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SPTLC2-driven sphingolipid reprogramming of neutrophils impairs anti-tumour immunity and drives liver cancer progression

Oncogene, Published online: 28 September 2026; doi:10.1038/s41388-026-03996-2

SPTLC2-driven sphingolipid reprogramming of neutrophils impairs anti-tumour immunity and drives liver cancer progression

Author Correction: Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours

Nature Biomedical Engineering, Published online: 10 September 2026; doi:10.1038/s41551-026-01810-8

Author Correction: Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours

L2IR: Revealing Latent Intent in Graph Fraud Detection

arXiv:2605.26040v1 Announce Type: new Abstract: Graph fraud detection has long depended on Graph Neural Networks (GNNs) to propagate and aggregate information across relational data. A critical obstacle in practice, however, is that fraudsters frequently disguise themselves by forging numerous connections with benign users, causing fraud signals to be progressively diluted during neighborhood aggregation and undermining detection reliability. While recent efforts have used Large Language Models (LLMs) to provide rich semantic cues for fraud detection, the underlying intent behind suspicious connections remains insufficiently explored. Compounding this issue, the scarcity of annotated fraud samples makes it difficult to train detectors that remain robust under heavy camouflage. To address these gaps, we propose L2IR, an LLM-driven Latent Intent Revealing framework for graph fraud detection. By uncovering latent intent from both user behaviors and suspicious connections, L2IR extracts intent-aware representations from raw behavioral traces and reasons about the true purpose behind individual connections, effectively distinguishing supportive links from misleading ones. It further incorporates adaptive self-training to enhance robustness under limited supervision. Evaluations on two real-world datasets characterized by pervasive camouflage demonstrate that L2IR surpasses strong baselines and can function as a plug-in enhancement for a range of GNN-based detectors, improving AUPRC by up to 8.27%.

Agent Learning via Early Experience

arXiv:2510.08558v3 Announce Type: replace Abstract: A long-term goal of language agents is to learn and improve through their own experience, ultimately outperforming humans in complex, real-world tasks. However, training agents from experience data with reinforcement learning remains difficult in many environments, which either lack verifiable rewards (e.g., websites) or require inefficient long-horizon rollouts (e.g., multi-turn tool use). As a result, most current agents rely on supervised fine-tuning on expert data, which is challenging to scale and generalizes poorly. This limitation stems from the nature of expert demonstrations: they capture only a narrow range of scenarios, and expose the agent to limited environment diversity. We address this limitation with a middle-ground paradigm we call early experience: interaction data generated by the agent's own actions, where the resulting future states serve as supervision without reward signals. Within this paradigm, we study two strategies of using such data: (1) implicit world modeling, which uses collected states to ground the policy in environment dynamics; and (2) self-reflection, where the agent learns from its suboptimal actions to improve reasoning and decision-making. Evaluation across eight diverse environments and multiple model families shows that our approaches consistently improve effectiveness and out-of-domain generalization, highlighting the value of early experience. Moreover, in environments with verifiable rewards, our results provide promising signals that early experience offers a strong foundation for subsequent reinforcement learning, making it a practical bridge between imitation learning and fully experience-driven agents.

ProcCtrlBench: Evaluating Process-Level Defects and Control Preservation in LLM Coding Agents

arXiv:2605.20251v4 Announce Type: replace-cross Abstract: Existing benchmarks for LLM coding agents primarily evaluate final outcomes. While useful for measuring overall capability, these metrics provide limited visibility and often miss defects that arise during execution. We present ProcCtrlBench, a benchmark for execution-process evaluation in LLM coding agents. ProcCtrlBench organizes recurrent execution defects into a reusable ontology covering 11 defect types in 4 categories, and evaluates agent trajectories through standardized process evidence rather than final outcomes alone. To support comparison across heterogeneous agents, ProcCtrlBench standardizes raw logs into a unified trajectory representation and reports calibrated scorecards over process-level findings. In addition, ProcCtrlBench uses control preservation as a way to quantify execution-process quality, capturing whether execution remains interpretable, interruptible, correctable, reversible, and able to hand back authority when needed. We evaluate ProcCtrlBench on 200 cases sampled from three benchmarks: AndroidBench, TerminalBench, and SWE-bench-Verified. Results show that ProcCtrlBench can be instantiated with useful reliability, provides more stable semantics than direct thresholding, and reveals meaningful differences in execution quality that are often overlooked by conventional outcome-based evaluation.

