数据日期 2026-10-29 · 生成时间 2026-10-29 06:03
证据级别：摘要级。本条依据 PubMed 结构化摘要与元数据撰写，付费墙全文未获取、未逐节核验，本站未做任何数值推算补全。
研究问题
The molecular mechanisms linking type 2 diabetes to increased neurodegenerative risk remain poorly defined.
方法
Given the critical involvement of microglial dysfunction in neurodegeneration, we constructed a temporal single-cell atlas integrating transcriptomic and epigenomic profiles of microglia from diabetic (db/db) and control (db/m) mice across the lifespan.
核心结论
We delineated a nonlinear, diabetes-specific pathological trajectory characterized by early inflammatory activation, a mid-stage inflection in neurodegeneration-associated signaling and metabolic stress, and late-stage dysfunction.；Chromatin accessibility profiling revealed early and persistent epigenomic priming of neurodegeneration-associated pathways, accompanied by stage-specific enhancer rewiring.；Pseudotime analysis identified a disease-associated microglial (DAM) state as a candidate transition node, characterized by biased polarization and accelerated maturation under diabetic conditions.；Targeted validation using freshly isolated microglia and primary microglial cultures further supported the early expansion of the DAM population, a bias toward homeostatic-to-DAM activation, and Arhgap15-dependent regulation of phagocytic… ‖ 结论：Targeted validation using freshly isolated microglia and primary microglial cultures further supported the early expansion of the DAM population, a bias toward homeostatic-to-DAM activation, and Arhgap15-dependent regulation of phagocytic activity.
局限
未能获取全文，具体设计细节、失访与统计学处理无法核验。
对本项目的价值
★★☆☆☆ 方法学进展决定我们能否在有限样本下检出真实效应，属基础设施级收益。
原文题录
- 英文标题：Single-Cell Dissection of Microglial Dysfunction in Diabetes-Associated Neurodegenerative Vulnerability.
- 期刊与标识：Adv Sci (Weinh) · PMID 42949627 · DOI 10.1002/advs.202600023**
B 级证据分级：B 级（同行评议临床前研究，主要为动物模型）
本文核心结论来自动物模型或体外细胞学，属临床前证据，不能外推至人体。「延长健康寿命」「改善功能」等表述在小鼠中的意义，与人类临床结局之间仍有距离。
关于本文的文献来源：本站依据 IMA 知识库「五刊监控·深度文献卡片」（SOP §4.2 摘要级）撰写，依据期刊公开摘要与 PubMed 元数据；付费墙全文未获取之处已标注「待补全文」，未做任何数值推算补全。