SummaryThe core functions of stem cells (SCs) are critically regulated by their cellular redox status. Glutathione is the most abundant non-protein thiol functioning as an antioxidant and a redox regulator. However, an investigation into the relationship between glutathione-mediated redox capacity and SC activities is hindered by lack of probe. Here, we demonstrate that cyanoacrylamide-based coumarin derivatives are ratiometric probes suitable for the real-time monitoring of glutathione levels in living SCs. These probes revealed that glutathione levels are heterogeneous among subcellular organelles and among individual cells and show dynamic changes and heterogeneity in repopulating SCs depending on oxidative stress or culture conditions. Importantly, a subpopulation of SCs with high glutathione levels exhibited increased stemness and migration activities in vitro and showed improved therapeutic efficiency in treating asthma. Our results indicate that high glutathione levels are required for maintaining SC functions, and monitoring glutathione dynamics and heterogeneity can advance our understanding of the cellular responses to oxidative stress.

UV irradiation elicits acute inflammation in the skin by increasing proinflammatory cytokine production in keratinocytes. However, the downstream protein target(s) that link UV radiation to the activation of signaling pathways responsible for cytokine expression have not been fully elucidated. In this study, we report a novel role of transglutaminase 2 (TG2), a member of the TG enzyme family whose activities are critical for cornified envelope formation, in mediating UV-induced inflammation. Our results showed that TG2-deficient mice exhibited reduced inflammatory responses to UV irradiation, including reduced erythema, edema, dilation of blood vessels, inflammatory cell infiltration, and levels of inflammatory cytokines. Using primary mouse keratinocytes and HaCaT cells, we found that UV irradiation-induced cytokine production by activating TG2, but not by upregulating TG2 expression, and that ER calcium release triggered by the UV-induced activation of phospholipase C was required for TG2 activation. Moreover, TG2 activity enhanced p65 phosphorylation, leading to an increase in NF-κB transcriptional activity. These results indicate that TG2 is a critical mediator of cytokine expression in the UV-induced inflammatory response of keratinocytes, and suggest that TG2 inhibition might be useful for preventing UV-related skin disorders, such as photoaging and skin cancer caused by chronic UV exposure.

We investigated the magnetic and microstructural properties of Nd–Fe–B sintered magnets doped with DyF3, DyHx, and a mixture of DyF3 and DyHx powders. In the DyHx-doped magnet, diffusion of Dy occurs predominantly via grain boundary diffusion. However, the proportion of Dy being diffused by lattice diffusion is increased in the DyF3-doped magnet due to the different influences of F− and H+ ions. The detailed mechanism of the microstructural changes in terms of the diffusional behavior of Dy induced by the DyF3 and DyHx powder doping is discussed. The formation of a Dy-segregated Nd-rich oxide phase (RE-rich, Dy–Nd–O) was suppressed only in the DyF3-doped magnet, and the (00L) alignment of Nd2Fe14B grains in the sintered magnet increased when it was doped with the DyHx powder. We obtained the optimum microstructural and magnetic properties of the Nd–Fe–B sintered magnet through doping with a mixture of DyF3 and DyHx powders, which compensated for the drawbacks of using each powder alone.

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