Normal view
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cs.AI, q-bio.NC updates on arXiv.org
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Mr.LHDR: A Benchmark for Multimodal Real-World Long-Horizon Deep Research Agents
arXiv:2609.11318v2 Announce Type: replace Abstract: Deep research agents are increasingly capable of web search, tool use, multimodal evidence analysis, and information synthesis. However, existing benchmarks mainly evaluate medium-horizon exploration and rarely test whether agents can sustain long, dependency-heavy research processes. We introduce Mr. LHDR (Multimodal real-world Long-Horizon Deep Research), a benchmark for evaluating real-world deep research over long, irreducible chains of in
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Omics in Gastric
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MCAT-mediated mitochondrial fatty acid metabolism regulates Lauren subtype divergence and suppresses gastric cancer progression through ROS/P53-dependent mitophagy and ferroptosis
Cell Death Differ. 2026 Sep 8. doi: 10.1038/s41418-026-01867-7. Online ahead of print.ABSTRACTGastric cancer (GC) displays marked heterogeneity under the Lauren classification, yet the metabolic determinants of subtype divergence remain unclear. Here, we identify Malonyl-CoA:ACP transacylase (MCAT), a Lauren subtype-associated gene encoding a key mitochondrial fatty acid synthesis (mtFAS) enzyme, as a subtype-specific tumor suppressor in GC. Integrative multi-omics profiling revealed that MCAT e
MCAT-mediated mitochondrial fatty acid metabolism regulates Lauren subtype divergence and suppresses gastric cancer progression through ROS/P53-dependent mitophagy and ferroptosis
Cell Death Differ. 2026 Sep 8. doi: 10.1038/s41418-026-01867-7. Online ahead of print.
ABSTRACT
Gastric cancer (GC) displays marked heterogeneity under the Lauren classification, yet the metabolic determinants of subtype divergence remain unclear. Here, we identify Malonyl-CoA:ACP transacylase (MCAT), a Lauren subtype-associated gene encoding a key mitochondrial fatty acid synthesis (mtFAS) enzyme, as a subtype-specific tumor suppressor in GC. Integrative multi-omics profiling revealed that MCAT expression is enriched in intestinal-type GC and correlates with favorable prognosis. Mechanistically, MCAT overexpression drives metabolic reprogramming through mitochondrial free fatty acid overload, suppressing β-oxidation while elevating mitochondrial reactive oxygen species (ROS), which triggers P53 phosphorylation at Ser15. This event concurrently activates PINK1/Parkin-mediated mitophagy and suppresses the SLC7A11/GPX4 axis to induce ferroptosis. Genetic rescue experiments confirmed that P53-Ser15 phosphorylation is essential for both mitophagy and ferroptosis induction. Endogenous MCAT levels are sufficient to determine basal ROS/P53/mitophagy/ferroptosis axis activity, and knockdown in high-expressing cells reverses these phenotypes, supporting a physiological, threshold-dependent role. In vivo, MCAT overexpression suppresses tumor growth and enhances mitophagy and ferroptosis markers. Collectively, these findings establish MCAT as a metabolic switch that links mtFAS to ROS/P53-dependent cell death, providing a potential biomarker and therapeutic target for GC.
PMID:42711380 | DOI:10.1038/s41418-026-01867-7
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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A programmed cell death learning signature predicts immunotherapy response and identifies AP1S1 as a regulator of immune exclusion in breast cancer
Chin J Cancer Res. 2026 Aug 30;38(4):480-500. doi: 10.21147/j.issn.1000-9604.2026.04.08.ABSTRACTOBJECTIVE: Breast cancer remains a leading cause of global cancer mortality, characterized by profound heterogeneity. While immune checkpoint blockade (ICB) has transformed oncology, its efficacy in breast cancer is often hindered by "immune-cold" microenvironments and immune exclusion. Programmed cell death (PCD) is a critical regulator of tumor immune microenvironment (TIME). However, its role in th
A programmed cell death learning signature predicts immunotherapy response and identifies AP1S1 as a regulator of immune exclusion in breast cancer
Chin J Cancer Res. 2026 Aug 30;38(4):480-500. doi: 10.21147/j.issn.1000-9604.2026.04.08.