A framework for building a synthetic cell from the SynCell Asia Initiative

Nature Biotechnology, Published online: 26 May 2026; doi:10.1038/s41587-026-03153-w

Building a living cell from scratch requires overcoming a bottleneck that has remained unresolved despite decades of progress: orchestrating the spatiotemporal integration of core functional modules. To tackle this barrier, the SynCell Asia Initiative outlines a strategy for developing core functional modules followed by their systems-level integration through the establishment of a centralized, artificial intelligence (AI)-driven biofoundry.

Electric dipole moment drives the dynamics of the TNFR1 complex I signalosome

Nature, Published online: 01 April 2026; doi:10.1038/s41586-026-10304-1

Long-range interactions mediated by protein electric dipole moments have a role in driving the assembly and disassembly of super-signalling complex I for promoting NF-κB signalling.

Integrative Multi-omics Analysis of Buti Huatan Tang in Chronic Obstructive Pulmonary Disease

J Vis Exp. 2026 Mar 13;(229). doi: 10.3791/70383.

ABSTRACT

This study utilized a multi-omics and computational biology framework to investigate the therapeutic potential of the Traditional Chinese Medicine (TCM) formula Buti Huatan Tang (BTHTT) against chronic obstructive pulmonary disease (COPD). Significant physiological improvements were observed in a rat model following BTHTT intervention. Histological analysis showed a reversal of lung pathological damage, while biochemical assays, and transcriptomics confirmed the normalization of IL-1β and IL-1R2 levels. Additionally, metabolic profiling revealed that BTHTT corrected disruptions in T3 and T4 thyroid hormone levels. A negative correlation was observed between the IL-1β/IL-1R2 axis and these thyroid hormones, indicating that their regulation is associated with the formula's therapeutic effect. Beyond direct measurements, machine learning algorithms identified ten COPD signature genes from clinical databases. Pathway enrichment analysis suggests that BTHTT may act through cytokine-cytokine-receptor interactions and thyroid hormone synthesis pathways. Furthermore, while 283 components were identified in vivo, compounds such as tanshinone IIA and cryptotanshinone are currently considered candidate active substances. Their role as primary drivers is supported by a model in which they stably bind to IL-1R2; this inference is based on molecular docking and molecular dynamics (MD) simulations rather than direct experimental isolation. Overall, the data support a model in which BTHTT exerts a multi-target effect on COPD by modulating inflammation and metabolic homeostasis. This integrated approach provides a refined scientific basis for the clinical application of BTHTT and highlights specific pathways for future experimental validation.

PMID:41911070 | DOI:10.3791/70383

Integrative Multi-omics Analysis of Buti Huatan Tang in Chronic Obstructive Pulmonary Disease

J Vis Exp. 2026 Mar 13;(229). doi: 10.3791/70383.

ABSTRACT

This study utilized a multi-omics and computational biology framework to investigate the therapeutic potential of the Traditional Chinese Medicine (TCM) formula Buti Huatan Tang (BTHTT) against chronic obstructive pulmonary disease (COPD). Significant physiological improvements were observed in a rat model following BTHTT intervention. Histological analysis showed a reversal of lung pathological damage, while biochemical assays, and transcriptomics confirmed the normalization of IL-1β and IL-1R2 levels. Additionally, metabolic profiling revealed that BTHTT corrected disruptions in T3 and T4 thyroid hormone levels. A negative correlation was observed between the IL-1β/IL-1R2 axis and these thyroid hormones, indicating that their regulation is associated with the formula's therapeutic effect. Beyond direct measurements, machine learning algorithms identified ten COPD signature genes from clinical databases. Pathway enrichment analysis suggests that BTHTT may act through cytokine-cytokine-receptor interactions and thyroid hormone synthesis pathways. Furthermore, while 283 components were identified in vivo, compounds such as tanshinone IIA and cryptotanshinone are currently considered candidate active substances. Their role as primary drivers is supported by a model in which they stably bind to IL-1R2; this inference is based on molecular docking and molecular dynamics (MD) simulations rather than direct experimental isolation. Overall, the data support a model in which BTHTT exerts a multi-target effect on COPD by modulating inflammation and metabolic homeostasis. This integrated approach provides a refined scientific basis for the clinical application of BTHTT and highlights specific pathways for future experimental validation.

