Search

Hot dry rock (HDR) geothermal energy has become promising resources for relieving the energy crisis and global warming. The exploitation of HDR geothermal energy usually needs an enhanced geothermal system (EGS) with artificial fracture networks by hydraulic fracturing. Fault reactivation and seismicity induced by hydraulic fracturing raise a great challenge. In this paper, we investigated the characteristics of fault slip and seismicity by numerical simulation. The study was based on a hydraulic fracturing project in the geothermal field of Yishu fault zone in China. It revealed that fluid injection during hydraulic fracturing can cause the faults that exist beyond the fluid-pressurized region to slip and can even induce large seismic event. It was easier to cause felt earthquakes when hydraulic fracturing was carried out in different layers simultaneously. We also examined the effects of the location, permeability, and area of the fracturing region on fault slip and magnitude of the resulting events. The results of the study can provide some useful references for establishing HDR EGS in Yishu fault zone.

A novel and simple scheme for the realization of the terahertz (THz) fundamental-mode composite right/left-handed leaky-wave antennas (CRLH LWAs) is proposed. The CRLH LWAs are reconstructed by graphene-based coplanar waveguide transmission line (CPW TL) unit cells. Their signal lines are grounded by narrow graphene strips to achieve the shunt inductances, and parallel-plates are periodically added along the signal line to obtain the series capacitances. The propagation properties of the LWAs are detailed. The LWAs have both left-handed (LH) and right-handed (RH) regions by varying frequency. By numerical simulations, the LWAs are verified. Their backfire-to-endfire beam-steering capabilities through frequency scanning are confirmed. Compared with the CRLH LWAs at THz proposed in previous literature, the graphene-based CRLH LWAs operate in the Quasi-TEM mode. They possess low fabrication, excitation, and impedance matching difficulty. They also show the possibility of integration with other micro-devices. With the application of graphene, the LWAs exhibit strong tunable characteristics that conventional CRLH LWAs are absent. Therefore, the proposed CRLH LWAs have great potential applications for the development of beam-steering antennas at THz.

In this paper, a novel miniaturized triple-band planar monopole antenna combing single-cell metamaterial structure and defected ground plane is proposed. The miniaturization and triple-band charact...

Repetitive transcranial magnetic stimulation (rTMS) treatment is widely accepted as an evidence-based treatment option for depression and anxiety. However, the underlying mechanism of this treatment maneuver has not been clearly understood. The chronic unpredictable mild stress (CUMS) procedure was used to establish depression and anxiety-like behavior in rats. The rTMS was performed with a commercially available stimulator for seven consecutive days, and then depression and anxiety-like behaviors were subsequently measured. The expression of nuclear factor-E2-related factor 2 (Nrf2) was measured by western-blot, and the level of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and interleukin-6 (IL-6) was measured with Enzyme-linked immunesorbent assay (ELISA) analyzing kits. Furthermore, a small interfering RNA was employed to knockdown Nrf2, after which the neurobehavioral assessment, Nrf2 nuclear expression, and the amount of inflammation factors were evaluated. Application of rTMS exhibited a significant antidepressant and anxiolytic-like effect, which was associated with the increased Nrf2 nuclear translocation and reduced level of TNF-α, iNOS, IL-1β, and IL-6 in the hippocampus. Following Nrf2 silencing, the antidepressant and anxiolytic-like effect produced by rTMS was abolished. Moreover, the elevated Nrf2 nuclear translocation, and the reduced production of TNF-α, iNOS, IL-1β, and IL-6 in hippocampus mediated by rTMS, were reversed by Nrf2 knockdown. Together, these results reveal that the Nrf2-induced anti-inflammation effect is crucial in regulating antidepressant-related behaviors produced by rTMS.

Astrocytes experience significant metabolic shifts in the "sensitive period" of neurological function recovery following cerebral ischemia. However, the changes in astrocyte lipid metabolism and their implications for neurological recovery remain unknown. In the present study, we employed a mouse middle cerebral artery occlusion model to investigate the changes in de novo lipogenesis and interleukin-33 (IL-33) production in astrocytes and elucidate their role in blood-brain barrier (BBB) repair in the subacute phase of cerebral ischemia. Neurological behavior evaluation was used to assess functional changes in mice. Pharmacological inhibition and astrocyte-specific downregulation of fatty acid synthase (FASN) were used to evaluate the role of de novo lipogenesis in brain injury. Intracerebroventricular administration of recombinant IL-33 was performed to study the contribution of IL-33 to BBB disruption. Extravasation of Evans blue dye, dextran and IgG were used to assess BBB integrity. Western blotting of tight junction proteins ZO-1, Occludin, and Claudin-5 were performed at defined time points to evaluate changes in BBB. It was found that de novo lipogenesis was activated, and IL-33 production increased in astrocytes at the subacute stage of cerebral ischemia injury. Inhibition of lipogenesis in astrocytes decreased IL-33 production in the peri-infarct area, deteriorated BBB damage and interfered with neurological recovery. In addition, supplementation of IL-33 alleviated BBB destruction and improved neurological recovery worsened by lipogenesis inhibition. These findings indicate that astrocyte lipogenesis increases the production of IL-33 in the peri-infarct area, which promotes BBB repair in the subacute phase of cerebral ischemia injury and improves long-term functional recovery.

PurposeConcerning that limited explanation exists examining the function of corporate governance in trust processing within entrepreneurial network development, the purpose of this paper is to explore trust evolution and the role of corporate governance in an entrepreneurial network.Design/methodology/approachThis paper makes an innovative exploration based on the case study of NVC Lighting Holding Limited.FindingsIt proposes that in the initial period of network relationship which is based on entrepreneur’s individual social network and embodies sole social network embeddness, entrepreneurial network relies more on affective trust than contractual trust. When stepping into extending period of network relationship which reflects separate embeddedness of social and market network, however, entrepreneurial network has an equal reliance on both affective trust and contractual trust. With further development, when ushering in the phase of maturity which undergoes superimposing embeddedness of both social and market network, entrepreneur network inclines to rely more heavily on affective trust than contractual trust. During the whole process, it can be found that the reliance of entrepreneurial network on trust has the tendency to transfer from affective trust to contractual trust. Furthermore, decreasing of equity ratio of founders and strengthening of controlling right heterogeneity in the corporate governance have facilitated the transfer process and the entrepreneurs’ authority has restraining effect on the evolution of the process.Originality/valueThrough case study, this paper presents the trust evolution process in different stages of entrepreneurial network. Another important theoretic contribution of this paper is that it reveals the function of corporate governance in trust processing within entrepreneurial network development.

Currently extensive attentions on application of LiFePO4 batteries in electric vehicles are attracted to the researchers. Owing to the high cost of raw materials and burdensome preparation process, the re-synthesis of LiFePO4 from spent batteries becomes an economical and convenient way. Herein, a novel closed-loop regeneration process simultaneously from spent LiFePO4 cathode and graphite anode is proposed. Spent LiFePO4 cathode material is first successfully regenerated through Li+ compensation and structure reshaping via hydrothermal method, and then graphene oxide is recovered from spent graphite anode via Hummers method. The as-regenerated LiFePO4/reduced graphene oxide composites present spherical morphology, smaller and more uniform particles. The composite mode of LiFePO4 and graphene includes LiFePO4 distributing in the interlayer structure of graphene and the graphene evenly covering on the surface of the particles. The regenerated LiFePO4/reduced graphene oxide batteries exhibit reversible capacities of 162.6 mAhg−1 and high columbic efficiency, stable cycle performances at 0.2 and 1C and excellent rate capacity. Through comparison, the regenerated LiFePO4/reduced graphene oxide composites from hydrothermal process shows better prosperities than those of regenerated LiFePO4 from solid phase roasting method whatever electrochemical properties or economical efficiency in the booming electric vehicles and hybrid electric vehicles industrialization.

