标题： 使用无标记拉曼光谱结合微流控芯片探测细胞中的铁死亡网络 显示英文标题

标题： Using Label-Free Raman Spectroscopy Integrated with Microfluidic Chips to Probe Ferroptosis Networks in Cells

摘要： 铁死亡是一种由氧化应激和脂质过氧化驱动的细胞死亡形式，已成为在各种细胞环境中具有重要意义的研究重点。 在本研究中，我们采用了一种多方面的方法，结合无标记拉曼光谱和微流控技术来研究铁死亡的机制。 我们的研究包括基于不同细胞状态下1436 cm-1处脂质拉曼带变化的铁死亡启动、活性氧（ROS）的生成、脂质过氧化、DNA损伤/修复以及线粒体功能障碍。 重要的是，我们的工作突显了关键细胞组分如NADPH、铁氧还蛋白簇以及关键基因如GPX-4、VDAC2和NRF2的动态作用，它们共同影响细胞对氧化还原失衡和氧化应激的反应。 量子力学（QM）和分子对接模拟（MD）进一步提供了铁氧还蛋白（含有4Fe-4S簇）、NADPH和ROS之间相互作用的证据，导致细胞内活性铁物种的产生。 因此，我们的方法提供了对铁死亡的实时、多维视角，超越了传统的生物学方法，并为多种生物医学背景下的治疗干预提供了有价值的见解。 显示英文摘要

摘要： Ferroptosis, a regulated form of cell death driven by oxidative stress and lipid peroxidation, has emerged as a pivotal research focus with implications across various cellular contexts. In this study, we employed a multifaceted approach, integrating label-free Raman spectroscopy and microfluidics to study the mechanisms underpinning ferroptosis. Our investigations included the ferroptosis initiation based on the changes in the lipid Raman band at 1436 cm-1 under different cellular states, the generation of reactive oxygen species (ROS), lipid peroxidation, DNA damage/repair, and mitochondrial dysfunction. Importantly, our work highlighted the dynamic role of vital cellular components, such as NADPH, ferredoxin clusters, and key genes like GPX-4, VDAC2, and NRF2, as they collectively influenced cellular responses to redox imbalance and oxidative stress. Quantum mechanical (QM) and molecular docking simulations (MD) provided further evidence of interactions between the ferredoxin (containing 4Fe-4S clusters), NADPH and ROS which led to the production of reactive Fe species in the cells. As such, our approach offered a real-time, multidimensional perspective on ferroptosis, surpassing traditional biological methods, and providing valuable insights for therapeutic interventions in diverse biomedical contexts.