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MMSDH facilitates ACSL4 propionylation to counteract ferroptosis upon hypoxia and impairs PDAC chemotherapy efficacy

Nature Cancer, Published online: 11 September 2026; doi:10.1038/s43018-026-01236-w

Zheng et al. describe how hypoxia-induced methylmalonate semialdehyde dehydrogenase lactylation promotes acyl-CoA synthetase long-chain family member 4 propionylation and degradation, thereby suppressing ferroptosis induced by chemotherapy, and develop a blocking peptide that increased chemotherapy efficacy in pancreatic ductal adenocarcinoma.

StructBreak: Structural Cognitive Overload-Induced Safety Failures in MLLMs

arXiv:2605.25534v1 Announce Type: new Abstract: Multimodal Large Language Models (MLLMs) excel at structural reasoning yet suffer from a sharp logical brittleness in structural consistency. We term this phenomenon Structural Cognitive Overload (SCO), a byproduct of the contention between deep reasoning and safety alignment. However, prior work has predominantly targeted typographic and pixel-level perturbations, leaving the study of SCO largely unexplored. To this end, we propose StructBreak, an automated end-to-end framework designed to quantify SCO. By leveraging StructBreak, we uncover a novel higher-order cognitive overload attack paradigm; notably, this attack operates under a practical black-box setting, requiring no internal model access. Consequently, we utilize this framework to establish a comprehensive benchmark spanning ten diverse threat scenarios. Empirical evaluations on six leading MLLMs reveal that SCO readily triggers toxic generation, yielding a 92% average ASR (up to 97% on Gemini 2.5). To elucidate the mechanism of SCO, we further conduct model-level interpretations spanning attention dynamics, latent space topology, and geometric analysis. Our findings reveal that StructBreak acts as a novel structural channel to circumvent safety filters. Furthermore, the limited efficacy of inherent safety mechanisms underscores that current alignment paradigms are insufficient for the era of complex multimodal reasoning.

Scaling Teams or Scaling Time? Memory Enabled Lifelong Learning in LLM Multi-Agent Systems

arXiv:2604.03295v1 Announce Type: cross Abstract: Large language model (LLM) multi-agent systems can scale along two distinct dimensions: by increasing the number of agents and by improving through accumulated experience over time. Although prior work has studied these dimensions separately, their interaction under realistic cost constraints remains unclear. In this paper, we introduce a conceptual scaling view of multi-agent systems that jointly considers team size and lifelong learning ability, and we study how memory design shares this landscape. To this end, we propose \textbf{LLMA-Mem}, a lifelong memory framework for LLM multi-agent systems under flexible memory topologies. We evaluate LLMA-Mem on \textsc{MultiAgentBench} across coding, research, and database environments. Empirically, LLMA-Mem consistently improves long-horizon performance over baselines while reducing cost. Our analysis further reveals a non-monotonic scaling landscape: larger teams do not always produce better long-term performance, and smaller teams can outperform larger ones when memory better supports the reuse of experience. These findings position memory design as a practical path for scaling multi-agent systems more effectively and more efficiently over time.

GPA: Learning GUI Process Automation from Demonstrations

arXiv:2604.01676v2 Announce Type: replace-cross Abstract: GUI Process Automation (GPA) is a lightweight but general vision-based Robotic Process Automation (RPA), which enables fast and stable process replay with only a single demo. Addressing the fragility of traditional RPA and the non-deterministic risks of current vision language model-based GUI agents, GPA introduces three core benefits: (1) Robustness via Sequential Monte Carlo-based localization to handle rescaling and detection uncertainty; (2) Deterministic and Reliability safeguarded by readiness calibration; and (3) Privacy through fast, fully local execution. This approach delivers the adaptability, robustness, and security required for enterprise workflows. It can also be used as an MCP/CLI tool by other agents with coding capabilities so that the agent only reasons and orchestrates while GPA handles the GUI execution. We conducted a pilot experiment to compare GPA with Gemini 3 Pro (with CUA tools) and found that GPA achieves higher success rate with 10 times faster execution speed in finishing long-horizon GUI tasks.

GPA: Learning GUI Process Automation from Demonstrations

arXiv:2604.01676v1 Announce Type: cross Abstract: GUI Process Automation (GPA) is a lightweight but general vision-based Robotic Process Automation (RPA), which enables fast and stable process replay with only a single demo. Addressing the fragility of traditional RPA and the non-deterministic risks of current vision language model-based GUI agents, GPA introduces three core benefits: (1) Robustness via Sequential Monte Carlo-based localization to handle rescaling and detection uncertainty; (2) Deterministic and Reliability safeguarded by readiness calibration; and (3) Privacy through fast, fully local execution. This approach delivers the adaptability, robustness, and security required for enterprise workflows. It can also be used as an MCP/CLI tool by other agents with coding capabilities so that the agent only reasons and orchestrates while GPA handles the GUI execution. We conducted a pilot experiment to compare GPA with Gemini 3 Pro (with CUA tools) and found that GPA achieves higher success rate with 10 times faster execution speed in finishing long-horizon GUI tasks.

