Icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels in the hippocampus of the senescence-accelerated mouse

At 8 weeks after intragastric administration of icariin to senescence-accelerated mice （P8 strain）, Morris water maze results showed that escape latency was shortened, and the number of platform crossings was increased. Immunohistochemical staining and western blot assay detected significantly increased levels of cyclic adenosine monophosphate response element binding protein These results suggest that icariin upregulates phosphorylated cyclic adenosine monophosphate response element binding protein levels and improves learning and memory functions in hippocampus of the senescence-accelerated mouse.

Cyclic Voltammetric Responses of Nitrate Reductase on Chemical Modified Electrodes

Electrochemistry of nitrate reductases (NR) incorporated into 2-aminoethanethiol self-assembled on the gold electrode and polyacrylamide cast on the pyrolytic graphite electrode was examined. NR on chemical modified electrode showed electrochemical cyclic voltammetric responses in phosphate buffers.

Sevoflurane effects on cyclic adenosine monophosphate response element binding protein,phosphorylated cyclic adenosine monophosphate response element binding protein,and Livin expression in the cortex and hippocampus of a vascular cognitive impairment rat

BACKGROUND： Neuronal necrosis and apoptosis play important roles in the pathophysiology of cerebral ischemia and resulting cognitive impairment. However, inhibition of neuronal necrosis and apoptosis has been shown to attenuate cognitive impairment following cerebral ischemia. OBJECTIVE： To investigate the effects of sevoflurane on cyclic adenosine monophosphate response element binding protein （CREB）, phosphorylated CREB （pCREB）, and Livin expression in the cortex and hippocampus of a rat model of vascular cognitive impairment.DESIGN, TIME AND SETTING： A randomized, controlled experiment was performed in the Chongqing Key Laboratory of Neurology between June 2007 and July 2008.MATERIALS： Sevoflurane was provided by Abbott Laboratory, UK; Morris water maze was provided by Chinese Academy of Medical Sciences, China; goat anti-rat CREB, goat anti-rat pCREB and goat anti-rat Livin antibodies were provided by Biosource International, USA. METHODS： A total of 42 female, Wistar rats were randomly assigned to the following groups： sham operation, vascular cognitive impairment, and sevoflurane treatment. The vascular cognitive impairment rat model was established by permanent bilateral occlusion of both common carotid arteries, and 1.0 MAC sevoflurane was immediately administered by inhalation for 2 hours. MAIN OUTCOME MEASURES： CREB, pCREB, and Livin expression was measured in the cortex and hippocampus by Western blot and reverse transcription-polymerase chain reaction. Behavior was evaluated with Morris water maze. RESULTS： CREB, pCREB, and Livin expression in the sevoflurane treatment group was significantly greater than the vascular cognitive impairment group （P 〈 0.01）. However, expression of CREB and pCREB was significantly less in the sevoflurane treatment and vascular cognitive impairment groups, compared with the sham operation group （P 〈 0.01）. Livin expression in the sevoflurane treatment and vascular cognitive impairment groups was significantly greater than the sham operation group （P 〈 0.01）. Learning, memory, and behavior disorders were observed in the vascular cognitive impairment group. Sevoflurane treatment significantly improved these observed disorders. CONCLUSION： Sevoflurane improved cognitive impairment due to permanent bilateral occlusion of both common carotid arteries. Improved function was associated with increased CREB, pCREB, and Livin expression in the cortex and hippocampus.

Modeling and cyclic behavior of segmental bridge column connected with shape memory alloy bars

This paper examines the quasi-static cyclic behavior, lateral strength and equivalent damping capacities of a system of post-tensioned segmental bridge columns tied with large diameter martensitic Shape Memory Alloy （SMA） link-bars. Moment-curvature constitutive relationships are formulated and analysis tools are developed for the PT column, including a modified four-spring model prepared for the SMA bars. The suggested system is exemplified using a column with an aspect ratio of 7.5 and twelve 36.5 mm diameter NiTi martensitic SMA bars. A post-tensioning force of 40% to 60% of the tendon yield strength is applied in order to obtain a self re-centering system, considering the residual stress of the martensitie SMA bars. The cyclic response results show that the lateral strength remains consistently around 10% of the total vertical load and the equivalent viscous damping ratios reach 10%-12% of critical. When large diameter NiTi superelastic SMA bars are incorporated into the column system, the cyclic response varies substantially. The creep behavior of the superelastic SMA bar is accounted for since it affects the re-centering capability of the column. Two examples are presented to emphasize the modeling sensitivities for these special bars and quantify their cyclic behavior effects within the column assembly.