ABSTRACT
OBJECTIVE: Breast cancer remains a leading cause of global cancer mortality, characterized by profound heterogeneity. While immune checkpoint blockade (ICB) has transformed oncology, its efficacy in breast cancer is often hindered by "immune-cold" microenvironments and immune exclusion. Programmed cell death (PCD) is a critical regulator of tumor immune microenvironment (TIME). However, its role in the breast cancer immune microenvironment remains poorly understood.
METHODS: We integrated multi-omics data from six breast cancer cohorts (N=3,764) to develop a programmed cell death learning signature (PCDsig) using over 100 machine learning combinations. The model was benchmarked against 29 published signatures. Single-cell transcriptomic analysis decoded the immune landscape and cellular crosstalk. The role of adaptor-related protein complex 1 subunit sigma 1 (AP1S1) was validated through a clinical cohort, in vitro functional assays, and in vivo syngeneic mouse models.
RESULTS: PCDsig significantly stratified patient prognosis across all cohorts, consistently outperforming 29 existing models. High PCDsig scores correlated with immune-excluded phenotypes, reduced CD8+ T cell infiltration, and lower immunophenoscores. Single-cell analysis revealed that high-PCDsig tumors utilize vascular endothelial growth factor A (VEGFA) signaling to foster an immunosuppressive microenvironment. AP1S1 was identified as the core driver of immune exclusion. And our clinical cohort supported the immune exclusion effect of AP1S1. AP1S1 knockdown impaired tumor progression in vitro and fundamentally remodeled the tumor immune ecosystem in vivo. Combining AP1S1 inhibition with anti-programmed cell death ligand 1 (anti-PD-L1) therapy exerted profound synergistic effects, driven by massive infiltration and functional activation of cytotoxic Granzyme B (GZMB)+CD8+ T cells.
CONCLUSIONS: Our study establishes the PCDsig we developed is a potential prognostic and predictive biomarker for breast cancer. We provide the first evidence of AP1S1 as a core immunomodulatory oncogene that mediates immune exclusion. Targeting AP1S1 represents a highly promising strategy to sensitize cold breast tumors to ICB, offering a new perspective for precision immunotherapy.
PMID:42712842 | PMC:PMC13551362 | DOI:10.21147/j.issn.1000-9604.2026.04.08
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(Multiomics OR Omics) AND (Lung OR gastric OR Hepatocellular)
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MCAT-mediated mitochondrial fatty acid metabolism regulates Lauren subtype divergence and suppresses gastric cancer progression through ROS/P53-dependent mitophagy and ferroptosis
Cell Death Differ. 2026 Sep 8. doi: 10.1038/s41418-026-01867-7. Online ahead of print.ABSTRACTGastric cancer (GC) displays marked heterogeneity under the Lauren classification, yet the metabolic determinants of subtype divergence remain unclear. Here, we identify Malonyl-CoA:ACP transacylase (MCAT), a Lauren subtype-associated gene encoding a key mitochondrial fatty acid synthesis (mtFAS) enzyme, as a subtype-specific tumor suppressor in GC. Integrative multi-omics profiling revealed that MCAT e
MCAT-mediated mitochondrial fatty acid metabolism regulates Lauren subtype divergence and suppresses gastric cancer progression through ROS/P53-dependent mitophagy and ferroptosis
Cell Death Differ. 2026 Sep 8. doi: 10.1038/s41418-026-01867-7. Online ahead of print.
