Complete and robust energy conversion by sum frequency generation based on invariant engineering.

An analytical method is proposed in this paper to achieve complete energy conversion in sum frequency generation based on the Lewis-Riesenfeld invariants theory. In the proposed scheme, a quasi-adiabatic single control parameter model is established, and the value of single control parameter is selected to make the initial eigenstate perfectly converted to the final eigenstate as needed. Corresponding to the nonlinear frequency conversion process, a nonlinear crystal structure is designed by inverse engineering using the optimal control theory. It is robust against perturbations of the coupling coefficient and phase mismatch, including variations in the pump intensity and crystal polarization period, and achieves almost 100% conversion efficiency at any crystal length. Theoretical simulations show that frequency conversion can be achieved in the wavelength range of 2.6 µm-3.6 µm, and the spectral bandwidth of conversion efficiency exceeds 50% and approaches 400 nm when the crystal length L = 1 mm.

LncRNA RMST-mediated miR-107 transcription promotes OGD-induced neuronal apoptosis via interacting with hnRNPK.

The long noncoding RNA (lncRNA) rhabdomyosarcoma 2-associated transcript (RMST) silencing has been demonstrated to protect against ischemic brain injury in vivo and neuron injury in vitro. However, its underlying mechanisms in the progression of ischemic stroke have not been well explored. The expression of RMST in oxygen-glucose deprivation (OGD)-treated HT-22 hippocampal neuron cell line was examined using quantitative Real-Time PCR (qRT-PCR). CCK-8 cell viability and apoptotic cell detection using Annexin V-FITC and PI staining coupled with flow cytometry were performed to determine the pro-apoptotic role of RMST in HT-22 hippocampal neuron cell line. Furthermore, RNA pull-down, RNA immunoprecipitation (RIP), coimmunoprecipitation (Co-IP), chromatin immunoprecipitation (ChIP) and dual-Luciferase reporter assays were performed to determine the mechanism of RMST in OGD-induced HT-22 cell apoptosis. In the results, RMST was highly expressed in OGD-treated HT-22 cells. Altered RMST expression led to marked changes in HT-22 cell proliferation and apoptosis. Mechanistically, RMST indirectly activated p53/miR-107 signaling pathway via interacting with heterogeneous nuclear ribonucleoprotein K (hnRNPK) and fulfilled its pro-apoptotic function in HT-22 cells. In conclusion, our data indicated that the RMST/hnRNPK/p53/miR-107/Bcl2l2 axis plays an important role in regulating neuronal apoptosis.

LncRNA RMST activates TAK1-mediated NF-κB signaling and promotes activation of microglial cells via competitively binding with hnRNPK.

This study aimed to explore the biological role and molecular mechanism of long noncoding RNA (lncRNA) rhabdomyosarcoma 2-associated transcript (RMST) in regulating microglial activation. Mouse microglial BV2 cells were cultured to establish the cell model of cerebral ischemic stroke by oxygen-glucose deprivation (OGD). We observed highly expressed RMST, increased expression of M1, and decreased expression of M2 markers in BV2 microglial cells stimulated with OGD. These alterations were reversed by RMST knockdown. Activation of transforming growth factor-beta-activated kinase 1 (TAK1)-mediated nuclear factor-κB (NF-κB) pathway was observed upon OGD stimulation, which was promoted by RMST through competitively binding with heterogeneous nuclear ribonucleoprotein K (hnRNPK), confirmed by RNA pull down and RNA immunoprecipitation (RIP) assays. Furthermore, RMST overexpressing-BV2 cells effectively enhanced neuronal apoptosis. In conclusion, RMST promoted OGD-induced microglial M1 polarization by competitively interacting with hnRNPK via TAK1-mediated NF-κB pathway, which will provide a basis for understanding the pathogenesis of cerebrovascular diseases.

The dose-effectiveness of intranasal VEGF in treatment of experimental stroke.

