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Leptomeningeal metastatic cancer cells induce a permissive choroid plexus vasculature through extracellular-vesicle-derived 5-HIAA signaling

Nature Cancer, Published online: 03 April 2026; doi:10.1038/s43018-026-01145-y

Huang, Hou, Yang et al. demonstrate that leptomeningeal metastatic cells favor the formation of a premetastatic niche by remodeling the choroid plexus vasculature through the serotonin metabolite 5-hydroxyindoleacetic acid, which signals into endothelial cells through the aryl hydrocarbon receptor.

Genetically encoded fluorescent reporters to visualize α-synuclein pathology in live brain

The development of genetically encoded fluorescent reporters, along with their corresponding knock-in mouse lines for labeling α-Syn inclusions, enables diverse applications in studying the propagation and pathological effects of α-Syn inclusions in the live brain.

FlowPIE: Test-Time Scientific Idea Evolution with Flow-Guided Literature Exploration

arXiv:2603.29557v1 Announce Type: new Abstract: Scientific idea generation (SIG) is critical to AI-driven autonomous research, yet existing approaches are often constrained by a static retrieval-then-generation paradigm, leading to homogeneous and insufficiently divergent ideas. In this work, we propose FlowPIE, a tightly coupled retrieval-generation framework that treats literature exploration and idea generation as a co-evolving process. FlowPIE expands literature trajectories via a flow-guided Monte Carlo Tree Search (MCTS) inspired by GFlowNets, using the quality of current ideas assessed by an LLM-based generative reward model (GRM) as a supervised signal to guide adaptive retrieval and construct a diverse, high-quality initial population. Based on this population, FlowPIE models idea generation as a test-time idea evolution process, applying selection, crossover, and mutation with the isolation island paradigm and GRM-based fitness computation to incorporate cross-domain knowledge. It effectively mitigates the information cocoons arising from over-reliance on parametric knowledge and static literature. Extensive evaluations demonstrate that FlowPIE consistently produces ideas with higher novelty, feasibility and diversity compared to strong LLM-based and agent-based frameworks, while enabling reward scaling during test time.

LatentPilot: Scene-Aware Vision-and-Language Navigation by Dreaming Ahead with Latent Visual Reasoning

arXiv:2603.29165v1 Announce Type: cross Abstract: Existing vision-and-language navigation (VLN) models primarily reason over past and current visual observations, while largely ignoring the future visual dynamics induced by actions. As a result, they often lack an effective understanding of the causal relationship between actions and how the visual world changes, limiting robust decision-making. Humans, in contrast, can imagine the near future by leveraging action-dynamics causality, which improves both environmental understanding and navigation choices. Inspired by this capability, we propose LatentPilot, a new paradigm that exploits future observations during training as a valuable data source to learn action-conditioned visual dynamics, while requiring no access to future frames at inference. Concretely, we propose a flywheel-style training mechanism that iteratively collects on-policy trajectories and retrains the model to better match the agent's behavior distribution, with an expert takeover triggered when the agent deviates excessively. LatentPilot further learns visual latent tokens without explicit supervision; these latent tokens attend globally in a continuous latent space and are carried across steps, serving as both the current output and the next input, thereby enabling the agent to dream ahead and reason about how actions will affect subsequent observations. Experiments on R2R-CE, RxR-CE, and R2R-PE benchmarks achieve new SOTA results, and real-robot tests across diverse environments demonstrate LatentPilot's superior understanding of environment-action dynamics in scene. Project page:https://abdd.top/latentpilot/