In this paper, a new differential-drive traveling-wave electrode with wide bandwidth used to drive silicon-based Mach-Zehnder modulator (MZM) is proposed. The electrode is achieved by loading the partly removed Si substrate under the coplanar waveguide (CPW). By using the modified substrate, the transmission loss of the microwave signal can be effectively reduced compared with the signal with overlapping substrate. The bandwidth $\left(\left|S_{21}\right| \leqslant -3 \mathrm{dB}\right)$ of the presented electrode is well improved, which can reach at 28 GHz from 0.1 to 28.1 GHz. The electrode owns the merits of wide bandwidth, high phase shifting efficiency, and low cost. Thus, the proposed electrode has great values and broad prospects in the high-rate optical communication applications.

Background Sudden cardiac death (SCD) remains a great health threat and diagnostic challenge, especially those cases without positive autopsy findings. Molecular biomarkers have been urgently needed for the diagnosis of SCD displaying negative autopsy results. Due to their nature of stability, microRNAs (miRNAs) have emerged as promising diagnostic biomarkers for cardiovascular diseases. Methods This study investigated whether specific cardio-miRNAs (miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p) could serve as potential biomarkers for the diagnosis of SCD. Thirty-four SCD cases were selected, 18 categorized as SCD with negative autopsy (SCD-negative autopsy) findings and 16 as SCD with positive autopsy (SCD-positive autopsy) findings such as coronary atherosclerosis and gross myocardial scar. Carbon monoxide (CO) intoxication (n = 14) and fatal injury death (n = 14) that displayed no pathological changes of myocardium were selected as control group, respectively. Histological analyses were performed to reveal the pathological changes and real-time quantitative polymerase chain reaction (RT-qPCR) was used to determine the expression of those miRNAs. Results It showed that heart samples from the SCD-negative autopsy group displayed no remarkable difference with regard to the expression of cleaved-caspase3, CD31, and CD68 and the extent of fibrotic tissue accumulation when compared with control samples. The four cardio-miRNAs were significantly up-regulated in the SCD samples as compared with control. When discriminating SCD from controls, receiver operating characteristic (ROC) curve analysis revealed that the areas under the curve (AUC) of these 4 miRNAs were from 0.7839 to 0.9043 with sensitivity of 64.71–97.06% and specificity of 70–100%. Moreover, when discriminating the specific causes of SCD, the four miRNA expressions increased in the heart from the SCD-negative autopsy group as relative to that from the SCD-positive autopsy group, and a combination of two miRNAs presented higher diagnostic value (AUC = 0.7407–0.8667). Conclusion miR-3113-5p, miR-223-3p, miR-499a-5p, and miR-133a-3p may serve as independent diagnostic biomarkers for SCD, and a combination of two of these miRNAs could further discriminate detailed causes of SCD.

Adiponectin (ADPN) plays an important role in cerebral ischemia-reperfusion injury. Although previous studies have confirmed that ADPN pretreatment has a protective effect on ischemic stroke, the therapeutic effect of ADPN on ischemic stroke and the underlying mechanism are still unclear. In order to clarify these questions, focal transient cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in mice and ADPN was administered for three times at 6 h, 24 h, and 48 h after reperfusion. Meanwhile, a virus-delivered HIF-1α siRNA was used before ADPN administration. The infarct volume, neurological score, cellular apoptosis, and oxidative stress were assessed at 72 h after reperfusion. The long-term outcome of mice after stroke was recorded as well. The results indicated that ADPN treatment reduced the infarct volume ( P = 0.032 ), neurological deficits ( P = 0.047 ), cellular apoptosis ( P = 0.041 ), and oxidative responses ( P = 0.031 ) at 72 h after MCAO. Moreover, ADPN increased both the protein level and transcriptional activity of HIF-1α as evidenced by the transcription levels of VEGF ( P = 0.046 ) and EPO ( P = 0.043 ) at 72 h after MCAO. However, knockdown of HIF-1α partially reversed the antioxidant and treatment effect of ADPN after cerebral ischemia. In the observation of long-term outcome after ADPN treatment, it demonstrated that ADPN not only prevented the cerebral atrophy ( P = 0.031 ) and the neurological function decline ( P = 0.048 ), but also promoted angiogenesis ( P = 0.028 ) after stroke. In conclusion, our findings suggest that ADPN is effective in treatment of ischemic stroke which could be attributed to the increased antioxidant capacity regulated by HIF-1α.

Sustainable urbanization is promoted as a critical component of sustainable development trend across the globe because of their directly significant influence on sustainability. Public-Private Partnerships (PPPs) are utilized as a significant tool to address the problems of budgetary constraints and limited expertise in urbanization process. However,the private sectors’ excessive pursuit of short-term financial interests may jeopardize the achievement of sustainable development. A sustainability-oriented performance assessment is proposed as an effective way to create incentives that encourage the private sector to participate into more sustainable urbanization process. The study thus established a conceptual framework for identifying performance indicators that can be used for performance assessment purpose. The proposed framework provides a logic method for developing performance indicators from the perspective of sustainability objectives and lifecycle process of PPP urbanization projects. Indicators identified by the framework are corresponding to sustainability objectives and therefore beneficial for promoting the rapid urbanization process into a more sustainable direction. Besides, they cover the lifecycle process of PPP urbanization projects and thus capable of providing insight into the critical aspects in the process control of projects.

Hot dry rock (HDR) geothermal energy has many advantages, such as being renewable, clean, widely distributed, and without time and weather limitations. Hydraulic fracturing is usually needed for the exploitation of HDR geothermal energy. It has many hidden faults in the reservoir/caprock sequences. Injecting fluid into underground formations during hydraulic fracturing often induces fault slip and leads to earthquakes. Therefore, to well understand the induced fault slip and earthquakes is important for the applications and development of HDR geothermal exploitation. In this study, we investigated the hazardous injection area of the induced earthquakes during hydraulic fracturing. The study was based on a hydraulic fracturing test in Qiabuqia geothermal field in China. According to the field, a fault-surrounding rock-fracturing region system was developed to study the influences of fluid injection on the stability of the specific fault. A total of 60 hydraulic fracturing regions and 180 numerical experiments were designed. The results revealed that the hazardous injection regions that threaten the fault’s stability were near to the fault and concentrated on the following four areas: (a) above the top of the fault in underlying strata; (b) above the top of the hanging wall of the fault in underlying strata; (c) near to the fault planes in both footwall and hanging wall; (d) at the bottom of the footwall of the fault in underlying strata. The hazardous injection area can be controlled effectively by adjusting the injection pressure.

