Abstract：
Nonalcoholic fatty liver disease (NAFLD), along with its progressive forms nonalcoholic steatohepatitis (NASH) and NASH fibrosis, has emerged as a global health crisis. However, the absence of robust screening and risk evaluation tools contributes to the underdiagnosis of NAFLD. Herein, we reported a multichannel nanogenerator-assisted laser desorption/ionization mass spectrometry (LDI-MS) platform for early screening and risk evaluation of NAFLD. Specifically, titanium oxide nanosheets (TiNS) and covalent-organic framework nanosheets (COFNS) were employed as nanogenerators with excellent optical properties and exhibited efficient desorption/ionization during the LDI-MS process. Only ∼0.025 μL of serum without pretreatments and separation, serum metabolic fingerprints (SMFs) can be extracted within seconds. Notably, integrated SMFs from TiNS and COFNS significantly improved diagnostic performance and achieved the area under the curve (AUC) values of 1.000 with 100% sensitivity and 100% specificity for the validation sets of global diagnosis, early diagnosis, high-risk NASH, and NASH fibrosis evaluation. Additionally, four biomarker panels were identified, and their diagnostic AUC values were more than 0.944. Ultimately, key metabolic pathways indicating the change from simple NAFLD to high-risk NASH and NASH fibrosis were uncovered. This work provided a noninvasive and high-throughput screening and risk evaluation strategy for NAFLD healthcare management, thus contributing to the precise treatment of the NALFD.
摘要：
非酒精性脂肪性肝病（NAFLD），随着其进行性形式的非酒精性脂肪性肝炎（NASH）和NASH纤维化，已经成为全球健康危机。然而,缺乏可靠的筛查和风险评估工具导致NAFLD的诊断不足.在这里，我们报道了用于NAFLD早期筛查和风险评估的多通道纳米发生器辅助激光解吸/电离质谱(LDI-MS)平台.具体来说,氧化钛纳米片（TiNS）和共价有机骨架纳米片（COFNS）被用作具有优异光学性能的纳米发电机，并在LDI-MS过程中表现出有效的解吸/电离。仅~0.025μL血清，未经预处理和分离，血清代谢指纹(SMFs)可以在几秒钟内提取。值得注意的是,来自TNS和COFNS的整合SMFs显著提高了诊断性能，并实现了1.000的曲线下面积(AUC)值，对全局诊断的验证集具有100%的灵敏度和100%的特异性，早期诊断,高风险NASH，和NASH纤维化评估。此外,确定了四个生物标志物小组，其诊断AUC值均大于0.944。最终,揭示了从单纯NAFLD到高风险NASH和NASH纤维化的关键代谢途径.这项工作为NAFLD医疗保健管理提供了一种非侵入性和高通量的筛查和风险评估策略。从而有助于NALFD的精确治疗。
