Endogenous Norepinephrine Desensitizes α1D-Adrenoceptors in Cultured Rat Aorta

Desensitization is a process characterized by the loss of cellular response to an agonist when this is present for a long time. α1D-adrenergic receptor (α1D-AR) desensitization is important since this receptor is involved in the contraction of large caliber arteries, such as the aorta. The aim of this research was to evaluate the desensitization of α1D-AR due to the endogenous release of norepinephrine in cultured rat aorta. Wistar rat aorta was incubated for 2 h or 24 h in DMEM at 37°C, and then subjected to isometric tension and the action of added norepinephrine, in concentration-response curve (CRC). In some experiments, BMY-7378 (α1D-AR antagonist) or 5-methylurapidil (α1A-AR antagonist) was used to identify the α1-AR involved in the response, or BMY-7378 to protect the α1D-AR from desensitization. Results showed that α1D-AR was desensitized when the aorta was incubated for 24 h, since the CRC to exogenous norepinephrine showed lower maximal contraction and the curve was displaced to the right, indicating that the receptor involved in contraction was not the α1D-AR, as compared to the aorta incubated 2 h. The receptor stimulated by norepinephrine at 24 h was neither the α1A-AR, as shown by the lack of displacement of the curve by 5-methylurapidil, but rather it seems that α1B-AR is inducing contraction. When the aorta was incubated with BMY-7378 for 24 h, the α1D-AR antagonist protected the receptor from desensitization. Endogenous norepinephrine desensitizes α1D-AR in the cultured aorta, and the α1D-AR is protected by BMY-7378.

Plasma Norepinephrine and Hemorheology in Essential Hypertensive Patients with Different Patterns of Left Ventricular Hypertrophy

对80例不同类型高血压左室肥厚（LVH）患者的血浆去甲肾上腺素（NE）和血液流变学改变进行观察。结果显示，（1）向心性肥厚组（CH）高切变率下全血粘度（WBV230）显著升高；（2）不对称性室间隔肥厚组（ASH）血浆NE和收缩末期室壁应力（ESS）增高较明显；（3）多元回归分析显示，SBP，ESS和血浆NE是影响相对室壁厚度的重要因素。提示CH是一种对压力负荷过重而产生的代偿形式；ASH的形成除了负荷因素外血浆NE可能起更重要的作用。

Effects of electro-acupuncture on brain tissue norepinephrine contents in a morphine withdrawal anxiety mouse model

