简介：AbstractBackground:Perioperative neurocognitive disorders (PND) are a series of severe complications in the perioperative and anesthetic periods with a decline in memory, execution ability, and information processing speed as the primary clinical manifestation. This study aimed to evaluate the impact of edaravone (EDA) on PND and peripheral blood C-X-C motif chemokine ligand 13 (CXCL13) levels in elderly patients with hip replacement.Methods:A total of 160 elderly patients undergoing hip arthroplasty in Affiliated Dongguan People’s Hospital of Southern Medical University (from March 2016 to March 2018) were randomly and double-blindly categorized into an EDA group and a control group (CON). Group EDA was administered intravenously EDA 30 min before surgery, and group CON was administered intravenously saline. The cognitive function of the two groups was evaluated 1-day before the operation and at 1 and 12 months after surgery, and the incidence of post-operative delirium was tested on days 1, 3, and 7 after surgery using the Chinese version of the confusion assessment method. Serum CXCL13 and interleukin (IL)-6 concentrations were measured before anesthesia, during surgery (30 min after skin incision), and on days 1, 3, and 7 after surgery. The continuous variables in accordance with normal distribution were tested using the Student’s t test, the continuous variables without normal distribution using the Mann-Whitney U test, and categorical variables by the χ2 test or Fisher exact test.Results:The incidence of post-operative delirium within 7 days after surgery was significantly higher in group CON than that in group EDA (31.3% vs. 15.0%, t=-5.6, P < 0.001). The modified telephone interview for cognitive status and activities of daily life scores were significantly higher in the group EDA than those in the group CON at 1 month (39.63 ± 4.35 vs. 33.63 ± 5.81, t = -2.13, P < 0.05 and 74.3 ± 12.6 vs. 61.2 ± 13.1, t = -1.69, P < 0.05) and 12 months (40.13 ± 5.93 vs. 34.13 ± 5.36, t = -3.37, P < 0.05 and 79.6 ± 11.7 vs. 65.6 ± 16.6, t= -2.08, P < 0.05) after surgery; and the incidence of neurocognitive dysfunction was significantly lower in the group EDA than that in the group CON (P < 0.05). Serum CXCL13 and IL-6 concentrations were significantly lower in the group EDA than those in the group CON during and after surgery (P < 0.05).Conclusion:EDA can significantly reduce the serum concentrations of CXCL13 and IL-6 and improve the PND of patients.

简介：AbstractBackground:We previously found that the intestinal epithelial chemokine (C-C motif) ligand 7 (CCL7) plays an important role in the development of toxin-induced acute liver damage. The detailed effects of intestinal epithelial CCL7 on chronic diseases; however, are still unclear. Here, we aimed to investigate the impact of intestinal epithelial CCL7 overexpression on high-fat diet (HFD)-induced obesity and steatohepatitis in mice.Methods:Intestinal epithelial CCL7 overexpression (CCL7tgIEC) mice and their wild-type (WT) littermates were fed with normal chow or HFD for 16 weeks to induce obesity and non-alcoholic fatty liver disease. Body weight gain, as well as adipose tissue index were assessed. Liver injury was monitored by histological analysis and real time polymerase chain reaction. Gut microbial composition was analyzed by 16S rRNA gene sequencing.Results:We found that the CCL7tgIEC mice on a HFD had markedly decreased weight gain (8.9 vs. 17.0 g, P < 0.05) and a lower adipose tissue index that include mesenteric fat (1.0% vs. 1.76%, P < 0.05), gonadal fat (2.1% vs. 6.1%, P < 0.05), subcutaneous fat (1.0% vs. 2.8%, P < 0.05) compared to WT animals. HFD-induced glucose intolerance and insulin resistance were also significantly improved in CCL7tgIEC mice compared to WT. Furthermore, HFD-fed CCL7tgIEC mice displayed less hepatic lipid accumulation and lower expression of inflammatory factors than WT mice. 16S rRNA gene sequencing demonstrated that CCL7 overexpression in intestinal epithelial cells improved HFD-induced gut microbial dysbiosis.Conclusions:Our study revealed that CCL7 overexpression in the intestinal epithelium protects mice against the progression of diet-induced obesity, hepatic steatosis, and enteric dysbiosis.