DIAL: Decoupling Intent and Action via Latent World Modeling for End-to-End VLA

arXiv:2603.29844v1 Announce Type: cross Abstract: The development of Vision-Language-Action (VLA) models has been significantly accelerated by pre-trained Vision-Language Models (VLMs). However, most existing end-to-end VLAs treat the VLM primarily as a multimodal encoder, directly mapping vision-language features to low-level actions. This paradigm underutilizes the VLM's potential in high-level decision making and introduces training instability, frequently degrading its rich semantic representations. To address these limitations, we introduce DIAL, a framework bridging high-level decision making and low-level motor execution through a differentiable latent intent bottleneck. Specifically, a VLM-based System-2 performs latent world modeling by synthesizing latent visual foresight within the VLM's native feature space; this foresight explicitly encodes intent and serves as the structural bottleneck. A lightweight System-1 policy then decodes this predicted intent together with the current observation into precise robot actions via latent inverse dynamics. To ensure optimization stability, we employ a two-stage training paradigm: a decoupled warmup phase where System-2 learns to predict latent futures while System-1 learns motor control under ground-truth future guidance within a unified feature space, followed by seamless end-to-end joint optimization. This enables action-aware gradients to refine the VLM backbone in a controlled manner, preserving pre-trained knowledge. Extensive experiments on the RoboCasa GR1 Tabletop benchmark show that DIAL establishes a new state-of-the-art, achieving superior performance with 10x fewer demonstrations than prior methods. Furthermore, by leveraging heterogeneous human demonstrations, DIAL learns physically grounded manipulation priors and exhibits robust zero-shot generalization to unseen objects and novel configurations during real-world deployment on a humanoid robot.

Robust transcriptomic hallmarks targeting intratumor heterogeneity in intrahepatic cholangiocarcinoma

Cell Rep Med. 2026 Mar 30:102708. doi: 10.1016/j.xcrm.2026.102708. Online ahead of print.

ABSTRACT

Intratumor heterogeneity (ITH) undermines transcriptome-based stratification in intrahepatic cholangiocarcinoma (iCCA). Here, we integrate multi-omics data from multi-region, single-region, and single-cell RNA sequencing cohorts to systematically characterize gene expression ITH. We uncover that immune and stromal heterogeneity are primary drivers of ITH, leading to misclassification of a median 27.8% of tumors by existing subtyping systems. To overcome this, we identify a low-intratumor-heterogeneity/high-intertumor-variability (LIHV) gene set and develop an ITH-insensitive classification system defining five subgroups: inflammatory (SI), metabolic (SII), atypical (SIII-1), immune-silent (SIII-2), and neurodegenerative (SIII-3). These subgroups exhibit distinct clinical outcomes, molecular features, immune landscapes, and therapeutic vulnerabilities. GPRC5A and VTCN1 serve as robust immunohistochemical biomarkers for SI and SIII tumors, while serum CEA and CA19-9 identify inflammatory iCCA. Therapeutically, HSP90 inhibition synergizes with anti-PD1 in inflammatory iCCA, whereas combined anti-PD1 and anti-TIM3 suppresses neurodegenerative iCCA. Collectively, our study provides a robust molecular framework and actionable therapeutic strategies for iCCA.

PMID:41916296 | DOI:10.1016/j.xcrm.2026.102708

The Yin and Yang of tertiary lymphoid structures in primary liver cancer

Cancer Lett. 2026 Mar 27;648:218461. doi: 10.1016/j.canlet.2026.218461. Online ahead of print.

ABSTRACT

Tertiary lymphoid structures (TLSs) have emerged as key regulators of anti-tumor immunity and biomarkers for immunotherapy response in liver cancer, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and combined hepatocellular-cholangiocarcinoma (cHCC-iCCA). Advances in single-cell and spatial multi-omics technologies have revealed unprecedented complexity in TLSs, challenging the traditional binary classification of TLSs as simply "good" or "bad". Their functional diversity appears to be shaped by spatiotemporal context, cellular composition, and maturation status. This review provides a comprehensive synthesis of TLSs in liver cancer, employing the Yin-Yang paradigm to navigate their functional dualism and prognostic contradictions through a detailed analysis of their identification, classification, and spatiotemporal interactions within the TME. Mechanistically, we elucidate how TLS functions are orchestrated by complex interactions between tumor cells, immune cell subsets, stromal components, and systemic factors. Within this framework, key metabolic drivers, notably ATP citrate lyase (ACLY), and signaling axes such as cGAS-STING/mTOR have emerged as pivotal regulators of TLS ontogeny. In addition, we evaluate current preclinical animal models and therapeutic strategies for clinical TLS induction. Furthermore, we have discussed the key unanswered questions in the field, including the three-dimensional architecture of TLSs and the mechanisms by which they establish durable immunological memory independent of the primary tumor. Clinically, TLSs exhibit great promise as prognostic and predictive biomarkers, particularly in the context of immune checkpoint blockade and locoregional therapies. Finally, we identify challenges in standardization, mechanistic understanding, and translational applications, providing directions for future research to harness TLSs for improving liver cancer outcomes.