BACKGROUND： Following morphine withdrawal, anxiety is associated with abnormal norepinephrine content change. However, increasing blood lactic acid content can induce anxiety or panic in patients with anxiety disorder or endogenous opioid peptide functional disorder. OBJECTIVE： This study was designed to observe the effects of electro-acupuncture, at the ＂Sanyinjiao＂ point （SP 6）, on brain tissue norepinephrine and blood lactic acid content in anxiety-model mice after morphine withdrawal. DESIGN： A randomized controlled animal experiment. SETTING： This study was performed in the Laboratory of Acupuncture, Electro-acupuncture ＆ Tuina College, Chengdu University of Traditional Chinese Medicine, from June to September 2001. MATERIALS： A total of 50 healthy Kunming male mice were provided by the Laboratory Animal Center of Chengdu University of Traditional Chinese Medicine. The protocol was performed in accordance with ethical guidelines stated in the Guide for the use and care of laboratory animals, approved by the Committee on the Care and Use of Laboratory Animals of the Institute of Laboratory Animal Resources Commission on Life Sciences, National Research Council, China （1985）. Experimental reagents and equipment used were as follows： morphine hydrochloride （Lot No. 930503, Shenyang No.1 Pharmaceutical Factory, China）, norepinephrine （Sigma Chemical Company, USA）, fluorospectrophotometer （RF-510, Shimadzu Corporation, Japan）, Han electro-acupuncture apparatus （WQ 1002, No. zun （91）-227270-588, Beijing Anlong Photoelectricity-Technique Company, China）, and T-maze （self-made）. METHODS： A total of 50 mice were randomly divided into 5 groups, with 10 mice in each group： blank control, T-maze, model, model ＋ electro-acupuncture, and electro-acupuncture groups. Establishment of anxiety model after morphine withdrawal： the mouse hot plate assay was used to detect the activity of morphine. The median effective dose of morphine, 2.95 mg/kg, was defined as the base. Mice were subcutaneously administered morphine, 3 times a day, for 4 days successively （initially 2.95 mg/kg, then increased day by day, as described below）. Interventions： In the model ＋ electro-acupuncture group, after model induction, mice were subjected electro-acupuncture at bilateral ＂Sanyinjiao＂ （SP6） points using a Han electro-acupuncture apparatus with sparse-dense waves and frequency of 2-100 Hz, once a day, for 6 days. In the model group, after anxiety-model induction, mice were subjected to fixation as same as model ＋ electro-acupuncture group within 6 days of model induction. In the electro-acupuncture group, the anxiety model was not induced and mice were subjected to fixation, electro-acupuncture and the T-maze test. In the T-maze group, the anxiety model was not induced and mice were subjected to fixation. The T-maze test was performed in the 4 groups after experiment. In the blank control group, the anxiety model was not induced and mice were subjected to fixation only. MAIN OUTCOME MEASURES： Brain tissue norepinephrine content of morphine-withdrawal anxiety mice was detected by fluorospectrophotometry after 6 days of electro-acupuncture. Blood lactic acid content was detected by visible spectrophotometry. RESULTS： A total of 50 mice were included in the final analysis. Brain norepinephrine content was significantly greater in the model group compared to the T-maze, blank control, electro-acupuncture and model ＋ electro-acupuncture groups, （P 〈 0.05-0.01）. Brain norepinephrine content was similar between the model ＋ electro-acupuncture and the blank control groups （P 〉 0.05）. There was no significant difference in blood lactic acid content among the groups （P 〉 0.05）. CONCLUSION： Electro-acupuncture lowers brain norepinephrine content but does not influence peripheral blood lactic acid content in morphine-withdrawn, anxiety-modeled mice. These results demonstrate that anxiety-inhibiting effects of electro-acupuncture, after morphine withdrawal, might be related to regulation of norepinephrine release.

Clinical trials comparing norepinephrine with vasopressin in patients with septic shock:A meta-analysis

Background: To compare the mortality rates and benefits of norepinephrine and vasopressin in patients with septic shock. Methods: PubMed, EMBASE, and the Cochrane Library database were searched from database inception to December 2013. We selected randomized controlled trials in adults with septic shock and compared norepinephrine with vasopressin. After assessing the heterogeneity of treatment effects across trials using the I2 statistic, we used a fixed effects model(P≥0.1) and expressed the results as risk ratios(RRs) for dichotomous outcomes or as standardized mean differences(SMDs) for continuous data with 95% confidence intervals(CIs). Meta-analysis was conducted using Review Manager 5.1 software.Results: Seven trials(n=2323) met the inclusion criteria. Overall, the mortality rate in these seven trials was 36.2%(840/2323). There was no difference in mortality following the use of norepinephrine or vasopressin(RR 1.07; 95%CI 0.97-1.20; P=0.19). Compared to norepinephrine, vasopressin had no significant effect on heart rate(HR)(SMD 0.21; 95%CI-0.08-0.50; P=0.15), mean arterial pressure(MAP)(SMD 0.15; 95%CI-0.15-0.44; P=0.33), cardiac index(CI)(SMD-0.10; 95%CI-0.64-0.44; P=0.73), systemic vascular resistance index(SVRI)(SMD 0.15; 95%CI-0.39-0.70; P=0.58), oxygen delivery(DO2)(SMD-0.06; 95%CI-0.62-0.49; P=0.82), oxygen consumption(VO2)(SMD 0.03; 95%CI-0.52-0.59; P=0.91) or lactic acid(SMD 0.07; 95%CI-0.23-0.36; P=0.66). No significant heterogeneity was found in these comparisons(P≥0.1).Conclusions: There is not sufficient evidence to prove conclusively that norepinephrine is superior to vasopressin in terms of mortality and hemodynamics. The effects of norepinephrine and vasopressin on patients with septic shock require further study in large randomized controlled trials.

