阿芬太尼预处理通过抑制内质网应激发挥对心肌缺血再灌注损伤的保护作用

目的探究阿芬太尼预处理对心肌缺血再灌注损伤(myocardial Ischemia reperfusion injury,MIRI)大鼠的改善作用及可能存在的分子机制。方法纳入60只雄性SD大鼠,随机将其分为假手术组(Sham组,n=15)、模型组(MIRI组)、阿芬太尼低剂量预处理组(L-alfentanil组,3 mg/kg)及阿芬太尼高剂量预处理组(H-alfentanil组,6 mg/kg),每组15只;除去假手术组,剩余各组大鼠均构建MIRI模型。统计各组大鼠心功能参数[左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)]、血清心肌损伤因子[肌酸激酶同工酶(CK-MB)、肌钙蛋白Ⅰ(cTnI)]水平差异性;双染色法观察大鼠心肌梗死面积;HE染色分析心肌组织病理损伤;TUNEL检测心肌组织凋亡;免疫荧光及Western-blot检测各组大鼠心肌组织内质网应激蛋白(GRP78、CHOP、FAM134B)表达差异性。结果与Sham组相比,MIRI模型建立可以提升LVEDD、LVESD、CK-MB、cTnI水平、心肌梗死面积占比、心肌组织细胞凋亡程度及GRP78、CHOP表达及荧光强度,下调LVEF、LVFS水平及内质网应激蛋白FAM134B表达及荧光强度(P<0.05)。与MIRI组相比,阿芬太尼预处理可以下调LVEDD、LVESD、CK-MB、cTnI水平、心肌梗死面积占比、心肌组织细胞凋亡程度及GRP78、CHOP表达及荧光强度,上调LVEF、LVFS水平及内质网应激蛋白FAM134B表达及荧光强度(P<0.05)。与阿芬太尼低剂量组相比,阿芬太尼高剂量组大鼠LVEDD、LVESD、CK-MB、cTnI水平、心肌梗死面积占比、心肌组织细胞凋亡程度及GRP78、CHOP表达及荧光强度明显降低,LVEF、LVFS水平及内质网应激蛋白FAM134B表达及荧光强度明显提升,体现出剂量依赖性(P<0.05)。结论阿芬太尼预处理具有减轻心肌缺血再灌注大鼠心肌组织病理损伤,减少心肌梗死面积占比及抑制心肌组织细胞凋亡的作用,剂量依赖性明显,其分子机制可能与抑制内质网应激性程度有关,值得临床进一步研究。

线粒体关联性内质网膜与细胞Ca2+依赖性死亡的研究进展

线粒体关联性内质网膜(MAM)是线粒体和内质网发生交互作用的功能平台。研究发现有几十种蛋白质富集于两细胞器外膜之间,作为MAM蛋白质组成构成连接结构,功能上与Ca^(2+)信号传导等密切相关,影响生理或外源环境因素诱导的细胞转归和命运结局。文章重点阐述了MAM组成结构和功能调节及其在细胞Ca^(2+)依赖性死亡中的作用。

内质网源性转录因子对间歇性低氧大鼠心肌缺血再灌注损伤的影响

目的研究内质网源性转录因子(CHOP)对间歇性低氧大鼠心肌缺血再灌注损伤的影响。方法 54只大鼠随机分为三组:假手术组(n=18)、缺血再灌注组(n=18)、间歇性低氧+缺血再灌注组(n=18)。通过球囊结扎冠状动脉方法制作心肌缺血再灌注动物模型,将老鼠暴露在低氧循环中。制作间隙性低氧动物模型,用TUNEL法检测心肌细胞的凋亡,术后Western blot法检测CHOP蛋白表达。结果假手术组、缺血再灌注组及间歇性低氧+缺血再灌注组的心肌细胞凋亡率分别为(4.16±2.27)%、(38.68±4.58)%、(18.72±6.71)%,组间比较差异有统计学意义(P<0.05);假手术组、缺血再灌注组及间歇性低氧+缺血再灌注组的CHOP蛋白表达分别为(1.612±0.284)%、(0.946±0.372)%、(0.547±1.429)%,组间比较差异有统计学意义(P<0.05)。结论间歇性低氧在大鼠心肌缺血损伤中具有保护心脏的作用,其保护机制与CHOP蛋白表达下降有关。

