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Engineering human multi-organ tissue chip niches for drug absorption, distribution, metabolism, excretion and toxicity prediction

Nature Biomedical Engineering, Published online: 05 October 2026; doi:10.1038/s41551-026-01806-4

Multi-organ-on-a-chip systems aim to improve the prediction of human drug responses by replicating organ interactions in vitro. This Review discusses advances in niche-preserving engineering, scalable manufacturing and multimodal readouts needed to make these systems reliable tools.

Factor IX Padua AAV gene therapy in adolescents with hemophilia B: a phase 1 trial

Nature Medicine, Published online: 16 September 2026; doi:10.1038/s41591-026-04636-8

In this single-arm phase 1 trial, an AAV gene therapy carrying the Padua variant of factor IX was well tolerated in 11 adolescents with hemophilia B and led to reductions in annualized bleeding rate.

Pelican-Sim 1.0: A General World Model Simulator for Embodied Intelligence

arXiv:2609.12036v1 Announce Type: cross Abstract: In this technical report, we propose Pelican-Sim 1.0, a general world model simulator for embodied intelligence that predicts future observations from visual context and robot actions to support downstream learning and decision making. The model incorporates four key design features: (1) Unified action representation: a 28-dimensional action value space covering most mainstream embodiments, keeping one model valid across heterogeneous devices. (2) Action-visual injection: URDF- and camera-rendered action videos bridge actions and pixels, giving markedly better controllability across embodiments, scenes, and tasks (PSNR +0.904 over alternative fusion baselines). (3) Sparse mixture-of-experts (MoE): sparse MoE layers add capacity for heterogeneous dynamics and absorb the action modality while reducing inter-modality conflict (FVD -6.530 vs. the dense backbone). (4) Efficient rollout generation: causal adaptation and few-step distillation yield a four-step autoregressive simulator, achieving a 5.67-fold speedup over the 35-step model. Benefiting from these designs, we train on approximately one million real-world and simulated trajectories and obtain large gains in action controllability and video quality: PSNR improves over the strongest evaluated baselines by 4.636 on AgiBotWorld Beta, 2.080 on RoboMIND, and 10.343 on RoboTwin, with the adapted EWMBench DYN score up 0.426 on RoboTwin. Relying on this, four downstream applications on RoboTwin succeed: 500 generated trajectories added to 50 demonstrations per task raise policy success from 70% to 93%; policy evaluation reaches a Pearson correlation of 0.994 across five checkpoints; and relative success gains reach 47.7% for action selection and 20.3% for policy improvement. Qualitative generalization across trajectory, scene, object, embodiment, and viewpoint shifts highlights its potential as a general-purpose world model simulator.

Graph-of-Skills: Dependency-Aware Structural Retrieval for Massive Agent Skills

arXiv:2604.05333v4 Announce Type: replace Abstract: As LLM agents act across personal applications, web browsers, and other interfaces, their reusable skill libraries can scale to thousands of skills. This scale introduces two challenges. First, loading the full library saturates the context window, driving up token costs, hallucination, and latency. Second, semantic retrieval surfaces topically relevant skills but can miss upstream and downstream prerequisite skills, creating a prerequisite gap that leaves the retrieved bundle insufficient for execution. We present Graph-of-Skills (GoS), an inference-time structural retrieval layer for large skill libraries. GoS constructs an executable skill graph offline from skill packages, then retrieves a bounded, dependency-aware bundle through hybrid semantic-lexical seeding, reverse-aware Personalized PageRank, and context-budgeted hydration. Across SkillsBench and ALFWorld, with three model families (Claude Sonnet 4.5, MiniMax M2.7, and GPT-5.2 Codex), GoS attains the highest average reward in all six model-benchmark blocks, at a fraction of the token cost of loading the full library. On SkillsBench with GPT-5.2 Codex it raises average reward by 7.0 absolute points over full skill loading, a 25.6% relative gain, while cutting total tokens by 56.7%. Ablations isolate the mechanism: replacing reverse traversal with forward propagation costs 9.1 reward points, a larger loss than removing the graph altogether. The gain thus comes from traversing dependencies backwards, not from graph diffusion as such. A budget-matched retrieval study holding seeding, reranking, hydration, and context budget fixed reproduces the same ordering, with dependency-pair co-recovery falling from 0.654 to 0.362. Code is available at https://github.com/davidliuk/graph-of-skills

