Energy-based seismic design, which integrates both the accumulated hysteretic energy and plastic deformation of the structure, provides a more comprehensive evaluation of structural seismic performance compared to other performance-based seismic design methods. In damping control structures, the distribution of hysteretic energy is clearly defined, with the expected positions for energy dissipation and damage concentrated in the dampers. This facilitates the application of an energy-based design method in such structures. This research presented a novel direct energy-based design (DEBD) method for damping control reinforced concrete (RC) structures, following the principle that the energy dissipation capacity of the structural members and dampers exceeds the hysteretic energy dissipation demand. With this principle, an energy-based damage index, which is directly correlated with structural damage state, was introduced. Subsequently, a detailed energy-based design process was provided. To achieve the desired seismic performance, the required energy dissipation capacity of dampers was determined using a pre-select damage index, and thereby, identifying the design parameters of the dampers. Finally, to validate the feasibility of the proposed design method, an 8-story RC frame with friction dampers was chosen as an example. The energy dissipation capacity and damage state of the designed structure were evaluated through nonlinear time-history analyses, and the results demonstrate the successfully achievement of the predefined seismic performance.

探究sRNA GLmZ对大肠埃希菌(E.coli)代谢乙酸和柠檬酸的影响,为工业生产乙酸和柠檬酸提供依据.用高效液相色谱法(High Performance Liquid Chromatography,HPLC)测定和比较E.coli M15、转染空质粒的E.coli M15和转染sRNA GLmZ质粒的E.coli M15在各生长阶段代谢产生乙酸和柠檬酸的含量.与E.coli M15相比,转染sRNA GLmZ质粒的E.coli M15在对数期的生长速度明显减缓,经重复测量方差分析,3种细菌代谢产生的两种有机酸均有显著差异,再进行简单效应检验,转染sRNA GLmZ质粒的E.coli M15代谢产生的乙酸量降低,代谢产生的柠檬酸量显著增加(P<0.01).转染质粒可降低细菌的生长速度;sRNA GLmZ可以促进E.coli M15柠檬酸的产生,但也抑制乙酸的产生,因而提出将sRNA GLmZ质粒转染至细菌中,改造细菌乙酸和柠檬酸代谢途径的设想,为工业生产乙酸和柠檬酸提供参考.

OBJECTIVE:To study the neurotoxicity and mechanism of polychlorinated biphenyl( PCB) in BV-2 cells.METHODS:The experiment was divided into control group and PCB118, 138, 153, 180 treated group, the dosages were 0. 000, 0. 015, 0. 030, 0. 050, 0. 100, 0. 150 μmol/L. Through the statistical analysis of the survival rate of the cells, the final dose was divided into low, middle and high dose levels. Among them, the high dose group except PCB118 was 0. 15 μmol/L, the PCB138, 153, 180 concentration was 0. 015, 0. 05 and 0. 1 μmol/L for the low, medium and high dose groups. In vitro culture of mouse microglia cells with different doses of PCB after exposure, CCK-8 method to detect cell growth and viabilities; FITC Annexin V/PI method to detect cell apoptosis rate; detection of lactate dehydrogenase( LDH) release by ELISA kit; fluorescence probe method( Fluo-4 AM) to detect the intracellular calcium content changes.RESULTS:CCK-8 and FITC Annexin V/PI double staining experiments showed that PCB118, 138, 153, 180 could inhibit cell activity, and with the increase in dose, cell survival rate decreased, apoptosis rate increased. PCB118 dose in 0. 15 μmol/L toxicity increased, cytoactive was reduced to( 66. 56 ± 0. 10) %, apoptosis rate increased to( 27. 39 ± 1. 80) %; PCB138, 153 in 0. 1 μmol/L cell survival rate reached( 66. 66 ± 0. 10) % and( 67. 17 ± 0. 12) %, apoptosis rate reached( 48. 77 ± 2. 43) % and( 56. 42 ± 3. 59) %; PCB180 dose of 0. 015μmol/L cell survival rate reached( 92. 07 ± 0. 38) %, cell apoptosis rate was( 6. 82 ±0. 51) %, significantly higher than that of the control group, the difference was statistically significant( P < 0. 05). LDH assay showed that the release amount of LDH was proportional to the dose of PCB. The lactate dehydrogenase amounts of PCB118, 138, 153 and 180 were( 523. 78 ± 13. 58) U/L, ( 430. 37 ± 22. 03) U/L, ( 540. 58 ± 13. 08)U/L, ( 411. 88 ± 21. 92) U/L, which were significantly higher than those in the control group, the difference was statistically significant( P < 0. 05). The result of Fluo-4 and AM showed that the average fluorescence intensity of intracellular calcium( Ca~(2+)) in PCB exposed group increased obviously. The average fluorescence intensity of Ca~(2+) in the PCB118, 138, 153 and 180 groups was( 10. 14 ± 2. 36), ( 32. 47 ± 1. 56), ( 16. 54 ± 0. 97)and( 40. 46 ± 2. 19) when the dose was 0. 015 μmol/L, significantly higher than that of the control group, the difference was statistically significant( P < 0. 05).CONCLUSION:PCB could cause neurotoxicity damage, increase LDH, destroy cell membrane integrity, induce the balance disorder of cell calcium and lead to the cell apoptosis.

