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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.

AdaRoPE: Not All Attention Heads Should Rotate and Scale Equally

arXiv:2607.19363v3 Announce Type: replace Abstract: Rotary Position Embedding (RoPE) is widely adopted in Transformers to encode positional information, yet standard implementations enforce a uniform frequency schedule and scaling across all attention heads. Using simplified retrieval tasks and length generalization scenarios, we show -- both empirically and theoretically -- that heads with different functional roles require distinct frequency ranges and attention scaling factors to operate effectively. Ignoring this structure leads to suboptimal utilization of embedding dimensions and degraded performance, particularly under long-context settings. To address these limitations, we propose AdaRoPE, which equips each attention head with learnable rotation frequencies and attention scaling factors. Pretrained LLMs with AdaRoPE consistently outperform existing RoPE variants, including partial RoPE and NoPE baselines. For context extension, we further show that uniform frequency and attention scaling, used in methods such as YaRN, are suboptimal. By applying head-specific scaling, AdaRoPE enables better context extension while better preserving short-context performance in both the extrapolation setting and the long-context continued pretraining setting. These results highlight the importance of optimizing rotary position embedding at the level of individual attention heads.

Gut dysbiosis, metabolic signals, and pulmonary immune reprogramming: decoding the gut microbiota -immune axis in stroke-associated pneumonia

Front Immunol. 2026 Aug 27;17:1812306. doi: 10.3389/fimmu.2026.1812306. eCollection 2026.

ABSTRACT

Stroke-associated pneumonia (SAP) is the most common infectious complication following acute stroke. The limited efficacy of conventional antimicrobial therapy suggests that SAP may be fundamentally a syndrome driven by dysregulated cross-system interactions. This review proposes the "gut microbiota-immune axis" (GMIA) as a comprehensive framework for the development of SAP and systematically discusses the potential mechanisms by which post-stroke microbial-derived metabolic signals-including short-chain fatty acids (SCFAs), bile acids, tryptophan metabolites, and endotoxins-drive systemic immune reprogramming, predisposing patients to SAP. Based on the GMIA, we highlight several promising intervention strategies, including dietary modulation, precision antibiotic use, probiotics, fecal microbiota transplantation (FMT), supplementation with microbial metabolites, and receptor-targeted therapies, and summarize the current clinical translation related to the GMIA. Future research directions require high-quality clinical trials that integrate multi-omics data from the microbiome with immune biomarkers and clinical parameters. Such an approach is essential for constructing validated risk stratification models and advancing the management of SAP from empirical anti-infective treatment toward a precision medicine model centered on GMIA-based immune modulation.

PMID:42724580 | PMC:PMC13560329 | DOI:10.3389/fimmu.2026.1812306

Sequence and structural determinants of efficacious de novo chimaeric antigen receptors

Nature Biomedical Engineering, Published online: 09 September 2026; doi:10.1038/s41551-026-01790-9

A generative protein design workflow addresses important challenges with de novo protein engineering of chimaeric antigen receptors (CARs) to improve targeting of proteins important in cancer and create more effective CAR T therapies.

ViSR-KGC: Visual Subgraph Reasoning with Vision-Language Models for Multimodal Knowledge Graph Completion

arXiv:2608.05833v3 Announce Type: replace Abstract: Knowledge graph completion (KGC) aims to infer missing entities or relations from incomplete graph structures, and has evolved into multimodal knowledge graph completion (MMKGC), where entities are associated with multiple modalities such as text and images. Traditional representation learning approaches follow the embedding-based paradigm and may struggle when relation-specific evidence is limited. Meanwhile, LLM-based reasoning methods typically linearize graph structures into textual prompts, which obscures structural topology and neglects vital visual information. While vision-language models (VLMs) excel at multimodal reasoning, they cannot natively interpret structured graph topology, particularly when it comes to knowledge graphs where nodes and edges carry complex semantics. To bridge this gap, we propose ViSR-KGC, a visual subgraph reasoning approach for KGC. It integrates three complementary capabilities to capture semantic correlations: identifying global topology dependencies via representation learning, analyzing local multimodal evidence using VLMs, and providing necessary commonsense knowledge inherent in pre-trained models. Based on learned multimodal embeddings, our framework first extracts a compact and query-aware subgraph from the MMKG. Then, this subgraph is transformed into a visually interpretable image using a layout strategy selected through empirical comparison. Finally, the visualized subgraph, entity images, textual descriptions, and candidate answers are combined into a unified prompt, enabling the VLM to infer the missing entity.