The norepinephrine transporter gene is associated with the retardation symptoms of major depressive disorder in the Han Chinese population

The norepinephrine transporter plays an important role in the pathophysiology and pharmacological treatment of major depressive disorder. Consequently, the norepinephrine transporter gene is an attractive candidate in major depressive disorder research. In the present study, we evaluated the depression symptoms of subjects with major depressive disorder, who were all from the North of China and of Hart Chinese origin, using the Hamilton Depression Scale. We examined the relationship between two single nucleotide polymorphisms in the norepinephrine transporter, rs2242446 and rs5569, and the retardation symptoms of major depressive disorder using quantitative trait testing with the UNPHASED program, rs5569 was associated with depressed mood, and the GG genotype may be a risk factor for this; rs2242446 was associated with work and interest, and the TT genotype may be a risk factor for loss of interest. Our findings suggest that rs2242446 and rs5569 in the norepinephrine transporter gene are associated with the retardation symptoms of depression in the Hart Chinese population.

Effect of the Melatonin on Morning Blood Pressure Surge and Norepinephrine Endovenous Infusion in Healthy Volunteers

Melatonin, the pineal gland hormone, has been considered as a central hypotension factor. However their roles in the regulation of the human blood pressure and its possible use as antihyper-tensive drug have not been fully determined. The objective of this trial was to determine the effect of melatonin on blood pressure morning increase and a peripheral vasoconstriction challenge in healthy volunteers. Twelve healthy male volunteers were included in a prospective, comparative, randomized, crossover trial in which changes on blood pressure (BP) and heart rate (HR) after the first morning orthostatism and endovenous norepinephrine (NE) infusion were measured one hour after the administration of placebo (PL) or 10 mg of melatonin in double blind conditions. Melatonin blunted the effects of the first orthostatism on BP and HR. Melatonin also reduces the pressor effect of NA. One concludes that melatonin has central and peripheral hypotensive effects that support a potential role of this hormone in cardiovascular therapeutics.

Effect of Higher Mean Arterial Pressure with Norepinephrine on Tissue Oxygenation and Perfusion in Patients of Septic Shock

The current survival sepsis guideline proposes the use of vasopressors and fluid resuscitation to maintain the mean arterial pressure (MAP) ≥ 65 mmHg. Titrating catecholamine infusion to achieve higher MAP has been demonstrated to improve tissue oxygenation, microcirculation, renal function and overall outcome of the patient in some studies and literature on actual hemodynamic goals is scarce. AIM: To study the influence of two MAP on tissue oxygenation and perfusion parameters in patients of septic shock on norepinephrine infusion. SUBJECT AND MATERIALS: Forty adult patients with the diagnosis of septic shock were enrolled. In all patients norepinephrine was titrated to first stabilize the MAP at 65 ± 5 mmHg (Set I), followed by MAP of 85 ± 5 mmHg (Set II). Heart rate (HR), Central venous oxygen saturation (SCVO2), Transcutaneous partial pressure of oxygen (PtcO2) by TCM 400/TINA (using miniature Clark electrode), Arterial partial pressure of oxygen(PaO2), PtO2/PaO2 ratio, Urine output and Serum Base deficit were recorded in each Set after 2 hrs of stabilization. RESULTS: There was a significant increase in transcutaneous partial pressure of oxygen PtcO2 (p tO2/PaO2 (p < 0.0001), ScvO2 (p < 0.0001), urine output (p < 0.006) on increasing the MAP from 65mmHg to 85mmHg. Serum base deficit also improved (p < 0.0001). CONCLUSION: Higher MAP with norepinephrine is associated with better perfusion, oxygenation parameters in patients with established septic shock. These findings suggest that there is improvement in tissue oxygenation parameters using escalating doses of norepinephrine to achieve higher MAP without inherent adverse