简介：AbstractBackground:Macrophages play an important role in renal ischemia reperfusion injury, but the functional changes of macrophages under hypoxia/reoxygenation and the related mechanism are unclear and need to be further clarified.Methods:The effects of hypoxia/reoxygenation on functional characteristics of RAW264.7 macrophages were analyzed through the protein expression detection of pro-inflammatory factors TNF-α and CD80, anti-inflammatory factors ARG-1 and CD206. The functional implications of C-X3-C motif chemokine receptor 1(CX3CR1) down-regulation in hypoxic macrophages were explored using small interfering RNA technology. Significance was assessed by the parametric t-test or nonparametric Mann-Whitney test for two group comparisons, and a one-way ANOVA or the Kruskal-Wallis test for multiple group comparisons.Results:Hypoxia/reoxygenation significantly increased the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and chemokine C-X3-C motif chemokine ligand 1 (CX3CL1)/CX3CR1 and inhibited the protein expression of M2-related anti-inflammatory factors ARG-1 and CD206 in a time-dependent manner in RAW264.7 cells. However, the silencing of CX3CR1 in RAW264.7 cells using specific CX3CR1-siRNA, significantly attenuated the increase in protein expression of TNF-α (P < 0.05) and CD80 (P < 0.01) and the inhibition of ARG-1 (P < 0.01) and CD206 (P < 0.01) induced by hypoxia/reoxygenation. In addition, we also found that hypoxia/reoxygenation could significantly enhance the migration (2.2-fold, P < 0.01) and adhesion capacity (1.5-fold, P < 0.01) of RAW264.7 macrophages compared with the control group, and CX3CR1-siRNA had an inhibitory role (40% and 20% reduction, respectively). For elucidating the mechanism, we showed that the phosphorylation levels of ERK (P < 0.01) and the p65 subunit of NF-κB (P < 0.01) of the RAW264.7 cells in the hypoxic/reoxygenation group were significantly increased, which could be attenuated by down-regulation of CX3CR1 expression (P < 0.01, both). ERK inhibitors also significantly blocked the effects of hypoxic/reoxygenation on the protein expression of M1-related pro-inflammatory factors TNF-α, CD80 and M2-related anti-inflammatory factors ARG-1 and CD206. Moreover, we found that conditioned medium from polarized M1 macrophages induced by hypoxia/reoxygenation, notably increased the degree of apoptosis of hypoxia/reoxygenation-induced TCMK-1 cells, and promoted the protein expression of pro-apoptotic proteins bax (P < 0.01) and cleaved-caspase 3 (P < 0.01) and inhibited the expression of anti-apoptotic protein bcl-2 (P < 0.01), but silencing CX3CR1 in macrophages had a protective role. Finally, we also found that the secretion of soluble CX3CL1 in RAW264.7 macrophages under hypoxia/reoxygenation was significantly increased.Conclusions:The findings suggest that hypoxia/reoxygenation could promote M1 polarization, cell migration, and adhesion of macrophages, and that polarized macrophages induce further apoptosis of hypoxic renal tubular epithelial cells by regulating of CX3CL1/CX3CR1 signaling pathway.

简介：摘要目的探讨外周血CXC型趋化因子配体13（CXCL13）检测在pSS患者中的临床意义。方法纳入60例研究对象，其中30例初诊的pSS患者为疾病组，30名健康体检者为对照组，采用ELISA法检测血清CXCL13水平，并采用Pearson相关系数及Spearman相关系数，分析其与外周血B细胞比例、免疫球蛋白（Ig）G、IgM、IgA、C3、C4、自身抗体等免疫相关指标、腺体结构和功能指标，以及SS疾病相关指数EULAR干燥综合征疾病活动度指数（ESSDAI）和EULAR干燥综合征患者报告指数（ESSPRI）的相关性。结果pSS组患者外周血CXCL13水平明显高于对照组[（139±94）pg/ml和（36±20）pg/ml]，差异有统计学意义（t=5.838，P<0.01）。pSS患者外周血CXCL13水平与外周血B细胞比例（r=0.364，P=0.048）、IgG水平（r=0.369，P=0.045）、唇腺淋巴细胞浸润程度（r=0.592，P=0.001），以及ESSDAI（r=0.415，P=0.023）、ESSPRI评分（r=0.431，P=0.017）均呈正相关；与未刺激状态下唾液流率呈负相关（r=-0.381，P=0.038）。pSS患者中有系统累及者24例，有系统累及的pSS患者血清CXCL13水平较无系统累及者明显升高，且差异有统计学意义（Z=-2.256，P=0.024），但与系统累及数无明显相关性（r=0.344，P=0.062）。结论pSS患者外周血中CXCL13的检测有助于疾病活动程度及腺体破坏程度的判断。