Rosmarinic acid (RA), a natural polyphenol, possesses potent antioxidant and anti-inflammatory activities. To evaluate the ability of RA to cure ischemic stroke and post-stroke depression (PSD), rats were treated with various doses of RA after cerebral ischemia. Neurological deficits and infarct volume of the brain were measured. The activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were examined at different time points. In addition, a forced swimming test and sucrose preference test were performed to detect the anti-depressive effects of RA. Our results revealed RA administration significantly alleviated neurological deficits and reduced infarct volumes. RA attenuated the decrease of SOD, CAT activities and GSH levels in the ischemic penumbra of the brain. Most importantly, RA treatment alleviated the depression behaviors. Increased expression of Nrf2 was also induced by RA, while down regulation Nrf2 by Nrf2-short-hairpin RNA sequences reversed the increasing activity of SOD and CAT induced by RA, as well as the protection against PSD. The present study indicates that RA exerts a potent neuroprotective effect against stroke and PSD, which could be a promising therapeutic intervention for stroke.

Postmenopausal women have a higher incidence of stroke compared to the age-matched males, and the estrogen was thought to be the main cause of such difference. However, estrogen replacement therapy for the prevention of postmenopausal stroke shows controversial results and is widely disputed because of its serious side effects after chronic administration. Genistein (Gen), a natural phytestrogen with fewer side effects, has a protective effect against cerebral ischemia damage. However, whether Gen could effectively prevent postmenopausal stroke has not been elucidated. In the current study, reproductively senescent mice were treated with Gen (10 mg/kg) for 2 weeks before having transient cerebral ischemia insults. Neurological scores, infarct volumes, and cell apoptosis were evaluated 24 h after reperfusion. The levels of inflammatory factors and nod-like receptor protein 3 (NLRP3) inflammasome-related proteins were also examined. The results showed that Gen treatment reduced infarct volumes, improved neurological scores, attenuated apoptosis, and decreased inflammatory factor release. The expression of NLRP3 inflammasome-related proteins in microglia was downregulated by Gen. However, the overexpression of NLRP3 in microglia abrogated the Gen-induced inhibition of inflammatory factor release and reversed the neuroprotective effect of Gen. Taken together, the results suggest that Gen treatment could attenuate the acute injury induced by cerebral ischemia in reproductively senescent mice via the inhibition of the NLRP3 inflammasome in microglia, indicating that Gen could be a candidate drug for the treatment of stroke in postmenopausal women.

Studies have failed to translate more than 1000 experimental treatments from bench to bedside, leaving stroke as the second leading cause of death in the world. Thrombolysis within 4.5 hours is the recommended therapy for stroke and cannot be performed until neuroimaging is used to distinguish ischemic stroke from hemorrhagic stroke. Therefore, finding a common and critical therapeutic target for both ischemic and hemorrhagic stroke is appealing. Here, we report that the expression of myeloid differentiation protein 2 (MD2), which is traditionally regarded to be expressed only in microglia in the normal brain, was markedly increased in cortical neurons after stroke. We synthesized a small peptide, Trans-trans-activating (Tat)-cold-inducible RNA binding protein (Tat-CIRP), which perturbed the function of MD2 and strongly protected neurons against excitotoxic injury in vitro. In addition, systemic administration of Tat-CIRP or genetic deletion of MD2 induced robust neuroprotection against ischemic and hemorrhagic stroke in mice. Tat-CIRP reduced the brain infarct volume and preserved neurological function in rhesus monkeys 30 days after ischemic stroke. Tat-CIRP efficiently crossed the blood-brain barrier and showed a wide therapeutic index for stroke because no toxicity was detected when high doses were administered to the mice. Furthermore, we demonstrated that MD2 elicited neuronal apoptosis and necroptosis via a TLR4-independent, Sam68-related cascade. In summary, Tat-CIRP provides robust neuroprotection against stroke in rodents and gyrencephalic nonhuman primates. Further efforts should be made to translate these findings to treat both ischemic and hemorrhagic stroke in patients.

Background Sevoflurane preconditioning induces brain ischemic tolerance, but the mechanism remains poorly elucidated. Nitration is an important form of post-translational modification in pathological signaling. This study was to investigate the role of thioredoxin-1 (Trx-1) nitration in neuroprotection effect induced by sevoflurane preconditioning in a transient stroke model in rats. Methods Adult male Sprague–Dawley rats were preconditioned with 2% sevoflurane or vehicle oxygen exposure, 1 h per day, for 5 consecutive days. At 24 h after the last exposure, rats were subjected to focal brain ischemia induced by middle cerebral artery occlusion (MCAO) for 90 min, followed by 72-h reperfusion. Trx-1 expression and activity, as well as the content of nitrotyrosine at penumbra were detected at 24 h after preconditioning and 2, 8, 24, 72 h after MCAO. Nitrated Trx-1 was examined by immunoprecipitation at 8 h after MCAO. The role of Trx-1 nitration in ischemic tolerance was assessed by administration of nitrated human-Trx-1 prior to MCAO. Neurological scores, brain infarct volumes and TUNEL staining were evaluated at 24 h after reperfusion. Results Ischemic stroke decreased Trx-1 activity but not the expression in penumbra tissue. The content of nitrotyrosine was elevated after MCAO. Preconditioning with sevoflurane increased Trx-1 activity and reduced its nitration at 8 h after MCAO in comparison with vehicle preconditioning. The decrement of Trx-1 activity was correlated with its nitration level. Exogenous administration of nitrated human-Trx-1 reversed the brain ischemic tolerance of sevoflurane preconditioning, exacerbating brain infarct volume, neurobehavioral defects and apoptosis, while administration of human-Trx-1 had no effect on the sevoflurane preconditioning-induced neuroprotection. Conclusion Ischemic stroke reduces Trx-1 activity via post-translational nitrative modulation in rats. Sevoflurane preconditioning induces brain ischemic tolerance and anti-apoptosis by partially preserving Trx-1 activity via inhibiting nitration.

The role of autophagy varies with the type of acute brain injury. In general, autophagy mediates a clear neuroprotective effect in intoxication caused by various psychoactive agents, subarachnoid hemorrhage and spinal cord injury. In contrast, autophagic cell death has also been reported to actively contribute to neuronal loss in neonatal hypoxic ischemic encephalopathy. However, it still remains to be determined whether autophagy pays a cytoprotective or a cytotoxic role in stroke. Previous studies focused primarily on the role of neurons rather than the role of astrocytes in brain injury. Thus, it is unknown whether modulating the autophagy flux of astrocytes contributes to improving neuronal survival after stroke. In the current study, we investigated the time course of autophagy flux in vitro using cocultured astrocytes and neurons exposed to oxygen-glucose deprivation/reoxygenation, which mimicked the process of ischemia/reperfusion. Autophagy flux of astrocytes was regulated by treatment with the autophagy inducer rapamycin, autophagy inhibitor 3-methyladenine, and the transduction of small interfering RNA against autophagy-related gene 5. In addition, AAV-GFAP-ATG7 was used to induce astrocyte autophagy flux in mice subjected to focal cerebral ischemia. We found that induction of autophagy flux of astrocytes in vitro enhanced the viability of neurons and decreased neuronal apoptosis. Furthermore, induction of astrocyte autophagy flux in mice improved neurological outcomes. In contrast, inhibition of autophagy flux in astrocytes decreased the viability of neurons and increased neuronal apoptosis. These results suggest that upregulation of autophagy flux in astrocytes may contribute to endogenous neuroprotective and neurorecovery mechanisms after stroke.