Biochemical properties of norepinephrine as a kind of neurotransmitter secreted by bone marrow-derived neural stem cells induced and differentiated in vitro

BACKGROUND： It has been proved by many experimental studies from the aspects of morphology and immunocytochemistry in recent years that bone marrow stromal cells （BMSCs） can in vitro induce and differentiate into the cells possessing the properties of nerve cells. But the functions of BMSCs-derived neural stem cells（NSCs） and the differentiated neuron-like cells are still unclear. OBJECTIVE： To observe whether bone marrow-derived NSCs can secrete norepinephrine （NE） under the condition of in vitro culture, induce and differentiation, and analyze the biochemical properties of BMSCs-derived NSCs. DESIGN： A non-randomized and controlled experimental observation SETTING ： Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University MATERIALS： This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5- month-old healthy New Zealand white rabbits. METHODS： This experiment was carried out in the Institute of Neuromedicine of Chinese PLA, Zhujiang Hospital, Southern Medical University. The bone marrow used in the experiment was collected from 1.5 month-old healthy New Zealand white rabbits. BMSCs of rabbits were isolated and performed in vitro culture, induce and differentiation with culture medium of NSCs and differentiation-inducing factor, then identified with immunocytochemical method. Experimental grouping： ①Negative control group： L-02 hepatic cell and RPMI1640 culture medium were used. ② Background culture group： Only culture medium of NSCs as culture solution was added into BMSCs to perform culture, and 0.1 volume fraction of imported fetal bovine serum was supplemented 72 hours later. ③Differentiation inducing factor group： After culture for 72 hours, retinoic acid and glial cell line-derived neurotrophic factors were added in the culture medium of BMSCs and NSCs as corresponding inducing factors. The level of NE in each group was detected on the day of culture and 5, 7, 14 and 20 days after culture with high performance liquid chromatography （HPLC）. The procedure was conducted 3 times in each group.Standard working curve was made according to the corresponding relationship of NE concentration and peak area. The concentration of NE every 1×10^7 cells was calculated according to standard curve and cell counting. MAIN OUTCOME MEASURES ： The level of NE of cultured cells was detected with HPLC; immunocytochemistrical identification of Nestin and neuron specific nuclear protein was performed. RESULTS： ① On the 14^th day after cell culture, BMSCs turned into magnus and round cells which presented Nestin-positive antigen, then changed into neuron-like cells with long processus and presented neuron specific nuclear protein -positive antigen at the 20^th day following culture. ② The ratio of NE concentration and peak area has good linear relationship, and regression equation was Y=1.168 36＋0.000 272 8X,r=-0.998 4. Coefficient variation （CV） was 〈 5% and the recovery rate was 92.39%（ Y referred to concentration and X was peak area）.③NE was well detached within 10 minutes under the condition of this experiment. ④ NE was detected in NSCs and their culture mediums, which were cultured for 7, 14 and 20 days respectively, but no NE in BMSCs, NSCs-free culture medium and L-02 hepatic cell which were as negative control under the HPLC examination. Analysis of variance showed that the level of NE gradually increased following the elongation of culture time （P 〈 0.01 ）. No significant difference in the level of NE existed at the same time between differentiation inducing factor group and basic culture group（P 〉 0.05）. CONCLUSION ： BMSCs of rabbits can proliferate in vitro and express Nestin antigen; They can differentiate into neuron-like cells, express specific neucleoprotein of mature neurons, synthesize and secrete NE as a kind of neurotransmitter.

