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FOXD3 Is Functionally Linked to NF-κB Signaling in KRAS G12C-Mutant NSCLC Cells

Cells. 2026 Aug 28;15(17):1564. doi: 10.3390/cells15171564.

ABSTRACT

KRAS G12C mutation is a clinically relevant driver in non-small cell lung cancer (NSCLC), yet the signaling networks that modulate malignant behavior in this context remain incompletely defined. In this study, we examined the functional role of FOXD3 and its relationship with NF-κB signaling in KRAS G12C-mutant NSCLC models. Stable FOXD3 overexpression was established in SW1573 and LU65 cells. FOXD3 reduced cell viability, migration, and invasion while increasing caspase 3/7 activity in both cell lines. Transcriptomic profiling in LU65 cells followed by Hallmark enrichment analysis identified TNFα signaling via NF-κB as a prominently altered pathway associated with FOXD3 overexpression. Consistently, NF-κB dual-luciferase assays showed reduced basal NF-κB transcriptional activity in FOXD3-overexpressing cells. TNFα stimulation partially reversed the inhibitory effects of FOXD3 on proliferation, migration, and invasion and attenuated FOXD3-induced apoptosis. In addition, stable FOXD3 overexpression suppressed xenograft growth in vivo. Collectively, these findings support a functional association between FOXD3 overexpression and reduced NF-κB-related transcriptional activity in KRAS G12C-mutant NSCLC models, although the present data do not establish direct causal mediation by NF-κB.

PMID:42738858 | PMC:PMC13564895 | DOI:10.3390/cells15171564

Skin-innervating glutamatergic neurons modulate aging

Within the skin, glutamatergic neurons expressing neurofilament heavy chain (Nefh) play a role in aging. Loss of Nefh during aging drives skin fibroblast senescence and collagen loss, whereas glutamate supplementation improves skin aging phenotypes.

AffordTissue: Dense Affordance Prediction for Tool-Action Specific Tissue Interaction

arXiv:2604.01371v1 Announce Type: cross Abstract: Surgical action automation has progressed rapidly toward achieving surgeon-like dexterous control, driven primarily by advances in learning from demonstration and vision-language-action models. While these have demonstrated success in table-top experiments, translating them to clinical deployment remains challenging: current methods offer limited predictability on where instruments will interact on tissue surfaces and lack explicit conditioning inputs to enforce tool-action-specific safe interaction regions. Addressing this gap, we introduce AffordTissue, a multimodal framework for predicting tool-action specific tissue affordance regions as dense heatmaps during cholecystectomy. Our approach combines a temporal vision encoder capturing tool motion and tissue dynamics across multiple viewpoints, language conditioning enabling generalization across diverse instrument-action pairs, and a DiT-style decoder for dense affordance prediction. We establish the first tissue affordance benchmark by curating and annotating 15,638 video clips across 103 cholecystectomy procedures, covering six unique tool-action pairs involving four instruments (hook, grasper, scissors, clipper) and their associated tasks: dissection, grasping, clipping, and cutting. Experiments demonstrate substantial improvement over vision-language model baselines (20.6 px ASSD vs. 60.2 px for Molmo-VLM), showing that our task-specific architecture outperforms large-scale foundation models for dense surgical affordance prediction. By predicting tool-action specific tissue affordance regions, AffordTissue provides explicit spatial reasoning for safe surgical automation, potentially unlocking explicit policy guidance toward appropriate tissue regions and early safe stop when instruments deviate outside predicted safe zones.

Optimizing RAG Rerankers with LLM Feedback via Reinforcement Learning

arXiv:2604.02091v1 Announce Type: cross Abstract: Rerankers play a pivotal role in refining retrieval results for Retrieval-Augmented Generation. However, current reranking models are typically optimized on static human annotated relevance labels in isolation, decoupled from the downstream generation process. This isolation leads to a fundamental misalignment: documents identified as topically relevant by information retrieval metrics often fail to provide the actual utility required by the LLM for precise answer generation. To bridge this gap, we introduce ReRanking Preference Optimization (RRPO), a reinforcement learning framework that directly aligns reranking with the LLM's generation quality. By formulating reranking as a sequential decision-making process, RRPO optimizes for context utility using LLM feedback, thereby eliminating the need for expensive human annotations. To ensure training stability, we further introduce a reference-anchored deterministic baseline. Extensive experiments on knowledge-intensive benchmarks demonstrate that RRPO significantly outperforms strong baselines, including the powerful list-wise reranker RankZephyr. Further analysis highlights the versatility of our framework: it generalizes seamlessly to diverse readers (e.g., GPT-4o), integrates orthogonally with query expansion modules like Query2Doc, and remains robust even when trained with noisy supervisors.

RooflineBench: A Benchmarking Framework for On-Device LLMs via Roofline Analysis

arXiv:2602.11506v3 Announce Type: replace-cross Abstract: The transition toward localized intelligence through Small Language Models (SLMs) has intensified the need for rigorous performance characterization on resource-constrained edge hardware. However, objectively measuring the theoretical performance ceilings of diverse architectures across heterogeneous platforms remains a formidable challenge. In this work, we propose a systematic framework based on the Roofline model that unifies architectural primitives and hardware constraints through the lens of operational intensity (OI). By defining an inference-potential region, we introduce the Relative Inference Potential as a novel metric to compare efficiency differences between Large Language Models (LLMs) on the same hardware substrate. Extensive empirical analysis across diverse compute tiers reveals that variations in performance and OI are significantly influenced by sequence length. We further identify a critical regression in OI as model depth increases. Additionally, our findings highlight an efficiency trap induced by hardware heterogeneity and demonstrate how structural refinements, such as Multi-head Latent Attention (M LA), can effectively unlock latent inference potential across various hardware substrates. These insights provide actionable directions for hardware-software co-design to align neural structures with physical constraints in on-device intelligence. The released code is available in the Appendix C.
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