We present a new spine solution for the locomotion of human-scale robots on steep, rocky surfaces, known as linearly-constrained spines. The spine stiffness is low in the normal direction but high with respect to lateral and bending loads. The solution differs from previous spine arrays used for small robots in having a much higher spine density and less spine scraping over asperities. We present theoretical and empirical results to demonstrate that this solution is capable of shear stresses of over 200kPa, enabling human-scale robots to apply forces parallel to steep rock surfaces for climbing, bracing, etc. The analysis includes the effects of spine geometry, stiffness, backlash and three-dimensional loading angle to predict the overall forces possible in three dimensions of both single and opposed configurations of spine arrays. Demonstrated applications include a gripper for a “smart staff” aimed at helping humanoid robots to negotiate steep terrain and a palm that provides over 700N in shear for the RoboSimian quadruped.

Summary Astrocytic glycogen is an important energy reserve in the brain and is believed to supply fuel during energy crisis. However, the pattern of glycogen metabolism in ischemic stroke and its potential therapeutic impact on neurological outcomes are still unknown. Here, we found extensive brain glycogen accumulation after reperfusion in ischemic stroke patients and primates. Glycogenolytic dysfunction in astrocytes is responsible for glycogen accumulation, caused by inactivation of the protein kinase A (PKA)-glycogen phosphorylase kinase (PhK)-glycogen phosphorylase (GP) cascade accompanied by the activation of glycogen synthase kinase-3β (GSK3β). Genetic or pharmacological augmentation of astrocytic GP could promote astrocyte and neuron survival and improve neurological behaviors. In addition, we found that insulin exerted a neuroprotective effect, at least in part by rescuing the PKA-PhK-GP cascade to maintain homeostasis of glycogen metabolism during reperfusion. Together, our findings suggest a promising intervention for undesirable outcomes in ischemic stroke., Graphical Abstract, Highlights • Glycogen accumulates upon cerebral reperfusion in humans, primates, and rodents • Impaired glycogenolysis underlies excess glycogen during cerebral reperfusion • Activating glycogenolysis protects against acute and subacute reperfusion insult • Insulin mediates neuroprotection partly by rescuing glycogenolysis upon reperfusion, Neuroscience; Molecular Neuroscience; Cellular Neuroscience

We present a hand specialized for climbing unstructured rocky surfaces. Articulated fingers achieve grasps commonly used by human climbers. The gripping surfaces are equipped with dense arrays of spines that engage with asperities on hard rough materials. A load-sharing transmission system divides the shear contact force among spine tiles on each phalanx to prevent premature spine slippage or grasp failure. Taking advantage of the hand’s kinematic and load-sharing properties, the wrench space of achievable forces and moments can be computed rapidly. Bench-top tests show agreement with the model, with average wrench space errors of 10–15%, despite the stochastic nature of spine/surface interaction. The model provides design guidelines and control strategy insights for the SpinyHand and can inform future work.

Underactuated, compliant, tendon-driven robotic hands are suited for deep-sea exploration. The robust Ocean One hand design utilizes elastic finger joints and a spring transmission to achieve a variety of pinch and wrap grasps. Compliance in the fingers and transmission determines the degree of load-sharing among contacts and the hands’ ability to secure irregularly shaped objects. However, it can also decrease external grasp stiffness and acquisition reliability. SimGrasp, a flexible dynamic hand simulator, enables parametric studies of the hand for acquisition and pull-out tests with varying transmission spring rates. In the present application, we take advantage of achieving different stiffnesses by reversing the direction of tendon windup using a torsional spring-loaded winch. With this provision, the hand can be relatively soft for handling delicate objects and stiff for tasks requiring strength. Two hands were field-tested as part of the Ocean One humanoid platform, which acquired a vase from the La Lune shipwreck site at a 91 m depth in the Mediterranean Sea.

Customers are regarded as the key intangible assets of a firm. Therefore, it is necessary for firms to have the capability to anticipate customer value. The study investigates the relationships among customer value anticipation, product innovativeness, and customer lifetime value from the customer's perspective. Empirical evidence from 178 MBA students shows that customer perceived customer value anticipation can significantly influence product innovativeness and the relationship is partially mediated by product innovativeness. In addition, both functional and emotional advertising are found to play a moderating role in the relationship between product innovativeness and customer lifetime value. The paper concludes with a discussion of the theoretical and managerial implications of the empirical study.

It is known that preconditional treatment with volatile anesthetics can induce tolerance of the brain to stroke. A previous study demonstrated that the involvement of TREK-1, a two-pore domain K+ channel, in sevoflurane preconditioning induced neuroprotection against focal cerebral ischemia in rats. The present study testified whether TREK-2, another anesthetic-target K+ channel, is also associated with volatile anesthetic-induced neuroprotection, and further explored its potential mechanism. Rats preconditioned with isoflurane were subjected to 1.4vol% isoflurane plus 98% O

Background The steroid hormone estrogen (17-β-estradiol, E2) provides neuroprotection against cerebral ischemic injury by activating estrogen receptors. The novel estrogen receptor G protein-coupled receptor 30 (GPR30) is highly expressed in the brain and provides acute neuroprotection against stroke. However, the underlying mechanisms remain unclear. Methods In this study, ovariectomized female mice were subjected to middle cerebral artery occlusion (MCAO), and E2, G1, and ICI182780 were administered immediately upon reperfusion. The infarction volume, neurological scores, and neuronal injuries were examined. Primary microglial cells were subjected to oxygen-glucose deprivation (OGD), and the drugs were administered immediately upon reintroduction. The pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 in penumbra and microglia were assessed by ELISA. The cell viability and lactose dehydrogenase (LDH) release of neurons co-cultured with microglia were analyzed using cell counting kit-8 (CCK8) and LDH release assays. Microglial activation as well as GPR30, Iba1, and Toll-like receptor 4 (TLR4) protein expression and TLR4 mRNA expression were detected. Additionally, NF-κB activity was detected in lipopolysaccharide (LPS)-activated microglia after the activation of GPR30. Results GPR30 was highly expressed in microglia and significantly increased after ischemic injury. The activation of GPR30 significantly reduced the infarction volume, improved the neurological deficit, and alleviated neuronal injuries. Moreover, GPR30 activation significantly reduced the release of TNF-α, IL-1β, and IL-6 from ischemic penumbra and microglia subjected to OGD and alleviated neuronal injury as assessed using the CCK8 and LDH assays. Finally, the activation of GPR30 relieved microglial activation, reduced Iba1 and TLR4 protein expression and TLR4 mRNA levels, and inhibited NF-κB activity. Conclusions Microglial GPR30 exerts acute neuroprotective effects by inhibiting TLR4-mediated microglial inflammation, which indicates that GPR30 may be a potential target for the treatment of ischemic stroke. Electronic supplementary material The online version of this article (10.1186/s12974-018-1246-x) contains supplementary material, which is available to authorized users.