Modelling spiky acceleration response of dilative sand deposits during earthquakes with emphasis on large post-liquefaction deformation

The acceleration records at some liquefied sand deposits exhibit a distinctive spiky waveform, characterized by strong amplification and high-frequency components. A comprehensive constitutive model was used to analyze the mechanism of such spiky acceleration responses. An idealized single-degree-of-freedom（SDF） system was constructed, in which the force-displacement relation of the spring follows the stress-strain behavior of saturated sand during undrained shearing. The SDF system demonstrated that the spikes are directly related to the strain-hardening behavior of sand during post-liquefaction cyclic shearing. Furthermore, there exists a threshold shear strain length, which is in accordance with the limited amplitude of the fluid-like shear strain generated at instantaneous zero effective stress state during the post-liquefaction stage. The spiky acceleration can only occur when the cyclic shear strain exceeds the threshold shear strain length. It is also revealed that the time intervals between the acceleration spikes increase gradually along with the continuation of shaking because the threshold shear strain length increases gradually and then more time is needed to generate larger shear strain to cause strain hardening. Records at the Kushiro Port site and Port Island site during past earthquakes are simulated through the fully coupled method to validate the presented mechanism.

Cyclic deformation behaviors of Ti-46Al-2Cr-2Nb-0.15B alloy during thermo-mechanical fatigue tests

Thermo-mechanical fatigue tests were carried out on the gamma-TiAl alloy in the temperature range of 500-800℃ under mechanical strain control m order to evaluate its cyclic deformation behaviors at elevated temperature. Cyclic deformation curves, stress-strain hysteresis loops under different temperature--strain cycles were analyzed and dislocation configurations were also observed by TEM. The mechanisms of cyclic hardening or softening during thermo-mechanical fatigue （TMF） tests were also discussed. Results showed that thermo-mechanical fatigue lives largely depended on the applied mechanical strain amplitudes, applied types of strain and temperature. On the hysteresis loops appeared two apparent asymmetries： one was zero asymmetry and the other was tensile and compressive asymmetry. Dislocations configuration and slip behaviors were contributed to cyclic hardening or cyclic softening.

Antidepressant effect of electroacupuncture regulates signal targeting in the brain and increases brain- derived neurotrophic factor levels

Electroacupuncture improves depressive behavior faster and with fewer adverse effects than antidepressant medication. However, the antidepressant mechanism of electroacupuncture remains poorly understood. Here, we established a rat model of chronic unpredicted mild stress, and then treated these rats with electroacupuncture at Yintang （EX-HN3） and Baihui （DU20） with sparse waves at 2 Hz and 0.6 mA for 30 minutes, once a day. We found increased horizontal and vertical activity, and decreased immobility time, at 2 and 4 weeks after treatment. Moreover, levels of neurotransmitters （5-hydroxytryptamine, glutamate, and y-aminobutyric acid） and protein levels of brain-derived neurotrophic factor and brain-derived neurotrophic factor-related proteins （TrkB, protein kinase A, and phosphorylation of cyclic adenosine monophosphate response element binding protein） were increased in the hippocampus. Similarly, protein kinase A and TrkB mRNA levels were increased, and calcium-calmodulin-dependent protein kinase lI levels decreased. These findings suggest that electroacupuncture increases phosphorylation of cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor levels by regulating multiple targets in the cyclic adenosine rnonophosphate response element binding protein signal- ing pathway, thereby promoting nerve regeneration, and exerting an antidepressive effect.