ABSTRACT
Gastric cancer (GC) displays marked heterogeneity under the Lauren classification, yet the metabolic determinants of subtype divergence remain unclear. Here, we identify Malonyl-CoA:ACP transacylase (MCAT), a Lauren subtype-associated gene encoding a key mitochondrial fatty acid synthesis (mtFAS) enzyme, as a subtype-specific tumor suppressor in GC. Integrative multi-omics profiling revealed that MCAT expression is enriched in intestinal-type GC and correlates with favorable prognosis. Mechanistically, MCAT overexpression drives metabolic reprogramming through mitochondrial free fatty acid overload, suppressing β-oxidation while elevating mitochondrial reactive oxygen species (ROS), which triggers P53 phosphorylation at Ser15. This event concurrently activates PINK1/Parkin-mediated mitophagy and suppresses the SLC7A11/GPX4 axis to induce ferroptosis. Genetic rescue experiments confirmed that P53-Ser15 phosphorylation is essential for both mitophagy and ferroptosis induction. Endogenous MCAT levels are sufficient to determine basal ROS/P53/mitophagy/ferroptosis axis activity, and knockdown in high-expressing cells reverses these phenotypes, supporting a physiological, threshold-dependent role. In vivo, MCAT overexpression suppresses tumor growth and enhances mitophagy and ferroptosis markers. Collectively, these findings establish MCAT as a metabolic switch that links mtFAS to ROS/P53-dependent cell death, providing a potential biomarker and therapeutic target for GC.
PMID:42711380 | DOI:10.1038/s41418-026-01867-7
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(Multiomics OR Omics) AND (Pancreatic)
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A programmed cell death learning signature predicts immunotherapy response and identifies AP1S1 as a regulator of immune exclusion in breast cancer
Chin J Cancer Res. 2026 Aug 30;38(4):480-500. doi: 10.21147/j.issn.1000-9604.2026.04.08.ABSTRACTOBJECTIVE: Breast cancer remains a leading cause of global cancer mortality, characterized by profound heterogeneity. While immune checkpoint blockade (ICB) has transformed oncology, its efficacy in breast cancer is often hindered by "immune-cold" microenvironments and immune exclusion. Programmed cell death (PCD) is a critical regulator of tumor immune microenvironment (TIME). However, its role in th
A programmed cell death learning signature predicts immunotherapy response and identifies AP1S1 as a regulator of immune exclusion in breast cancer
Chin J Cancer Res. 2026 Aug 30;38(4):480-500. doi: 10.21147/j.issn.1000-9604.2026.04.08.
ABSTRACT
OBJECTIVE: Breast cancer remains a leading cause of global cancer mortality, characterized by profound heterogeneity. While immune checkpoint blockade (ICB) has transformed oncology, its efficacy in breast cancer is often hindered by "immune-cold" microenvironments and immune exclusion. Programmed cell death (PCD) is a critical regulator of tumor immune microenvironment (TIME). However, its role in the breast cancer immune microenvironment remains poorly understood.
METHODS: We integrated multi-omics data from six breast cancer cohorts (N=3,764) to develop a programmed cell death learning signature (PCDsig) using over 100 machine learning combinations. The model was benchmarked against 29 published signatures. Single-cell transcriptomic analysis decoded the immune landscape and cellular crosstalk. The role of adaptor-related protein complex 1 subunit sigma 1 (AP1S1) was validated through a clinical cohort, in vitro functional assays, and in vivo syngeneic mouse models.
RESULTS: PCDsig significantly stratified patient prognosis across all cohorts, consistently outperforming 29 existing models. High PCDsig scores correlated with immune-excluded phenotypes, reduced CD8+ T cell infiltration, and lower immunophenoscores. Single-cell analysis revealed that high-PCDsig tumors utilize vascular endothelial growth factor A (VEGFA) signaling to foster an immunosuppressive microenvironment. AP1S1 was identified as the core driver of immune exclusion. And our clinical cohort supported the immune exclusion effect of AP1S1. AP1S1 knockdown impaired tumor progression in vitro and fundamentally remodeled the tumor immune ecosystem in vivo. Combining AP1S1 inhibition with anti-programmed cell death ligand 1 (anti-PD-L1) therapy exerted profound synergistic effects, driven by massive infiltration and functional activation of cytotoxic Granzyme B (GZMB)+CD8+ T cells.