Oxidative stress is closely related to the pathogenesis of ischemic stroke. Protocatechualdehyde (PCA) is a phenolic acid compound that has the putative antioxidant activities. The present study was aimed to investigate the molecular mechanisms involved in the antioxidative effect of PCA against cerebral ischemia/reperfusion (I/R) injury. The experiment stroke model was produced in Sprague-Dawley rats via middle cerebral artery occlusion (MCAO). To model ischemia-like conditions in vitro, differentiated SH-SY5Y cells were exposed to transient oxygen and glucose deprivation (OGD). Treatment with PCA significantly improved neurologic score, reduced infarct volume and necrotic neurons, and also decreased reactive oxygen species (ROS) production, 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents at 24 h after reperfusion. Meanwhile, PCA significantly increased the transcription nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions in the ischemic cerebral cortex as shown by immunofluorescence staining and Western blot analysis. In vitro experiment showed that PCA protected differentiated SH-SY5Y cells against OGD-induced injury. Likewise, PCA also increased markedly the Nrf2 and HO-1 expressions in a dose-dependent manner. The neuroprotection effect of PCA was abolished by knockdown of Nrf2 and HO-1. Moreover, knockdown of protein kinase Cε (PKCε) also blocked PCA-induced Nfr2 nuclear translocation, HO-1 expression, and neuroprotection. Taken together, these results provide evidences that PCA can protect against cerebral ischemia-reperfusion-induced oxidative injury, and the neuroprotective effect involves the PKCε/Nrf2/HO-1 pathway.

Therapeutics targeting the Nogo-A signal pathway hold promise to promote recovery following brain injury. Based on the temporal characteristics of Nogo-A expression in the process of cerebral ischemia and reperfusion, we tested a novel asynchronous treatment, in which TAT-M9 was used in the early stage to decrease neuronal loss, and TAT-NEP1-40 was used in the delayed stage to promote neurite outgrowth after bilateral common carotid artery occlusion (BCCAO) in mice. Both TAT-M9 and TAT-NEP1-40 were efficiently delivered into the brains of mice by intraperitoneal injection. TAT-M9 treatment promoted neuron survival and inhibited neuronal apoptosis. Asynchronous therapy with TAT-M9 and TAT-NEP1-40 increased the expression of Tau, GAP43 and MAP-2 proteins, and enhanced short-term and long-term cognitive functions. In conclusion, the asynchronous treatment had a long-term neuroprotective effect, which reduced neurologic injury and apoptosis, promoted neurite outgrowth and enhanced functional recovery after ischemia. It suggests that this asynchronous treatment could be a promising therapy for cerebral ischemia in humans.

Grasping and manipulating uncooperative objects in space is an emerging challenge for robotic systems. Many traditional robotic grasping techniques used on Earth are infeasible in space. Vacuum grippers require an atmosphere, sticky attachments fail in the harsh environment of space, and handlike opposed grippers are not suited for large, smooth space debris. We present a robotic gripper that can gently grasp, manipulate, and release both flat and curved uncooperative objects as large as a meter in diameter while in microgravity. This is enabled by (i) space-qualified gecko-inspired dry adhesives that are selectively turned on and off by the application of shear forces, (ii) a load-sharing system that scales small patches of these adhesives to large areas, and (iii) a nonlinear passive wrist that is stiff during manipulation yet compliant when overloaded. We also introduce and experimentally verify a model for determining the force and moment limits of such an adhesive system. Tests in microgravity show that robotic grippers based on dry adhesion are a viable option for eliminating space debris in low Earth orbit and for enhancing missions in space.

The collapse of the blood-brain barrier (BBB) is one of the fundamental pathophysiology changes during cerebral ischemia reperfusion injury. Resveratrol has been recently reported to reduce cerebral ischemic damage by regulating the matrix metalloproteinase-9 (MMP-9). But, more direct evidence for the explanation of the BBB protected by resveratrol against cerebral ischemia reperfusion is still lacking. Therefore, the present study was aimed to investigate the regulation of BBB integrity by resveratrol after cerebral ischemia reperfusion and to determine the role of the MMP-9 and its endogenous inhibitor TIMP-1 balance in this process. Cerebral ischemia was induced by middle cerebral artery occlusion in rats. The BBB function was evaluated by brain water content and the Evans blue dye extravasation; the activities of MMP-9 and TIMP-1 were detected by using gelatin zymography analysis, and cellular apoptosis was examined by TUNEL staining. We confirmed that resveratrol reduced the cerebral ischemia reperfusion damage, brain edema, and Evans blue dye extravasation. Moreover, we found that resveratrol improved the balance of MMP-9/TIMP-1 in terms of their expressions and activities. A TIMP-1 neutralizing antibody reversed those neuroprotective effects of resveratrol. In conclusion, resveratrol attenuated the cerebral ischemia by maintaining the integrity of BBB via regulation of MMP-9 and TIMP-1.

We have previously shown that electroacupuncture (EA) pretreatment produces neuroprotective effects, which were mediated through an endocannabinoid signal transduction mechanism. Herein, we have studied the possible contribution of the phosphorylated form of glycogen synthase kinase-3β (GSK-3β) in EA pretreatment-induced neuroprotection via the cannabinoid CB1 receptor (CB1R). Focal transient cerebral ischemia was induced by middle cerebral artery occlusion in rats. Phosphorylation of GSK-3β at Ser-9 [p-GSK-3β (Ser-9)] was evaluated in the penumbra tissue following reperfusion. Infarct size and neurological score were assessed in the presence of either PI3K inhibitors or a GSK-3β inhibitor 72 h after reperfusion. Cellular apoptosis was evidenced by TUNEL staining and determination of the Bax/Bcl-2 ratio 24 h after reperfusion. The present study showed that EA pretreatment increased p-GSK-3β(Ser-9) 2 h after reperfusion in the ipsilateral penumbra. Augmented phosphorylation of GSK-3β induced similar neuroprotective effects as did EA pretreatment. By contrast, inhibition of PI3K dampened the levels of p-GSK-3β(Ser-9), and reversed not only the neuroprotective effect but also the anti-apoptotic effect following EA pretreatment. Regulation of GSK-3β by EA pretreatment was abolished following treatment with a CB1R antagonist and CB1R knockdown, whereas two CB1R agonists enhanced the phosphorylation of GSK-3β. Therefore we conclude that EA pretreatment protects against cerebral ischemia/reperfusion injury through CB1R-mediated phosphorylation of GSK-3β.

Tanshinone IIA (TSA), a principal component derived from the Traditional Chinese Medicine Danshen has been suggested to exert neuroprotective effect against experimental cerebral ischemic/reperfusion injury. But the associated underlying mechanisms still have not been understood. The current study characterized the role of nuclear factor erythroid two-related factor-induced antioxidant response in the neuroprotective efficacy of TSA treatment. The focal cerebral ischemia/reperfusion model was established by 60-minute middle cerebral artery occlusion. At the onset during reperfusion, mice were treated with 10 mg/kg TSA intraperitoneally. The mRNA and nuclear factor erythroid 2 (Nrf2) protein expression, the antioxidant enzymes, and oxidative production levels were measured. To further verify the role of Nrf2 in the neuroprotective effect induced by TSA, the Nrf2 small silenced RNA and Nrf2 knockout mice were used, the neurological function, brain infarct volume, and cellular apoptosis examination were assessed. TSA treatment improved neurological scores, reduced infarct volume, and attenuated the cellular apoptosis. TSA treatment upregulated the expression of Nrf2 mRNA and the contents of Nrf2 protein in nuclear extract. Nrf2 activation by TSA treatment increased the contents of antioxidant enzymes, and reduced the generation of oxidative productions. Either Nrf2 knockdown or Nrf2 knockout abolished the antioxidative and neuroprotective effect of TSA treatment. These results demonstrate that the Nrf2 activation contributes to TSA-induced neuroprotection from experimental ischemic stroke through maintaining antioxidant effect.