Inhibition of the MAPK/ERK cascade: a potential transcription-depen-dent mechanism for the amnesic effect of anesthetic propofol

Intravenous anesthetics are known to cause amnesia, but the underlying molecular mechanisms remain elusive. To identify a possible molecular mechanism, we recently turned our attention to a key intracellular signaling pathway organized by a family of mitogen-activated protein kinases （MAPKs）. As a prominent synapse-to-nucleus superhighway, MAPKs couple surface glutamate receptors to nuclear transcriptional events essential for the development and/or maintenance of different forms of synaptic plasticity （long-term potentiation and long-term depression） and memory formation. To define the role of MAPK-dependent transcription in the amnesic property of anesthetics, we conducted a series of studies to examine the effect of a prototype intravenous anesthetic propofol on the MAPK response to N-methyl-D-aspartate receptor （NMDAR） stimulation in hippocampal neurons. Our results suggest that propofol possesses the ability to inhibit NMDAR-mediated activation of a classic subclass of MAPKs, extracellular signal-regulated protein kinase 1/2 （ERK1/2）. Concurrent inhibition of transcriptional activity also occurs as a result of inhibited responses of ERK1/2 to NMDA. These findings provide first evidence for an inhibitory modulation of the NMDAR-MAPK pathway by an intravenous anesthetic and introduce a new avenue to elucidate a transcription-dependent mechanism processing the amnesic effect of anesthetics.

Shuganjieyu capsule increases neurotrophic factor expression in a rat model of depression

Shuganjieyu capsule has been approved for clinical treatment by the State Food and Drug Ad-ministration of China since 2008. In the clinic, Shuganjieyu capsule is often used to treat mild to moderate depression. In the rat model of depression established in this study, Shuganjieyu capsule was administered intragastrically daily before stress. Behavioral results conifrmed that depressive symptoms lessened after treatment with high-dose （150 mg/kg） Shuganjieyu capsule. Immunohistochemistry results showed that high-dose Shuganjieyu capsule signiifcantly increased phosphorylation levels of phosphorylation cyclic adenosine monophosphate response element binding protein and brain-derived neurotrophic factor expression in the medial prefrontal cortex and hippocampal CA3 area. Overall, our results suggest that in rats, Shuganjieyu capsule effec-tively reverses depressive-like behaviors by increasing expression levels of neurotrophic factors in the brain.

Low-cycle fatigue behavior of permanent mold cast and die-cast Al-Si-Cu-Mg alloys

Fatigue failure is one of the main failure forms of Al-Si-Cu-Mg aluminum alloys. To feature their mechanical aspect of fatigue behavior, the low-cycle fatigue behavior of permanent mold cast and die-cast AI-Si- Cu-Mg alloys at room temperature was investigated. The experimental results show that both permanent mold cast and die-cast AI-Si-Cu-Mg alloys mainly exhibit cyclic strain hardening. At the same total strain amplitude, the diecast AI-Si-Cu-Mg alloy shows higher cyclic deformation resistance and longer fatigue life than does the permanent mold cast AI-Si-Cu-Mg alloy. The relationship between both elastic and plastic strain amplitudes with reversals to failure shows a monotonic linear behavior, and can be described by the Basquin and Coffin-Manson equations, respectively.

GLYX-13 pretreatment ameliorates long-term isoflurane exposure-induced cognitive impairment in mice

Accumulating evidence indicates that inhalation anesthetics induce or increase the risk of cognitive impairment. GLYX-13（rapastinel） acts on the glycine site of N-methyl-D-aspartate receptors（NMDARs） and has been shown to enhance hippocampus-dependent learning and memory function. However, the mechanisms by which GLYX-13 affects learning and memory function are still unclear. In this study, we investigated these mechanisms in a mouse model of long-term anesthesia exposure. Mice were intravenously administered 1 mg/kg GLYX-13 at 2 hours before isoflurane exposure（1.5% for 6 hours）. Cognitive function was assessed using the contextual fear conditioning test and the novel object recognition test. The mRNA expression and phosphorylated protein levels of NMDAR pathway components, N-methyl-D-aspartate receptor subunit 2B（NR2B）-Ca2+/calmodulin dependent protein kinase II（CaMKII）-cyclic adenosine monophosphate response element binding protein（CREB）, in the hippocampus were evaluated by quantitative RT-PCR and western blot assay. Pretreatment with GLYX-13 ameliorated isoflurane exposure-induced cognitive impairment and restored NR2B, CaMKII and CREB mRNA and phosphorylated protein levels. Intracerebroventricular injection of KN93, a selective CaMKII inhibitor, significantly diminished the effect of GLYX-13 on cognitive function and NR2B, CaMKII and CREB levels in the hippocampus. Taken together, our findings suggest that GLYX-13 pretreatment alleviates isoflurane-induced cognitive dysfunction by protecting against perturbation of the NR2B/CaMKII/CREB signaling pathway in the hippocampus. Therefore, GLYX-13 may have therapeutic potential for the treatment of anesthesia-induced cognitive dysfunction. This study was approved by the Experimental Animal Ethics Committee of Drum Tower Hospital affiliated to the Medical College of Nanjing University, China（approval No. 20171102） on November 20, 2017.