An ab initio foundation model of wavefunctions that accurately describes chemical bond breaking

arXiv:2506.19960v2 Announce Type: replace-cross Abstract: Reliable description of bond breaking remains a major challenge for quantum chemistry due to the multireference character of the electronic structure in dissociating species. Multireference methods in particular suffer from large computational cost, which under the normal paradigm has to be paid anew for each system at a full price, ignoring commonalities in electronic structure across molecules. Quantum Monte Carlo with deep neural networks uniquely offers to exploit such commonalities by pretraining transferable wavefunction models, but all such attempts were so far limited in scope. Here, we bring this paradigm to fruition with Orbformer, a transferable wavefunction model pretrained on 22,000 equilibrium and dissociating structures that can be fine-tuned on unseen molecules reaching an accuracy-cost ratio rivalling classical multireference methods. On established benchmarks as well as more challenging bond dissociations and Diels-Alder reactions, Orbformer is the only method that consistently converges to chemical accuracy (1 kcal/mol). This work turns the idea of amortizing the cost of solving the Schr\"odinger equation over many molecules into a practical approach in quantum chemistry.

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 closed-loop testbed that makes native visual reasoning through generation trainable, verifiable, optimizable, and experimentally controllable. 1) Task scaling. VBVR-Pro turns visual reasoning into a controlled task space of 300 procedurally generated tasks. Models trained on VBVR-Pro show strong transfer beyond the proposed suite across seven external visual reasoning benchmarks such as RISE-Video, MME-CoF-Pro, and BabyVision. 2) Verifiable rewards. VBVR-Pro provides verifiable reward scorers for task-grounded evaluation. Through a systematic study of leading MLLMs as judges, we identify recurring failure modes of the prevalent VLM-as-a-judge paradigm. In contrast, the proposed scorers are grounded in deterministic, task-specific rules, achieve fine-grained alignment with human judgments. Importantly, they serve as reliable reward signals for large-scale multi-task reinforcement learning and demonstrate stronger post-RL performance across visual reasoning tasks. 3) Mechanism study. VBVR-Pro enables controlled modality studies across more than 30 image, video, and interleaved generators. Our analysis shows that video generation remains strongest for tasks requiring persistent spatiotemporal state tracking, while interleaved generation provides a compute-efficient alternative. Critically, ablations and probing suggest the presence of vision-native trajectories that are crucial to visual reasoning. We release all data, models, scorers, and code.

Author Correction: A base editor for the long-term restoration of auditory function in mice with recessive profound deafness

Nature Biomedical Engineering, Published online: 07 September 2026; doi:10.1038/s41551-026-01794-5

Author Correction: A base editor for the long-term restoration of auditory function in mice with recessive profound deafness

AgenticGen: Reward-Guided Agentic Video Generation for Advertising

arXiv:2609.09187v1 Announce Type: cross Abstract: Advertising video generation is not only a video synthesis task, but also a product-conditioned reasoning problem whose success is measured by online business metrics. Recent video foundation models can generate realistic clips from multimodal conditions, yet they do not optimize how a product should be transformed into an effective advertisement or how future generation should be improved from online business feedback. To close this loop, we propose AgenticGen, a reward-guided agentic framework that decomposes advertising video generation into two trainable reasoning stages, strategy selection and draft generation, thereby exposing optimization targets that online business feedback can supervise. AgenticGen learns a performance-based reward from accumulated online feedback and a complementary rubric-based reward aligned with human quality standards, then uses them to supervise policy optimization. DPO first moves the agentic policies toward online preferences, and GRPO further refines both stages with process and outcome rewards. Offline experiments validate the reward models and successive policy optimization. Online A/B experiments in the TikTok advertising system show that AgenticGen after DPO and GRPO improves CTR by 2.72%, CVR by 2.63%, and Advv by 9.61% over the SFT baseline.

Reliable Near-Field Multi-User Positioning Informed by Two-Stage MUSIC

arXiv:2609.09409v1 Announce Type: cross Abstract: Near-field localization is a promising technique for high-resolution multi-user positioning in future wireless systems, but its performance is often degraded by scattering-induced coherent propagation. Existing near-field localization methods, which require separate parameter estimation and path/source association, suffer from high computation overhead and accumulated errors, and usually do not provide any guarantee on reliability. In this paper, we propose \emph{MUSIC-Net}, an end-to-end near-field positioning deep learning (DL) framework informed by two-stage MUltiple SIgnal Classification (MUSIC) in mixed line-of-sight (LoS) and non-LoS (NLoS) multi-path scenarios, which embeds the two-stage MUSIC objects into training to isolate the LoS-related signal subspace and to identify a surrogate distance. The proposed framework directly recovers multi-user positions without the need for involved NLoS parameter estimation or path/source association. Furthermore, we introduce split conformal prediction (SCP) to move beyond point-estimation-based positioning towards statistically guaranteed (confidence) set estimation for all users. Numerical results show that the proposed MUSIC-Net achieves lower mean positioning error (MPER) than existing benchmarks and yields tighter SCP-calibrated prediction regions, demonstrating both accurate LoS localization and efficient uncertainty quantification (UQ) in coherent multi-path environments.