International audience; The promise of oceanic discovery has long intrigued scientists and explorers, whether with the idea of studying underwater ecology and climate change or with the hope of uncovering natural resources and historic secrets buried deep in archaeological sites. This quest to explore the oceans requires skilled human access, yet much of the oceans are inaccessible to human divers; nearly ninetenths of the ocean floor is at 1 km or deeper [1]. Accessing these depths is imperative since factors such as pollution and deep-sea trawling threaten ecology and archaeological sites. While remotely operated vehicles (ROVs) are inadequate for the task, a robotic avatar could go where humans cannot and still embody human intelligence and intentions through immersive interfaces.

We present a new palm design that features a dense array of micro-spines for the JPL Robosimian human-scale climbing robot. A linearly-constrained spine mechanism is introduced and analyzed using adhesion and stiffness models. This mechanism achieves a spine density of 19/cm2 and a mean adhesion of 67N (207kPa) on coarse concrete surfaces. The models are validated on two different surfaces with two sets of experiments. A 120×100mm palm consisting of 12 spine tiles and a pulley differential system for load sharing are designed and tested on 9 different surfaces. The mean shear adhesion goes up to 710N (183kPa) on concrete blocks. Design considerations include scaling efficiency and maximal single-spine force. Desirable properties for load sharing in the palm design are discussed.

Background and Purpose— Endogenous neuroprotection can be induced by ischemic and nonischemic preconditioning. However, not all subjects that undergo preconditioning exhibit similar favorable outcome. This study is to explore the molecules responsible for this phenomenon and find new therapeutic targets for stroke. Methods— Adult male Sprague–Dawley rats were subjected to transient middle cerebral artery occlusion. High-throughput proteomic technique, isobaric tag for relative and absolute quantification, was used to screen differentially expressed proteins in the rats that developed ischemic tolerance from hyperbaric oxygen (HBO) preconditioning. The proteomic results were verified by Western blot and ELISA. Then, short interfering RNA and gene knockout rats were used to further determine the pivotal role of candidate proteins in HBO preconditioning–induced endogenous neuroprotection. Finally, lysosomal permeability was tested to elaborate the mechanism underlying this intrinsic neuroprotective effect. Results— Nine proteins differentially expressed in the serum of rats, which acquired benefits from HBO preconditioning, were screened and identified. Western blot and ELISA revealed that cystatin C (CysC) and mannose-binding lectin protein C were uniquely changed in rats with smaller infarction after HBO preconditioning and cerebral ischemia. Knockdown and knockout of CysC abolished HBO-induced neuroprotection. Moreover, HBO-induced endogenous CysC elevation preserved lysosomal membrane integrity after stroke in wild-type rats but not in CysC siRNA infusion or CysC − /− rats. Most importantly, exogenous CysC also induced neuroprotection against ischemic/reperfusion injury. Conclusions— CysC is a crucial determinant contributing to endogenous neuroprotection. It is also a novel candidate for stroke treatment through maintaining lysosomal membrane integrity.

Background A wealth of evidence has demonstrated that sevoflurane preconditioning induces brain ischemic tolerance, but the mechanism remains poorly understood. This study was designed to investigate the role of canonical Notch signaling in the neuroprotection induced by sevoflurane preconditioning in a mouse model. Methods C57BL/6 mice were pretreated with 1-h sevoflurane exposure at a dose of 2.5% for 5 consecutive days. Twenty-four hours after the last exposure, all mice were subjected to focal cerebral ischemia by right middle cerebral artery occlusion for 60 min. Neurobehavioral scores, brain infarct volumes, and cellular apoptosis were determined at 72 h after reperfusion (n = 10 per group). The activation of Notch signaling was evaluated (n = 5 per group), and its role in ischemic tolerance was assessed by intraperitoneal administration of γ-secretase inhibitor DAPT (100 mg/kg, n = 10 per group) and conditional Notch-RBP-J knockout technique (n = 8 per group). Results Sevoflurane preconditioning reduced brain infarct volumes (42.5%), improved neurologic outcomes (P < 0.01 vs. control), and attenuated neuronal cell apoptosis (cells positive for terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate nick-end labeling reduced to 21.2%). The expression of Notch1 intracellular domain (1.35 folds) and the transcriptions of Hes1 (1.95 times) and Hes5 (1.48 times) were up-regulated. DAPT augmented the brain infarcts (1.64-fold) and decreased neurologic scores (P = 0.43 vs. sevoflurane) in sevoflurane-preconditioned mice. Brain infarct volumes, neurobehavioral scores, and apoptotic cell numbers showed no significance between Notch knockout mice with sevoflurane preconditioning and wild-type mice without preconditioning. Conclusions Sevoflurane preconditioning-induced protective effects against transient cerebral ischemic injuries are mediated by the activation of canonical Notch signaling pathway in mice.

This paper presents a computational model and design optimization strategy for shape memory alloy (SMA) flexural actuators. These actuators consist of curved SMA wires embedded within elastic structures, one potential application is positioning microcatheters inside blood vessels during clinical treatments. Each SMA wire is shape-set to an initial curvature and inserted along the neutral axis of a straight elastic member (cast polydimethylsiloxane, PDMS). The elastic structure preloads the SMA, reducing the equilibrium curvature of the composite actuator. Temperature-induced phase transformations in the SMA are achieved via Joule heating, enabling strain recovery and increased bending (increased curvature) in the actuator. Actuator behavior is modeled using the homogenized energy framework, and the effects of two critical design parameters (initial SMA curvature and flexural rigidity of the elastic sleeve) on activation curvature are investigated. Finally, a multi-objective genetic algorithm is utilized to optimize actuator performance and generate a Pareto frontier, which is subsequently experimentally validated.

Human behavior analysis is an important area of research in computer vision and is also driven by a wide spectrum of applications, such as smart video surveillance and human-computer interface. In this paper, we present a novel approach for human behavior analysis. Two research challenges, motion representation and behavior recognition, are addressed. A novel motion descriptor, which is an improved feature based on optical flow, is proposed for motion representation. Optical flow is improved with a motion filter, and feature fusion with the shape and trajectory information. To recognize the behavior, the support vector machine is employed to train the classifier where the concatenation of histograms is formed as the input features. Experimental results on the Weizmann behavior database and the Institute of Automation, Chinese Academy of Science real-world multiview behavior database demonstrate the robustness and effectiveness of our method.