Objective To study the effects of copper (Cu),iron (Fe),zinc (Zn),and aluminum (Al) exposure on oxidative stress and beta amyloid (Aβ) protein deposition in human neuroblastoma cell line (SH-SY5Y) and to provide evidences for senile dementia prevention.Methods SH-SY5Y cells were treated with various doses of Cu,Fe,Zn,and Al,respectively.The viability of the cells was determined with 3-[4,5-dimedthylthiazol]-2,5-diphenyltetrazolium bromide (MTT) assay.The activity of superoxide dismutase (SOD) in cultured SH-SY5Y cells was detected with xanthine oxidase method;the activity of glutathione peroxidase (GSH-PX) was measured with colorimetry;the content of malondialdehyde (MDA) in culture supematant fluid was assessed with thiobituric acid reaction (TBA) method.Cellular reactive oxygen species (ROS) level was detected using fluorescent probe of 2',7'-dichlorofluorescein diacetate (DCFH-DA).The content of Aβ1-42 was measured by enzyme-linked immunosorbent assay (ELISA).Results Cu,Fe,Zn,and Al could suppress the viability of SH-SY5Y cells in a concentration-dependent manner.When treated with copper sulfate (CuSO4) at the dosages of 50,200,and 400 μ mol/L,the survival rates of the SH-SY5 Y cells were 90.47％,74.81％,and 64.97％;at the dosages of 1,2,and 4 mmol/L,the survival rates of the SH-SY5Y cells were 93.08％,78.28％,and 56.10％ when exposed to ferrous sulfate (FeSO4) and 2.21％,85.30％,and 62.72％ when exposed to aluminum chloride (AlCl3);the survival rates of the the SH-SY5Y cells were 91.76％,76.51％,and 61.27％ when treated with zinc sulfate (ZnSO4) at the dosages of 50,100,and 200 μmol/L,respectively.The survival rates of the SH-SY5Y cells exposed to various concentrations of the four metallic compounds were all significantly lower than that of the blank control group (P ＜ 0.05 for all).When treated with the four metallic compounds,the intracellular activity of SOD decreased but the intracellular ROS increased significantly;the activity of GSH-PX declined but the content of MDA and Aβ1-42 increased significantly in culture supematant fluid compared to those of the control (all P ＜ 0.05).Conclusion Copper,iron,zinc,and aluminum compounds could induce damage in SH-SY5Y cells and result in deposition of Aβ protein by ROS generation and oxidative stress pathway.