黄芪续命汤对阿尔茨海默病患者认知功能及NE、DA、ChAT表达的影响

目的探究黄芪续命汤对阿尔茨海默病(Alzheimer’s disease,AD)患者认知功能及去甲肾上腺素(noradrenaline,NE)、多巴胺(dopamine,DA)、乙酰胆碱转移酶(acetylcholintransferase,ChAT)表达的影响。方法前瞻性选取2019年1月-2022年12月期间于南阳市第二人民医院接受治疗的110例AD患者,采用随机数字表法将患者分为研究组与对照组,各55例。对照组采用多奈哌齐配合小续命汤治疗,研究组使用多奈哌齐配合黄芪续命汤治疗,2组均连续治疗15 d。比较患者治疗前后蒙特利尔认知评价量表(Mo CA)评分变化、神经精神量表(NPI)、日常生活能力(ADL)、精神状态检查量表(MMSE)、NE、DA、ChAT、血清同型半胱胺酸(Hcy)、血清淀粉蛋白前b位分解酶1(BACE1)与脑源性神经营养因子(BDNF)等指标变化。结果与本组治疗前相比,研究组患者治疗后的Mo CA评分中的回忆力、命名力、抽象、语言、注意力、视空间和执行、定向力评分均有明显升高(均P<0.01),与对照组治疗后的Mo CA评分相比,研究组的回忆力、命名力、抽象、语言、注意力、视空间和执行、定向力评分更高(均P<0.01);与本组治疗前相比,研究组的NPI、ADL评分明显降低而MMSE评分明显提高(均P<0.01),与对照组治疗后相比,研究组的NPI、ADL评分更低而MMSE评分明显更高(均P<0.01);与本组治疗前相比,研究组的NE、DA、ChAT指标水平明显提升(均P<0.01),与对照组治疗后相比,NE、DA、ChAT指标水平均更高(均P<0.01);与本组治疗前相比,研究组的Hcy、BACE1水平降低而BDNF水平提高(均P<0.01),与对照组治疗后相比,研究组的Hcy、BACE1水平明显更低而BDNF水平明显更高(均P<0.01);治疗后将实验组与对照组的总有效率进行对比,实验组总有效率明显更高(P<0.05)。结论黄芪续命汤结合多奈哌齐治疗AD患者具有较为良好的临床疗效,其能进一步改善患者的认知功能、精神状况、智能水平,可提高患者NE、DA、ChAT、BDNF水平,降低患者Hcy、BACE1水平,值得进一步研究。

Effects of norepinephrine on dorsomedial hypothalamic nucleus of rat before and after synaptic blockade

Extracellular discharges of neurons in the dorsomedial nucleus（DMN）were recordedwith glass microelectrode from rat hypothalamic slices.The firing frequency decreased in 77 andincreased in 48 units during the addition of norepinephrine into the bath(NE,2×10-5 mol/L)of160 units when the slices were perfused with artificial cerebrospinal fluid （ACSF）.Most of theseresponses could be antagonized by Yohimbine(YOH,2×10-5～4×10-5 mol/L).Nevertheless,when the perfusion fluid was changed,i.e.,with low Ca2+-high Mg2+ ACSF（CM-ACSF）whichcould block the chemical synaptic transmission,26 out of 35 units were inhibited by NE and only1 unit excited.The inhibition could he blocked by YOH. A very significant difference（P【0.01）was seen between the data obtained in ACSF and those in CM-ACSF.Furthermore,all NE-inhibited units in ACSF were also NE-inhibited in CM-ACSF,but the majority of NE-excited u-nits in ACSF changed into NE-inhibited or NE-unresponsive in CM-ACSF.The results suggestedthat NE produced a direct inhibitory effect on neurons in DMN which was mediated by the post-synaptic alpha 2 adrenergic receptors.

Effects of 5-HT and norepinephrine on the neuronal activities of the nucleus tractus solitarii in medullary slices

The relationship between 5-HT receptor and α-adrenoceptor was investigated inrat medullary slice preparations.In 57 nucleus tractus solitarii(NTS)neurons,47(82.5%)responded to both serotonin(5-HT)and norepinephrine(NE).After synapse transmissionwas blocked by perfusion of artificial cerebrospinal fluid(ACSF)with low calcium andhigh magnesium,5 in 8 neurons were still sensitive to both 5-HT and NE.On the otherhand,3 in 5 neurons responding only to 5-HT or NA were sensitive to both 5-HT andNE after the synapse transmission blockage.In some neurons which exhibited excitatoryor inhibitory responses to 5-HT or NE alone,the responses were inversed when perfusedwith 5-HT and NE in combination.These results suggest that there may exist aninhibitory interaction between 5-HT receptors and α-adrenoceptors in NTS and that most5-HT and α-adrenoceptors coexist in the same NTS neurons.