CONCLUSIONS: Our study establishes the PCDsig we developed is a potential prognostic and predictive biomarker for breast cancer. We provide the first evidence of AP1S1 as a core immunomodulatory oncogene that mediates immune exclusion. Targeting AP1S1 represents a highly promising strategy to sensitize cold breast tumors to ICB, offering a new perspective for precision immunotherapy.
PMID:42712842 | PMC:PMC13551362 | DOI:10.21147/j.issn.1000-9604.2026.04.08
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Oncogenesis - nature.com science feeds
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Stanniocalcin 1 contributes to glioma stem cells phenotypic plasticity through NOTCH1/STAT3/GFPT2 axis
Oncogenesis, Published online: 29 August 2026; doi:10.1038/s41389-026-00653-xStanniocalcin 1 contributes to glioma stem cells phenotypic plasticity through NOTCH1/STAT3/GFPT2 axis
Stanniocalcin 1 contributes to glioma stem cells phenotypic plasticity through NOTCH1/STAT3/GFPT2 axis
Oncogenesis, Published online: 29 August 2026; doi:10.1038/s41389-026-00653-x
Stanniocalcin 1 contributes to glioma stem cells phenotypic plasticity through NOTCH1/STAT3/GFPT2 axis-
Pulmonary nodule
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A Comprehensive Review of Radiomics in Pulmonary Nodule Management: Clinical Applications and Standardization Dilemmas
Curr Med Imaging. 2026 Jun 22. doi: 10.2174/0115734056460566260609044755. Online ahead of print.ABSTRACTLung cancer is the most common and fatal malignant tumour. Early detection and treatment are likely to reduce mortality, but most pulmonary nodules identified during routine health checks are harmless. Consequently, a clear distinction between benign and malignant nodules is vital to improve early detection and reduce unnecessary interventions. Radiomics, a new omics technology, can be used to
A Comprehensive Review of Radiomics in Pulmonary Nodule Management: Clinical Applications and Standardization Dilemmas
Curr Med Imaging. 2026 Jun 22. doi: 10.2174/0115734056460566260609044755. Online ahead of print.
ABSTRACT
Lung cancer is the most common and fatal malignant tumour. Early detection and treatment are likely to reduce mortality, but most pulmonary nodules identified during routine health checks are harmless. Consequently, a clear distinction between benign and malignant nodules is vital to improve early detection and reduce unnecessary interventions. Radiomics, a new omics technology, can be used to extract high-dimensional quantitative features from medical images, providing a profound understanding of tumour pathophysiology. Radiomics has attracted the attention of medical researchers since its formal definition by the Dutch researcher Lambin et al. in 2012. The number of research papers on radiomics has grown tremendously over the past few years. At present, it is used to predict pulmonary nodule malignancy, for noninvasive risk stratification, for integration with genomics to identify genetic mutations associated with lung cancer, and for evaluation of therapeutic responses. With this review, we summarise the literature on radiomics of pulmonary nodules, discuss how it could be used in nodule management, and address the current challenges and future directions for improving precision oncology.