Harbor Adapters and Harbor-Index: Infrastructure and a Curated Meta-Dataset for Large-Scale Agentic Evaluation

arXiv:2609.04298v2 Announce Type: replace Abstract: Evaluating agents on the growing number of agentic benchmarks is challenging because they often require complex environments and agent integrations. We introduce Harbor Adapters, a unified evaluation infrastructure for agentic benchmarks. Our work makes three contributions. First, we develop benchmark adapters that port more than 80 benchmarks to evaluate arbitrary agents, and validate them through rigorous code review and parity experiments. Second, we conduct a large-scale evaluation of 8 models spanning capability tiers across 54 benchmarks; every model is run with Terminus-2 and with one of 3 native harnesses. This enables a broader analysis of agent capabilities and failure modes than was previously possible. Third, we introduce Harbor-Index, a curated set of 82 difficult, diverse, and high-quality tasks spanning 29 benchmarks, refined from the adapted suite through difficulty filtering, AI and human audit, and an audit-and-fix loop. Harbor-Index preserves the challenge and breadth of large-scale agentic evaluations while being affordable to run; no evaluated model-harness configuration exceeds 30% pass rate, and the strongest (GPT-5.5 with Codex) reaches 28.0%. We release the adapters, evaluation results, in-depth analysis, and Harbor-Index as open-source artifacts to support more reliable and comprehensive evaluation of language-model agents.

RAU: Reference-based Anatomical Understanding with Vision Language Models

arXiv:2509.22404v2 Announce Type: replace-cross Abstract: Anatomical understanding, which is the ability to identify, localize, or segment anatomical structures, is critical in medical image analysis; however, its progress is constrained by the scarcity of expert-labeled data. A promising remedy is to leverage an annotated reference image to guide the interpretation of an unlabeled target. Although recent vision-language models (VLMs) exhibit non-trivial visual reasoning, their reference-based understanding and fine-grained localization remain limited. We introduce RAU, a framework for reference-based anatomical understanding with VLMs. We first show that a VLM learns to identify anatomical regions through relative spatial reasoning between reference and target images, trained on a moderately sized dataset. We validate this capability through visual question answering (VQA) and bounding box prediction. Next, we demonstrate that the VLM-derived spatial cues can be seamlessly integrated with the fine-grained segmentation capability of SAM2, enabling localization and pixel-level segmentation of small anatomical regions, such as vessel segments. Across two in-distribution and two out-of-distribution datasets, RAU consistently outperforms a SAM2 fine-tuning baseline using the same memory setup, yielding more accurate segmentations and more reliable localization. More importantly, its generalization ability to unseen modalities makes it scalable to unseen datasets, a property crucial for medical image applications. To the best of our knowledge, RAU is the first to explore the capability of VLMs for reference-based identification, localization, and segmentation of anatomical structures in medical images. Its promising performance highlights the potential of VLM-driven approaches for anatomical understanding in automated clinical workflows.

An operational perturbation proteomics-based virtual cell model

Nature, Published online: 09 September 2026; doi:10.1038/s41586-026-11001-9

Temporal protein-abundance measurements from systematically perturbed breast cancer cell lines were generated to develop ProteinTalks, a virtual cell model that functions as an operational tool for diverse drug discovery tasks.

CAFs shape the immunosuppressive microenvironment of pancreatic cancer through the Lin28b-STING Axis

Nat Commun. 2026 Aug 7;17(1):9491. doi: 10.1038/s41467-026-76495-3.