Complete biosynthesis of the anticancer cephalotaxinone and homoerythratine

Complete biosynthetic pathways for cephalotaxinone and homoerythratine were elucidated from the endangered plant Cephalotaxus fortunei. Thirteen key enzymes were identified, including two homologous cytochrome P450 enzymes that catalyze a rare divergent oxidation process governing alkaloid scaffold diversification. Full pathway reconstitution in Nicotiana benthamiana establishes a foundation for the sustainable production of the anticancer agent homoharringtonine.

VectorArk: Learning Practical Image Vectorization with Rounded Polygon Representation

arXiv:2605.24398v1 Announce Type: cross Abstract: Recent vision-language model (VLM)-based approaches have achieved impressive results on image vectorization tasks. However, they are typically evaluated on synthetic benchmarks, where clean SVGs are rasterized at high resolution and then re-vectorized. As a result, these methods generalize poorly to real-world scenarios, such as images with unknown rasterization methods or those generated by text-to-image models. We introduce VectorArk, a new VLM-based model designed for robust and practical image vectorization. VectorArk employs a novel rounded polygon representation that simplifies the learning process while naturally producing smooth, visually appealing primitives. We also propose a degradation model that enhances robustness across diverse and imperfect inputs. Our experiments show that, in contrast to previous methods, VectorArk achieves superior geometric completeness and artifact suppression across multiple datasets, with comprehensive ablations validating the contribution of each component.

Step-TP: A Grounded, Step-Level Dataset with Chain-of-Thought Reasoning for LLM-Guided Tensor Program Optimization

arXiv:2605.25954v1 Announce Type: cross Abstract: Despite the strong reasoning capabilities of large language models (LLMs), optimizing the execution efficiency of tensor programs remains challenging due to the need for precise, composable transformation decisions. Recent LLM-guided approaches frame tensor program optimization as an iterative decision process, but existing datasets provide only end-to-end optimized program pairs using token-inefficient representations, lacking verifiable step-level supervision and interpretability. As a result, LLMs struggle to make reliable single-step decisions in large combinatorial optimization spaces. We introduce Step-TP, a post-training dataset for tensor program optimization that provides grounded, atomic, step-level supervision with structured chain-of-thought (CoT) reasoning. Step-TP forms a closed reasoning loop over intermediate program states, enabling reliable multi-step optimization rather than outcome imitation. Its design is guided by four principles: (i) a token-efficient, verifiable intermediate representation (IR) that deterministically lowers to TVM TIR; (ii) atomic and composable optimization strategies that decompose complex trajectories into interpretable single-step decisions; (iii) structured CoT supervision coupled with explicit IR-to-IR state transitions; and (iv) strategy filtering to balance coverage while preventing shortcut exploitation. The dataset and implementation are available at a GitHub link, https://github.com/LIUMENGFAN-gif/StepTP.

HiTeC: Hierarchical Contrastive Learning on Text-Attributed Hypergraph with Semantic-Aware Augmentation

arXiv:2508.03104v3 Announce Type: replace-cross Abstract: Contrastive learning (CL) has become a dominant paradigm for self-supervised hypergraph learning, enabling effective training without costly labels. However, node entities in real-world hypergraphs are often associated with rich textual information, which has been largely ignored in prior works. Directly applying existing CL-based methods to such text-attributed hypergraphs (TAHGs) leads to three key limitations: (1) The common use of graph-agnostic text encoders fails to capture the correlations between textual semantics and hypergraph topology, resulting in less expressive representations. (2) Their reliance on random data augmentations introduces noise and weakens the contrastive signals. (3) The primary focus on node- and hyperedge-level contrastive signals limits the ability to capture long-range dependencies, which is essential for effective representation learning. To address these challenges, we introduce HiTeC, a two-stage hierarchical contrastive learning framework for effective self-supervised learning on TAHGs. In the first stage, we pre-train the text encoder with a structure-aware contrastive objective to overcome the graph-agnostic nature of conventional methods. In the second stage, we begin by introducing semantic-aware augmentations, including structure-contextualized text augmentation and semantic-aware hyperedge dropping, to facilitate informative view generation. Subsequently, we propose a multi-scale contrastive loss with an $s$-walk-based subgraph-level objective to capture long-range dependencies. Extensive experiments on six real-world datasets validate the effectiveness of our proposed method.