PMID:42333843 | DOI:10.2174/0115734056460566260609044755
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cs.AI, q-bio.NC updates on arXiv.org
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How Much Thinking is Enough? Quantifying and Understanding Redundancy in LLM Reasoning
arXiv:2605.23926v1 Announce Type: new Abstract: Reasoning-capable large language models solve hard problems by emitting long chains of thought, paying heavily in latency, GPU time, and energy. Casual inspection of their traces reveals extensive reformulation, verification, and circular self-reflection, yet how much of this deliberation is actually necessary has never been measured at scale or explained from first principles. This paper closes both gaps. We formalise reasoning redundancy direc
How Much Thinking is Enough? Quantifying and Understanding Redundancy in LLM Reasoning
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cs.AI, q-bio.NC updates on arXiv.org
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SkillEvolBench: Benchmarking the Evolution from Episodic Experience to Procedural Skills
arXiv:2605.24117v1 Announce Type: new Abstract: Large language model (LLM) agents accumulate rich episodic trajectories while solving real-world tasks, but it remains unclear whether such experience can be distilled into reusable procedural skills. We introduce SkillEvolBench, a diagnostic benchmark for evaluating this step from experience reuse to skill formation. It contains 180 tasks across six real-world agent environments, organized into role-conditioned task families with shared latent pr
SkillEvolBench: Benchmarking the Evolution from Episodic Experience to Procedural Skills
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cs.AI, q-bio.NC updates on arXiv.org
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Detecting Unfaithful Chain-of-Thought via Circuit-Guided Internal-External Discrepancy
arXiv:2605.25603v1 Announce Type: new Abstract: Chain-of-thought (CoT) reasoning improves the problem-solving ability of large language models (LLMs), but generated reasoning traces may not faithfully reflect the model's actual decision process. Existing CoT unfaithfulness detectors mainly rely on external signals from generated rationales, such as textual plausibility or answer consistency, while overlooking evidence from the model's internal computation. Although recent circuit tracing method
Detecting Unfaithful Chain-of-Thought via Circuit-Guided Internal-External Discrepancy
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cs.AI, q-bio.NC updates on arXiv.org
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Inference-Time Alignment of Diffusion Models via Trust-Region Iterative Twisted Sequential Monte Carlo
arXiv:2605.25123v1 Announce Type: cross Abstract: We study inference-time alignment for diffusion-based generative models, aiming to steer a base model toward high-reward outputs without updating its weights. Recent Sequential Monte Carlo (SMC)-based steering methods approximate reward-tilted target distributions in a principled way, but their proposals remain largely tied to the base sampler. Since reward information is mainly used after propagation through particle reweighting and resampling,
Inference-Time Alignment of Diffusion Models via Trust-Region Iterative Twisted Sequential Monte Carlo
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cs.AI, q-bio.NC updates on arXiv.org
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Strat-Reasoner: Reinforcing Strategic Reasoning of LLMs in Multi-Agent Games
arXiv:2605.04906v2 Announce Type: replace Abstract: While Large Language Models (LLMs) excel in certain reasoning tasks, they struggle in multi-agent games where the final outcome depends on the joint strategies of all agents. In multi-agent games, the non-stationarity of other agents brings significant challenges on the evaluation of the reasoning process and the credit assignment over multiple reasoning steps. Existing single-agent reinforcement learning (RL) approaches and their multi-agent
Strat-Reasoner: Reinforcing Strategic Reasoning of LLMs in Multi-Agent Games
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cs.AI, q-bio.NC updates on arXiv.org
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JAEGER: Joint 3D Audio-Visual Grounding and Reasoning in Simulated Physical Environments
arXiv:2602.18527v2 Announce Type: replace-cross Abstract: Current audio-visual large language models (AV-LLMs) are predominantly restricted to 2D perception, relying on RGB video and monaural audio. This design choice introduces a fundamental dimensionality mismatch that precludes reliable source localization and spatial reasoning in complex 3D environments. We address this limitation by presenting JAEGER, a framework that extends AV-LLMs to 3D space, to enable joint spatial grounding and reaso
JAEGER: Joint 3D Audio-Visual Grounding and Reasoning in Simulated Physical Environments
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cs.AI, q-bio.NC updates on arXiv.org
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Safety in Embodied AI: A Survey of Risks, Attacks, and Defenses