The aim of the present study was to assess the dose-effectiveness of intranasal (IN) vascular endothelial growth factor (VEGF)in the treatment of experimental stroke. Sprague-Dawley rats were randomized into four groups as IN low (100 microg/ml), IN middle (200 microg/ml) and IN high (500 microg/ml) VEGF-treated group, and IN saline-treated group (n=12), given recombinant human VEGF 165 or saline intranasally. Focal cerebral ischemia was induced by transient (90 min) middle cerebral artery occlusion (MCAO) method. Behavioral neurological deficits were assessed 1, 7 and 14 d after the onset of MCAO. Rats were sacrificed at 14 d, the brain sections were stained and an image analysis system was used to calculate the infarct volume. Microvessels were labeled by FITC-dextran and the segment lengths, diameters and number of microvessels were measured by Image Pro-Plus Version 6.0 software. Fourteen days post MCAO, infarct volume significantly reduced (P<0.01) in rats which received the middle dose of IN VEGF when compared to IN saline. And middle dose of VEGF significantly improved behavioral recovery (P<0.01). No significant difference in the behavioral recovery and infarct volume was observed between the saline-treated group and the low or high VEGF-treated groups (P>0.05). Compared to IN saline, middle and high doses of VEGF significantly increased the segment length, diameter and number of microvessels (P<0.01). No significant difference in the segment length, diameter and number of microvessels was observed between the IN saline-treated group and the low VEGF-treated group (P>0.05). The middle dose of IN VEGF was most effective on reducing infarct volume, improving behavioral recovery and enhancing angiogenesis in stroke brain, which can be used in the following treatments to further evaluate the effect of VEGF.

Direct transport of VEGF from the nasal cavity to brain.

The aim of the present study was to assess the potential of delivering VEGF directly into the central nervous system (CNS) following intranasal administration. Adult Sprague-Dawley rats were randomized into two groups, given [(125)I]-VEGF intranasally or intravenously. VEGF was intranasally administered in both nares alternately, the single dose is 10 microl with time interval of 2 min for about 18.5 min. The intravenous (IV) group was treated with 100 microl [(125)I]-VEGF intravenously. Thirty minutes after administration, rats were killed following blood sample collections, then the brains were removed, and olfactory bulb, striatum corpora, cortex, thalamus, pons, cerebella, medulla, hippocampus, cervical cord and other tissues were collected, weighted, under auto gamma counting and autoradiography analysis. Cisternal sampling of cerebrospinal fluid (CSF) was performed in an additional group of animals. Both gamma counting and high resolution phosphor imaging of tissue sections showed that intranasal administration of [(125)I]-VEGF resulted in substantial delivery throughout the CNS. The highest CNS tissue concentration following IN delivery was found in the trigeminal nerve, followed by the optic nerve, olfactory bulbs, olfactory tubercle, striatum, medulla, frontal cortex, midbrain, pons, appendix cerebri, thalamus, hippocampus, cerebellum. Intranasal administration of [(125)I]-VEGF also targeted the deep cervical lymph nodes. CSF did not contain [(125)I]-VEGF following intranasal administration. Intravenous [(125)I]-VEGF resulted in blood and peripheral tissue exposure higher concentrations than that intranasal administration, but CNS concentrations were significantly lower. The results suggest intranasally delivered VEGF can bypass the blood-brain barrier via olfactory- and trigeminal-associated extracellular pathways to directly entry into the CNS. Intranasal administration of VEGF may provide an effective way for the treatments of CNS diseases.

Intranasally delivered bFGF enhances neurogenesis in adult rats following cerebral ischemia.

Basic fibroblast growth factor (bFGF) is a very important mitogenic factor with proved neurogenesis effects in the central nervous system. Intranasal administration can bypass blood-brain barrier and deliver drugs into the brain directly. We investigated whether intranasal administration of bFGF at later time points after ischemia could promote adult neurogenesis and improve neurologic functions. Rats received bFGF or saline intranasally once daily for 6 consecutive days, starting at 1 day after transient middle cerebral artery occlusion (MCAO). Bromodeoxyuridine (BrdU) was injected at 5 and 6 days after MCAO. Rats were killed at 7 or 28 days after MCAO. Neurogenesis was assessed by immunostaining for BrdU and cell type-specific markers. Neurological functions were evaluated by the modified Neurological Severity Scores. Compared with the control animals, intranasal administration of bFGF improved behavioral recovery without affecting infarct size, and enhanced proliferation of progenitor cells in the subventricular zone and the subgranular zone of the dentate gyrus (DG). Furthermore, the new proliferated cells could differentiate into neurons (BrdU+NeuN+ cells) in the striatum and DG at 28 days after MCAO. Intranasal administration of bFGF offers a non-invasive alternative for the treatment of stroke.