PMID:41905709 | DOI:10.1016/j.canlet.2026.218461

PhySe-RPO: Physics and Semantics Guided Relative Policy Optimization for Diffusion-Based Surgical Smoke Removal

arXiv:2603.22844v2 Announce Type: new Abstract: Surgical smoke severely degrades intraoperative video quality, obscuring anatomical structures and limiting surgical perception. Existing learning-based desmoking approaches rely on scarce paired supervision and deterministic restoration pipelines, making it difficult to perform exploration or reinforcement-driven refinement under real surgical conditions. We propose PhySe-RPO, a diffusion restoration framework optimized through Physics- and Semantics-Guided Relative Policy Optimization. The core idea is to transform deterministic restoration into a stochastic policy, enabling trajectory-level exploration and critic-free updates via group-relative optimization. A physics-guided reward imposes illumination and color consistency, while a visual-concept semantic reward learned from CLIP-based surgical concepts promotes smoke-free and anatomically coherent restoration. Together with a reference-free perceptual constraint, PhySe-RPO produces results that are physically consistent, semantically faithful, and clinically interpretable across synthetic and real robotic surgical datasets, providing a principled route to robust diffusion-based restoration under limited paired supervision.

Three Creates All: You Only Sample 3 Steps

arXiv:2603.22375v1 Announce Type: cross Abstract: Diffusion models deliver high-fidelity generation but remain slow at inference time due to many sequential network evaluations. We find that standard timestep conditioning becomes a key bottleneck for few-step sampling. Motivated by layer-dependent denoising dynamics, we propose Multi-layer Time Embedding Optimization (MTEO), which freeze the pretrained diffusion backbone and distill a small set of step-wise, layer-wise time embeddings from reference trajectories. MTEO is plug-and-play with existing ODE solvers, adds no inference-time overhead, and trains only a tiny fraction of parameters. Extensive experiments across diverse datasets and backbones show state-of-the-art performance in the few-step sampling and substantially narrow the gap between distillation-based and lightweight methods. Code will be available.

Retrieval-Augmented Generation with Covariate Time Series

arXiv:2603.04951v2 Announce Type: replace Abstract: While RAG has greatly enhanced LLMs, extending this paradigm to Time-Series Foundation Models (TSFMs) remains a challenge. This is exemplified in the Predictive Maintenance of the Pressure Regulating and Shut-Off Valve (PRSOV), a high-stakes industrial scenario characterized by (1) data scarcity, (2) short transient sequences, and (3) covariate coupled dynamics. Unfortunately, existing time-series RAG approaches predominantly rely on generated static vector embeddings and learnable context augmenters, which may fail to distinguish similar regimes in such scarce, transient, and covariate coupled scenarios. To address these limitations, we propose RAG4CTS, a regime-aware, training-free RAG framework for Covariate Time-Series. Specifically, we construct a hierarchal time-series native knowledge base to enable lossless storage and physics-informed retrieval of raw historical regimes. We design a two-stage bi-weighted retrieval mechanism that aligns historical trends through point-wise and multivariate similarities. For context augmentation, we introduce an agent-driven strategy to dynamically optimize context in a self-supervised manner. Extensive experiments on PRSOV demonstrate that our framework significantly outperforms state-of-the-art baselines in prediction accuracy. The proposed system is deployed in Apache IoTDB within China Southern Airlines. Since deployment, our method has successfully identified one PRSOV fault in two months with zero false alarm.

Metaphor-based Jailbreak Attacks on Text-to-Image Models

arXiv:2512.10766v2 Announce Type: replace-cross Abstract: Text-to-image (T2I) models commonly incorporate defense mechanisms to prevent the generation of sensitive images. Unfortunately, recent jailbreak attacks have shown that adversarial prompts can effectively bypass these mechanisms and induce T2I models to produce sensitive content, revealing critical safety vulnerabilities. However, existing attack methods implicitly assume that the attacker knows the type of deployed defenses, which limits their effectiveness against unknown or diverse defense mechanisms. In this work, we reveal an underexplored vulnerability of T2I models to metaphor-based jailbreak attacks (MJA), which aims to attack diverse defense mechanisms without prior knowledge of their type by generating metaphor-based adversarial prompts. Specifically, MJA consists of two modules: an LLM-based multi-agent generation module (LMAG) and an adversarial prompt optimization module (APO). LMAG decomposes the generation of metaphor-based adversarial prompts into three subtasks: metaphor retrieval, context matching, and adversarial prompt generation. Subsequently, LMAG coordinates three LLM-based agents to generate diverse adversarial prompts by exploring various metaphors and contexts. To enhance attack efficiency, APO first trains a surrogate model to predict the attack results of adversarial prompts and then designs an acquisition strategy to adaptively identify optimal adversarial prompts. Extensive experiments on T2I models with various external and internal defense mechanisms demonstrate that MJA achieves stronger attack performance while using fewer queries, compared with six baseline methods. Additionally, we provide an in-depth vulnerability analysis suggesting that metaphor-based adversarial prompts evade safety mechanisms by inducing semantic ambiguity, while sensitive images arise from the model's probabilistic interpretation of concealed semantics.

