Ulcerative colitis (UC) is associated with a hypoxic microenvironment that stabilizes hypoxia-inducible factor-1α (HIF-1α), driving glycolytic flux and lactate accumulation. Ferroptosis, an iron-dependent cell death process linked to lactate metabolism, has been implicated in UC pathogenesis; however, whether HIF-1α regulates ferroptosis through protein lactylation remains unclear. Bioinformatic analysis identified HIF-1α as a pivotal node connecting lactylation and ferroptosis signatures, with the lactylation score showing a strong positive correlation with ferroptosis activity, suggesting its upstream regulatory role. In cellular UC models, both protein lactylation and ferroptosis markers were significantly elevated. Inhibition of lactate synthesis reduced intracellular Fe2+ overload and normalized expression of ferroptosis-related proteins. Mechanistically, knockdown of HIF-1α in colonic epithelial cells downregulated key glycolytic enzymes, including HK2, decreased lactate production and subsequent protein lactylation, and ultimately attenuated lipid peroxidation and reactive oxygen species (ROS) accumulation, thereby suppressing ferroptosis. Conversely, HIF-1α overexpression promoted ferroptosis-associated alterations in a glycolysis-dependent manner, and exogenous lactate partially restored these alterations upon HIF-1α silencing, supporting a HIF-1α-lactate-lactylation-ferroptosis cascade. We further screened for pharmacological inhibitors of HIF-1α and identified quercetin as a candidate through molecular docking and binding kinetics. Functional validation in vitro and in vivo demonstrated that quercetin directly binds and inhibits HIF-1α, thereby blocking the lactylation-ferroptosis axis and ameliorating colitis. Collectively, this study elucidates a novel HIF-1α-lactylation-ferroptosis regulatory axis in UC and proposes quercetin as a potential therapeutic agent that targets this "metabolism-cell death" network.
Optically pumped magnetometers (OPM) are widely used for their exceptional sensitivity in detecting weak magnetic fields, with applications mainly in the biomedical field. However, their spatial resolution is limited by inherent factors such as vapor cell size, stand-off distance and magnetic noise, restricting their ability to spatially resolve small magnetic features. In this work, we investigate the potential of commercially available rod-shaped magnetic flux guides to address this limitation for magnetic fields perpendicular to a sample surface. Through simulations and experiments, we demonstrate that integrating flux guides into OPM systems can significantly enhance spatial resolution while maintaining sensitivity. We combine finite element simulations with measurements on current-driven meander structures of varying pitch and quantify performance via the minimum resolvable pitch and the magnetic flux transfer coefficient K. After applying a tailored demagnetization procedure to minimize residual magnetization and noise, the integrated OPM–flux-guide system reduces the minimum resolvable pitch from a 5 mm without a flux guide to 1 mm with a rod shaped flux guide with a diameter for 1 mm, at a magnetic contrast of 3.43 pT and an SNR of 18 dB. The spatial resolution was found to be constrained by the flux guide diameter and by spatial averaging over the finite OPM cell, consistent across simulations and experiments. These findings emphasize the importance of jointly selecting flux guide dimensions, magnetic state and sensor geometry. The results demonstrate resolution enhancement for controlled local magnetic-field patterns and provide a basis for future investigations of OPM-based magnetic sensing in applications such as non-destructive testing.
Magnetic tunnel junctions (MTJs) study in the past three decades, resulting in over 25,000 publications while adding 1000 more each year, has become among the most persuasive areas of research. MTJ devices lead the ubiquitous success of spintronics for technological advancement from most aspects of information technology to health sciences, with unprecedented, all-encompassing benefits to the society. We navigate through the evolution of the developing field of MTJs and the related technologies, with continued efforts for improving the tunnel magnetoresistance ratio. The MTJs' excellent ability to convert spin signals to charge signals secures their extensive commercial applications in magnetic data storage and field sensing. More advanced implementation and progress such as with neuromorphic and probabilistic computing entail from here.
