No abstract

Under physiological conditions microglia, the immune sentinels of the brain, constantly monitor their microenvironment. In the case of danger, damage or cell/tissue dyshomeostasis, they react with changes in process motility, polarization, directed process movement, morphology and gene expression profile; release pro‐ and anti‐inflammatory mediators; proliferate; and clean brain parenchyma by means of phagocytosis. Based on recent transcriptomic and in vivo Ca2+ imaging data, we argue that the local cell/tissue dyshomeostasis is sensed by microglia via intracellular Ca2+ signals, many of which are mediated by Ca2+ release from the intracellular Ca2+ stores. These signals encode the strength, duration and spatiotemporal pattern of the stimulus and, at the same time, relay this information further to trigger the respective Ca2+‐dependent effector pathways. We also point to the fact that microglial Ca2+ signalling is sexually dimorphic and undergoes profound changes across the organism's lifespan. Interestingly, the first changes in microglial Ca2+ signalling are visible already in 9‐ to 11‐month‐old mice, roughly corresponding to 40‐year‐old humans. image

No abstract

Design of chemical probes with high specificity and responses are particularly intriguing. In this work, a fluorescent probe (M–OH–SO 3 ) with dual-channel spectral responses toward human serum albumin (HSA) is presented. By employing dinitrobenzenesulfonate as a recognition site as well as a fluorescence quencher, probe M–OH–SO 3 displayed weak fluorescence, which, nevertheless, exhibits extensive yellow (575 nm) and red (660 nm) fluorescence emissions toward HSA under excitations at 400 and 500 nm, respectively. Interestingly, M–OH–SO 3 displayed the best performance toward HSA with distinctly higher selectivity than that of its counterparts M–SO 3 , M–H–SO 3 , and M–F–SO 3 , which were prepared simply by modulating the functional group at the ortho position of the dicyanoisophorone core. Molecular docking results revealed that M–OH–SO 3 possesses the lowest binding energy among the tested derivatives and accordingly the strongest binding affinity. Probe M–OH–SO 3 showed a good linear relationship toward HSA in a range of 0.5–18 μM with a limit of detection of 35 nM. Cell imaging results demonstrated that probe M–OH–SO 3 could visualize the variation HSA levels in hepatocarcinoma cells. In addition, probe M–OH–SO 3 could also be employed for the recognition of glutathione through the cleavage of the dinitrobenzenesulfonate group along with an enhancement of emission at 575 nm. The site-dependent properties inspired a novel paradigm for design of fluorescent probes with optimized selectivity and responses.

Intermetallic compounds (IMCs) are essential in the soldering of electronic products and are composed mainly of Cu6Sn5 and Cu3Sn. They must maintain reliable mechanical and electrical connections. As they are usually only a few microns thick, and it is difficult to study their mechanical properties by traditional methods. In this study, a 100 Å × 100 Å × 100 Å polycrystal with 10 grains was created by Atomsk through Voronoi tessellation based on a Cu6Sn5 unit cell. The effects of the temperature and strain rate on the tensile properties of the polycrystalline Cu6Sn5 were analyzed based on MEAM potential function using a molecular dynamics (MD) method. The results show that Young’s modulus and ultimate tensile strength (UTS) of the polycrystalline Cu6Sn5 decrease approximately linearly with an increase in temperature. At high strain rates (0.001–100 ps−1), Young’s modulus and UTS of the Cu6Sn5 are logarithmic with respect to the strain rate, and both increase with an increase in strain rate. In addition, at low strain rates (0.00001–0.0005 ps−1), the UTS has a quadratic increase as the strain rate increases.