Objective To explore the effects of copper, iron, zinc and aluminum on the neurotoxi-city and mechanism in SH-SY5Y cells.Methods SH-SY5Y cells were treated with different concentrations of copper sulfate (50,200,400μmol/L),iron sulfate and aluminum chloride (1,2,4 mmol/L),and zinc sulfate(50,100,200 μmol/L) respectively.Cell viabilities were measured by MTT assay.ELISA kit method were performed to evaluate the deliverances of glycogen synthase kinase-3β(GSK-3β), phosphorylation of the sites in GSK-3β-Ser9, Akt and phosphorylated Akt(Ser473).The apoptosis rate of detected cells was by double-staining with Annexin-V and PI.Results With the increase of the concentration of copper, iron, zinc and aluminum increased, the viability of SH-SY5Y cell decreased gradually.The cell viability of each dose group were significantly lower than that of control group(P<0.05).The expressions of Akt were significantly lower in iron and aluminum group, than that in control group (P<0.05).The expression of GSK-3β had no significant difference(P>0.05).The levels of phosphorylation of GSK-3β and Akt in all groups were significantly lower than those of control group(P<0.05).With the concentration of copper, iron, zinc and aluminum increased, the apoptosis rates were significantly higher than that of control group (P<0.05).Conclusions Copper, iron, zinc, aluminum could induce neurotoxicity, inhibit the activity of Akt, activate the glycogen synthase kinase 3β and lead to the neuronal apoptosis.

The exact cause of Alzheimer's disease (AD) and the role of metals in its etiology remain unclear. We have used an analytical approach, based on inductively coupled plasma mass spectrometry coupled with multivariate statistical analysis, to study the profiles of a wide range of metals in AD patients and healthy controls. AD cannot be cured and the lack of sensitive biomarkers that can be used in the early stages of the disease may contribute to this treatment failure. In the present study, we measured plasma levels of amyloid-β1-42(0.142±0.029μg/L)and furin(2.292±1.54μg/L), together with those of the metalloproteinases, insulin-degrading enzyme(1.459±1.14μg/L) and neprilysin(0.073±0.015μg/L), in order to develop biomarkers for AD. Partial least squares discriminant analysis models were used to refine intergroup differences and we discovered that four metals(Mn, Al, Li, Cu) in peripheral blood were strongly associated with AD. Aberration in homeostasis of these metals may alter levels of proteinases, such as furin, which are associated with neurodegeneration in AD and can be a used as plasma-based biomarkers.

Objective To determine the changes of serum contents of five phosphatides in patients with type 2 diabetes mellitus using high performance liquid chromatography (HPLC).Methods Serum samples were collected from 70 patients with type 2 diabetes mellitus and 81 normal controls for determination of phosphatidylserine (PS),phosphatidylinostiol (PI),phosphatidylcholine (PC),phosphatidylethanolamine (PE) and sphingomyelin (SM) by HPLC,and for comparison between the two groups.Results The serum contents of PS ((0.139±0.031) mg/L vs.(0.154±0.029) mg/L)),PI ((0.021±0.016) mg/L vs.(0.027±0.017) mg/L),PC ((0.150±0.039) mg/Lvs.(0.385±0.022) mg/L) and PE ((0.070±0.026) mg/Lvs.(0.087± 0.044) mg/L) were lower in the patients with type 2 diabetes mellitus than in the normal controls,with statistically significant differences (all P＜0.05).No statistically significant difference was discovered in the serum content of SM ((0.039±0.026) mg/L vs.(0.044±0.028) mg/L) between the two groups (P＞0.05).Conclusions Serum PS,PI,PC and PE decline in the patients with type 2 diabetes mellitus,and they may play adjuvant roles in the screening of diabetes mellitus among normal population.