OBJECTIVE The goal of this study was to demonstrate that repetitive pure oxygen exposure preconditioning (O2PC) for 8 hours per day for 3 or 7 days, a practicable preconditioning for clinical use, is able to induce cerebral ischemic tolerance (IT) and further clarify the accompanying changes in the blood-brain barrier (BBB) that may be involved. METHODS A total of 68 adult male Sprague-Dawley rats and eight 1-day-old rat pups were used in this study. The adult rats were exposed to pure O2 (38 rats) 8 hours a day for 3 or 7 days or to room air (in an identical setup) for 8 hours a day for 7 days as controls (30 rats). Arterial O2 tension (PaO2) was measured in 6 rats exposed to O2 and 3 controls. Focal cerebral ischemia was elicited by middle cerebral artery occlusion (MCAO) in 37 rats, of which 21 had been exposed to pure O2 for 3 or 7 days and 16 to room air for 7 days as controls. Neurological behavior was scored with the Garcia score in 15 MCAO rats, of which 10 had been exposed to pure O2 for 3 or 7 days and 5 to room air for 7 days as controls, and cerebral infarct volumes were assessed with TTC (2,3,5-triphenyltetrazolium chloride) staining in 10 rats (5 from each group) after 7 days of exposure. Formamide-extraction method was used to detect leakage of Evans blue (EB) dye in 7 rats exposed to pure O2 for 7 days and 7 exposed to room air for 7 days. Fluorescence microscopy was used to analyze the leaked EB in the nonischemic areas of 4 rats exposed to pure O2 for 7 days and 4 exposed to room air for 7 days before MCAO and the brain of the rats that had not been subjected to MCAO. Astrocyte changes associated with O2PC were evaluated by means of fluorescence microscopy and electron microscopy in 14 rats that were exposed to the same O2 or control conditions as the MCAO rats but without MCAO. Astrocytes were also obtained from 8 rat pups and cultured; levels of AQP4 and VEGF were detected by Western blot and ELISA in cells with and without O2 treatment. RESULTS A significant increase in PaO2 was seen after O2PC. The neurological score was significantly increased in the O2PC groups (10.6 ± 0.6 in the 3-day O2PC group, p < 0.05; 12 ± 0.84 in the 7-day O2PC group, p < 0.05) compared with the control group (7 ± 0.55). The ratio of cerebral infarct volume to contralateral cerebral hemisphere volume was significantly lower in the O2PC group than in the control group (0.204 ± 0.03 vs 0.48 ± 0.05, p < 0.05). The amount of leaked EB in the ischemic cerebral hemisphere was also lower in the O2-treated rats than in controls (7.53 ± 1.4 vs 11.79 ± 3.3 μg EB/g brain weight, p < 0.05). However, fluorescence microscopy showed significantly greater BBB permeability in the nonischemic areas in the O2PC group than in controls (p < 0.05). More red fluorescence could be observed in the nonischemic areas in both the ipsilateral and contralateral sides of the ischemic brain in the O2PC animals than in the nonischemic areas in the corresponding sides of the controls. Further investigation of the effect of the O2PC itself on the BBB of rats that were not subjected to MCAO showed that there was no EB leakage in the brain parenchyma in the rats exposed to room air, but some red fluorescence patches were noticed in the normal brain from the rats in the O2PC group. Astrocytes, including those from areas around the BBB, were activated in the O2PC group. Levels of both aquaporin 4 (AQP4) and vascular endothelial growth factor (VEGF) were significantly increased in cultured astrocytes after O2PC. CONCLUSIONS These findings suggest that O2PC is able to induce IT, which makes it a strong candidate for clinical use. Moreover, O2PC can also promote BBB opening, which may contribute to the induction of IT as well as representing a possible strategy for promoting drug transportation into the CNS. Activated astrocytes are likely to be involved in these processes through astrocyte-derived factors, such as AQP4 and VEGF.

Tower-like ZnO structures have been prepared by a simple carbon thermal reduction method and the possible growth mechanism of such structures was discussed. Comparing with microrods and nanowires, the photoluminescence images and spectra of tower-like ZnO were examined to understand the origins of their visible emissions, which is vital to future ultraviolet display devices. The visible photoluminescence locations of ZnO structures were studied by the near-field scanning optical microscopy. The experimental data indicate that the structure defects, surface impurities or dust, and adsorbed oxygen molecules can induce the visible emission of various ZnO nanostructures.

Pinching is an important capability for mobile robots handling small items or tools. Successful pinching requires force-closure and, in underwater applications, gentle suction flow at the fingertips can dramatically improve the handling of light objects by counteracting the negative effects of water lubrication and enhancing friction. In addition, monitoring the flow gives a measure of suction-engagement and can act as a binary tactile sensor. Although a suction system adds complexity, elastic tubes can double as passive spring elements for desired finger kinematics.

We present a light, actuated smart staff with 5DOF tip force sensing which can be used by a humanoid robot operating in challenging terrain. The staff has an extension mechanism that employs mechanical multiplexing to achieve a high extension ratio in a stiff and compact package. The tip force sensor uses two metal diaphragms to achieve decoupling of axial and radial forces and the ability to tune the maximum range of forces in each direction independently. With the force sensor, the robot can characterize the coefficient of friction and orientation of a surface with simple motion primitives. Two sets of experiments were conducted with the smart staff manipulated by a 7 DOF robot arm. Using the sensor, the robot was able to determine the orientations of sloped surfaces within two degrees in two orthogonal directions.

Stroke remains the third leading cause of death. The rising of stroke illness and the continuous aging of the global population requires a collaboration of stroke services systems based on relations and exchange of information to address needs of caregiver and patients in the healthcare community. The collaborative stroke services system involves interconnected changes and the development of integrated healthcare information systems and novel healthcare services. We present the SS4CSHC, a services system for the collaboration in stroke healthcare cycle, to contribute to information sharing and cooperation for the stroke surveillance, prevention, emergency therapy, diagnosis, treatment, and rehabilitation. Some of critical and novel stroke healthcare services are developed and deployed, and innovative models and services for delivery and the coordination of stroke healthcare are explored by the stroke healthcare center. The feasibility and efficiency of our services systems are validated in the local medical institutes.

Deregulation of Akt signaling is important in the brain injuries caused by cerebral ischemia in diabetic animals, and the underlying mechanism is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following focal cerebral ischemia in type 2 diabetic db/db mice and their control littermates non-diabetic db/+ mice. db/db mice showed a significant elevation in the expression of CTMP compared to db/+ mice under normal physiological conditions. After ischemia, db/db mice exhibit higher levels of CTMP expression, decreased Akt kinase activity, adverse neurological deficits and cerebral infarction than db/+ mice. To further certain the effectiveness of Akt signaling to the final outcome of cerebral ischemia, the animals were treated with LY294002, an inhibitor of the Akt pathway, which aggravated the ischemic injury in db/+ mice but not in db/db mice. RNA interference-mediated depletion of CTMP were finally applied in db/db mice, which restored Akt activity, improved neurological scores and reduced infarct volume. These results suggest that elevation of CTMP in diabetic mice suppresses Akt activity and ultimately negatively affects the outcome of ischemia. Inhibitors specifically targeting CTMP may be beneficial in the treatment of cerebral ischemia in patients with diabetes.

