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Chronic Ileitis Ameliorates Hyperglycemia via a 3-HB/NKX6.1 Axis in Mice

Mol Cell Endocrinol. 2026 Sep 24:112920. doi: 10.1016/j.mce.2026.112920. Online ahead of print.

ABSTRACT

Clinical evidence suggests a complex link between inflammatory bowel disease and systemic glucose homeostasis, yet the underlying molecular mechanisms remain elusive. Here, we report that chronic ileitis, induced by dextran sulfate sodium (DSS) or IL10 deficiency under a high-fat diet(HFD), paradoxically ameliorates systemic glucose intolerance and preserves pancreatic Ξ²-cell mass in mice. Multi-omics analysis of ileal contents revealed a specific enrichment of Akkermansia muciniphila (AKK) and elevated levels of the metabolite 3-hydroxybutyrate (3-HB). Mechanistically, 3-HB activated HCAR2/CREB-associated signaling and increased NKX6.1 expression. NKX6.1 loss-of-function markedly attenuated 3-HB-induced insulin gene expression and glucose-stimulated insulin secretion, establishing NKX6.1 as an important functional mediator of the Ξ²-cell response to 3-HB. Furthermore, exogenous administration of 3-HB recapitulated these protective effects in diabetic mice. This study identifies a novel gut-islet axis where microbiota-derived 3-HB preserves Ξ²-cell functional identity via HCAR2 dependent regulation of NKX6.1, offering a potential therapeutic strategy for type 2 diabetes.

PMID:42785509 | DOI:10.1016/j.mce.2026.112920

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RASA: Routing-Aware Safety Alignment for Mixture-of-Experts Models

arXiv:2602.04448v2 Announce Type: replace-cross Abstract: Mixture-of-Experts (MoE) language models introduce unique challenges for safety alignment due to their sparse routing mechanisms, which can enable degenerate optimization behaviors under standard full-parameter fine-tuning. In our preliminary experiments, we observe that naively applying full-parameter safety fine-tuning to MoE models can reduce attack success rates through routing or expert dominance effects, rather than by directly repairing Safety-Critical Experts. To address this challenge, we propose RASA, a routing-aware expert-level alignment framework that explicitly repairs Safety-Critical Experts while preventing routing-based bypasses. RASA identifies experts disproportionately activated by successful jailbreaks, selectively fine-tunes only these experts under fixed routing, and subsequently enforces routing consistency with safety-aligned contexts. Across two representative MoE architectures and a diverse set of jailbreak attacks, RASA achieves near-perfect robustness, strong cross-attack generalization, and substantially reduced over-refusal, while preserving general capabilities on benchmarks such as MMLU, GSM8K, and TruthfulQA. Our results suggest that robust MoE safety alignment benefits from targeted expert repair rather than global parameter updates, offering a practical and architecture-preserving alternative to prior approaches.
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An Embedding-based Approach to Inconsistency-tolerant Reasoning with Inconsistent Ontologies

arXiv:2304.01664v3 Announce Type: replace Abstract: Inconsistency handling is an important issue in knowledge management. Especially in ontology engineering, logical inconsistencies may occur during ontology construction. A natural way to reason with an inconsistent ontology is to utilize the maximal consistent subsets of the ontology. However, previous studies on selecting maximum consistent subsets have rarely considered the semantics of the axioms, which may result in irrational inference. In this paper, we propose a novel approach to reasoning with inconsistent ontologies in description logics based on the embeddings of axioms. We first give a method for turning axioms into distributed semantic vectors to compute the semantic connections between the axioms. We then define an embedding-based method for selecting the maximum consistent subsets and use it to define an inconsistency-tolerant inference relation. We show the rationality of our inference relation by considering some logical properties. Finally, we conduct experiments on several ontologies to evaluate the reasoning power of our inference relation. The experimental results show that our embedding-based method can outperform existing inconsistency-tolerant reasoning methods based on maximal consistent subsets.
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