Objective Using HPLCtechnique, the red cell membrane phospholipids content analysis in patients with acute is-chemic stroke and explore the red cell membrane phospholipids level in acute ischemic stroke in the occurrence and devel-opment mechanism. Methods Using cross-sectional survey methods, from July to October 2015were 22 groups, healthy con-trol group 24, with HPLC of erythrocyte membrane separation, XBP-Silica column separation and determination of phospho-lipid content of erythrocyte membrane in two groups, data using SPSS 20.0 statistical analysis software. Results 5 kinds of phospholipid phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylserine (PS) three cases (0.3796± 0.1387), (0.4498 ±0.1786), (0.3301 ± 0.0327) and control group (0.4897±0.0154), (0.5523±0.0107),( 0.6351±0.0599) value was statisti-cally significant the difference (P< 0.05), phosphatidylinositol (PI) and sphingomyelin (SM) showed no significant difference (P>0.05). Conclusion The level of red cell membrane phospholipids participation influence the development process of acute ischemic stroke, and may be an inducing mechanism of the development of acute ischemic stroke.

目的 探讨鄂温克族骨性关节炎患者血浆中21种微量元素的含量水平.方法 采用0.3 ml HNO3 +0.3 ml H2O2混合消解液消化血浆样品,用电感耦合等离子体质谱(ICP-MS)测定血浆中Li、Mg、Al、Ca、Ti、V、Cr、Mn、Fe、Co、Ni、Cu、Zn、As、Se、Sr、Mo、Cd、Ba、Tl、Pb等21种微量元素,用t检验方法统计分析.结果 病例组和对照组血浆中6种元素(Ti、V、Ni、As、Mo、Tl)低于方法的定量检出限;其他15种元素均检出,其中,病例组血浆中4种元素Al,Ca,Cr,Cd的含量低于对照组;11种元素Li,Mg,Mn,Fe,Co,Cu,Zn,Se,Sr,Ba,Pb的含量高于对照组,且Co和Pb含量在两组间比较具有统计学意义(P＜0.05).结论 鄂温克族骨性关节炎患者血浆中微量元素普遍高于正常对照水平,且Co与Pb元素水平与骨性关节炎患者发病存在潜在的相关性.

痛风(gout)是一种代谢性疾病.研究发现,啤酒中嘌呤的代谢异常会导致血液中尿酸浓度升高.尿酸不能及时排出体外,尿酸钙盐就会沉积在软骨、肾脏和关节腔内,造成高尿酸血症,导致了关键剧烈疼痛及肿胀,引发了关节性病变.因此了解啤酒中的嘌呤含量进而选择啤酒对于喜爱饮酒的痛风病人有重要的意义.本文选取了市面某国外品牌的小麦啤酒和大麦啤酒,利用高效液相色谱法(HPLC)测定其腺嘌呤(A)、鸟嘌呤(G)、次黄嘌呤(H)、黄嘌呤(X)含量.发现小麦芽中A、G、X含量低于大麦芽啤酒,而H则略高于大麦啤酒.因此该品牌小麦啤酒中嘌呤引发痛风的可能性生要低于大麦啤酒.

Objective To investigate the effects of nutritional intervention on brain insulin degrading enzyme ( IDE) and neprilysin(NEP) levels in APP?PSN transgenic mice with Alzheimer?s disease(AD), and to study the mechanism of combined nutrients on prevention and remission for AD. Methods Seventy?two APP?PSN transgenic mice aged two months were randomly divided into the intervention group supplied with compound recipe in the diet and the model group fed with basic feed, and the intervention group were divided into high?and low?dose group. Another 24 APP?PSN transgenic negative mice were selected as negative control group. After intervention for 7 months, immunohistochemistry staining was used to evaluate the pathology in brain, and the levels of IDE and NEP in mice brain were detected by ELISA. Results By immunohistochemical staining with antibody against beta Amyloid1?42 ( Aβ1?42 ) , hippocampus and cerebral cortex in model group mice appeared more typical flaxen plaque deposition (+++) , and high?and low?dose group showed less pale yellow plaque deposition (+) , and plaque deposits was not found in negative control group (-) . Compared with model group, the levels of IDE and NEP in high?and low?dose groups showed significant difference( P<0?05) . Conclusions Compound nutrition intervention may improve AD,through improving the activity and levels of IDE and NEP in APP?PSN double transgenic mice and delaying the deposition of amyloid plaques in the cerebral cortex and the hippocampus of APP?PSN mice.

