged exposure to MKIs led to the down-regulation of FDX1 protein levels, resulting in MKI resistance and cuproptosis tolerance in HCC both in vitro and in vivo. Mechanistically, we found that MKIs inactivated protein kinase B (PKB, also known as AKT)-mechanistic target of rapamycin (mTOR) signaling, thereby suppressing the SET and MYND domain-containing protein 2 (SMYD2)-mediated methylation of YTH domain family protein 1 (YTHDF1) at lysine 515 (K515). Hypomethylated YTHDF1 was degraded via next to BRCA1 gene 1 protein (NBR1)-dependent autophagy, leading to the repression of N6-methyladenosine modification-dependent translation of FDX1 mRNA. FDX1 deficiency drove MKI resistance by reactivating AKT survival signaling while impairing cuproptosis through reduced divalent copper ions (Cu2+) to monovalent copper ions (Cu+) conversion and the loss of protein lipoylation. Additionally, restoring FDX1 expression through NBR1 knockdown or YTHDF1 overexpression overcame MKI resistance and resensitized HCC cells to cuproptosis. Finally, a nanoliposomal system, super cuproptosis detonator liposome, designed for the codelivery of NBR1 small interfering RNA, a copper ionophore, and sorafenib restored FDX1-dependent cuproptosis and exhibited marked anti-HCC efficacy, suppressing HCC growth in vivo. Conclusions: MKIs suppressed SMYD2-mediated YTHDF1 methylation at K515 via the inactivation of AKT-mTOR signaling. This led to the inhibition of FDX1 translation, resulting in AKT signaling reactivation and protein lipoylation impairment, effects that contributed to both MKI resistance and cuproptosis tolerance in HCC. Overcoming MKI resistance and resensitizing cells to cuproptosis by targeting NBR1-mediated YTHDF1 degradation using a nanoliposomal codelivery system represents a promising strategy for HCC treatment.
PMID:42729649 | PMC:PMC13562797 | DOI:10.34133/cancomm.0048
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Cell Death Discovery nature.com science feeds
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MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism
Cell Death Discovery, Published online: 11 March 2026; doi:10.1038/s41420-026-02990-7MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism
MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism
Cell Death Discovery, Published online: 11 March 2026; doi:10.1038/s41420-026-02990-7
MAPK14/SLC7A11/GPX4 axis dysregulation drives podocyte ferroptosis via mediating glycerophospholipid metabolism-
cs.AI, q-bio.NC updates on arXiv.org
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More Bang for the Buck: Process Reward Modeling with Entropy-Driven Uncertainty
arXiv:2503.22233v4 Announce Type: replace-cross Abstract: We introduce the Entropy-Driven Uncertainty Process Reward Model (EDU-PRM), a novel entropy-driven training framework for process reward modeling that enables dynamic, uncertainty-aligned segmentation of complex reasoning steps, eliminating the need for costly manual step annotations. Unlike previous Process Reward Models (PRMs) that rely on static partitioning and human labeling, EDU-PRM automatically anchors step boundaries at tokens w
More Bang for the Buck: Process Reward Modeling with Entropy-Driven Uncertainty
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cs.AI, q-bio.NC updates on arXiv.org
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Benchmarking MLLM-based Web Understanding: Reasoning, Robustness and Safety
arXiv:2509.21782v2 Announce Type: replace Abstract: Multimodal large language models (MLLMs) are increasingly deployed as the core reasoning engine for web-facing systems, powering GUI agents and front-end automation that must interpret page structure, select actionable widgets, and execute multi-step interactions reliably. However, existing benchmarks largely emphasize visual perception or UI code generation, showing insufficient evaluation on the reasoning, robustness and safety capability re
Benchmarking MLLM-based Web Understanding: Reasoning, Robustness and Safety
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cs.AI, q-bio.NC updates on arXiv.org
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A Very Big Video Reasoning Suite
arXiv:2602.20159v1 Announce Type: cross Abstract: Rapid progress in video models has largely focused on visual quality, leaving their reasoning capabilities underexplored. Video reasoning grounds intelligence in spatiotemporally consistent visual environments that go beyond what text can naturally capture, enabling intuitive reasoning over spatiotemporal structure such as continuity, interaction, and causality. However, systematically studying video reasoning and its scaling behavior is hindere