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Ischemic stroke (IS) greatly threatens human health resulting in high mortality and substantial loss of function. Recent studies have shown that the outcome of IS has sex specific, but its mechanism is still unclear. This study is aimed at identifying the sexually dimorphic to peripheral immune response in IS progression, predicting potential prognostic biomarkers that can lead to sex-specific outcome, and revealing potential treatment targets. Gene expression dataset GSE37587, including 68 peripheral whole blood samples which were collected within 24 hours from known onset of symptom and again at 24-48 hours after onset (20 women and 14 men), was downloaded from the Gene Expression Omnibus (GEO) datasets. First, using Bioconductor R package, two kinds of differentially expressed genes (DEGs) (nonsex-specific- and sex-specific-DEGs) were screened by follow-up (24-48 hours) vs. baseline (24 hours). 30 nonsex-specific DEGs (1 upregulated and 29 downregulated), 79 female-specific DEGs (25 upregulated and 54 downregulated), and none of male-specific DEGs were obtained finally. Second, bioinformatics analysis of female-specific DEGs was performed. Gene Ontology (GO) functional annotation analysis shows that DEGs were mainly enriched in translational initiation, cytosolic ribosome, and structural constituent of ribosome. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis shows that the top 6 enrichment pathways are ribosome, nuclear factor-­kappa B (NF-kappa B) signaling pathway, apoptosis, mineral absorption, nonalcoholic fatty liver disease, and pertussis. Three functional modules were clustered in the protein–protein interaction (PPI) network of DEGs. The top 10 key genes of the PPI network constructed were selected, including RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2. Sex difference of ribosome in stroke-induced peripheral immunosuppression may be the potential mechanism of sex disparities in outcome after IS, and women are more likely to have stroke-induced immunosuppression. RPS14, RPS15A, RPS24, FAU, RPL27, RPL31, RPL34, RPL35A, RSL24D1, and EEF1B2 may be novel prognostic biomarkers and potential therapeutic targets for IS.

Mechanical oscillators can be implemented to store and transfer information or to build hybrid systems. In order to couple a mechanical oscillator to a superconducting qubit, we fabricate a superconducting capacitor, in which diluted photoresist or electron beam photoresist is used as sacrificial layers. The upper plate of the capacitor, a suspended membrane, acts as a mechanical oscillator. We obtain its mechanical resonant frequency and response to the input microwave. Such mechanical oscillators can be used as the capacitor of a superconducting qubit to form a coupled system. In order to control the resonant frequency of the mechanical oscillator and the microwave resonator, we introduce a dc voltage bias between the upper and lower plates of the capacitor. We analyze the electromechanical coupling such as pull-in effect and experimentally demonstrate the dependence of the resonant frequency on the applied dc voltage. These results will contribute to the design and fabrication of hybrid systems comprising voltage-controlled mechanical oscillators and other systems.

In order to obtain experimental evidence for the influence of flux focusing effect on the characteristics of planar grain boundary (GB) Josephson junctions, we measured the current–voltage characteristics and magnetic-field-dependent current–voltage steps of integrated YBa2Cu3O7- δ bicrystal GB Junctions with different junction widths. Under the self-magnetic field, the critical current of the GB junction is proportional to the square root of the junction width, which is different from the traditional linear relationship between the critical current and the junction width. When a vertical magnetic field is applied, the flux flow current–voltage step could be observed, and the step voltage increases monotonously with an increase in the junction width. When a magnetic field rotating in the bc plane is applied, the voltage value of the flux flow step decreases slowly as the magnetic field inclined angle increases when the field inclined angle is relatively large. Based on these results, we demonstrate the presence of the magnetic flux focusing effect on YBa2Cu3O7- δ GB Josephson junctions. The size of flux focusing in the GB is closely associated with the width of the junctions and the orientation of the magnetic field.

By measuring the dependence of transverse (Hall) and longitudinal magnetoresistance on temperature, the vortex easy-flow channel effect in an YBCO microbridge with an inclined GB was studied when the magnetic field was rotated in the ac plane of the film. In addition, the magnetic field angular dependence of critical current density in an YBCO microbridge with a GB perpendicular to bridge was measured when the magnetic field was rotated in the ab plane of the film. These measurement results demonstrate that there still can be vortex components moving inside and along the plane of the GB even though the vortices diagonally cross the GB.