教师教育的情感维度及其建构

教师的情感人文素质是教师专业发展的“内质性”条件,它不仅从内部保证教师的教育信念、教育热情,而且在技艺层面上保证教师的教育教学效率。中小学教师要回归职场,在职场中不断锤炼、提升自己的情感能力。在新的时代背景下,教师专业发展面临着更为复杂的情境,需进一步深入研究和认识教师职业的专业性,在“职前培养—入职适应—在职胜任—发展成熟—自我更新”的不同专业发展阶段,建构其专业发展的情感基础,以教师情感表达为切入点,加强教师情感研究,从形上思辨走向人文实证,实现可能性的突围。

内质网应激相关蛋白在肾纤维化大鼠肾组织中的表达

探究内质网应激(ERS)相关蛋白在单侧输尿管梗阻(UUO)大鼠肾间质纤维化中表达的调节。将大鼠随机分为假手术组及UUO模型组,UUO组行左侧输尿管结扎术,于术后3、7和14d Masson染色观察肾脏病理变化;眼底静脉丛取血,分离血清测定血尿素氮及肌酐;Masson染色对肾间质胶原相对面积进行半定量分析;免疫组化法检测α平滑肌肌动蛋白(α-SMA);Western blot检测葡萄糖调节蛋白78(GRP78)、内质网源性转录因子(CHOP)、凋亡相关蛋白半胱氨酸天门冬氨酸蛋白酶3(caspase-3)及caspase-12蛋白表达。模型组与对照组比较大鼠肾小管间质损伤指数、肾间质纤维化程度、血清Scr、BUN水平及肾组织CHOP、caspase-3蛋白表达有差异(P<0.05;P<0.01)。与假手术组相比,UUO模型组可见:1)肾小管扩张和肾间质纤维化程度随输尿管梗阻时间延长而渐进性加重;2)GRP78、CHOP、caspase-3及caspase-12蛋白表达在术后3d均有上调,随着梗阻时间延长,上述蛋白表达更显著(P<0.01)。内质网应激相关标志性蛋白在UUO大鼠肾间质纤维化的早期即存在表达上调,可能促进了肾间质纤维化不断进展。有望通过干扰内质网应激特异转录因子的传导通路,抑制细胞凋亡的表达,从而可减缓肾间质纤维化的发生和发展。

单侧输尿管梗阻的大鼠内质网应激相关蛋白表达上调

目的探究内质网应激(ERS)相关凋亡通路在单侧输尿管梗阻(UUO)大鼠肾间质纤维化中的作用机制。方法将大鼠随机分为假手术组及UUO模型组,UUO组行左侧输尿管结扎术,于术后3、7和14 d HE和Masson染色观察肾脏病理变化;眼底静脉丛取血,分离血清测定血尿素氮及肌酐;Western blot检测葡萄糖调节蛋白78(GRP78)、内质网源性转录因子(CHOP)、凋亡相关蛋白半胱氨酸天门冬氨酸蛋白酶3(caspase-3)及caspase-12蛋白表达。结果与假手术组相比,UUO模型组可见:1)肾小管扩张和肾间质纤维化程度随输尿管梗阻时间延长而渐进性加重;2)GRP78、CHOP、caspase-3及caspase-12蛋白表达在术后3 d均有上调,随着梗阻时间延长,上述蛋白表达更显著(P<0.01)。结论内质网应激相关标志性蛋白在UUO大鼠肾间质纤维化的早期即存在表达上调,可能促进了肾间质纤维化不断进展。