Vision-DeepResearch: Incentivizing DeepResearch Capability in Multimodal Large Language Models

arXiv:2601.22060v3 Announce Type: replace-cross Abstract: Multimodal large language models (MLLMs) have achieved remarkable success across a broad range of vision tasks. However, constrained by the capacity of their internal world knowledge, prior work has proposed augmenting MLLMs by ``reasoning-then-tool-call'' for visual and textual search engines to obtain substantial gains on tasks requiring extensive factual information. However, these approaches typically define multimodal search in a naive setting, assuming that a single full-level or entity-level image query and few text query suffices to retrieve the key evidence needed to answer the question, which is unrealistic in real-world scenarios with substantial visual noise. Moreover, they are often limited in the reasoning depth and search breadth, making it difficult to solve complex questions that require aggregating evidence from diverse visual and textual sources. Building on this, we propose Vision-DeepResearch, which proposes one new multimodal deep-research paradigm, i.e., performs multi-turn, multi-entity and multi-scale visual and textual search to robustly hit real-world search engines under heavy noise. Our Vision-DeepResearch supports dozens of reasoning steps and hundreds of engine interactions, while internalizing deep-research capabilities into the MLLM via cold-start supervision and RL training, resulting in a strong end-to-end multimodal deep-research MLLM. It substantially outperforming existing multimodal deep-research MLLMs, and workflows built on strong closed-source foundation model such as GPT-5, Gemini-2.5-pro and Claude-4-Sonnet. The code will be released in https://github.com/Osilly/Vision-DeepResearch.

Tuning the sensitivity of mechanosensory receptors through histidine scanning

Histidine scanning represents a broadly applicable technique for the identification of critical interaction sites within TCRs and other mechanosensory receptors to enhance receptor signaling strength and augment therapeutic efficacy via the catch bond mechanism.

From Text to Forecasts: Bridging Modality Gap with Temporal Evolution Semantic Space

arXiv:2603.12664v1 Announce Type: cross Abstract: Incorporating textual information into time-series forecasting holds promise for addressing event-driven non-stationarity; however, a fundamental modality gap hinders effective fusion: textual descriptions express temporal impacts implicitly and qualitatively, whereas forecasting models rely on explicit and quantitative signals. Through controlled semi-synthetic experiments, we show that existing methods over-attend to redundant tokens and struggle to reliably translate textual semantics into usable numerical cues. To bridge this gap, we propose TESS, which introduces a Temporal Evolution Semantic Space as an intermediate bottleneck between modalities. This space consists of interpretable, numerically grounded temporal primitives (mean shift, volatility, shape, and lag) extracted from text by an LLM via structured prompting and filtered through confidence-aware gating. Experiments on four real-world datasets demonstrate up to a 29 percent reduction in forecasting error compared to state-of-the-art unimodal and multimodal baselines. The code will be released after acceptance.

Multi-Omics and Single-Cell Mendelian Randomization Reveal a Potential Role of VNN2 in Lung Adenocarcinoma in Resting Natural Killer Cells

World J Oncol. 2026 Mar 5;17(2):247-255. doi: 10.14740/wjon2689. eCollection 2026 Apr.

ABSTRACT

BACKGROUND: We aimed to evaluate the potential association between genetically predicted vanin-2 (VNN2) expression and lung adenocarcinoma (LUAD) risk, and to explore the immune cell subtype that may underlie this relationship.