Effects of Testosterone on Norepinephrine Release in Isolated Rat Heart

The effects of testosterone on norepinephrine release were investigated in the isolated rat hearts.Sprague-Dawley male rats (n=120) were randomized to testosterone and control groups.The rats in testosterone group were perfused with modified Krebs-Henseleit buffer containing different concentrations of testosterone (0.1,1.0,10.0,and 100.0 nmol/L,respectively).Myocardial ischemia was induced by globally stopping the perfusion flow.Exocytotic norepinephrine release was induced by electrical field stimulation at 5 V (effective voltage) and 6 Hz (pulse width of 2 ms) for 1 min.The overflow of norepinephrine was determined by high pressure liquid chromatography and electrochemical detec-tion (HPLC-EC).Following acute ischemia,testosterone (1.0,10.0 and 100.0 nmol/L) significantly re-duced norepinephrine release (P<0.01),and the norepinepherine overflow was similar between the con-trol and 0.1 nmol/L testosterone group (P>0.05).Electrical stimulation of the ventricle evoked norepi-nepherine release,and this was diminished by the perfusion with testosterone at the concentrations of 1.0,10.0 and 100.0 nmol/L (P<0.01).It is suggested that testosterone suppresses ischemia-and electri-cal stimulationinduced norepinepherine release in the isolated rat hearts.

A geochemical perspective on the genesis of Cenozoic basic volcanism in northeastern Turkey:an overview of metasomatism and heterogeneity of the sub-continental lithospheric mantle in a post-collisional setting

The post-collisional Cenozoic basic volcanic rocks in NE Turkey show temporal variations in whole-rock lithophile element and highly siderophile element(HSE)systematics that are mainly associated with the nature of sub-continental lithospheric mantle(SCLM)sources and parental melt generation.So far,the traditional whole-rock lithophile geochemical data of these basic volcanic rocks have provided important constraints on the nature of SCLM sources.Integrated lithophile element and HSE geochemical data of these basic volcanic rocks also reveal the heterogeneity of the SCLM source,which is principally related to variable metasomatism resulting from previous subduction(s)and post-collisional mantle-crust interactions in an extensional setting.Lithophile element geochemical features suggest that the parental magmas have derived from metasomatized spinel-to garnet-bearing SCLM sources for Eocene and Miocene basic volcanic rocks with subduction signatures whereas originated from spinel-to garnet-bearing SCLM sources for Mio-Pliocene and Plio-Quaternary basaltic volcanic rocks without the subduction signature.Lithophile element and HSE geo-chemistry also reveal that Eocene and Miocene basic vol-canic rocks were affected by more pronounced crustal contamination than the basaltic volcanic rocks of Mio-Pliocene and Quaternary.Furthermore,the integrated lithophile element and HSE compositions of these basic volcanic rocks,together with the regional asymmetric lithospheric delamination model,reveal that the compositional variation(especially due to metasomatism)was significant temporally in the heterogeneity of the SCLM sources from which parental magmas formed during the Cenozoic era.

Mechanisms of Depressor Effect of Norepinephrine Injected into Subnucleus Commissuriu of Nucleus Solitarius Tractus in Rabbits

This experiment aimed to investigate the effect of adrenergic system in the subnucleus commissuriu of nucleus solitrius tractus (CNTS) on renal nerve discharges. Norepinephrine (NE) was microinjected into the CNTS of rabbits and mean arterial blood pressure (MAP) and renal nerve discharges (FRND) were synchronously recorded. The results indicated that (1) microinjection of norepinephine into the CNTS of rabbit could significantly attenuate the frequency of renal nerve discharge, and at the same time decrease markedly the mean arterial pressure. (2) Microinjection of 0.3 nmol yohimbin into CNTS had no significant influence on FRND and MAP, but could attenuate and even reverse the effects of NE on FRND and MAP. These results suggest that microinjection of NE into CNTS may activate the alpha-adrenorecptor located in CNTS and secondarily produce a depressor effect by attenuating the activity of peripheral sympathetic nervous system.