简介：<正>Fasligand(FasL)wasfirstdescribedfunctionallyasaninduciblecellsurfacemoleculeusedbycytotoxicTcellstoinduceapoptoticcelldeathintumorcellsandactivatedlymphocytes.WiththeidentificationofFasastheIprgeneproduct,FasLbecamerecognizedasamoleculeinvolvedindown-regulationoftheimmunesystem.WhileFasLcanbeusedtoefficientlykillFas-expressingtumorcellsaswellasactivatedTandBlymphocytesinvitro,attemptstouseFasLtherapeuticallytotreatcancerortopreventtransplant

简介：无

简介：HydrophilicligandexchangecomplexeswithdifferentchemicalenvironmentinchiralcavitywerepreparedandusedasstationaryphasesofHPLCtoresolveDL-aminoacids.Themechanismandmodelsofresolutionwerestudied.

简介：Receptor-ligandinteractionsinbloodflowarecrucialtoinitiatesuchbiologicalprocessesasinflammatorycascade,plateletthrombosis,aswellastumormetastasis.Tomediatecelladhesion,theinteractingreceptorsandligandsmustbeanchoredontotwoapposingsurfacesoftwocellsoracellandasubstratum,i.e.,two-dimensional(2D)binding,whichisdifferentfromthebindingofasolubleligandinfluidphasetoareceptor,i.e.,three-dimensional(3D)binding.Whilenumerousworkshavebeenfocusedon3Dkineticsofreceptor-ligandinteractionsintheimmunesystem,2Dkineticsanditsregulationshavebeenlessunderstood,sincenotheoreticalframeworkorexperimentalassayswereestablisheduntil1993.Notonlydoesthemolecularstructuredominate2Dbindingkinetics,buttheshearforceinbloodflowalsoregulatescelladhesionmediatedbyinteractingreceptorsandligands.Here,weprovideanoverviewofcurrentprogressin2Dbindingandregulations,mainlyfromourgroup.Relevantissuesoftheoreticalframeworks,experimentalmeasurements,kineticratesandbindingaffinities,andforceregulationsarediscussed.

简介：在血流动的Receptor-ligand相互作用是关键的作为煽动性的串联，血小板血栓，以及肿瘤转移开始生物过程。为了调停，房间粘附，交往的受体和ligands必须被抛锚到二个房间或一个房间和一个基础的二apposing表面上，即，二维(2D)绑定，与在到受体的液体阶段的可溶的ligand的绑定不同，三维(3D)有约束力。当众多的工作在免疫系统集中于receptor-ligand相互作用的3D动力学时，2D动力学和它的规定少些被理解，自从没有理论框架和试验性的试金被建立了直到1993。不仅分子的结构统治在血流动的力量也调整的2D绑定动力学，而是shear房间粘附由交往的受体和ligands调停了。这里，我们在2D绑定和规定提供了当前的进步的概述。理论框架，试验性的大小，运动的率和有约束力的亲密关系的相关问题，和力量规定，被讨论。

简介：Themetal-organicchemicalvapordeposition(MOCVD)techniqueisapromisingprocessforhigh-temperaturesuperconductorYBa2Cu3O7-δ(YBCO)preparation.Inthistechnique,itisachallengetoobtainbariumprecursorswithhighvolatility.Inaddition,thepurity,evaporationcharacteristicsandthermostabilityofadoptedprecursorsinthewholeprocesswoulddecidethequalityandreproducibleresultsofYBCOfilm.Inthepresentreport,thebariumprecursorcontaining2,2,6,6-tetramethylheptane-3,5-dionate...

