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SUMMARYPurpose: The metabolic and biochemical changes that occur during epileptogenesis remain to be determined. 18 F-Fluorodeoxyglucose positron emission tomography (FDG-PET) and proton magnetic resonance spectroscopy ( 1 H MRS) are noninvasive techniques that provide indirect information on ongoing pathologic changes. We, therefore, utilized these methods to assess changes in glucose metabolism and metabolites in the rat lithium-pilocarpine model of epilepsy as markers of epileptogenesis from baseline to chronic spontaneous recurrent seizures (SRS). Methods: PET and MRS were performed at baseline, and during the acute, subacute, silent, and chronic periods after lithium-pilocarpine induced status epilepticus (SE). Sequential changes in glucose metabolism on 18 F-FDG PET using SPM2 and the ratios of percent injected dose per gram (%ID)/g of regions of interest (ROIs) in the bilateral amygdala, hippocampus, basal ganglia with the thalamus, cortex, and hypothalamus normalized to the pons were determined. Voxels of interest (VOIs) on 1 H MRS were obtained at the right hippocampus and the basal ganglia. NAA/Cr levels and Cho/Cr at various time points were compared to baseline values. Key Findings: Of 81 male Sprague-Dawley rats, 30 progressed to SRS.18 F-FDG PET showed widespread global hypometabolism during the acute period, returning to baseline level during the subacute period. Glucose metabolism, however, declined in part of the hippocampus during the silent period, with the hypometabolic area progressively expanding to the entire limbic area during the chronic period. 1 H MRS showed that the NAA/Cr levels in the hippocampus and basal ganglia were reduced during the acute period and were not restored subsequently from the subacute to the chronic period without any significant change in the Cho/Cr ratio throughout the entire experiment. Significance: Serial metabolic and biochemical changes in the lithium-pilocarpine model of epilepsy indirectly represent the process of human epileptogenesis. Following initial irreversible neural damage by SE, global glucose metabolism transiently recovered during the subacute period without neuronal recovery. Progressive glucose hypometabolism in the limbic area during the silent and chronic periods may reflect the important role of the hippocampus in the formation of ongoing epileptic network during epileptogenesis.

We previously demonstrated the safety and feasibility of mesenchymal stem cell (MSC) transplantation for bronchopulmonary dysplasia (BPD) in preterm infants in a phase I clinical trial. We thus investigated the therapeutic efficacy of MSCs for BPD in premature infants. A phase II double-blind, randomized, placebo-controlled clinical trial was conducted on preterm infants at 23 to 28 gestational weeks (GW) receiving mechanical ventilator support with respiratory deterioration between postnatal days 5 and 14. Infants were stratified by 23 to 24 GW and 25 to 28 GW and randomly allocated (1:1) to receive stem cells (1 × 10 7 cells/kg, n = 33) or placebo (n = 33). Although the inflammatory cytokines in the tracheal aspirate fluid were significantly reduced with MSCs, the primary outcome of death or severe/moderate BPD in the control group (18/33, 55%) was not significantly improved with MSC transplantation (17/33, 52%). In the subgroup analysis, the secondary outcome of severe BPD was significantly improved from 53% (8/15) to 19% (3/16) with MSC transplantation in the 23 to 24 GW group but not in the 25 to 28 GW subgroup. In summary, although MSC transplantation might be safe and feasible, this small study was underpowered to detect its therapeutic efficacy in preterm infants at 23 to 28 GW. Accordingly, we are now conducting an additional larger and controlled phase II clinical trial focusing on infants at 23 to 24 GW (NCT03392467). ClinicalTrials.gov identifier: NCT01828957.

The realization of lasers as small as possible has been one of the long-standing goals of the laser physics and quantum optics communities. Among multitudes of recent small cavities, the one-dimensional nanobeam cavity has been actively investigated as one of the most attractive candidates for effective photon confinement thanks to its simple geometry. However, the current injection into the ultra-small nano-resonator without critically degrading the quality factor remains still unanswered. Here we report an electrically driven, one-dimensional, photonic-well, single-mode, room-temperature nanobeam laser whose footprint approaches the smallest possible value. The small physical volume of ~4.6 × 0.61 × 0.28 μm3 (~8.2(λ n−1)3) was realized through the introduction of a Gaussian-like photonic well made of only 11 air holes. In addition, a low threshold current of ~5 μA was observed from a three-cell nanobeam cavity at room temperature. The simple one-dimensional waveguide nature of the nanobeam enables straightforward integration with other photonic applications such as photonic integrated circuits and quantum information devices.

SummaryHorse oil contains linoleic, palmitoleic and unsaturated fatty acids that are similar to those in human skin, and may therefore be an ideal substance from which to isolate biosurfactants for cosmetic products to improve human skin quality. Herein, an innovative approach was developed to synthesise sophorolipids from horse oil by hydrolysis, followed by fermentation using the yeast Candida bombicola. The yield of sophorolipids from direct fermentation of horse oil and hydrolysed horse oil was 40.6 ± 1.3 g l−1 and 58.4 ± 1.8 g l−1 respectively. To further increase the yield, 30–40 g l−1 glucose was added in a fed‐batch fermentation process to maintain the pH between 4.0 and 4.5, resulting in a conversion yield of 71.7 ± 0.8 g l−1. The purity and structure of the synthesised sophorolipids were analysed by ultra‐performance liquid chromatography‐mass spectrometry and nuclear magnetic resonance. An in vitro human dermal fibroblast model was used as a surrogate for human skin to measure elastase inhibition activity. Antiwrinkle properties of isolated sophorolipids were better than those of horse oil or hydrolysed horse oil in several in vitro assays. Furthermore, no cytotoxicity was observed at a concentration of 50 μg ml−1, and wound‐healing capacity was evident in a cell culture model. Additionally, the synthesised sophorolipids attenuated lipopolysaccharide‐induced expression of inflammatory cytokines in macrophages, and efficiently inhibited several strains of bacteria and yeast. In conclusion, fed‐batch fermentation of hydrolysed horse oil is a novel and efficient approach for producing high‐quality and high‐yield sophorolipids that exhibit great potential as cosmetic ingredients.

These results strongly suggest that transplanted Wnt3a secreting fibroblasts promote axonal regeneration and functional improvement after SCI. Although further investigation will be necessary to clarify the intracellular mechanism by which Wnt signaling promotes axonal regeneration and functional improvement, this approach could be a highly promising therapeutic strategy for SCI.

We report one-dimensional (1-D) parabolic-beam photonic crystal (PhC) lasers in which the width of the PhC slab waveguide is parabolically tapered. A few high-Q resonant modes are confirmed in the vicinity of the tapered region where Gaussian-shaped photonic well is formed. These resonant modes originate from the dielectric PhC guided mode and overlap with the gain medium efficiently. It is also shown that the far-field radiation profile is closely associated with the symmetry of the structural perturbation.

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