RESUMEN
Victims of a radiation terrorist event will include pregnant women and unborn fetuses. Mitochondrial dysfunction and oxidative stress are key pathogenic factors of fetal irradiation injury. The goal of this preclinical study is to investigate the efficacy of mitigating fetal irradiation injury by maternal administration of the mitochondrial-targeted gramicidin S (GS)- nitroxide radiation mitigator, JP4-039. Pregnant female C57BL/6NTac mice received 3 Gy total body ionizing irradiation (TBI) at mid-gestation embryonic day 13.5 (E13.5). Using novel time- and-motion-resolved 4D in utero magnetic resonance imaging (4D-uMRI), we found TBI caused extensive injury to the fetal brain that included cerebral hemorrhage, loss of cerebral tissue, and hydrocephalus with excessive accumulation of cerebrospinal fluid (CSF). Histopathology of the fetal mouse brain showed broken cerebral vessels and elevated apoptosis. Further use of novel 4D Oxy-wavelet MRI capable of probing in vivo mitochondrial function in intact brain revealed significant reduction of mitochondrial function in the fetal brain after 3Gy TBI. This was validated by ex vivo Oroboros mitochondrial respirometry. Maternal administration JP4-039 one day after TBI (E14.5), which can pass through the placental barrier, significantly reduced fetal brain radiation injury and improved fetal brain mitochondrial respiration. This also preserved cerebral brain tissue integrity and reduced cerebral hemorrhage and cell death. As JP4-039 administration did not change litter sizes or fetus viability, together these findings indicate JP4-039 can be deployed as a safe and effective mitigator of fetal radiation injury from mid-gestational in utero ionizing radiation exposure. One Sentence Summary: Mitochondrial-targeted gramicidin S (GS)-nitroxide JP4-039 is safe and effective radiation mitigator for mid-gestational fetal irradiation injury.
RESUMEN
This paper reports a simple yet effective droplet manipulation approach that can displace aqueous droplets over a long distance within the working plane. Repeated patterns with surface gradient wettability were created on a super-hydrophobic surface by laser irradiation. Aqueous droplets as small as 2 µL are moved on the patterns over a long distance under in-plane symmetric cyclic vibration. Typical droplet manipulation actions including droplet movement along a pre-determined trajectory, droplet mixing, and selective movement of multiple droplets were successfully demonstrated. Biochemical detection using this approach was demonstrated via a bicinchoninic acid (BCA) assay. This approach allows for long-distance droplet movement and simultaneous manipulation of multiple droplets without sacrificing the manipulation efficiency or increasing the cross-contamination risk. The device can be fabricated outside cleanrooms and operated without special equipment. It provides a solid technical basis for developing the next generation of affordable open channel microfluidic devices for various applications.
RESUMEN
Surface wrinkles formed by the buckling of a strained stiff layer attached to a soft elastomer foundation have been widely used in a variety of applications. Micropatterning of wrinkled topographies is, however, limited by process/system complexities. In this article, we report an approach to write surface wrinkles with desired pattern geometries on poly(dimethylsiloxane) (PDMS) elastomers using a commercial infrared laser engraver with a spot size of 127 µm. Wrinkled micropatterns with wavelength from <50 to >300 µm were obtained in minutes without using special facilities or atmospheres. The minimal achievable pattern sizes of one-dimensional and two-dimensional patterns and the change of the minimal achievable pattern size with wrinkle orientation were investigated under a given set of operating parameters. Sub-spot size patterning was also demonstrated. To reduce surface cracking, a typical problem in large-area wrinkle patterning, a patterning scheme that separates neighboring laser exposure areas by nonexposure gaps was developed. In addition, micropatterns with gradient wrinkles were created on the surface. This is the first report that patterns microscale surface wrinkles on elastomer surfaces using infrared laser irradiation. The simple and versatile approach is expected to provide a fast yet controllable way to create wrinkled micropatterns at low cost to facilitate a broad array of studies in surface engineering, cellular biomechanics, and optics.