咪康唑对大鼠缺氧缺血性早产儿脑白质损伤的保护作用

目的探讨咪康唑对早产儿脑白质损伤(WMD)大鼠髓鞘的保护作用。方法新生3日龄SD大鼠随机分为假手术组、WMD模型组、10 mg/(kg·d))和40 mg/(kg·d)咪康唑组,每组15只;采用结扎右侧颈总动脉,缺氧80 min的方法制作早产儿WMD模型。咪康唑组于建模后第1~5天腹腔注射10 mg/(kg·d)和40 mg/(kg·d)咪康唑,WMD模型组注射等浓度二甲基亚砜(DMSO)。采用髓鞘碱性蛋白(MBP)免疫荧光染色及Western blot检测脑白质特异性MBP表达量,超微结构电镜观察髓鞘超微结构变化,并比较各组幼鼠体质量变化。结果 WMD大鼠经咪康唑治疗后,胼胝体MBP表达量较WMD模型组高,差异有统计学意义(P<0.05)。咪康唑治疗组MBP的表达量较模型对照组增高。模型对照组胼胝体髓鞘疏松,髓鞘内小空泡形成,呈筛网状改变,髓鞘厚度明显降低,结构紊乱。经咪康唑治疗后可明显改善缺氧缺血所致的脱髓鞘改变。WMD模型组幼鼠体质量增长速度较假手术组明显减慢,咪康唑治疗后大鼠的体质量生长速度增快。结论咪康唑可通过促进髓鞘形成保护新生大鼠脑缺氧缺血诱导的白质损伤,并改善大鼠的生长发育情况。

Deformation behavior of materials in micro-forming with consideration of intragranular heterogeneities

To describe the relationship between the whole material deformation behavior and each grain deformation behavior inmicro-forming,experimental and numerical modelling methods were employed.Tensile test results reveal that contrary to the valueof flow stress,the scatter of flow stress decreases with the increase of thickness-to-grain diameter(T/d)ratio.Microhardnessevaluation results show that each grain owns unique deformation behavior and randomly distributes in each specimen.The specimenwith less number of grains would be more likely to form an easy deformation zone and produce the concentration of plasticdeformation.Based on the experiment results,a size-dependent model considering the effects of grain size,geometry size,and thedeformation behavior of each grain was developed.And the effectiveness and practicability of the size-dependent model wereverified by experimental results.

The Life of a Protein Molecule——Protein Quality Control

The research progress in molecular chaperones, unfolded protein response （UPR） and ER-associated degradation （ERAD） involved in the protein quality control was summarized in this paper, and then the existing problems and the future devel- opment prospect were also discussed. It was pointed out that the life process of protein experienced four stages including synthesizing, folding, assembling and degradation, while each stage required strict quality control. In endoplasmic reticulum （ER）, a variety of proteins had been synthesized, folded and modified to form func- tional proteins with certain conformation. When the folding was blocked in ER, the unfolded proteins would aggregate and induce the UPR, which up-regulated the level of modification enzymes folded by a series of molecular chaperones and proteins to help them accomplish folding and assembling. If these proteins were still folded incorrectly, they would enter into ERAD for being degraded.

Composition and immuno-stimulatory properties of extracellular DNA from mouse gut flora

AIM To demonstrate that specific bacteria might release bacterial extracellular DNA(e DNA) to exert immunomodulatory functions in the mouse small intestine.METHODS Extracellular DNA was extracted using phosphate buffered saline with 0.5 mmol/L dithiothreitol combined with two phenol extractions. TOTO-1 iodide, a cell-impermeant and high-affinity nucleic acid stain, was used to confirm the existence of e DNA in the mucus layers of the small intestineand colon in healthy Male C57 BL/6 mice. Composition difference of e DNA and intracellular DNA(i DNA) of the small intestinal mucus was studied by Illumina sequencing and terminal restriction fragment length polymorphism(T-RFLP). Stimulation of cytokine production by e DNA was studied in RAW264.7 cells in vitro.RESULTS TOTO-1 iodide staining confirmed existence of e DNA in loose mucus layer of the mouse colon and thin surface mucus layer of the small intestine. Illumina sequencing analysis and T-RFLP revealed that the composition of the e DNA in the small intestinal mucus was significantly different from that of the i DNA of the small intestinal mucus bacteria. Illumina Miseq sequencing showed that the e DNA sequences came mainly from Gram-negative bacteria of Bacteroidales S24-7. By contrast, predominant bacteria of the small intestinal flora comprised Grampositive bacteria. Both e DNA and i DNA were added to native or lipopolysaccharide-stimulated Raw267.4 macrophages, respectively. The e DNA induced significantly lower tumor necrosis factor-α/interleukin-10(IL-10) and IL-6/IL-10 ratios than i DNA, suggesting the predominance for maintaining immune homeostasis of the gut.CONCLUSION Our results indicated that degraded bacterial genomic DNA was mainly released by Gram-negative bacteria, especially Bacteroidales-S24-7 and Stenotrophomonas genus in gut mucus of mice. They decreased pro-inflammatory activity compared to total gut flora genomic DNA.