Confidence Calibration under Ambiguous Ground Truth

arXiv:2603.22879v1 Announce Type: cross Abstract: Confidence calibration assumes a unique ground-truth label per input, yet this assumption fails wherever annotators genuinely disagree. Post-hoc calibrators fitted on majority-voted labels, the standard single-label targets used in practice, can appear well-calibrated under conventional evaluation yet remain substantially miscalibrated against the underlying annotator distribution. We show that this failure is structural: under simplifying assumptions, Temperature Scaling is biased toward temperatures that underestimate annotator uncertainty, with true-label miscalibration increasing monotonically with annotation entropy. To address this, we develop a family of ambiguity-aware post-hoc calibrators that optimise proper scoring rules against the full label distribution and require no model retraining. Our methods span progressively weaker annotation requirements: Dirichlet-Soft leverages the full annotator distribution and achieves the best overall calibration quality across settings; Monte Carlo Temperature Scaling with a single annotation per example (MCTS S=1) matches full-distribution calibration across all benchmarks, demonstrating that pre-aggregated label distributions are unnecessary; and Label-Smooth Temperature Scaling (LS-TS) operates with voted labels alone by constructing data-driven pseudo-soft targets from the model's own confidence. Experiments on four benchmarks with real multi-annotator distributions (CIFAR-10H, ChaosNLI) and clinically-informed synthetic annotations (ISIC~2019, DermaMNIST) show that Dirichlet-Soft reduces true-label ECE by 55-87% relative to Temperature Scaling, while LS-TS reduces ECE by 9-77% without any annotator data.

3DCity-LLM: Empowering Multi-modality Large Language Models for 3D City-scale Perception and Understanding

arXiv:2603.23447v1 Announce Type: cross Abstract: While multi-modality large language models excel in object-centric or indoor scenarios, scaling them to 3D city-scale environments remains a formidable challenge. To bridge this gap, we propose 3DCity-LLM, a unified framework designed for 3D city-scale vision-language perception and understanding. 3DCity-LLM employs a coarse-to-fine feature encoding strategy comprising three parallel branches for target object, inter-object relationship, and global scene. To facilitate large-scale training, we introduce 3DCity-LLM-1.2M dataset that comprises approximately 1.2 million high-quality samples across seven representative task categories, ranging from fine-grained object analysis to multi-faceted scene planning. This strictly quality-controlled dataset integrates explicit 3D numerical information and diverse user-oriented simulations, enriching the question-answering diversity and realism of urban scenarios. Furthermore, we apply a multi-dimensional protocol based on text-similarity metrics and LLM-based semantic assessment to ensure faithful and comprehensive evaluations for all methods. Extensive experiments on two benchmarks demonstrate that 3DCity-LLM significantly outperforms existing state-of-the-art methods, offering a promising and meaningful direction for advancing spatial reasoning and urban intelligence. The source code and dataset are available at https://github.com/SYSU-3DSTAILab/3D-City-LLM.

MemReward: Graph-Based Experience Memory for LLM Reward Prediction with Limited Labels

arXiv:2603.19310v2 Announce Type: replace-cross Abstract: Recent advances in large language models (LLMs) have been driven by reinforcement-learning-based post-training, which requires multiple rollouts with rewards. However, obtaining ground truth labels for the calculation of rewards on a scale often requires expensive human labeling or time-consuming verification procedures. For instance, evaluating mathematical proofs demands expert review, and open-ended question answering lacks definitive ground truth. When ground truth labels are scarce, the effectiveness of reinforcement learning fine-tuning can be constrained. We introduce MemReward, a graph-based experience memory framework: an initial LLM policy generates rollouts for each query, each comprising a thinking process and a final answer, and these rollouts are stored as experience memory. Queries, thinking processes, and answers form nodes in a heterogeneous graph with similarity and structural edges; a GNN trained on labeled rollouts propagates rewards to unlabeled rollouts during online optimization. Experiments on Qwen2.5-3B and 1.5B in mathematics, question answering, and code generation demonstrate that MemReward, with only 20% labels, achieves 97.3% of Oracle performance on 3B and 96.6% on 1.5B, surpassing Oracle in out-of-domain tasks. Performance scales smoothly with label budget, reaching 99.4% of Oracle at 70% labels.

A clinical environment simulator for dynamic AI evaluation

Nature Medicine, Published online: 12 March 2026; doi:10.1038/s41591-026-04252-6

The authors propose a framework for clinical AI evaluation within simulated digital hospital environments that capture the evolving constraints, and cascading effects, of clinical decisions.
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