CD300ld on pathologically activated neutrophils promotes tumor immune suppression by binding phosphatidylserine on CD8<sup>+</sup> T cells

Nature Cancer, Published online: 15 May 2026; doi:10.1038/s43018-026-01169-4

Zhao and colleagues show that CD300ld, upregulated in pathologically activated neutrophils, mediates contact-dependent suppression of cytotoxic CD8+ T cells by binding to phosphatidylserine, inhibiting antitumor immune responses.

An Orally Deliverable, Food-Compatible Lyophilized Recombinant Whole-Cell Catalyst for Alcohol-Associated Liver Injury

Microorganisms. 2026 Mar 26;14(4):746. doi: 10.3390/microorganisms14040746.

ABSTRACT

Effective oral interventions for alcohol-induced metabolic stress and liver injury remain limited. Pre-absorptive gastrointestinal alcohol handling is gaining interest as a non-pharmacological strategy to reduce hepatic burden. In this study, we developed a formulation-integrated, food-compatible lyophilized recombinant whole-cell catalyst based on Escherichia coli Nissle 1917 engineered to express alcohol dehydrogenase and acetaldehyde dehydrogenase. Rather than focusing exclusively on strain-level genetic modification, the engineered cells were protected by lyophilization combined with a food-grade chitosan-alginate layer-by-layer coating, forming an artificial cell wall designed to enhance survivability during oral delivery. The formulation resisted simulated gastric acid, sodium taurocholate, and ethanol, retained enzymatic activity after storage, and demonstrated formulation stability. In alcohol-exposed mice, oral administration reduced blood ethanol and acetaldehyde levels, improved liver biochemical parameters, attenuated hepatic steatosis, and partially restored oxidative stress indicators. Integrated multi-omics analyses indicated coordinated gut-associated metabolic and inflammatory responses to alcohol and intervention, rather than a single dominant pathway. These findings provide hypothesis-generating evidence; causality remains to be established. Overall, this study demonstrates a proof-of-concept, food-compatible lyophilized recombinant whole-cell catalyst that integrates enzymatic function with formulation stability and gastrointestinal resilience, highlighting an applied, food-compatible microbial framework for exploring alcohol-related metabolic stress.

PMID:42075143 | PMC:PMC13119499 | DOI:10.3390/microorganisms14040746

Respiratory viral infections prime accelerated lung cancer growth

Severe COVID-19 is associated with an increased subsequent risk of lung cancer. Viral pneumonia induces durable lung epigenetic imprinting that promotes tumor-supportive neutrophils and impairs T cell immunity, which is reversible with combined CXCR2 inhibition and PD-L1 blockade.

Asymmetric selection of a rice immune module and rebuild of disease resistance

Nature, Published online: 08 April 2026; doi:10.1038/s41586-026-10361-6

Stacking XA48-mediated effector-triggered immunity with XA21-mediated pattern-triggered immunity in Oryza sativa japonica reconstitutes the broad-spectrum resistance from wild rice.

TSPO: Breaking the Double Homogenization Dilemma in Multi-turn Search Policy Optimization

arXiv:2601.22776v2 Announce Type: replace Abstract: Multi-turn tool-integrated reasoning enables Large Language Models (LLMs) to solve complex tasks through iterative information retrieval. However, current reinforcement learning (RL) frameworks for search-augmented reasoning predominantly rely on sparse outcome-level rewards, leading to a "Double Homogenization Dilemma." This manifests as (1) Process homogenization, where the thinking, reasoning, and tooling involved in generation are ignored. (2) Intra-group homogenization, coarse-grained outcome rewards often lead to inefficiencies in intra-group advantage estimation with methods like Group Relative Policy Optimization (GRPO) during sampling. To address this, we propose Turn-level Stage-aware Policy Optimization (TSPO). TSPO introduces the First-Occurrence Latent Reward (FOLR) mechanism, allocating partial rewards to the step where the ground-truth answer first appears, thereby preserving process-level signals and increasing reward variance within groups without requiring external reward models or any annotations. Extensive experiments demonstrate that TSPO significantly outperforms state-of-the-art baselines, achieving average performance gains of 24% and 13.6% on Qwen2.5-3B and 7B models, respectively. Code is available at https://github.com/Flipped-May/TSPO.