简介：AIMTo在真菌的部件zymosan在.METHODSHCFs是的有教养的人的角膜的成纤维细胞(HCF)导致的proinflammatorycytokine和chemokine表示上调查triptolide的效果在zymosan或triptolide的缺席或存在有教养。interleukin(IL)的版本-6,IL-8，和进文化上层清液的单核白血球chemoattractantprotein-1(MCP-1)与连接酶的immunosorbent试金被测量。细胞的许多为这些蛋白质的mRNAs被反向的抄写和即时聚合酶链反应分析决定。激活mitogen的蛋白质kinases(MAPK)和内长的原子factor-κ的phosphorylation；B(NF-κ；B)禁止者Iκ；B-α；被immunoblot分析检验。版本喂奶从HCF的脱氢酶(LDH)活动被测量，比色的assay.RESULTSTriptolide禁止了从在一个集中依赖者和时间依赖者举止的HCF的IL-6，IL-8，和MCP-1的导致zymosan的版本。它也在这些房间禁止了IL-6，IL-8，和MCP-1mRNA丰富的导致zymosan的起来规定。而且，triptolide稀释了MAPK的导致zymosan的phosphorylation细胞外的调整信号的kinase(英皇家空军之阶级最低之兵)，c6月NH2-terminalkinase(JNK)，和象Iκ的phosphorylation和降级一样的p38；B-α；。Triptolide没多半展出cytotoxicity因为HCFs.CONCLUSIONTriptolide由暴露于zymosan的HCF禁止了proinflammatorycytokine和chemokine生产，随这个行动被MAPK和NF-κ的抑制调停；B发信号小径。这混合物可能因此被期望限制煽动性的房间的渗入进与真菌的感染联系的角膜。

简介：IncreasedexpressionofFasbyhematopoieticprogenitorsinaplasticanemia(AA)suggeststhatFas/Fasligand(FasL)systemplaysakeyroleintheformationofseverepancytopenia.Tofurtherconfirmtheabovehypothesis,Tcellsfrom8patientswithAAweresystematicallystudiedfortheirFasL'sdistributionpattern,releasingmannerandproapoptoticactivity,comparedwithnormalrestingTcellsandartificiallyactivatedTcellblasts.TheresultsdemonstratedthatAATcellsabnormallyexpressedlowlevelsofmembrane-boundFasLandcontainedhighlevelsofintracellularFasLwhichcouldbetriggeredtoreleasebyhigh-dosephytohemagglutinin(PHA)pulse-stimulation.ThesupernatantsfromthePHA-stimulatedAATcellshadapparentcytotoxicityagainstFasL-sensitiveJurkatcells,whichcouldbesignificantlyinhibitedbymonoclonalantibodyagainstFasLinadose-dependentmanner,ornearlycompletelyabrogatedbyultracentrifugation.TheabovephenomenaalsoappearedonartificiallyactivatedTcellblasts,butthiswasnotthecaseonnormalrestingTcells.TheseresultsindicatethatAATcellisatypeof'preactivated'Tlymphocyte,characterizedbyoverexpressionofFasL,especiallyintracellularFasLwhichcanbestimulatedtoreleaseinbioavtiveexosomesboundform.Takentogether,ourdataprovidefurtheranddirectevidenceforthehypothesisthatTcellsmightmediatethedestructionofhematopieticprogenitorinAAthroughFas/FasLsystem.

简介：摘要 作为化学学科一大独有的特色标志，化学方程式既是化学教学的重头戏也是化学教学的拦路虎。一方面，化学方程式是化学教学中的一个重要部分，化学中化学反应的表示、反应原理的解释以及物质的化学性质说明都离不开化学方程式，它是学生学好化学形成正确的科学思想和积极的学习态度的重要基础；另一方面，同时亦是化学教学中的难点之一，学生往往在学习化学方程式时采用死记硬背的方法，加之不能清楚地理解化学方程式所要表达出来的微观结构蕴意，使得初三学生在初接触化学学科时困难重重，学习兴趣降低，对接下来的化学学习造成了负面的影响。本文主要采用文献法和个案研究法，通过阅读大量的参考文献，阐述化学方程式的含义，强调化学方程式的基础性和重要性；在此基础上，学习与分析有关化学方程式的教学案例，从中领悟总结出适合中学生学习化学方程式的方法。

