❌

Reading view

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

  •  

Large Language Model for Discrete Optimization Problems: Evaluation and Step-by-step Reasoning

arXiv:2603.07733v1 Announce Type: new Abstract: This work investigated the capabilities of different models, including the Llama-3 series of models and CHATGPT, with different forms of expression in solving discrete optimization problems by testing natural language datasets. In contrast to formal datasets with a limited scope of parameters, our dataset included a variety of problem types in discrete optimization problems and featured a wide range of parameter magnitudes, including instances with large parameter sets, integrated with augmented data. It aimed to (1) provide an overview of LLMs' ability in large-scale problems, (2) offer suggestions to those who want to solve discrete optimization problems automatically, and (3) regard the performance as a benchmark for future research. These datasets included original, expanded and augmented datasets. Among these three datasets, the original and augmented ones aimed for evaluation while the expanded one may help finetune a new model. In the experiment, comparisons were made between strong and week models, CoT methods and No-CoT methods on various datasets. The result showed that stronger model performed better reasonably. Contrary to general agreement, it also showed that CoT technique was not always effective regarding the capability of models and disordered datasets improved performance of models on easy to-understand problems, even though they were sometimes with high variance, a manifestation of instability. Therefore, for those who seek to enhance the automatic resolution of discrete optimization problems, it is recommended to consult the results, including the line charts presented in the Appendix, as well as the conclusions drawn in this study for relevant suggestions.
  •  

BD-Merging: Bias-Aware Dynamic Model Merging with Evidence-Guided Contrastive Learning

arXiv:2603.03920v1 Announce Type: cross Abstract: Model Merging (MM) has emerged as a scalable paradigm for multi-task learning (MTL), enabling multiple task-specific models to be integrated without revisiting the original training data. Despite recent progress, the reliability of MM under test-time distribution shift remains insufficiently understood. Most existing MM methods typically assume that test data are clean and distributionally aligned with both the training and auxiliary sources. However, this assumption rarely holds in practice, often resulting in biased predictions with degraded generalization. To address this issue, we present BD-Merging, a bias-aware unsupervised model merging framework that explicitly models uncertainty to achieve adaptive reliability under distribution shift. First, BD-Merging introduces a joint evidential head that learns uncertainty over a unified label space, capturing cross-task semantic dependencies in MM. Second, building upon this evidential foundation, we propose an Adjacency Discrepancy Score (ADS) that quantifies evidential alignment among neighboring samples. Third, guided by ADS, a discrepancy-aware contrastive learning mechanism refines the merged representation by aligning consistent samples and separating conflicting ones. Combined with general unsupervised learning, this process trains a debiased router that adaptively allocates task-specific or layer-specific weights on a per-sample basis, effectively mitigating the adverse effects of distribution shift. Extensive experiments across diverse tasks demonstrate that BD-Merging achieves superior effectiveness and robustness compared to state-of-the-art MM baselines.
  •  
❌