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We have previously demonstrated a rapid secretion of matrix metalloproteinase‐2 (MMP‐2) in the ischemic brain. Since Scube2 can interact with Sonic hedgehog (Shh) to maintain blood–brain barrier (BBB) integrity via regulating the interaction between brain capillary endothelial cells (ECs) and perivascular astrocytes, and it is also a substrate of MMP‐2, we hypothesized that the secreted MMP‐2 could degrade Scube2 and contribute to ischemic BBB disruption. Using an in vitro ischemic model of 90‐min oxygen–glucose deprivation/3‐h reoxygenation (OGD/R) and an in vivo mouse stroke model of 90‐min middle cerebral artery occlusion (MCAO) with 3‐h reperfusion, we established an important role of MMP‐2‐mediated Scube2 degradation in early ischemic BBB disruption. Exposure of C8‐D1A cells and bEnd.3 cells to OGD/R increased MMP secretion in both cells, and C8‐D1A cells appeared to secrete more MMPs than bEnd.3 cells. Co‐IP and double‐immunostaining revealed that Scube2 co‐localized well with MMP‐2 in C8‐D1A cells and could be pulled down by MMP‐2 antibodies. In MCAO mice, Scube2 protein showed a drastic reduction in ischemic brain tissue, which was accompanied by suppressed expression of Shh and its downstream molecules. Of note, specific knockdown of astrocytic Scube2 with AAV‐shScube2 augmented MCAO‐induced Shh suppression and exacerbated BBB leakage and inflammatory reactions in the ischemic brain. Last, incubation of bEnd.3 cells with conditioned medium derived from OGD‐treated C8‐D1A cells led to a significant inhibition of the Shh pathway in bEnd.3 cells and degradation of VE‐cadherin and ZO‐1. Inhibition of MMP‐2 with SB‐3CT or over‐expression of Scube2 with plasmids in C8‐D1A cells alleviated the above effect of C8‐D1A cells‐derived conditioned medium. Taken together, our data indicate that ischemia‐induced secretion of MMP‐2 may contribute to early BBB disruption in ischemic stroke via interrupting the shared Scube2‐Shh pathway between brain capillary ECs and perivascular astrocytes. [ABSTRACT FROM AUTHOR]

Two‐dimensional (2D) materials have aroused widespread interest due to the high potential in modern photoelectronics. The strategy for improving the stability of 2D materials in the air, reinforcing formation, and transport of photoexcited carriers would open up promising routes toward flexible facilities. In this paper, surface engineering is executed on 2D InSe by decorating Au species for a lower bandgap allowing for efficient sunlight harvesting and decreased barrier with the substrate for improved electron transport. Moreover, hot electrons produced by Au nanoparticles under light irradiation pour into InSe for boosting photocurrent. Au nanoparticles also serve as conducting bridges in InSe−Au photoanode, where the contact resistance is two orders of magnitude lower than that of InSe electrode. Compared with InSe and other 2D counterparts, InSe−Au flexible photoelectrochemical detectors behave with outstanding performances under sunlight irradiation, including responsibility 55.4 µA W−1, detectivity 4.18 × 109 Jones. Importantly, the working electrode shows excellent ON/OFF switching stability after bending for 5000 times (3 months of storage in the air). This surface engineering provides a general strategy to tailor 2D materials for wearable photoelectronic devices in the future. [ABSTRACT FROM AUTHOR]

In this study, magnetically assisted laser beam welding was experimentally carried out on Al/steel dissimilar materials in a lap configuration. Weld morphology, interfacial microstructure, element distribution, precipitated phases and mechanical properties of laser-welded joints were carefully investigated. The strengthening mechanism of Al/steel joints was also explored. The results revealed that good weldments were successfully acquired with the assistance of an alternating magnetic field. The microstructures at interface were mainly constituted by nubbly structures, island-shaped structures and banded structures. Fe-Al compounds at interface were expectedly dispersed due to the magnetic field-driven effect on liquid metal. During laser beam welding, the susceptibility to weld cracking was obviously decreased on the premise of inhibition of the composition segregation. The Fe/Al interface zone was mainly composed of η-Fe 2 Al 5 phase, β 2 -FeAl phase, ζ-FeAl 2 phase and θ-FeAl 3 phase. The maximum tensile load and elongation of the tested joints subjected to a magnetic field reached 122.22 % and 145.76 % of joints without magnetic field, respectively. Performance enhancement of welded joints was mainly attributive to the effective regulation of weld microstructure and composition during magnetically assisted laser beam welding. [ABSTRACT FROM AUTHOR]

Cl− movement and Cl−-sensitive signal pathways contributes to the survival and switch of inflammatory phenotype of microglia and are believed to play a key role in the inflammatory brain injury after ischemic stroke. Here, we demonstrated an important role of Cl− transmembrane transporter Swell1, in the survival and M2-like polarization of microglia in ischemic stroke. Knockdown or overexpression of Swell1 in cultured microglia inhibited or increased hypotonic-activated Cl− currents, respectively, and these changes were completely blocked by the volume-regulated anion channels (VRACs) inhibitor DCPIB. Swell1 conditional knock-in mice promoted microglia survival in ischemic brain region and resulted in significant reductions in neural cell death, infarction volume and neurological deficits following transient middle cerebral artery occlusion (tMCAO). Using gene manipulating technique and pharmacological inhibitors, we further revealed that Swell1 opening led to SGK1 (a Cl−-sensitive kinase)-mediated activation of FOXO3a/CREB as well as WNK1 (another Cl−-sensitive kinase)-mediated SPAK/OSR1-CCCs activation, which promoted microglia survival and M2-like polarization, thereby attenuating neuroinflammation and ischemic brain injury. Taken together, our results demonstrated that Swell1 is an essential component of microglia VRACs and its activation protects against ischemic brain injury through promoting microglia survival and M2-like polarization. • Swell1 is an essential component of microglia VRAC and is significantly upregulated induced by ischemic stroke. • Swell1 conditional knock-in mice ameliorates ischemic injury and neuroinflammatory after ischemic stroke. • Swell1 opening promotes microglial survival and M2-type polarization via activating the Cl−-sensitive kinase signaling pathway. [ABSTRACT FROM AUTHOR]