简介：

简介：Ahallmarkofallformsofneurodegenerativediseasesisimpairmentofneuronalfunctions,andinmanycasesneuronalcelldeath.Althoughtheetiologyofneurodegenerativediseasesmaybedistinct,differentdiseasesdisplayasimilarpathogenesis,forexampleabnormalimmunitywithinthecentralnervoussystem(CNS),activationofmacrophage/microgliaandtheinvolvementofproinflammatorycytokines.Recentstudiesshowthatneuronsinaneurodegenerativestateundergoahighlyregulatedprogrammedcelldeath,alsocalledapoptosis.TNF-relatedapoptosis-inducingligand(TRAIL),amemberoftheTNFfamily,hasbeenshowntobeinvolvedinapoptosisduringmanydiseases.Asonememberofadeathligandfamily,TRAILwasoriginallythoughttotargetonlytumorcellsandwasnotpresentinCNS.However,recentdatashowedthatTRAILwasunregulatedinHIV-1-infectedandimmune-activatedmacrophages,amajordiseaseinducingcellduringHIV-1-associateddementia(HAD).TRAILisalsoinducedonneuronbyβ-amyloidprotein,animportantpathogenforAlzheimer'sdisease.Inthisreview,wesummarizethepossiblecommonaspectsthatTRAILinvolvedthoseneurodegenerativediseases,TRAILinducedapoptosissignalingintheCNScells,andspecificroleofTRAILinindividualdiseases.Cellular&MolecularImmunology.2005;2(2):113-122.

简介：

简介：Colorectalcancer(CRC)isthethirdmostcommoncancerinmenandthesecondmostcommoncancerinwomen,worldwide.Intheearlystagesofthedisease,biomarkerspredictingearlyrelapsewouldimprovesurvivalrates.Inmetastaticpatients,theuseofpredictivebiomarkerscouldpotentiallyresultinmorepersonalizedtreatmentsandbetteroutcomes.TheCXCfamilyofchemokines(CXCL1to17)aresmall(8to10kDa)secretedproteinsthatattractneutrophilsandlymphocytes.Thesechemokinessignalthroughchemokinereceptors(CXCR)1to8.Severalstudieshavereportedthatthesechemokinesandreceptorshavearoleineitherthepromotionorinhibitionofcancer,dependingontheircapacitytosuppressorstimulatetheactionoftheimmunesystem,respectively.Ingeneralterms,activationoftheCXCR1/CXCR2pathwayortheCXCR4/CXCR7pathwayisassociatedwithtumoraggressivenessandpoorprognosis;therefore,thespecificinhibitionofthesereceptorsisapossibletherapeuticstrategy.Ontheotherhand,thelesserknownCXCR3andCXCR5axesaregenerallyconsideredtobetumorsuppressorsignalingpathways,andtheirstimulationhasbeensuggestedasawaytofightcancer.Thesepathwayshavebeenstudiedintumortissues(usingimmunohistochemistryormeasuringmRNAlevels)orserum[usingenzyme-linkedimmunosorbentassay(ELISA)ormultiplexingtechniques],amongothersampletypes.CommonvariantsingenesencodingfortheCXCchemokineshavealsobeeninvestigatedaspossiblebiomarkersofthedisease.ThisreviewsummarizesthemostrecentfindingsontheroleofCXCchemokinesandtheirreceptorsinCRCanddiscussestheirpossiblevalueasprognosticorpredictivebiomarkersaswellasthepossibilityoftargetingthemasatherapeuticstrategy.

简介：AbstractBackground:Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS’s response to SD.Methods:Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes.Results:CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted.Conclusions:These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.

简介：

简介：新奇chiral为ligand交换层析(CLEC)的静止阶段(CSP1)被第一把dimethylchlorosilane用作在硅石胶化的表面上为减少的剩余silanol组盖住试剂的结束准备，然后同时作为一个chiral选购者和恐水病的辛基组把l职业人员介绍给硅石胶化表面。CSP1上的14dl氨基的酸的enantioseparations被完成，enantioselectivity和在0.8和6.3之间的决定R从1.09～2.44。有用参考方法准备的结合的阶段(CSP2)的CSP1的色析法的表演被比较。结果证明chiral的列效率和决定R静止阶段能被使用上述修改方法改进。