Sympathetic stimulation with norepinephrine may come at a cost

Norepinephrine(NE;also known as noradrenaline)is the body’s primary adrenergic neurotransmitter which belongs to the catecholamine family.Norepinephrine has pharmacologic effects on theα1(Suita et al.,2015),α2(Schwartz,1997),β1,β2 andβ3(Tsukada et al.,2003)adrenoceptors.In the brain,norepinephrine increases arousal and alertness,promotes vigilance,enhances formation and retrieval of memory,and focuses attention.It also increases restlessness and anxiety.In the remainder of the body,norepinephrine increases heart rate and blood pressure,triggers the release of glucose from energy stores,increases blood flow to skeletal muscle and increases muscle contraction,reduces blood flow to the gastrointestinal system and its motility and lastly,inhibits voiding of the bladder(Goldstein,2010).This last point is particularly interesting in the context of this perspective piece.

Wind-Vortex-Induced Vibrations of a Deepwater Jacket Pipe and Vibration Suppression Using a Nonlinear Energy Sink

The purpose of this study is to investigate the suppression effect of a nonlinear energy sink(NES)on the wind-vortex-induced pipe vibration and explore the influence of damping,stiffness,and NES installation position on the suppression effect.In this work,the wind-vortex-induced vibration of an elastic pipe of a deepwater jacket was studied,and vibrations were suppressed by using an NES.A van der Pol wake oscillator was used to simulate vortex-induced force,and the dynamic equation of the pipe considering the NES was established.The Galerkin method was applied to discretize the motion equation,and the vortex-induced vibration(VIV)of the pipe at reduced wind speeds was numerically analyzed.The novelty of this research is that particle swarm optimization was used to optimize the parameters of the NES to improve vibration suppression.The influence of the installation position,nonlinear stiffness,and damping parameters of the NES on vibration suppression was analyzed.Results showed that the optimized parameter combinations of the NES can effectively reduce wind-vortex-induced pipe vibration.The installation position of the NES had a significant effect on vibration suppression,and the midpoint of the pipe was the optimal NES installation position.An increase in stiffness or a 10% decrease in damping may cause vibration suppression failure.The results of this study provide some guidance for VIV suppression in deepwater jacket pipes.

Dynamic performance and parameter optimization of a half-vehicle system coupled with an inerter-based X-structure nonlinear energy sink

Inspired by the demand of improving the riding comfort and meeting the lightweight design of the vehicle, an inerter-based X-structure nonlinear energy sink(IXNES) is proposed and applied in the half-vehicle system to enhance the dynamic performance. The X-structure is used as a mechanism to realize the nonlinear stiffness characteristic of the NES, which can realize the flexibility, adjustability, high efficiency, and easy operation of nonlinear stiffness, and is convenient to apply in the vehicle suspension, and the inerter is applied to replacing the mass of the NES based on the mass amplification characteristic. The dynamic model of the half-vehicle system coupled with the IX-NES is established with the Lagrange theory, and the harmonic balance method(HBM) and the pseudo-arc-length method(PALM) are used to obtain the dynamic response under road harmonic excitation. The corresponding dynamic performance under road harmonic and random excitation is evaluated by six performance indices, and compared with that of the original half-vehicle system to show the benefits of the IX-NES. Furthermore, the structural parameters of the IX-NES are optimized with the genetic algorithm. The results show that for road harmonic and random excitation, using the IX-NES can greatly reduce the resonance peaks and root mean square(RMS) values of the front and rear suspension deflections and the front and rear dynamic tire loads, while the resonance peaks and RMS values of the vehicle body vertical and pitching accelerations are slightly larger.When the structural parameters of the IX-NES are optimized, the vehicle body vertical and pitching accelerations of the half-vehicle system could reduce by 2.41% and 1.16%,respectively, and the other dynamic performance indices are within the reasonable ranges.Thus, the IX-NES combines the advantages of the inerter, X-structure, and NES, which improves the dynamic performance of the half-vehicle system and provides an effective option for vibration attenuation in the vehicle engineering.