We fabricate a microscale electromechanical system, in which a suspended superconducting membrane, treated as a mechanical oscillator, capacitively couples to a superconducting microwave resonator. As the microwave driving power increases, nonmonotonic dependence of the resonance frequency of the mechanical oscillator on the driving power has been observed. We also demonstrate the optical switching of the resonance frequency of the mechanical oscillator. Theoretical models for qualitative understanding of our experimental observations are presented. Our experiment may pave the way for the application of a mechanical oscillator with its resonance frequency controlled by the electromagnetic and/or optical fields, such as a microwave-optical interface and a controllable element in a superqubit-mechanical oscillator hybrid system., 8 pages,4 figures

An impedance matched parametric amplifier (IMPA) with Josephson junctions is fabricated and characterized. A hybrid structure containing coplanar and strip structures is implemented to realize an impedance taper line and a plate capacitor in an LC nonlinear resonator based on Josephson junctions. The upper plate of the capacitor is isolated with SiN x without grounding as well as the strips. Such easily-prepared designs greatly reduce the requirements for lithography alignment and precision, which makes the fabrication process more reliable. The experimental results show that in such IMPA a gain higher than 25 dB with a bandwidth of about 100 MHz can be obtained. This broadband amplifier operates close to the quantum limit. By adjusting the working point, a higher bandwidth of about 400 MHz can be obtained with a gain of about 17 dB.

We design and fabricate λ/2 coplanar waveguide NbN resonators, the thickness and length of which are only several nanometers and hundred microns, respectively. The quality factor of such compact resonators can reach up to 7.5 × 104 at single photon power level at 30 mK with the resonance frequency around 6.835 GHz. In order to tune the resonant frequency, the resonator is terminated to the ground with a dc-SQUID. By tuning the magnetic flux in the dc-SQUID, the effective inductance of the dc-SQUID is varied, which leads to the change in the resonant frequency of the resonator. The tunability range is more than 30 MHz and the quality factor is about 3 × 103. These compact and tunable NbN resonators have potential applications in the quantum information processing, such as in the precision measurement, coupling and/or reading out the quantum states of qubits.

Ligustilide (LIG) is a principal active ingredient of traditional Chinese medicine, Radix Angelica sinensis, which has versatile pharmacological activities including neuroprotection. Previous studies have demonstrated that LIG has beneficial effects on cognition deficits associated with cerebral damage or neurodegenerative disorders. In present study, we investigated the neuroprotective effect of LIG on cognitive impairment and neurotoxicity in the brain of aging mouse induced by d-galactose (d-gal). The aging model mice were induced by subcutaneous (S.C.) injection of d-gal once daily for 8 weeks and LIG (80 mg/kg) was simultaneously administered orally. The Morris water maze (MWM) test was used to assess the spatial learning and memory abilities. The activity of Na(+)-K(+)-ATPase and the content of lipid peroxidation product malondialdehyde (MDA) in brain were examined. The levels of glial fibrillary acidic protein (GFAP), growth-associated protein GAP-43, and cleaved caspase-3 in brain were also determined by immunohistochemistry. The MWM test showed that LIG administration markedly improved behavioral performance of d-gal treated mice. This action could be partly explained by the results that LIG reduced the level of MDA as well as increased the activity of Na(+)-K(+)-ATPase in the brain of d-gal induced aging mice. Moreover, LIG significantly raised the expression of GAP-43 and reduced cleaved caspase-3 and GFAP levels in the brain of d-gal treated mice. These results demonstrated that LIG improves d-gal-induced cognitive dysfunction and brain toxicity, which suggests that LIG may be developed as a new medicine for the treatment of aged-related conditions.

By applying a coupling microwave field gated by random-telegraph-noise (RTN), we report the experimental demonstration of dynamically modulated Autler-Townes effect (ATE) in an artificial atom---a superconducting transmon qubit---and obtain the distinguished characteristics when a system is affected by RTN. By further applying another coupling microwave filed on the transmon, we use an intense bichromatic field to couple the energy levels. Depending on the detuning of the couplers, remarkable interference patterns emerge in the spectrum, which come from the dressed states induced by the modulated ATE. Numerical calculations agree well with the experimental data.

The objective of the study was to evaluate the effect of hydroxypropyl-sulfobutyl-β-cyclodextrin (HP-SBE-βCD) on the bioavailability and intestinal absorption of edaravone, and identify its mechanism of action. We devised HP-SBE-βCD as a carrier and modulator of P-glycoprotein (Pgp) efflux pump, and edaravone as a model drug, and prepared edaravone/HP-SBE-βCD inclusion complex. HP-SBE-βCD improved the water solubility and enhanced the bioavailability of edaravone by 10.3-fold in rats. Then, in situ single-pass intestinal perfusion showed that HP-SBE-βCD had an effect of improving the permeability and inhibiting the efflux of edaravone. Furthermore, the effects of HP-SBE-βCD on Pgp were achieved through interfering with the lipid raft and depleting the cholesterol of enterocytes membrane. From the results, we presented the novel mechanisms. First, edaravone/HP-SBE-βCD had a lower release from the inclusion compound to protect edaravone from the low pH of the stomach. Then, HP-SBE-βCD modulated the membrane microenvironment of intestinal absorption epithelial cells. At last, the result was that HP-SBE-βCD enhanced the absorption of edaravone by interfering with Pgp. In conclusion, HP-SBE-βCD improves the bioavailability of drug not only because of its enhancing water solubility of the drug, but also because it modulates the Pgp-mediated efflux from enterocytes.