Inter- and intra-hemispheric EEG coherence in patients with mild cognitive impairment at rest and during working memory task

Objective： To assess functional relationship by calculating inter- and intra-hemispheric electroencephalography （EEG） coherence at rest and during a working memory task of patients with mild cognitive impairment （MCI）. Methods： The sample consisted of 69 subjects： 35 patients （n = 17 males, n = 18 females; 52-71 years old） and 34 normal controls （n = 17 males, n = 17 females; 51 -63 years old）. Mini-mental state examination （MMSE） of two groups revealed that the scores of MCI patients did not differ significantly from those of normal controls （P〉0.05）. In EEG recording, subjects were performed at rest and during working memory task. EEG signals from F3-F4, C3-C4, P3-P4, T5-T6 and O1-O2 electrode pairs are resulted from the inter-hemispheric action, and EEG signals from F3-C3, F4-C4, C3-P3, C4-P4, P3-O1, P4-O2, T5-C3, T6-C4, T5-P3 and T6-P4 electrode pairs are resulted from the intra-hemispheric action for delta （1.0-3.5 Hz）, theta （4.0-7.5 Hz）, alpha-1 （8.0-10.0 Hz）, alpha-2 （10.5-13.0 Hz）, beta-1 （13.5-18.0 Hz） and beta-2 （18.5-30.0 Hz） frequency bands. The influence of inter- and intra-hemispheric coherence on EEG activity with eyes closed was examined using fast Fourier transformation from the 16 sampled channels. Results： During working memory tasks, the inter- and intra-hemispheric EEG coherences in all bands were significantly higher in the MCI group in comparison with those in the control group （P〈0.05）. However, there was no significant difference in inter- and intra-hemispheric EEG coherences between two groups at rest. Conclusion： Experimental results comprise evidence that MCI patients have higher degree of functional connectivity between hemispheres and in hemispheres during working condition, It suggests that MCI may be associated with compensatory processes during working memory tasks between hemispheres and in hemispheres. Moreover, failure of normal cortical connections may exist in MCI patients.

道与逻各斯之比较

道与逻各斯分别是中西文化传统中具有再生性的核心概念和范畴,它们都对各自的文化、哲学、思想、社会以及文艺学产生了巨大而深刻的影响。在全球化的语境下,比较分析它们的同与异,寻找它们各自的本源性内质,挖掘它们各自深藏的思想资源,探讨二者的互补给中西文化所带来的发展启示,确实是个有趣的话题。