Low cycle fatigue behavior of die cast Mg-Al-Mn-Ce magnesium alloy

Fatigue failure is a main failure mode for magnesium and other alloys. It is beneficial for fatigue design and fatigue life improvement to investigate the low cycle fatigue behavior of magnesium alloys. In order to investigate the low cycle fatigue behavior of die cast Mg-AI-Mn-Ce magnesium alloy, the strain controlled fatigue experiments were performed at room temperature and fatigue fracture surfaces of specimens were observed with scanning election microscopy for the alloys under die-cast and aged states. Cyclic stress response curves, strain amplitude versus reversals to failure curve, total strain amplitude versus fatigue life curves and cyclic stress-strain curves of Mg-AI-Mn-Ce alloys were analyzed. The results show that the Mg-AI-Mn-Ce alloys under die-cast （F） and aged （T5） states exhibit cyclic strain hardening under the applied total strain amplitudes, and aging treatment could greatly increase the cyclic stress amplitudes of die cast Mg-AI-Mn-Ce alloys. The relationships between the plastic strain amplitude, the elastic strain amplitude and reversals to failure of Mg-AI-Mn-Ce magnesium alloy under different treatment states could be described by Coffin-Manson and Basquin equations, respectively. Observations on the fatigue fracture surface of specimens reveal that the fatigue cracks initiate on the surface of specimens and propagate transgranularly.

Dynamic Characteristics and Simplified Numerical Methods of An All-Vertical-Piled Wharf in Offshore Deep Water

There has been a growing trend in the development of offshore deep-water ports in China. For such deep sea projects, all-vertical-piled wharves are suitable structures and generally located in open waters, greatly affected by wave action. Currently, no systematic studies or simplified numerical methods are available for deriving the dynamic characteristics and dynamic responses of all-vertical-piled wharves under wave cyclic loads. In this article, we compare the dynamic characteristics of an all-vertical-piled wharf with those of a traditional inshore high-piled wharf through numerical analysis; our research reveals that the vibration period of an all-vertical-piled wharf under cyclic loading is longer than that of an inshore high-piled wharf and is much closer to the period of the loading wave. Therefore, dynamic calculation and analysis should be conducted when designing and calculating the characteristics of an all-vertical-piled wharf. We establish a dynamic finite element model to examine the dynamic response of an all-vertical-piled wharf under wave cyclic loads and compare the results with those under wave equivalent static load; the comparison indicates that dynamic amplification of the structure is evident when the wave dynamic load effect is taken into account. Furthermore, a simplified dynamic numerical method for calculating the dynamic response of an all-vertical-piled wharf is established based on the P-Y curve. Compared with finite element analysis, the simplified method is more convenient to use and applicable to large structural deformation while considering the soil non-linearity. We confirmed that the simplified method has acceptable accuracy and can be used in engineering applications.

Experimental study on out-of-plane seismic performance of precast composite sidewalls of utility tunnel with grouting-sleeve joints

The precast composite reinforced concrete wall with the advantages of fewer joints,superior impermeability and rapid construction provides an efficient and environmental friendly alternative in the construction of underground utility tunnels in the last few years.To investigate the seismic performance of precast concrete composite walls of utility tunnels with grouting-sleeve connection under out-ofplane loads,a series of quasi-static cyclic tests were performed on the full-scale sidewall specimens with different axial compression ratios in this study.The experimental results including the failure modes,crack distributions,and the influence of different connections on the out-of-plane seismic performance of precast concrete composite wall were carefully examined and compared with those from the cyclic tests of the cast-in-place sidewalls of the utility tunnel.The test results show that the seismic performance of the precast concrete composite sidewall specimen,such as the hysteresis curves,the ultimate bearing capacity,stiffness degradation pattern and the ductility ratio,is basically the same as that of the cast-in-place specimen,indicating that the seismic performance of the prefabricated structure is equivalent to that of the cast-in-place structure.Moreover,the grouting-sleeves of the joints can effectively transfer the reinforcement stress until the failure of the precast concrete composite sidewall specimens,which exhibits excellent out-of-plane ductility and serviceability.