ABSTRACT

Cancer-associated fibroblasts comprise diverse functionally distinct cellular subsets, with certain subpopulations exerting pivotal influence in shaping the pancreatic cancer immune microenvironment. Here we show that Lin28b+ cancer-associated fibroblasts contribute to establishing an immunologically cold tumor microenvironment in pancreatic ductal adenocarcinoma. Mechanistically, Lin28b directly binds to STING mRNA and promotes its degradation, thereby suppressing STING expression and downstream type I interferon signaling. Loss of Lin28b in cancer-associated fibroblasts activates the cGAS-STING-interferon signaling cascade, enhancing dendritic cell antigen presentation and CD8+ T cell cytotoxic function. Importantly, genetic inhibition of Lin28b in cancer-associated fibroblasts enhances sensitivity to anti-PD-L1 immune checkpoint blockade therapy. These findings reveal that targeting the Lin28b-STING axis represents a promising therapeutic strategy for overcoming the intrinsic resistance of pancreatic ductal adenocarcinoma to immunotherapy.

PMID:42693143 | PMC:PMC13542369 | DOI:10.1038/s41467-026-76495-3

Evolutionary Enhanced Multi-Agent Reinforcement Learning for Cooperative Air Combat

arXiv:2605.25091v1 Announce Type: new Abstract: As modern air combat evolves toward beyond-visual-range (BVR) multi-aircraft cooperative engagements, autonomous decision-making for unmanned combat aerial vehicles (UCAVs) faces significant challenges due to high-dimensional state spaces, discrete action commands, and strongly adversarial dynamic environments. To overcome the limitations of existing multi-agent reinforcement learning (MARL) methods in such settings, namely insufficient exploration efficiency, low sample utilization, and poor policy generalization, we propose Adversarial Curriculum and Evolutionary-enhanced Multi-agent Proximal Policy Optimization (ACE-MAPPO), a hybrid learning framework that integrates evolutionary algorithms with MAPPO. Specifically, a genetic soft update mechanism is introduced to enhance population diversity and mitigate convergence to local optima. An evolutionary-augmented prioritized trajectory replay strategy is further employed to improve the utilization of sparse high-value samples. In addition, an adversarial evolutionary curriculum learning mechanism is designed to enable adaptive training with progressively increasing difficulty. Extensive experimental results demonstrate that the proposed method outperforms MAPPO and other baseline algorithms in terms of training stability, convergence speed, and win rate, validating its effectiveness in multi-aircraft cooperative air combat scenarios.

SimuWoB: Simulating Real-World Mobile Apps for Fast and Faithful GUI Agent Benchmarking

arXiv:2605.25160v1 Announce Type: new Abstract: Mobile GUI agents powered by large language models have progressed rapidly, creating urgent needs for realistic and comprehensive evaluation. Existing benchmarks prioritize reproducibility but are often limited to open-source apps or file-operation tasks for the difficulty of constructing rewards on real applications, leaving a gap between benchmark settings and real-world usage. Moreover, most benchmarks focus on basic grounding and navigation, with limited coverage of complex, long-horizon interactions. To address these limitations, we introduce SimuWoB, a fully synthetic benchmark for mobile GUI agents with 120 challenging tasks spanning diverse types and difficulty levels. We build a robust virtual environment generation framework that synthesizes high-fidelity tasks and environments, and automatically provides valid rewards for each task. Each environment is deployed as a backend-free webpage accessible via URL, enabling efficient and reproducible evaluation. We conduct comprehensive experiments on several state-of-the-art mobile GUI agents. The average success rate is only 27.92%, dropping to 17.82% on long-horizon tasks, which reveals substantial weaknesses in current agents under complex scenarios. Evaluation result comparison with real-world sample tasks demonstrate that agent assessments based on our synthetic environment generalize well. We further provide diagnostic insights across key capability dimensions and discuss implications for future mobile GUI agent development.

FrontierOR: Benchmarking LLMs' Capacity for Efficient Algorithm Design in Large-Scale Optimization

arXiv:2605.25246v2 Announce Type: new Abstract: Large language models (LLMs) are increasingly used for optimization modeling and solver-code generation, yet practical operations research and optimization problems often require a harder capability: designing scalable algorithms that exploit problem structure and outperform direct formulation-and-solve baselines. Existing benchmarks are limited to small or simplified examples far below real-world scale and complexity. We introduce FrontierOR, among the first benchmarks to systematically evaluate LLM-based efficient algorithm design for realistic large-scale optimization problems. FrontierOR includes 180 tasks derived from methodologically diverse papers published in top-tier operations research venues, each with standardized instances and a hidden, expert-verified evaluation suite. We evaluate seven LLMs spanning frontier, cost-effective, and open-source models both in one-shot and test-time evolution settings. The results reveal that frontier models still struggle to move from executable formulations to efficient optimization algorithms: the strongest one-shot model outperforms Gurobi in only 31% of cases in both solution quality and computational efficiency, and even strong coding agents with test-time evolution achieve only 50% on selected hard tasks. FrontierOR establishes a practical evaluation platform for LLM-based optimization algorithm design, which enables future LLMs and agents to be systematically tested on whether they can move beyond correct formulation toward a feasible, high-quality, and efficient algorithm.