PMID:41911070 | DOI:10.3791/70383

DreamAudio: Customized Text-to-Audio Generation with Diffusion Models

arXiv:2509.06027v2 Announce Type: replace-cross Abstract: With the development of large-scale diffusion-based and language-modeling-based generative models, impressive progress has been achieved in text-to-audio generation. Despite producing high-quality outputs, existing text-to-audio models mainly aim to generate semantically aligned sound and fall short of controlling fine-grained acoustic characteristics of specific sounds. As a result, users who need specific sound content may find it difficult to generate the desired audio clips. In this paper, we present DreamAudio for customized text-to-audio generation (CTTA). Specifically, we introduce a new framework that is designed to enable the model to identify auditory information from user-provided reference concepts for audio generation. Given a few reference audio samples containing personalized audio events, our system can generate new audio samples that include these specific events. In addition, two types of datasets are developed for training and testing the proposed systems. The experiments show that DreamAudio generates audio samples that are highly consistent with the customized audio features and aligned well with the input text prompts. Furthermore, DreamAudio offers comparable performance in general text-to-audio tasks. We also provide a human-involved dataset containing audio events from real-world CTTA cases as the benchmark for customized generation tasks.

Deep Expert Injection for Anchoring Retinal VLMs with Domain-Specific Knowledge

arXiv:2603.07131v1 Announce Type: cross Abstract: Large Vision Language Models (LVLMs) show immense potential for automated ophthalmic diagnosis. However, their clinical deployment is severely hindered by lacking domain-specific knowledge. In this work, we identify two structural deficiencies hindering reliable medical reasoning: 1) the Perception Gap, where general-purpose visual encoders fail to resolve fine-grained pathological cues (e.g., microaneurysms); and 2) the Reasoning Gap, where sparse visual evidence is progressively overridden by massive language priors in deeper transformer layers, leading to ungrounded hallucinations. To bridge these gaps, we propose EyExIn, a data-efficient framework designed to anchor retinal VLMs with expert knowledge via a Deep Expert Injection mechanism. Our architecture employs an Expert-Aware Dual-Stream encoding strategy that decouples visual representation into a general stream for anatomical context and a specialized expert stream for pathological semantics. To ensure high-fidelity integration, we design a Semantic-Adaptive Gated Fusion module, which dynamically amplifies subtle lesion signals while filtering irrelevant background noise. Furthermore, we introduce Adaptive Deep Expert Injection to embed persistent "Vision Anchors" by integrating fused visual features as residual biases directly into intermediate LLM layers. This mechanism creates a visual shortcut that forces the reasoning stack to remain strictly grounded in visual evidence. Extensive experiments across four benchmarks demonstrate that our model consistently outperforms massive proprietary systems. EyExIn significantly enhances domain-specific knowledge embedding and achieves state-of-the-art precision in ophthalmic visual question answering, advancing the development of trustworthy ophthalmic AI.

Arginine methylation-dependent stabilization of SUV39H1 promotes breast cancer growth

Oncogene, Published online: 07 March 2026; doi:10.1038/s41388-026-03712-0

Arginine methylation-dependent stabilization of SUV39H1 promotes breast cancer growth

