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Local lactate-driven H3K18 lactylation impairs anti-influenza immunity through NRF2-dependent dendritic cell dysfunction

Cell Rep. 2026 Sep 3;45(9):117943. doi: 10.1016/j.celrep.2026.117943. Online ahead of print.

ABSTRACT

Metabolic alterations are increasingly recognized during influenza virus infection, but how local lactate accumulation shapes antiviral immunity remains poorly characterized. By integrating time-series targeted energy metabolomics, single-cell RNA sequencing, flow cytometry, and functional perturbation, we show that influenza virus infection preferentially increases lactate within the lung microenvironment, where it restrains pulmonary CD8+ T cell response. Mechanistically, extracellular lactate enters dendritic cells through monocarboxylate transporter (MCT)-dependent transport and induces a tolerogenic-like state marked by impaired maturation, reduced costimulation, and diminished CD8+ T cell-priming capacity. Direct experimental evidence identifies H3K18la as a prominent lactate-responsive histone lactylation mark, while multi-omics integration links it to enhancer accessibility and NRF2 pathway activation. Functional studies further show that NRF2 promotes dendritic cell suppression by reinforcing tolerogenic programs and limiting mtROS-dependent XBP1 splicing. Together, these findings reveal a lactate-driven histone lactylation-NRF2 pathway that modulates antiviral immunity during influenza infection.

PMID:42690934 | DOI:10.1016/j.celrep.2026.117943

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From Patterns to Policy: A Scoping Review Based on Bibliometric Analysis (ScoRBA) of Intelligent and Secure Smart Hospital Ecosystems

arXiv:2603.30004v1 Announce Type: new Abstract: This study examines the evolution of Intelligent and Secure Smart Hospital Ecosystems using a Scoping Review with Bibliometric Analysis (ScoRBA) to map research patterns, identify gaps, and derive policy implications. Analyzing 891 journal articles from Scopus (2006-2025) through co-occurrence analysis, network visualization, overlay analysis, and the Enhanced Strategic Diagram (ESD), the study applies the PAGER framework to link Patterns, Advances, Gaps, Research directions, and Evidence-based policy implications. Findings reveal three interrelated clusters: AI-driven intelligent healthcare systems, decentralized privacy-preserving digital health ecosystems, and scalable cloud-edge infrastructures, showing a convergence toward integrated ecosystem architectures where intelligence, trust, and infrastructure reinforce each other. Despite progress in AI, blockchain, and cloud computing, gaps remain in interoperability, real-world implementation, governance, and cross-layer integration. Emerging themes such as explainable AI, federated learning, and privacy mechanisms highlight areas needing further research. Policy-relevant recommendations focus on coordinated governance, scalable infrastructure, and secure data ecosystems, particularly for developing country contexts. The study bridges bibliometric evidence with actionable policies, supporting informed decision-making in smart hospital development.
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Understanding vs. Generation: Navigating Optimization Dilemma in Multimodal Models

arXiv:2602.15772v2 Announce Type: replace-cross Abstract: Current research in multimodal models faces a key challenge where enhancing generative capabilities often comes at the expense of understanding, and vice versa. We analyzed this trade-off and identify the primary cause might be the potential conflict between generation and understanding, which creates a competitive dynamic within the model. To address this, we propose the Reason-Reflect-Refine (R3) framework. This innovative algorithm re-frames the single-step generation task into a multi-step process of "generate-understand-regenerate". By explicitly leveraging the model's understanding capability during generation, we successfully mitigate the optimization dilemma, achieved stronger generation results and improved understanding ability which are related to the generation process. This offers valuable insights for designing next-generation unified multimodal models. Code is available at https://github.com/sen-ye/R3.
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