Kinetics of Norepinephrine- and Serotonin-Induced BDNF Release in Cultured Embryonic Hippocampal Neurons

The primary neurotransmitters targeted by currently used antidepressants, such as duloxetine, venlafaxine and fluoxetine, are serotonin and norepinephrine, which also are released in significant amounts in the central nervous system in response to sympathetic nervous system activation. In cultured hippocampal neurons, we have previously shown that norepinephrine induces increased expression of brain-derived neurotrophic factor (BDNF), the PI-3 K/Akt, MAPK pro-survival pathways, the BDNF receptor, TrkB, a transcription factor, and cyclic AMP response element binding protein (CREB). In the present study, we extend these findings of increased BDNF expression to its kinetics of release into the surrounding media. We also evaluate these two cell survival pathways, TrkB and CREB, in response to application of serotonin and/or norepinephrine. Serotonin elicits an earlier, but brief expression and release of BDNF, whereas norepinephrine elicits a more delayed and sustained release of BDNF. In response to both norepinephrine and 5-HT, the presence of BDNF in lysates and subsequent release into the media is significantly increased out to 4 h, as is PI-3 K/Akt activation. Together, these two neurotransmitters increase BDNF expression and release covering the entire 8 h continuum evaluated. The results of this study provide further evidence for a G protein-coupled receptor and a crosstalk-to-TrkB receptor with transactivation signaling across pathways.

Dynamics and vibration reduction performance of asymmetric tristable nonlinear energy sink

With its complex nonlinear dynamic behavior,the tristable system has shown excellent performance in areas such as energy harvesting and vibration suppression,and has attracted a lot of attention.In this paper,an asymmetric tristable design is proposed to improve the vibration suppression efficiency of nonlinear energy sinks(NESs)for the first time.The proposed asymmetric tristable NES(ATNES)is composed of a pair of oblique springs and a vertical spring.Then,the three stable states,symmetric and asymmetric,can be achieved by the adjustment of the distance and stiffness asymmetry of the oblique springs.The governing equations of a linear oscillator(LO)coupled with the ATNES are derived.The approximate analytical solution to the coupled system is obtained by the harmonic balance method(HBM)and verified numerically.The vibration suppression efficiency of three types of ATNES is compared.The results show that the asymmetric design can improve the efficiency of vibration reduction through comparing the chaotic motion of the NES oscillator between asymmetric steady states.In addition,compared with the symmetrical tristable NES(TNES),the ATNES can effectively control smaller structural vibrations.In other words,the ATNES can effectively solve the threshold problem of TNES failure to weak excitation.Therefore,this paper reveals the vibration reduction mechanism of the ATNES,and provides a pathway to expand the effective excitation amplitude range of the NES.

Q355NE钢特厚板坯凝固过程模拟研究

以(475×2000)mm断面的Q355NE钢特厚板坯为研究对象,通过射钉法和红外测温方法测量凝壳厚度及表面温度,将其作为凝固模型计算结果的验证。使用ProCAST软件进行凝固传热过程模拟,分析了不同拉速、过热度、比水量对铸坯温度场和凝固终点的影响规律。结果表明:与过热度和比水量的影响相比,拉速对其凝固终点、温度场影响较大,拉速每提高0.05 m/min,凝固终点平均后移4.54 m,铸坯完全凝固后的铸坯心部温度升高81℃左右;而比水量每降低10%,铸坯凝固终点后移0.33 m左右;过热度每升高5℃,铸坯凝固终点后移0.38 m左右。