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Integrative Multi-Omics Analysis Identifies FTO as a Genetic and Epigenetic Link Between Metabolic Susceptibility and Staphylococcus aureus-Induced Airway Remodeling in Chronic Rhinosinusitis

13 April 2026 at 18:00

Chem Biol Drug Des. 2026 Apr;107(4):e70297. doi: 10.1111/cbdd.70297.

ABSTRACT

This study identifies fat mass and obesity-associated protein (FTO) as a pivotal link between metabolic predisposition and pathogenesis associated with Staphylococcus aureus in chronic rhinosinusitis (CRS). These findings were established through the application of an integrative multi-omics framework. We demonstrate that S. aureus upregulates FTO, which functions as an m6A demethylase to stabilize the Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1). This molecular axis suppresses GSK-3Ξ² and promotes Ξ²-catenin nuclear translocation, thereby driving epithelial-mesenchymal transition (EMT) and pathological mucosal remodeling. By mapping the FTO-MALAT1-GSK-3Ξ²/Ξ²-catenin signaling network, this research elucidates how metabolic susceptibility facilitates infection-triggered epithelial reprogramming. These findings establish FTO as a promising biomarker and potential therapeutic target, providing a systemic foundation for personalized CRS treatment strategies.

PMID:41973807 | DOI:10.1111/cbdd.70297

Policy Gradient with Adaptive Entropy Annealing for Continual Fine-Tuning

arXiv:2602.14078v1 Announce Type: cross Abstract: Despite their success, large pretrained vision models remain vulnerable to catastrophic forgetting when adapted to new tasks in class-incremental settings. Parameter-efficient fine-tuning (PEFT) alleviates this by restricting trainable parameters, yet most approaches still rely on cross-entropy (CE) loss, a surrogate for the 0-1 loss, to learn from new data. We revisit this choice and revive the true objective (0-1 loss) through a reinforcement learning perspective. By formulating classification as a one-step Markov Decision Process, we derive an Expected Policy Gradient (EPG) method that directly minimizes misclassification error with a low-variance gradient estimation. Our analysis shows that CE can be interpreted as EPG with an additional sample-weighting mechanism: CE encourages exploration by emphasizing low-confidence samples, while EPG prioritizes high-confidence ones. Building on this insight, we propose adaptive entropy annealing (aEPG), a training strategy that transitions from exploratory (CE-like) to exploitative (EPG-like) learning. aEPG-based methods outperform CE-based methods across diverse benchmarks and with various PEFT modules. More broadly, we evaluate various entropy regularization methods and demonstrate that lower entropy of the output prediction distribution enhances adaptation in pretrained vision models.
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