[This corrects the article DOI: 10.1371/journal.pone.0143135.].

Acrylamide (ACR) is known to induce neurotoxicity in humans and occupational exposure to ACR has an effect on human health. Since some animal experiments indicate the metabolic change caused by the ACR based on the metabolomics, increasing concern is the change of metabolite profiles by the low-dose ACR. In the present study, a low-dose of ACR (18 mg kg(-1)) was administered to male Wistar rats for 40 days. Ultra performance liquid chromatography/time of flight mass spectrometry (UPLC-Q-TOF MS) was used to examine urine samples from ACR-dosed and control animals. Multiple statistical analyses with principal component analysis (PCA) were used to investigate metabolite profile changes in urine samples, and to screen for potential neurotoxicity biomarkers. PCA showed differences between the ACR-dosed and control groups 20 days after the start of dosing; a bigger separation between the two groups was seen after dosing for 40 days. Levels of 4-guanidinobutanoic acid and 2-oxoarginine were significantly higher in urine from the ACR-dosed group than in urine from the control group after 10 days (p < 0.05). Receiver operator characteristic (ROC) curve analysis suggested that 4-guanidinobutanoic acid and 2-oxoarginine were the major metabolites. Our results suggest that high levels of 4-guanidinobutanoic acid and 2-oxoarginine may be related to ACR neurotoxicity. These metabolites could, therefore, act as sensitive biomarkers for ACR exposure and be useful for investigating toxic mechanisms. They may also provide a scientific foundation for assessing the effects of chronic low-dose ACR exposure on human health.

As the worldwide elderly population has grown, the incidence and prevalence of Alzheimer's disease (AD) has steadily increased. The differential lifelong exposure of populations to dietary fatty acids has raised concerns about the potential links between cognitive impairments and nutrition. However, few studies have addressed the levels of free fatty acids (FFAs) in AD patient serum. In this study, gas chromatography-mass spectrometry (GC-MS) was used to determine the levels of 15 serum FFAs in 31 AD patients and 33 healthy controls. The optimized methodology entailed the formation of methyl esters using 10% v/v H2SO4/CH3OH at 62°C for 2 hours. The linear range was 0.55-300 μg/mL, the range of recovery was 85.1-104.3%, and the detection limit was 0.03-0.08 μg/mL. Several FFAs in the AD patient significantly decreased when compared to the control, including three saturated fatty acids (C14:0, C16:0, and C18:0) and six unsaturated fatty acids (C16:1, C18:1, C18:2, γ-C18:3, C20:2, and C22:6). The serum level of C18:3 was significantly higher in the AD patients. The FFA profiles of the AD patients differed significantly from those of controls. The method effectively determined the FFA levels and could facilitate future studies regarding the relationship between AD and the metabolism of FFAs.

The approximate solution usually can only be obtained on solving the problem of statics,dynamics and buckling of laminated beams with arbitrary height.Based on the theory of elasticity and the method of state space,the state equation for isotropic laminated beam with simply supported edges is established without any assumptions about displacement models and stress distributions.Series expansion was carried out on the variables of the state equation.Using Caley-Hamilton theory,the exact closed analytical solutions are presented for statics,dynamics and buckling of laminated beams with arbitrary height.The method of calculating critical loads is improved in present.Numerical results of the example are obtained and compared with finite element method.The results show that the convergent solution can be achieved with high accuracy.

目的 探讨电感耦合等离子体质谱法(ICP-MS)测定人血浆样品中21种金属元素的最佳前处理方法.方法 分别采用HNO3直接稀释、HNO3-H2O2水浴消解、HNO3-H2O2烘箱高温消解3种方法进行血浆前处理,电感耦合等离子体质谱法测定.结果 血浆样品消解液中硝酸最适浓度为6％;21种元素相关系数优于0.999,检出限为0.00100μg/L～1.52 μg/L; HNO3直接稀释、HNO3-H2O2水浴消解、HNO3-H2O2烘箱高温消解3种前处理方法加标回收率范围分别为77.45％ ～ 125.2％、77.45％～ 128.6％、82.27％～118.8％; RSD分别介于0.31％～7.7％、0.082％～9.3％、0.080％～ 3.8％之间.结论 HNO3-H2O2烘箱高温消解前处理方法操作简便、干扰小、重现性好、准确度高,适合应用于ICP-MS进行生物样本中多元素的测定及大样本分析.