脂质运载蛋白-2在川崎病相关心肌损伤中的作用及机制研究

目的探讨川崎病(KD)相关心肌损伤的可能机制。方法将45只(1月龄) SD大鼠随机分为对照组、干酪乳杆菌细胞壁成分(LCWE)模型组和4-苯基丁酸(4-PBA)治疗组。建立大鼠川崎病模型4周后,用酶联免疫吸附剂测定法(ELISA)检测KD大鼠血浆和心肌组织匀浆中脂质运载蛋白(Lcn) 2的含量;超声心动图检测大鼠心脏功能;各组大鼠心肌组织制作石蜡切片并进行细胞凋亡TUNEL染色;蛋白质印迹法(Western blot)检测大鼠心肌内质网应激的标志物表达变化。离体实验采用原代培养新生大鼠心肌细胞,Lcn 2处理48 h后检测细胞活力、半胱氨酸天冬氨酸蛋白酶(Caspase) 3活性以及内质网应激程度。结果与对照组比较,KD大鼠血浆和心肌组织匀浆中Lcn2的含量显著升高(P <0. 05)。用Lcn 2(10 ng/ml)处理原代培养的心肌细胞48 h后可导致心肌细胞活力显著降低(P <0. 05),同时内质网应激的标志物活化转录因子(ATF) 6、CCAAT/增强子结合蛋白同源蛋白(CHOP)、磷酸化的蛋白激酶R样内质网激酶(p-PERK)、磷酸化的真核起始因子(p-elF) 2α均出现升高,导致凋亡信号Caspase 12和活化的Caspase(cleave-Caspase) 3水平显著增高(P <0. 05)。KD大鼠心肌出现促凋亡性内质网应激,ATF6、CHOP、p-PERK、p-elF2α均显著升高,导致凋亡信号Caspase 12和cleave-Caspase 3水平显著增高(P <0. 05)。同时伴有左室舒张末期内径(LVIDd)显著增加(P <0. 05),左室射血分数(LVEF)显著降低(P <0. 05)。使用4-PBA后能够有效抑制KD状态下的心肌内质网应激程度,降低ATF6、CHOP、p-PERK、p-elF2α水平,降低Caspase 12和cleave-Caspase 3水平(P <0. 05),同时有效提升LVEF(P <0. 05),改善KD大鼠心脏泵血功能,减少LVIDd(P <0. 05),并最终改善KD大鼠舒张功能。结论 KD诱发心脏收缩舒张功能障碍同时伴有Lcn 2显著升高。Lcn 2对心肌细胞的直接作用是促凋亡性内质网应激。抑制KD状态下的心肌内质网应激可抑制心肌凋亡改善心脏功能。

Research on Behavior of Corrugated Packing in Vacuum Distillation Tower

The corrugated packing is prone to break down easily, which can affect the tower efficiency substantially. It is the inner environment of the vacuum distillation tower including the temperature and chemical nature of fluid that lead to the packing damage. The theoretical analysis indicates that it is the inner material flow of vacuum distillation tower that leads to the vibration of packing, which can affect the corrosion fatigue of packing significantly. Meanwhile, the modal shape and inherent frequency of packing under prestress can be obtained by means of mathematical analysis. Based on the two kinds of analysis, the flow induced vibration and corrosion fatigue are accountable for the failure of packing.

JNKs,insulin resistance and inflammation:A possible link between NAFLD and coronary artery disease

The incidence of obesity has dramatically increased in recent years.Consequently,obesity and associated disorders such as nonalcoholic fatty liver disease constitute a serious problem.Therefore,the contribution of adipose tissue to metabolic homeostasis has become a focus of interest.In this review,we discuss the latest discoveries that support the role of lipids in nonalcoholic fatty liver disease.We describe the common mechanisms(cJun aminoterminal kinases,endoplasmic reticulum stress,unfolded protein response,ceramide,lowgrade chronic inflammation)by which lipids and their derivatives impair insulin responsiveness and contribute to inflammatory liver and promote plaque instability in the arterial wall.Presenting the molecular mechanism of lipid activation of proinflammatory pathways,we attempt to find a link between nonalcoholic fatty liver disease,metabolic syndrome and cardiovascular diseases.Describing the common mechanisms by which lipid derivatives,through modulation of macrophage function,promote plaque instability in the arterial wall,impair insulin responsiveness and contribute to inflammatory liver and discussing the molecular mechanism of lipid activation of proinflammatory pathways,the key roles played by the proliferatoractivated receptor and liver X receptorα,nuclear receptorslipid sensors that link lipid metabolism and inflammation,should be emphasized.Further studies are warranted of antiinflammatory drugs such as aspirin,antiinterleukin6 receptors,immunemodulators(calcineurin inhibitors),substances enhancing the expression of heat shock proteins(which protect cells from endoplasmic reticulum stressinduced apoptosis),and anticJun aminoterminal kinases in welldesigned trials to try to minimize the high impact of these illnesses,and the different expressions of the diseases,on the whole population.