METHODS: We integrated whole-blood expression quantitative trait loci (eQTL) data from eQTLGen, plasma protein quantitative trait loci (pQTL) data from deCODE, and LUAD genome-wide association study (GWAS) data from European-ancestry cohorts, together with differential expression analysis using GEPIA2, to identify candidate genes for subsequent single-cell eQTL (sc-eQTL) Mendelian randomization (MR) analysis. For the sc-eQTL analysis, VNN2-associated eQTLs from 14 immune cell types profiled in the OneK1K single-cell eQTL resource were tested for associations with LUAD risk.

RESULTS: Bulk-level MR analysis showed that genetically predicted increases in VNN2 expression and protein levels were significantly associated with a reduced risk of LUAD (eQTL-MR: odds ratio (OR) = 0.964, 95% confidence interval (95% CI), 0.934-0.995; P = 0.024; pQTL-MR: OR = 0.946, 95% CI, 0.921-0.970; P = 2.87 × 10-5). Transcriptomic analyses confirmed significant downregulation of VNN2 in LUAD tumors compared with normal lung tissues. sc-eQTL MR identified the strongest association in resting natural killer (rNK) cells (OR = 0.896, 95% CI, 0.829-0.967; P = 0.005).

CONCLUSIONS: Multi-omics and sc-eQTL MR analyses indicated that genetically predicted increases in VNN2 expression were associated with a reduced risk of LUAD, with the most pronounced effect observed in rNK cells. These findings suggest a potential cell type-specific role of VNN2 in LUAD susceptibility and warrant further studies to validate its biological relevance and clinical implications.

PMID:41822323 | PMC:PMC12978397 | DOI:10.14740/wjon2689

Profiling of the mycobiome and metabolome: a comparative study of benign pulmonary nodules and lung adenocarcinoma

Front Cell Infect Microbiol. 2026 Feb 23;16:1732958. doi: 10.3389/fcimb.2026.1732958. eCollection 2026.

ABSTRACT

INTRODUCTION: Lung adenocarcinoma (LUAD), the most common subtype of non-small cell lung cancer, is a form of malignant pulmonary nodule that requires clinical differentiation from benign pulmonary nodules (BPN). The mechanisms underlying the development of LUAD are complex, and effective non-invasive methods for differentiating BPN from LUAD are lacking. This study aimed not only to distinguish BPN from LUAD using gut fungi and serum metabolites, but also to establish an integrated network of gut fungi-metabolite-cytokine interactions.

METHODS: Fecal and serum samples from individuals with BPN and patients with LUAD were subjected to internal transcribed spacer sequencing, ultra-performance liquid chromatography-tandem mass spectrometry, and multiplex Luminex assays to quantify gut fungi, metabolites, and cytokines, respectively.

RESULTS: A significant difference in gut fungal communities was observed between the BPN and LUAD groups. Multiple genera and species were more abundant in LUAD than in BPN. Docosapentaenoic acid n-6 (DPAn-6), indole-3-propionic acid (IPA), and interferon-γ-induced protein 10 (IP-10) were significantly elevated in the LUAD group. The integrated model established using a combination of gut fungi and metabolites demonstrated excellent performance in distinguishing BPN from LUAD. A network of interactions was established among differentially abundant gut fungi, serum metabolites, and cytokines.

CONCLUSION: Our study identifies a novel panel of fungal and metabolite biomarkers for differentiating between BPN and LUAD, and constructs a multi-omics network that provides new insights into investigating the mechanistic role of gut mycobiota dysbiosis in LUAD.

PMID:41809995 | PMC:PMC12968269 | DOI:10.3389/fcimb.2026.1732958

Facile induction of immune tolerance by an interleukin-2–TGFβ surrogate agonist

Nature, Published online: 11 March 2026; doi:10.1038/s41586-026-10208-0

A fusion protein designed to comprise IL-2 and a helminth-derived TGFβ mimic activates IL-2 and TGFβ signalling pathways in IL-2 receptor-expressing T cells and induces stable antigen-specific regulatory T cells in peripheral lymphoid organs.

Risk-adaptive therapy guided by dynamic ctDNA in nasopharyngeal carcinoma

Nature, Published online: 11 March 2026; doi:10.1038/s41586-026-10244-w

A clinical trial testing whether monitoring ctDNA clearance during treatment for nasopharyngeal cancer could be used to inform decisions about an individual’s subsequent therapeutic programme shows promising results.
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