Correlated necklace dislocations in highly oriented nanotwinned metals

In this paper, we review recent progress in the understanding of a novel dislocation mechanism, named correlated necklace dislocations(CNDs), activated in highly oriented nanotwinned(NT) metals under monotonic and cyclic loading applied parallel to the twin boundaries(TBs). This mechanism was initially revealed to be responsible for the continuous strengthening behavior of NT metals when the TB spacing(λ) is reduced to around 1 nm. It was later found that the presence of a crack-like defect could trigger the operation of CNDs at much larger TB spacings. Most recently, atomistic modeling and experiments demonstrated a history-independent and stable cyclic response of highly oriented NT metals governed by CNDs formed in the NT structure under cyclic loading. CNDs move along the twin planes without directional lattice slip resistance, thus contributing to a symmetric cyclic response of the NT structure regardless of pre-strains imposed on the sample before cyclic loading. We conclude with potential research directions in the investigation of this unique deformation mechanism in highly oriented NT metals.

Low-Cycle Fatigue and Creep-Fatigue Behaviors of a Second-Generation Nickel-Based Single-Crystal Superalloy at 760℃

Low-cycle fatigue(LCF)behaviors of a second-generation nickel-based single-crystal superalloys with[001]orientation at 760℃ have been investigated.Different strain amplitudes were introduced to investigate the creep-fatigue effects.The LCF life of none tensile holding(NTH)was higher than that of the 60-s tensile hold(TH)at any strain amplitude.As the strain amplitude was 0.7%,the stacking and cross-slip dislocations appeared together at the γ/γ’coherent microstructure in both TH and NTH specimens.At the strain amplitude of 0.9%,plenty of the cross-slip dislocations appeared inγchannel and other dislocations were stacking at γ/γ’interfaces.However,the SFs still appeared in γ’phase with 60-s TH which caused cyclic softening.As the strain amplitude increased up to 1.2%,the dislocations are piling up at the γ/γ’interfaces and cutting through the γ’phase in both TH and NTH tests,which caused cyclic hardening.The influences of strain amplitude and holding time were complicated.Different stress response behaviors occurred in different loading conditions.The surface characteristic and fracture mechanism were observed by scanning electron microscopy.This result is helpful for building the relationship of various blade fatigue failure modes,cyclic stress response and microstructure deformation under different strain amplitudes.

Underlying Mechanisms of Memory Deficits Induced by Etomidate Anesthesia in Aged Rat Model： Critical Role of Immediate Early Genes

Background： Etomidate （R- 1 -[ 1 -ethylphenyl] imidazole-5-ethyl ester） is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurohiological mechanisms of cognitive impairments that caused by etomidate. Methods： A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection ofeiomidate or vehicle. Then, the rats＇ spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3＇,5＇-monophosphate response element-binding （CREB） protein phosphorylation and immediate early gene （IEG, including Arc, c-fos, and Egrl） expression levels using Western blot analysis. Results： Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning （day 4：27.26 ± 5.33 s vs. 35.52 ± 3.88s, t 2.988, P 0.0068; day 5： 15.84±4.02svs.30.67±4.23s,t=3.013,P=0.0057;day6：9.47±2.35svs.25.66±4.16s,t=3.567, P = 0.0036） and menaory ability （crossing times： 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P 0.0072; duration： 34.00± 4.24 s vs. 18.07 ±4.79 s, t = 3.023, P= 0.0053; total swimming distance： 40.73 ±3.45 cm vs. 27.40± 6.56 cm, t = 2.798, P = 0.0086） but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple lEGs （Arc： vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P 0.0086; c-los： Vehicle treated rats 100%, etomidate treated rats 72%, t =2.996, P = 0.0076; Egrl ： Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P=0.0057） were significantly reduced in hippocampi ofetomidate-treated rats. Conclusion： Our data suggested that etomidate might induce memory impairment in rats via inhibition of lEG expression.