Pretrained Vision-Language-Action Models are Surprisingly Resistant to Forgetting in Continual Learning

arXiv:2603.03818v1 Announce Type: cross Abstract: Continual learning is a long-standing challenge in robot policy learning, where a policy must acquire new skills over time without catastrophically forgetting previously learned ones. While prior work has extensively studied continual learning in relatively small behavior cloning (BC) policy models trained from scratch, its behavior in modern large-scale pretrained Vision-Language-Action (VLA) models remains underexplored. In this work, we found that pretrained VLAs are remarkably resistant to forgetting compared with smaller policy models trained from scratch. Simple Experience Replay (ER) works surprisingly well on VLAs, sometimes achieving zero forgetting even with a small replay data size. Our analysis reveals that pretraining plays a critical role in downstream continual learning performance: large pretrained models mitigate forgetting with a small replay buffer size while maintaining strong forward learning capabilities. Furthermore, we found that VLAs can retain relevant knowledge from prior tasks despite performance degradation during learning new tasks. This knowledge retention enables rapid recovery of seemingly forgotten skills through finetuning. Together, these insights imply that large-scale pretraining fundamentally changes the dynamics of continual learning, enabling models to continually acquire new skills over time with simple replay. Code and more information can be found at https://ut-austin-rpl.github.io/continual-vla
  • ✇cs.AI, q-bio.NC updates on arXiv.org
  • ToolRLA: Multiplicative Reward Decomposition for Tool-Integrated Agents Pengbo Liu
    arXiv:2603.01620v2 Announce Type: replace Abstract: Tool-integrated agents that interleave reasoning with API calls are promising for complex tasks, yet aligning them for high-stakes, domain-specific deployment remains challenging: existing reinforcement learning approaches rely on coarse binary rewards that cannot distinguish tool selection errors from malformed parameters. We present ToolRLA, a three-stage post-training pipeline (SFT $\rightarrow$ GRPO $\rightarrow$ DPO) for domain-specific t
     

ToolRLA: Multiplicative Reward Decomposition for Tool-Integrated Agents

arXiv:2603.01620v2 Announce Type: replace Abstract: Tool-integrated agents that interleave reasoning with API calls are promising for complex tasks, yet aligning them for high-stakes, domain-specific deployment remains challenging: existing reinforcement learning approaches rely on coarse binary rewards that cannot distinguish tool selection errors from malformed parameters. We present ToolRLA, a three-stage post-training pipeline (SFT $\rightarrow$ GRPO $\rightarrow$ DPO) for domain-specific tool agents. The core contribution is a fine-grained reward function with multiplicative correctness decomposition spanning four dimensions -- format validity, tool selection, parameter accuracy, and regulatory compliance -- that encodes domain priority orderings as inductive biases in the reward landscape. Deployed on a financial advisory copilot (80+ advisors, 1,200+ daily queries), ToolRLA achieves over three months: a 47\% improvement in task completion rate ($62\%\rightarrow91\%$), a 63\% reduction in tool invocation errors ($38\%\rightarrow14\%$), and a 93\% reduction in regulatory violations ($12\%\rightarrow0.8\%$), within sub-2-second latency. Ablation studies show the multiplicative reward design accounts for 7 percentage points of improvement over additive alternatives. Generalization is further validated on ToolBench and API-Bank.

Vision-Zero: Scalable VLM Self-Improvement via Strategic Gamified Self-Play

arXiv:2509.25541v2 Announce Type: replace-cross Abstract: Although reinforcement learning (RL) has emerged as a promising approach for improving vision-language models (VLMs) and multimodal large language models (MLLMs), current methods rely heavily on manually curated datasets and costly human verification, which limits scalable self-improvement in multimodal systems. To address this challenge, we propose Vision-Zero, a label-free, domain-agnostic multi-agent self-play framework for self-evolving VLMs through competitive visual games generated from arbitrary image inputs. Specifically, Vision-Zero encompasses three main attributes: (1) Strategic Self-Play Framework: Vision-Zero trains VLMs in "Who Is the Spy"-style games, where the models engage in strategic reasoning and actions across multiple roles. Through interactive gameplay, models autonomously generate their training data without human annotation. (2) Gameplay from Arbitrary Images: Unlike existing gamified frameworks, Vision-Zero can generate games from arbitrary images, thereby enhancing the model's reasoning ability across diverse domains and showing strong generalization to different tasks. We demonstrate this versatility using three distinct types of image datasets: CLEVR-based synthetic scenes, charts, and real-world images. (3) Sustainable Performance Gain: We introduce Iterative Self-Play Policy Optimization (Iterative-SPO), a novel training algorithm that alternates between Self-Play and reinforcement learning with verifiable rewards (RLVR), mitigating the performance plateau often seen in self-play-only training and achieving sustained long-term improvements. Despite using label-free data, Vision-Zero achieves state-of-the-art performance on reasoning, chart question answering, and vision-centric understanding tasks, surpassing other annotation-based methods. Models and code have been released at https://github.com/wangqinsi1/Vision-Zero.

