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Efficient amyloid-β degradation in Alzheimer’s disease using SPYTACs

SPYTAC is a synthetic peptide-programmed targeted protein degradation platform harnessing LRP1 to drive lysosomal degradation of extracellular amyloid-β in the brain and periphery. In 5×FAD mice, SPYTAC treatment efficiently degrades amyloid-β, preserves neurons, and improves cognition with reduced neuroinflammation and microhemorrhage when compared with antibody therapy.

Med-CMR: A Fine-Grained Benchmark Integrating Visual Evidence and Clinical Logic for Medical Complex Multimodal Reasoning

arXiv:2512.00818v2 Announce Type: replace Abstract: MLLMs MLLMs are beginning to appear in clinical workflows, but their ability to perform complex medical reasoning remains unclear. We present Med-CMR, a fine-grained Medical Complex Multimodal Reasoning benchmark. Med-CMR distinguishes from existing counterparts by three core features: 1) Systematic capability decomposition, splitting medical multimodal reasoning into fine-grained visual understanding and multi-step reasoning to enable targeted evaluation; 2) Challenging task design, with visual understanding across three key dimensions (small-object detection, fine-detail discrimination, spatial understanding) and reasoning covering four clinically relevant scenarios (temporal prediction, causal reasoning, long-tail generalization, multi-source integration); 3) Broad, high-quality data coverage, comprising 20,653 Visual Question Answering (VQA) pairs spanning 11 organ systems and 12 imaging modalities, validated via a rigorous two-stage (human expert + model-assisted) review to ensure clinical authenticity. We evaluate 18 state-of-the-art MLLMs with Med-CMR, revealing GPT-5 as the top-performing commercial model: 57.81 accuracy on multiple-choice questions (MCQs) and a 48.70 open-ended score, outperforming Gemini 2.5 Pro (49.87 MCQ accuracy, 45.98 open-ended score) and leading open-source model Qwen3-VL-235B-A22B (49.34 MCQ accuracy, 42.62 open-ended score). However, specialized medical MLLMs do not reliably outperform strong general models, and long-tail generalization emerges as the dominant failure mode. Med-CMR thus provides a stress test for visual-reasoning integration and rare-case robustness in medical MLLMs, and a rigorous yardstick for future clinical systems.

Thinking in Streaming Video

arXiv:2603.12938v1 Announce Type: cross Abstract: Real-time understanding of continuous video streams is essential for interactive assistants and multimodal agents operating in dynamic environments. However, most existing video reasoning approaches follow a batch paradigm that defers reasoning until the full video context is observed, resulting in high latency and growing computational cost that are incompatible with streaming scenarios. In this paper, we introduce ThinkStream, a framework for streaming video reasoning based on a Watch--Think--Speak paradigm that enables models to incrementally update their understanding as new video observations arrive. At each step, the model performs a short reasoning update and decides whether sufficient evidence has accumulated to produce a response. To support long-horizon streaming, we propose Reasoning-Compressed Streaming Memory (RCSM), which treats intermediate reasoning traces as compact semantic memory that replaces outdated visual tokens while preserving essential context. We further train the model using a Streaming Reinforcement Learning with Verifiable Rewards scheme that aligns incremental reasoning and response timing with the requirements of streaming interaction. Experiments on multiple streaming video benchmarks show that ThinkStream significantly outperforms existing online video models while maintaining low latency and memory usage. Code, models and data will be released at https://github.com/johncaged/ThinkStream

Latilactobacillus curvatus IM01 Alleviates Allergic Airway Inflammation Through Microbial and Metabolic Crosstalk Along the Gut-Lung Axis

Nutrients. 2026 Mar 4;18(5):834. doi: 10.3390/nu18050834.

ABSTRACT

Background: Gut microbiota dysbiosis is critically implicated in the pathogenesis of allergic airway inflammation (AAI) via the gut-lung axis. While Latilactobacillus curvatus is a promising probiotic candidate, its specific immunomodulatory mechanisms in respiratory diseases remain poorly understood. Objective: In this study, we investigated the protective effects and underlying mechanisms of L. curvatus IM01 in an ovalbumin (OVA)-induced murine AAI model using an integrated multi-omics approach. Results: Our results demonstrated that oral administration of L. curvatus IM01 significantly attenuated airway inflammation, suppressed Th2-type immune responses, and reduced serum IgE levels. Crucially, our multi-omics integration revealed a coherent gut-lung axis narrative driven by microbial and metabolic crosstalk. Specifically, 16S rRNA sequencing indicated that L. curvatus IM01 was closely linked to structural shifts in the gut microbial community, notably characterized by an enrichment trend for beneficial genera such as Odoribacter and Lactobacillus. This microbial restructuring was closely associated with a modulated cecal metabolic profile, as untargeted metabolomics exhibited a clear trend toward the restoration of key systemically active immunoregulatory metabolites, including indolelactic acid (ILA) and choline, which have been previously linked to the alleviation of AAI symptoms. Further linking this metabolic shift to respiratory immune tolerance, lung transcriptomic analysis showed that the treatment is strongly associated with the promotion of the differentiation of CD4+ T cells into Foxp3+ regulatory T cells (Tregs). Conclusions: Collectively, these findings suggest a novel potential pathway by which L. curvatus IM01 modulates the gut-lung axis through coordinated microbial and metabolic interventions, highlighting its potential as a therapeutic functional food ingredient for AAI.