A World Model of Radiologist Reading for Medical Image Representation Learning

arXiv:2605.23992v1 Announce Type: cross Abstract: Radiologist eye-tracking data provide a rich record of how experts search, compare, and accumulate evidence during image reading; yet, existing methods exploit this signal only partially, either as a static spatial prior or as an auxiliary prediction target decoupled from diagnosis. We propose GazeWorld, a medical imaging world model that treats the image as the world and the radiologist's fixation sequence as a trajectory through it. GazeWorld autoregressively predicts the latent representation of the next fixated patch from all previously visited ones, while a spatial-completion branch covers unvisited regions. At inference, GazeWorld generates a sequence of patch representations from the image alone without requiring real gaze data. Frozen GazeWorld features achieve state-of-the-art diagnostic accuracy across all nine supervised settings on CheXpert, RSNA Pneumonia, and SIIM-ACR Pneumothorax, as well as the highest zero-shot accuracy on all three benchmarks. On the GazeSearch benchmark, a generic decoder trained on the same frozen features outperforms the purpose-built LogitGaze-Med by over 16\% in ScanMatch and 22\% in SED, despite not being explicitly trained to predict gaze. GazeWorld demonstrates that modeling how experts read, not just what they conclude, offers a promising pretraining paradigm for medical imaging AI.

VisualOverload: Probing Visual Understanding of VLMs in Really Dense Scenes

arXiv:2509.25339v3 Announce Type: replace-cross Abstract: Is basic visual understanding really solved in state-of-the-art VLMs? We present VisualOverload, a slightly different visual question answering (VQA) benchmark comprising 2,720 question-answer pairs, with privately held ground-truth responses. Unlike prior VQA datasets that typically focus on near global image understanding, VisualOverload challenges models to perform simple, knowledge-free vision tasks in densely populated (or, overloaded) scenes. Our dataset consists of high-resolution scans of public-domain paintings that are populated with multiple figures, actions, and unfolding subplots set against elaborately detailed backdrops. We manually annotated these images with questions across six task categories to probe for a thorough understanding of the scene. We hypothesize that current benchmarks overestimate the performance of VLMs, and encoding and reasoning over details is still a challenging task for them, especially if they are confronted with densely populated scenes. Indeed, we observe that even the best model (o3) out of 37 tested models only achieves 19.6% accuracy on our hardest test split and overall 69.5% accuracy on all questions. Beyond a thorough evaluation, we complement our benchmark with an error analysis that reveals multiple failure modes, including a lack of counting skills, failure in OCR, and striking logical inconsistencies under complex tasks. Altogether, VisualOverload exposes a critical gap in current vision models and offers a crucial resource for the community to develop better models. Benchmark: http://paulgavrikov.github.io/visualoverload

FG-CLIP 2: A Bilingual Fine-grained Vision-Language Alignment Model

arXiv:2510.10921v3 Announce Type: replace-cross Abstract: Fine-grained vision-language understanding requires precise alignment between visual content and linguistic descriptions, a capability that remains limited in current models, particularly in non-English settings. While models like CLIP perform well on global alignment, they often struggle to capture fine-grained details in object attributes, spatial relations, and linguistic expressions, with limited support for bilingual comprehension. To address these challenges, we introduce FG-CLIP 2, a bilingual vision-language model designed to advance fine-grained alignment for both English and Chinese. Our approach leverages rich fine-grained supervision, including region-text matching and long-caption modeling, alongside multiple discriminative objectives. We further introduce the Textual Intra-modal Contrastive (TIC) loss to better distinguish semantically similar captions. Trained on a carefully curated mixture of large-scale English and Chinese data, including a newly released 12M Chinese region-text dataset, FG-CLIP 2 achieves powerful bilingual performance. To enable rigorous evaluation, we present a new benchmark for Chinese multimodal understanding, featuring long-caption retrieval and bounding box classification. Extensive experiments on 29 datasets across 8 tasks show that FG-CLIP 2 outperforms existing methods, achieving state-of-the-art results in both languages. We release the model, code, and benchmark to facilitate future research on bilingual fine-grained vision-language alignment.
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