Improving Discrete Optimisation Via Decoupled Straight-Through Estimator

arXiv:2410.13331v2 Announce Type: replace-cross Abstract: The Straight-Through Estimator (STE) is the dominant method for training neural networks with discrete variables, enabling gradient-based optimisation by routing gradients through a differentiable surrogate. However, existing STE variants conflate two fundamentally distinct concerns: forward-pass stochasticity, which controls exploration and latent space utilisation, and backward-pass gradient dispersion i.e how learning signals are distributed across categories. We show that these concerns are qualitatively different and that tying them to a single temperature parameter leaves significant performance gains untapped. We propose Decoupled Straight-Through (Decoupled ST), a minimal modification that introduces separate temperatures for the forward pass ($\tau_f$) and the backward pass ($\tau_b$). This simple change enables independent tuning of exploration and gradient dispersion. Across three diverse tasks (Stochastic Binary Networks, Categorical Autoencoders, and Differentiable Logic Gate Networks), Decoupled ST consistently outperforms Identity STE, Softmax STE, and Straight-Through Gumbel-Softmax. Crucially, optimal $(\tau_f, \tau_b)$ configurations lie far off the diagonal $\tau_f = \tau_b$, confirming that the two concerns do require different answers and that single-temperature methods are fundamentally constrained.

Step 3.5 Flash: Open Frontier-Level Intelligence with 11B Active Parameters

arXiv:2602.10604v2 Announce Type: replace-cross Abstract: We introduce Step 3.5 Flash, a sparse Mixture-of-Experts (MoE) model that bridges frontier-level agentic intelligence and computational efficiency. We focus on what matters most when building agents: sharp reasoning and fast, reliable execution. Step 3.5 Flash pairs a 196B-parameter foundation with 11B active parameters for efficient inference. It is optimized with interleaved 3:1 sliding-window/full attention and Multi-Token Prediction (MTP-3) to reduce the latency and cost of multi-round agentic interactions. To reach frontier-level intelligence, we design a scalable reinforcement learning framework that combines verifiable signals with preference feedback, while remaining stable under large-scale off-policy training, enabling consistent self-improvement across mathematics, code, and tool use. Step 3.5 Flash demonstrates strong performance across agent, coding, and math tasks, achieving 85.4% on IMO-AnswerBench, 86.4% on LiveCodeBench-v6 (2024.08-2025.05), 88.2% on tau2-Bench, 69.0% on BrowseComp (with context management), and 51.0% on Terminal-Bench 2.0, comparable to frontier models such as GPT-5.2 xHigh and Gemini 3.0 Pro. By redefining the efficiency frontier, Step 3.5 Flash provides a high-density foundation for deploying sophisticated agents in real-world industrial environments.

Cautious Optimizers: Improving Training with One Line of Code

arXiv:2411.16085v4 Announce Type: replace-cross Abstract: AdamW has been the default optimizer for transformer pretraining. For many years, our community searched for faster and more stable optimizers with only constrained positive outcomes. In this work, we propose a \textbf{one-line modification in Pytorch} to any momentum-based optimizer, which we rename cautious optimizer, e.g. C-AdamW and C-Lion. Our theoretical result shows that this modification preserves Adam's Hamiltonian function and it does not break the convergence guarantee under the Lyapunov analysis. In addition, a whole new family of optimizers is revealed by our theoretical insight. Among them, we pick the simplest one for empirical experiments, showing not only consistent speed-up on LLM pretraining, but also image classification, with minimum extra tuning on hyperparameters. Code is available at https://github.com/kyleliang919/C-Optim.
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