PMID:41830004 | PMC:PMC12987261 | DOI:10.3390/nu18050834

Latilactobacillus curvatus IM01 Alleviates Allergic Airway Inflammation Through Microbial and Metabolic Crosstalk Along the Gut-Lung Axis

Nutrients. 2026 Mar 4;18(5):834. doi: 10.3390/nu18050834.

ABSTRACT

Background: Gut microbiota dysbiosis is critically implicated in the pathogenesis of allergic airway inflammation (AAI) via the gut-lung axis. While Latilactobacillus curvatus is a promising probiotic candidate, its specific immunomodulatory mechanisms in respiratory diseases remain poorly understood. Objective: In this study, we investigated the protective effects and underlying mechanisms of L. curvatus IM01 in an ovalbumin (OVA)-induced murine AAI model using an integrated multi-omics approach. Results: Our results demonstrated that oral administration of L. curvatus IM01 significantly attenuated airway inflammation, suppressed Th2-type immune responses, and reduced serum IgE levels. Crucially, our multi-omics integration revealed a coherent gut-lung axis narrative driven by microbial and metabolic crosstalk. Specifically, 16S rRNA sequencing indicated that L. curvatus IM01 was closely linked to structural shifts in the gut microbial community, notably characterized by an enrichment trend for beneficial genera such as Odoribacter and Lactobacillus. This microbial restructuring was closely associated with a modulated cecal metabolic profile, as untargeted metabolomics exhibited a clear trend toward the restoration of key systemically active immunoregulatory metabolites, including indolelactic acid (ILA) and choline, which have been previously linked to the alleviation of AAI symptoms. Further linking this metabolic shift to respiratory immune tolerance, lung transcriptomic analysis showed that the treatment is strongly associated with the promotion of the differentiation of CD4+ T cells into Foxp3+ regulatory T cells (Tregs). Conclusions: Collectively, these findings suggest a novel potential pathway by which L. curvatus IM01 modulates the gut-lung axis through coordinated microbial and metabolic interventions, highlighting its potential as a therapeutic functional food ingredient for AAI.

PMID:41830004 | PMC:PMC12987261 | DOI:10.3390/nu18050834

Mozi: Governed Autonomy for Drug Discovery LLM Agents

arXiv:2603.03655v1 Announce Type: new Abstract: Tool-augmented large language model (LLM) agents promise to unify scientific reasoning with computation, yet their deployment in high-stakes domains like drug discovery is bottlenecked by two critical barriers: unconstrained tool-use governance and poor long-horizon reliability. In dependency-heavy pharmaceutical pipelines, autonomous agents often drift into irreproducible trajectories, where early-stage hallucinations multiplicatively compound into downstream failures. To overcome this, we present Mozi, a dual-layer architecture that bridges the flexibility of generative AI with the deterministic rigor of computational biology. Layer A (Control Plane) establishes a governed supervisor--worker hierarchy that enforces role-based tool isolation, limits execution to constrained action spaces, and drives reflection-based replanning. Layer B (Workflow Plane) operationalizes canonical drug discovery stages -- from Target Identification to Lead Optimization -- as stateful, composable skill graphs. This layer integrates strict data contracts and strategic human-in-the-loop (HITL) checkpoints to safeguard scientific validity at high-uncertainty decision boundaries. Operating on the design principle of ``free-form reasoning for safe tasks, structured execution for long-horizon pipelines,'' Mozi provides built-in robustness mechanisms and trace-level audibility to completely mitigate error accumulation. We evaluate Mozi on PharmaBench, a curated benchmark for biomedical agents, demonstrating superior orchestration accuracy over existing baselines. Furthermore, through end-to-end therapeutic case studies, we demonstrate Mozi's ability to navigate massive chemical spaces, enforce stringent toxicity filters, and generate highly competitive in silico candidates, effectively transforming the LLM from a fragile conversationalist into a reliable, governed co-scientist.

High-order Knowledge Based Network Controllability Robustness Prediction: A Hypergraph Neural Network Approach

arXiv:2603.02265v1 Announce Type: cross Abstract: In order to evaluate the invulnerability of networks against various types of attacks and provide guidance for potential performance enhancement as well as controllability maintenance, network controllability robustness (NCR) has attracted increasing attention in recent years. Traditionally, controllability robustness is determined by attack simulations, which are computationally time-consuming and only applicable to small-scale networks. Although some machine learning-based methods for predicting network controllability robustness have been proposed, they mainly focus on pairwise interactions in complex networks, and the underlying relationships between high-order structural information and controllability robustness have not been explored. In this paper, a dual hypergraph attention neural network model based on high-order knowledge (NCR-HoK) is proposed to accomplish robustness learning and controllability robustness curve prediction. Through a node feature encoder, hypergraph construction with high-order relations, and a dedicated dual hypergraph attention module, the proposed method can effectively learn three types of network information simultaneously: explicit structural information in the original graph, high-order connection information in local neighborhoods, and hidden features in the embedding space. Notably, we explore for the first time the impact of high-order knowledge on network controllability robustness. Compared with state-of-the-art methods for network robustness learning, the proposed method achieves superior performance on both synthetic and real-world networks with low computational overhead.
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