Enhancing Foundation VLM Robustness to Missing Modality: Scalable Diffusion for Bi-directional Feature Restoration

arXiv:2602.03151v2 Announce Type: replace Abstract: Vision Language Model (VLM) typically assume complete modality input during inference. However, their effectiveness drops sharply when certain modalities are unavailable or incomplete. Current research on missing modality primarily faces two dilemmas: Prompt-based methods struggle to restore missing yet indispensable features and degrade the generalizability of VLM. Imputation-based approaches, lacking effective guidance, are prone to generating semantically irrelevant noise. Restoring precise semantics while sustaining VLM's generalization remains challenging. Therefore, we propose a general missing modality restoration strategy in this paper. We introduce an enhanced diffusion model as a pluggable mid-stage training module to effectively restore missing features. Our strategy introduces two key innovations: (I) Dynamic Modality Gating, which adaptively leverages conditional features to guide the generation of semantically consistent features; (II) Cross-Modal Mutual Learning mechanism, which bridges the semantic spaces of the dual models to achieve bi-directional alignment. Notably, our strategy maintains the original integrity of the pre-trained VLM, requiring no fine-tuning of the backbone models while significantly boosting resilience to information loss. Zero-shot evaluations across benchmark datasets demonstrate that our approach consistently outperforms existing baselines, establishing it as a robust and scalable extension that ensures VLM reliability across diverse missing rates and conditions. Our code and models will be publicly available.

AeroTherm-GPT: A Verification-Centered LLM Framework for Thermal Protection System Engineering Workflows

arXiv:2604.01738v1 Announce Type: new Abstract: Integrating Large Language Models (LLMs) into hypersonic thermal protection system (TPS) design is bottlenecked by cascading constraint violations when generating executable simulation artifacts. General-purpose LLMs, treating generation as single-pass text completion, fail to satisfy the sequential, multi-gate constraints inherent in safety-critical engineering workflows. To address this, we propose AeroTherm-GPT, the first TPS-specialized LLM Agent, instantiated through a Constraint-Closed-Loop Generation (CCLG) framework. CCLG organizes TPS artifact generation as an iterative workflow comprising generation, validation, CDG-guided repair, execution, and audit. The Constraint Dependency Graph (CDG) encodes empirical co-resolution structure among constraint categories, directing repair toward upstream fault candidates based on lifecycle ordering priors and empirical co-resolution probabilities. This upstream-priority mechanism resolves multiple downstream violations per action, achieving a Root-Cause Fix Efficiency of 4.16 versus 1.76 for flat-checklist repair. Evaluated on HyTPS-Bench and validated against external benchmarks, AeroTherm-GPT achieves 88.7% End-to-End Success Rate (95% CI: 87.5-89.9), a gain of +12.5 pp over the matched non-CDG ablation baseline, without catastrophic forgetting on scientific reasoning and code generation tasks.

NCCL EP: Towards a Unified Expert Parallel Communication API for NCCL

arXiv:2603.13606v3 Announce Type: replace-cross Abstract: Mixture-of-Experts (MoE) architectures have become essential for scaling large language models, driving the development of specialized device-initiated communication libraries such as DeepEP, Hybrid-EP, and others. These libraries demonstrate the performance benefits of GPU-initiated RDMA for MoE dispatch and combine operations. This paper presents NCCL EP (Expert Parallelism), a ground-up MoE communication library built entirely on NCCL's Device API. NCCL EP provides unified ncclEpDispatch and ncclEpCombine primitives with both C and Python interfaces, supporting Low-Latency (LL) mode for inference decoding and High-Throughput (HT) mode for training and inference prefill. LL targets small batch sizes (1-128 tokens) using direct all-to-all RDMA+NVLink mesh connectivity with double-buffered communication for overlapping dispatch and combine phases. HT targets large batches (4096+ tokens) using hierarchical communication that aggregates tokens within NVLink domains before inter-node RDMA transmission. Both modes leverage Device API for both intra- and inter-node communications, taking advantage of its topology awareness and optimized GPU-initiated implementation. We evaluate NCCL EP on an H100-based cluster across multi-node configurations, demonstrating competitive LL kernel performance and presenting end-to-end results with vLLM integration. By building MoE communication natively within NCCL, NCCL EP provides a supported path for expert parallelism on current and emerging NVIDIA platforms.

Ferritin aggregation cell engager for CAR T avidity engineering against refractory leukemias

Li et al. developed a ferritin aggregation cell engager that helps CAR T cells better recognize and attack leukemia cells without re-engineering the CAR itself. This versatile platform overcomes antigen modulation and enables combination with chemotherapy.

Hijacking ERAD for targeted degradation of transmembrane proteins

Development of an ERAD-hijacking technology overcomes the challenges of current targeted protein degradation approaches to achieve degradation of transmembrane proteins.
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