目的 基于高效液相色谱法测定阿尔茨海默病(Alzheimer's disease,AD)患者血清中维生素A、D3、B1、B2 、B12的水平,并探讨与AD的相关性. 方法 采用横断面病例对照研究,测定110例AD患者及130例健康对照血清中维生素A、D3、B1、B2、B12的水平.维生素A、D3测定用甲醇沉淀蛋白,正己烷提取,氮吹浓缩,无水乙醇定容,维生素B1、B2 、B12用C18小柱提取,甲醇/水(80％)定容,高效液相色谱仪紫外检测器(HPLC-UVD)测定.结果 AD患者血清中维生素A、D3、B1、B2、B12的水平与正常人有显著性差异(P＜0.05). 结论 AD的发生、转归与维生素A、D3、B1、B2、B12密切相关,提示在预防治疗AD中进行营养干预有一定的实际意义.

伴随人口老龄化,阿尔茨海默病逐渐成为引起老年人死亡的第四大病因.其致病因素和发病机制目前尚未清晰,发病机制以β淀粉样蛋白(Aβ)沉积、tau蛋白过度磷酸化和神经元变性死亡等学说为主.有关此病的研究多数着眼于治疗层面,尤其以药物的靶点为多,但因其病因的复杂多样性,随着研究的深入,药物的作用靶点也不断有新的发现,本文综述了抗阿尔茨海默病的非治疗药物及新靶点研究进展.

OBJECTIVES:Phthalates are environmental chemicals with reproductive toxicity and estrogenic effects in animals. They are of increasing concern to human health. AIM:To determine whether phthalate levels in semen were associated with infertility. METHODS:Using semen samples from 107 infertile and 94 fertile men, the presence and quantity of five phthalate esters were measured using high-performance liquid chromatography (HPLC). Using data collected from questionnaires and clinical examinations, the correlation between phthalate exposure and semen quality was analyzed. RESULTS:The cumulative levels of the measured phthalate esters were significantly higher in the infertility group compared to the control group (P<0·05). Concentrations of the five phthalate esters in men varied by age with older men showing higher cumulative levels. CONCLUSIONS:The presence of phthalates may contribute to male infertility in our study population.

OBJECTIVE:To observe the early prevention effect of the compound nutrients recipe for cognitive dysfunction of Alzheimer' s disease model-APP-PSN transgenic mouse.METHODS:36 APP-PSN transgenic mice aged two months randomly were divided into the intervention group supplied with compound recipe in the diet and the control group fed based feed, the former had high dose and low dose, 12 APP-PSN transgenic negative mice aged two months as the negative control were fed based feed. After 3 months' intervention, four groups' cognitive functions were evaluated using the Morris water maze, active avoidance experiment and jumping stair experiment.RESULTS:There was not statistically different between all the four groups for the weight and food intake. Compared with the control group, Morris water maze's incubation period of the intervention group was lower obviously, and jumping stair experiment's incubation period of the intervention group was higher obviously. In the active avoidance experiment, the high and low dose intervention group' s conditioned response accounted about 46.67% and 45.00% respectively, and the control group's conditioned response accounted about 20.83%. The differences of the three behavioral experiments between control group and intervention group had the statistical significance (P < 0.05), so the same as between control group and negative control group (P < 0.05). And there was no difference between intervention group and negative control group for the three behavioral experiments.CONCLUSION:The early supplementation with compound nutrition could postpone the occurrence and development of Alzheimer' s disease mice model's cognitive dysfunction.