Z-ligustilide (LIG), the main lipophilic component of Radix Angelica sinensis, has been shown to protect against brain ischemic damage in rodents by oral and intra-peritoneal treatments. The present study aimed to confirm the therapeutic effect of LIG administered intravenously on 2h middle cerebral artery occlusion (MCAO) and 22 h reperfusion injury in rats since oral administration has low bioavailability, slow absorption and distribution. Moreover, whether LIG activated the NF-E2-related factor 2/ heme oxygenase-1 (Nrf2/HO-1) pathway was also investigated in vivo and in vitro to further elucidate the precise protective mechanisms. In vivo, rats treated intravenously with LIG immediately after the surgery was finished had less neurological dysfunction and smaller infarct volume than that of the vehicle-treated rats. Additionally, LIG promoted Nrf2 nuclear translocation, and further remarkably increased Nrf2 and HO-1 protein expression. In vitro, LIG induced Nrf2 nuclear translocation and up-regulated HO-1 expression in a time-dependent and concentration-dependent manner. Furthermore, LIG treatment reduced cell death induced by OGD, however, the protective action was abolished while Nrf2/HO-1 expression was knockdown by RNA interference. These results noted that intravenous post-treatment with LIG exhibits noticeable neuroprotective properties against brain damage by ischemia-reperfusion and the ability of LIG to activate Nrf2/HO-1 pathway may be partly responsible for it.

The ball surface and sub-surface defects can be test by the eddy current nondestructive method. The core part of the eddy current system is the sensor’s design, including the coil and the process of induction signals. At the end, through experiment of detecting a set of defect ball, with a better result. It’s shows that the amplitude of the detection signal is proportional to the depth of the steel balls crack.

Ethnopharmacological relevance Ligustilide (LIG), a main lipophilic component of Danggui (Chinese Angelica root, Radix Angelica sinensis ) which is a popular used herb to treat menstrual disorders in traditional chinese medicine, has been reported to possess some neuroprotective effects on permanent focal ischemia and transient forebrain ischemia. Aim of the study Based on previous work, we intended to investigate the protective effects of LIG on parietal cortex and hippocampus of rats in chronic cerebral hypoperfusion model. Materials and methods Chronic cerebral hypoperfusion was induced by permanent, bilateral common carotid artery's occlusion (2VO). The rats were treated with LIG (80 mg/kg, by oral) from the eighth day after surgery for seven consecutive days. Their spatial learning and memory abilities were assessed using the Morris water maze. After six days for maze test, rats were sacrificed. Coronal sections in cortex and hippocampus were stained with cresyl violet or labeled with NeuN (Neuronal Nuclei), MAP-2 (Microtubule-Associated Protein-2), Caspase-3 and GFAP (Glial Fibrillary Acidic Protein) antibodies. Results LIG treatment for seven days decreased escape latency and swimming distance of 2VO rats from the third day in maze tests, and increased percent time in the target quadrant. LIG prevented neuronal loss, dendrites damage and neuronal apoptosis in both parietal cortex and hippocampus of 2VO rats; and it also inhibited astrocytic activation and proliferation stimulated by hypoperfusion. Conclusions These results demonstrate that LIG show obvious neuroprotective potential for treating chronic cerebral hypoperfusion injury, which may be attributed to its anti-apoptosis of neuron and anti-proliferation of astrocyte both in cortex and in hippocampus of 2VO rats. We suggest that LIG can be developed as an effective drugs for the prevention of vascular dementia (VD).

We investigated the current–voltage characteristics and the critical current density (J c) of a YBa2Cu3O7−δ grain boundary (GB) long Josephson junction with respect to magnetic field (H) under different application directions. When H is rotated within the bc-plane of the film, a small peak of J c is observed when H is parallel to the c-axis, which denotes that there are some residual c-axis dislocations in the GB. When H is rotated within the ac-plane, some vortex-flow steps can be observed in the current–voltage curve at a high inclination angle of H. The vortex-flow step becomes smaller and wider with the decreasing angle between H and the c-axis. These results are a clear demonstration of vortex splitting at the GB plane in YBa2Cu3O7−δ GB long Josephson junctions.