酿酒酵母PMT1与PMT2双基因过表达菌株构建及其复制寿命研究

目的构建酿酒酵母蛋白质O-甘露糖转移酶PMT1与PMT2双基因过表达菌株,研究其对酵母细胞复制性寿命的影响。方法以PCR技术为基础,通过分子克隆的方法构建PMT2基因表达载体;通过同源重组实现PMT1和PMT2双基因在酵母细胞中过表达;实时定量PCR验证过表达菌株中相关基因的转录水平;光学显微镜下分离和计数酵母目细胞产生子细胞的数目,检测酵母细胞的复制性寿命。结果通过克隆技术成功构建PMT2基因过表达载体(pRS305-PMT2-ox),并转化和筛选出PMT1与PMT2双基因过表达菌株(PMT1ox PMT2ox);转录水平分析证明PMT1和PMT2基因表达上调;复制性寿命检测结果显示:与野生型菌株比较,PMT1ox PMT2ox菌株的平均寿命无明显变化。结论过表达PMT1与PMT2基因不影响酵母菌株的平均复制性寿命,提示PMT1与PMT2双基因过表达不参与酵母复制性寿命的调节。

EfectofAmphipathicPEG-PEontheCirculationTimeofLi┐posomesinvivoMaster'sDegree

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Relationship between Creasing-Recovery Force and Crease-Recovery Angle

To find out the reason of resulting in the crease recovery of a fabric and provide theoretical guidance for designing a new material with good creasing-recovery property,the relationship between the creasing-recovery force and the crease-recovery angle of a woven fabric was investigated by self-setup experimental device.The results show that the crease-recovery angle of a woven fabric is correlated with the creasing-recovery force of the fabric in a linear relation.Furthermore,it is found that the internal stress is the principal force of affecting the creasing-recovery property of a woven fabric.In addition,the relationship between the tensile property of a woven fabric and the creasing-recovery property of the fabric has also been investigated,showing that the lower relaxation velocity of tensile stress of a fabric is,the better creasing-recovery property of the fabric has.

Regulation of Excited-State Intramolecular Proton Transfer Process and Photophysical Properties for Benzoxazole Isothiocyanate Fluorescent Dyes by Changing Atomic Electronegativity

Excited-state intramolecular proton transfer(ESIPT)is favored by researchers because of its unique optical properties.However,there are relatively few systematic studies on the effects of changing the electronegativity of atoms on the ESIPT process and photophysical properties.Therefore,we selected a series of benzoxazole isothiocyanate fluorescent dyes(2-HOB,2-HSB,and 2-HSe B)by theoretical methods,and systematically studied the ESIPT process and photophysical properties by changing the electronegativity of chalcogen atoms.The calculated bond angle,bond length,energy gap,and infrared spectrum analysis show that the order of the strength of intramolecular hydrogen bonding of the three molecules is 2-HOB<2-HSB<2-HSe B.Correspondingly,the magnitude of the energy barrier of the potential energy curve is 2-HOB>2-HSB>2-HSe B.In addition,the calculated electronic spectrum shows that as the atomic electronegativity decreases,the emission spectrum has a redshift.Therefore,this work will offer certain theoretical guidance for the synthesis and application of new dyes based on ESIPT properties.

Fluid-solid interaction of resistance loss of flexible hose in deep ocean mining

The resistance loss of transportation was studied and the influences of buoyancy layout,mineral content and elastic modulus of flexible hose were investigated based on three-dimensional finite element model of fluid-solid interaction by MSC.MARC/MENTAT software.The numerical results show that the resistance losses increase with the increase of mineral content Cv and velocity of internal fluid v and decrease with the increase of elastic modulus E of flexible hose.The buoyancy layout and the velocity of internal fluid have greater impacts on the resistance losses than the elastic modulus of flexible hose.In order to reduce the resistance losses and improve the efficiency of the deep-ocean mining,Cv and v must be restricted in a suitable range (e.g.10%-25% and 2.5-4 m/s).Effective buoyancy layout (such as Scheme C and D) should be adopted and the suitable material of moderate E should be used for the flexible hose in deep-ocean mining.