Background:Mechanism of sevoflurane preconditioning–induced cerebral ischemic tolerance is unclear. This study investigates the role of N-myc downstream–regulated gene-2 (NDRG2) in the neuroprotection of sevoflurane preconditioning in ischemic model both in vivo and in vitro.Methods:At 2 h after sevoflurane (2%) preconditioning for 1 h, rats were subjected to middle cerebral artery occlusion for 120 min. Neurobehavioral scores (n = 10), infarct volumes (n = 10), cellular apoptosis (n = 6), and NDRG2 expression (n = 6) were determined at 24 h after reperfusion. In vitro, cultural astrocytes were exposed to oxygen–glucose deprivation for 4 h. Cellular viability, cytotoxicity, apoptosis, and NDRG2 expression (n = 6) were evaluated in the presence or absence of NDRG2-specific small interfering RNA or NDRG2 overexpression plasmid.Results:Sevoflurane preconditioning decreased apoptosis (terminal deoxynucleotidyl transferase–mediated 2’-deoxyuridine 5’-triphosphate nick-end labeling–positive cells reduced to 31.2 ± 5.3% and cleaved Caspase-3 reduced to 1.42 ± 0.21 fold) and inhibited NDRG2 expression (1.28 ± 0.15 fold) and nuclear translocation (2.21 ± 0.29 fold) in ischemic penumbra. Similar effects were observed in cultural astrocytes exposed to oxygen–glucose deprivation. NDRG2 knockdown by small interfering RNA attenuated oxygen–glucose deprivation–induced injury (cell viability increased to 80.5 ± 4.1%; lactate dehydrogenase release reduced to 30.5 ± 4.0%) and cellular apoptosis (cleaved Caspase-3 reduced to 1.55 ± 0.21 fold; terminal deoxynucleotidyl transferase–mediated 2’-deoxyuridine 5’-triphosphate nick-end labeling–positive cells reduced to 18.2 ± 4.3%), whereas NDRG2 overexpression reversed the protective effects of sevoflurane preconditioning. All the data are presented as mean ± SD.Conclusion:Sevoflurane preconditioning inhibits NDRG2 up-regulation and nuclear translocation in astrocytes to induce cerebral ischemic tolerance via antiapoptosis, which represents one new mechanism of sevoflurane preconditioning and provides a novel target for neuroprotection.

This work has been supported by the KAUST Red SeaRobotics Research Exploratorium. H. Stuart and B. Gardineerare additionally supported by NSF graduate fellowships.The assistance of Eduardo Moreno, Oussama Khatib, TorstenKroeger, and Philip Mullins is gratefully acknowledged.

Background Because neuroprotective effects of estrogen remain controversial, we aimed to investigate the effect of different doses of estradiol (E2) on cerebral ischemia using both in vivo and in vitro experiments. Results PC12 cells were cultured at physiological (10 nM and 20 nM) or pharmacological (10 μM and 20 μM) dosages of E2 for 24 hours (h). The results of 5-bromodeoxyuridine (Brdu) incorporation and flow cytometric analysis showed that physiological doses of E2 enhanced cell proliferation and pharmacological doses of E2 inhibited cell proliferation. After the cells were exposed to oxygen and glucose deprivation (OGD) for 4 h and reperfusion for 20 h, the results of 3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyl tetrazolium bromide (MTT) assay, lactate dehydrogenase (LDH) release assay, flow cytometric analysis and Western blot analysis showed that physiological doses of E2 enhanced cell viability, reduced cell apoptosis and decreased the expression of pro-apoptotic protein caspase-3. In contrast, pharmacological doses of E2 decreased cell viability and induced cell apoptosis. In vivo, adult ovariectomized (OVX) female rats received continuous subcutaneous injection of different doses of E2 for 4 weeks. Transient cerebral ischemia was induced for 2 h using the middle cerebral artery occlusion (MCAO) technique, followed by 22 h of reperfusion. The results of Garcia test, 2, 3, 5-triphenyltetrazolium chloride (TTC) staining showed that 6 μg/kg and 20 μg/kg E2 replacement induced an increase in neurological deficit scores, a decrease in the infarct volume and a reduction in the expression of caspase-3 when compared to animals in the OVX group without E2 treatment. However, 50 μg/kg E2 replacement treatment decreased neurological deficit scores, increased the infarct volume and the expression of caspase-3 when compared to animals in the control group and 6 up/kg or 20 μg/kg E2 replacement group. Conclusion We conclude that physiological levels of E2 exhibit neuroprotective effects on cerebral ischemia; whereas, pharmacological or supraphysiological doses of E2 have damaging effects on neurons after cerebral ischemia.

Stroke has severe consequences in postmenopausal women. As replacement therapy of estrogen have various adverse effects and the undermined outcomes. Genistein, a natural phytoestrogen, has been suggested to be a potential neuroprotective agent for such stroke patients. However, the role of genistein and its underlying mechanism in ovariectomized mice has not yet been evaluated. In the present study, ovariectomized mice were treated with genistein (10 mg/kg) or vehicle daily for two weeks before developing transient cerebral ischemia (middle cerebral artery occlusion). The neurological manifestation was evaluated, and infarct volumes were demonstrated by 2,3,5-triphenyltetrazolium chloride staining at 24 h after reperfusion. In addition, phosphorylation of extracellular signal-regulated kinase (ERK) was detected by Western blotting and immunofluorescence staining, and cellular apoptosis was evaluated in the ischemic penumbra. We found that treatment with genistein reduced infarct volumes, improved neurological outcomes and attenuated cellular apoptosis at 24 h after reperfusion. ERK1/2 showed increased phosphorylation by genistein treatment after reperfusion, and an ERK1/2 inhibitor U0126 abolished this protective effect of genistein in terms of infarct volumes, neurological scores and cellular apoptosis. Our findings indicate that treatment with genistein can reduce the severity of subsequent stroke episodes, and that this beneficial function is associated with ERK activation.

Ethnopharmacological relevance Breviscapine injection is a Chinese herbal medicine standardized product extracted from Erigeron breviscapus (Vant.) Hand.-Mazz. It has been widely used for treating cardiovascular and cerebrovascular diseases. However, the therapeutic time window and the action mechanism of breviscapine are still unclear. The present study was designed to investigate the therapeutic time window and underlying therapeutic mechanism of breviscapine injection against cerebral ischemic/reperfusion injury. Materials and methods Sprague–Dawley rats were subjected to middle cerebral artery occlusion for 2 h followed by 24 h of reperfusion. Experiment part 1 was used to investigate the therapeutic time window of breviscapine. Rats were injected intravenously with 50 mg/kg breviscapine at different time-points of reperfusion. After 24 h of reperfusion, neurologic score, infarct volume, brain water content and serum level of neuron specific enolase (NSE) were measured in a masked fashion. Part 2 was used to explore the therapeutic mechanism of breviscapine. 4-Hydroxy-2-nonenal (4-HNE), 8-hydroxyl-2′- deoxyguanosine (8-OHdG) and the antioxidant capacity of ischemia cortex were measured by ELISA and ferric-reducing antioxidant power (FRAP) assay, respectively. Immunofluorescence and western blot analysis were used to analyze the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Results Part 1: breviscapine injection significantly ameliorated neurologic deficit, reduced infarct volume and water content, and suppressed the levels of NSE in a time-dependent manner. Part 2: breviscapine inhibited the increased levels of 4-HNE and 8-OHdG, and enhanced the antioxidant capacity of cortex tissue. Moreover, breviscapine obviously raised the expression of Nrf2 and HO-1 proteins after 24 h of reperfusion. Conclusion The therapeutic time window of breviscapine injection for cerebral ischemia/reperfusion injury seemed to be within 5 h after reperfusion. By up-regulating the expression of Nrf2/HO-1 pathway might be involved in the therapeutic mechanism of breviscapine injection.

This paper investigates the prediction of the far-field performances of high frequency projectors using the second source array method (SSAM). The far-field parameters can be calculated accurately using the complex acoustic pressure data of two very close parallel planes which lie in the near-field region of the projector. The paper simulates the feasibility of predicting the far-field parameters such as transmitting voltage response and the far-field directivity pattern. The predicting results are compared with that calculated using boundary element method (BEM). It shows very good agreement between the two methods. A planar high frequency projector is measured using the near-field method. In order to verify the predicting results, the far-field measurement is performed for the same projector. The comparison of the results shows that the near-field method is capable to precisely predict the far-field parameters of the projector.