Transferrin receptor (TfR1) and divalent metal transporter 1 (DMT1) are important proteins for cellular iron uptake, and both are regulated transcriptionally through the binding of hypoxia-inducible factor 1 (HIF-1) to hypoxia-responsive elements (HREs) under hypoxic conditions. These proteins are also regulated post-transcriptionally through the binding of iron regulatory protein 1 (IRP1) to iron-responsive elements (IREs) located in the mRNA untranslated region (UTR) to control cellular iron homeostasis. In iron-deficient cells, IRP1-IRE interactions stabilize TfR1 and DMT1 mRNAs, enhancing iron uptake. However, little is known about the impact of IRP1 on the regulation of cellular iron homeostasis under hypoxia. Thus, to investigate the role of IRP1 in hypoxic condition, overexpression and knockdown assays were performed using HepG2 cells. The overexpression of IRP1 suppressed the hypoxia-induced increase in TfR1 and DMT1 (+IRE) expression and reduced the stability of TfR1 and DMT1 (+IRE) mRNAs under hypoxia, whereas IRP1 knockdown further increased the hypoxia-induced expression of both proteins, preventing the decrease in IRE-dependent luciferase activity induced by hypoxia. Under hypoxic conditions, ferrous iron uptake, the labile iron pool (LIP), and total intracellular iron reduced when IRP1 was overexpressed and further increased when IRP1 was knocked down. IRP1 expression declined and TfR1/DMT1 (+IRE) expression increased with the time of hypoxia prolonged, whereas the binding of IRP1 to the IRE of TfR1/DMT1 mRNA maintained. In summary, IRP1 suppressed TfR1/DMT1 (+IRE) expression, limited the cellular iron content and decreased lactate dehydrogenase (LDH) release induced by hypoxia.

AimTo determine the association between HLA-DRB1 haplotypes and risk of cervical cancer in unselected and samples from Chinese ethnicities.MethodsA comprehensive search for articles from their inception to April 1st, 2013 was conducted from PubMed, Medline, Elsevier Science, Springer Link, Cochrane Library database, China biology medical literature database (CBM),China National Knowledge Infrastructure (CNKI),VIP,and Chinese literature database(Wang fang). A total of 1596 patients with cervical cancer and 2048 controls from the 12 studies on the relationship between gene polymorphism of HLA-DRB l and cervical cancer were performed and data were analyzed and processed using Review Manager 5.0 and Stata 11.0.ResultsAmong the 13 family alleles, two (DRB1*03 and DRB1*08) were found to be negatively associated with cervical cancer in all studies or in Uighur subgroups, and two (DRB1*10 and DRB1*15) were positively associated with in all studies or in Uighur subgroups. Among the 25 specific alleles, six (DRB1*0301, *0403,*0404, *0803, *1312 and *1502) were associated with an increased risk cervical cancer in all studies. No significant association was established for other HLA-DRB1 family alleles and specific alleles. Ethnicity partially explained the race influence of DRB1*12, DRB1*14, DRB1*0301, DRB1*0403, DRB1*0404, DRB1*0803, DRB1*1312 and DRB1*1502 phenotypes.ConclusionOur results support the hypothesis that the HLA-DRB1 family alleles and specific alleles might influence the susceptibility or resistance to cervical cancer, suggesting that immune regulation may play a key role in this disease, although further investigations are still needed.

Although ischemic preconditioning (IP) can provide powerful protection on brain against ischemic insult, it is rarely used in clinic to prevent the occurrence of ischemic stroke because of safety concerns. It is therefore necessary to seek the safer stimuli to initiate pharmacological preconditioning. Our previous work demonstrated that ginkgolide B (GB) could protect neurons against ischemia-induced apoptosis. Astrocytes are the most numerous cells in mammalian central nervous system and there is a close bi-directional communication between neurons and astrocytes in brain. Besides neurons, whether GB can exert the role of preconditioning on astrocytes through which to further improve neuronal survival under ischemic condition is not yet known. In the present study, primary cultured astrocytes were treated with GB for 24h or short-term ischemia (ischemia for 3h, as ischemic preconditioning/IP), and then cultured back to normoxia and normal medium for 24h to induce the preconditioning response. Astrocyte-conditioned medium (ACM) was then collected and used to incubate the cultured neurons for 24h before neurons were subjected to severe ischemia. Our results demonstrated that not only GB and IP increased astrocytic viability in ischemia, but also the conditioned medium from astrocytes treated with GB or IP increased cell viability and decreased the number of apoptosis of neurons in ischemia. We also found that GB and IP significantly stimulated astrocytes to express and secrete erythropoietin (EPO) into ACM, and the addition of anti-EPO antibody blocked the protective effect of GB or IP-treated astrocytes culture medium on neurons in ischemia. Further study of above protection revealed that ACM from astrocytes treated with GB or IP induced the inactivation of proapoptotic factor Bad by phosphorylation at serine 136 and 112 ((136)p-Bad and (112)p-Bad) in neurons. Together, our results suggest that GB is capable of preconditioning on astrocytes as IP and then protects neurons against ischemia-induced apoptosis, which is mediated by EPO.