arXiv:2605.02900v2 Announce Type: replace-cross Abstract: Embodied Artificial Intelligence (Embodied AI) integrates perception, cognition, planning, and interaction into agents that operate in open-world, safety-critical environments. As these systems gain autonomy and enter domains such as transportation, healthcare, and industrial or assistive robotics, ensuring their safety becomes both technically challenging and socially indispensable. Unlike digital AI systems, embodied agents must act un
Safety in Embodied AI: A Survey of Risks, Attacks, and Defenses
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cs.AI, q-bio.NC updates on arXiv.org
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Fill the GAP: A Granular Alignment Paradigm for Visual Reasoning in Multimodal Large Language Models
arXiv:2605.12374v4 Announce Type: replace-cross Abstract: Visual latent reasoning lets a multimodal large language model (MLLM) create intermediate visual evidence as continuous tokens, avoiding external tools or image generators. However, existing methods usually follow an output-as-input latent paradigm and yield unstable gains. We identify evidence for a feature-space mismatch that can contribute to this instability: dominant visual-latent models build on pre-norm MLLMs and reuse decoder hid
Fill the GAP: A Granular Alignment Paradigm for Visual Reasoning in Multimodal Large Language Models
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npj Digital Medicine
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Personalized neoadjuvant treatment regimen selection in locally advanced rectal cancer based on regimen-specific response modeling
npj Digital Medicine, Published online: 26 May 2026; doi:10.1038/s41746-026-02798-wPersonalized neoadjuvant treatment regimen selection in locally advanced rectal cancer based on regimen-specific response modeling
Personalized neoadjuvant treatment regimen selection in locally advanced rectal cancer based on regimen-specific response modeling
npj Digital Medicine, Published online: 26 May 2026; doi:10.1038/s41746-026-02798-w
Personalized neoadjuvant treatment regimen selection in locally advanced rectal cancer based on regimen-specific response modeling-
cs.AI, q-bio.NC updates on arXiv.org
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A Learning-Based Cooperative Coevolution Framework for Heterogeneous Large-Scale Global Optimization
arXiv:2604.01241v1 Announce Type: cross Abstract: Cooperative Coevolution (CC) effectively addresses Large-Scale Global Optimization (LSGO) via decomposition but struggles with the emerging class of Heterogeneous LSGO (H-LSGO) problems arising from real-world applications, where subproblems exhibit diverse dimensions and distinct landscapes. The prevailing CC paradigm, relying on a fixed low-dimensional optimizer, often fails to navigate this heterogeneity. To address this limitation, we propos
A Learning-Based Cooperative Coevolution Framework for Heterogeneous Large-Scale Global Optimization
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cs.AI, q-bio.NC updates on arXiv.org
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ExpertFlow: Efficient Mixture-of-Experts Inference via Predictive Expert Caching and Token Scheduling
arXiv:2410.17954v2 Announce Type: replace Abstract: Sparse Mixture-of-Experts (MoE) models can outperform dense large language models at similar computation by activating only a small set of experts per token. However, stacking many expert modules introduces substantial parameter memory, which makes MoE models difficult to deploy in memory-constrained environments such as single-GPU devices. Offloading alleviates this issue by storing inactive experts in CPU memory and loading them on demand, b
ExpertFlow: Efficient Mixture-of-Experts Inference via Predictive Expert Caching and Token Scheduling
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cs.AI, q-bio.NC updates on arXiv.org
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Trace2Skill: Distill Trajectory-Local Lessons into Transferable Agent Skills
arXiv:2603.25158v3 Announce Type: replace Abstract: Equipping Large Language Model (LLM) agents with domain-specific skills is critical for tackling complex tasks. Yet, manual authoring creates a severe scalability bottleneck. Conversely, automated skill generation often yields fragile or fragmented results because it either relies on shallow parametric knowledge or sequentially overfits to non-generalizable trajectory-local lessons. To overcome this, we introduce Trace2Skill, a framework that
Trace2Skill: Distill Trajectory-Local Lessons into Transferable Agent Skills
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Nature - Issue - nature.com science feeds
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Dual-symmetry-guided assembly of complex lattices
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10364-3A dual-symmetry-guided strategy is used to assemble a broad class of complex Archimedean lattices and two-dimensional quasicrystalline structures, providing a general and experimentally accessible route to complex-symmetry materials.
Dual-symmetry-guided assembly of complex lattices
Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10364-3
A dual-symmetry-guided strategy is used to assemble a broad class of complex Archimedean lattices and two-dimensional quasicrystalline structures, providing a general and experimentally accessible route to complex-symmetry materials.