简介：BACKGROUND:Microgliaareverysensitivetoenvironmentalchanges,oftenbecomingactivatedbypathologicalconditions.Activatedmicrogliacanexertadualroleininjuryandrepairinvariousdiseasesofthecentralnervoussystem,includingcerebralischemia,Parkinson’sdisease,andAlzheimer’sdisease.OBJECTIVE:Animmortalmicroglialcellline,BV2,wastreatedwithvaryingconcentrationsoflipopolysaccharide(LPS)toinduceapathologicalsituation.Supernatantwasharvestedandincubatedwithbonemarrowmesenchymalstemcellsand,concomitantly,bonemarrowmesenchymalstemcelldifferentiationwasobserved.DESIGN:Acontrolledobservation,invitroexperiment.SETTING:DepartmentofNeurology,FirstAffiliatedHospitalofChinaMedicalUniversity.MATERIALS:Fivemale2–3-week-oldSpragueDawleyratswerepurchasedfromAnimalLaboratoryCenterofChinaMedicalUniversityandincludedinthisstudy.Theprotocolwasperformedinaccordancewithethicalguidelinesfortheuseandcareofanimals.ThemicroglialcelllineBV2wasproducedbyCellResearchInstituteofChineseAcademyofSciences.LPSwasproducedbySigmaCompany,USA.METHODS:ThisstudywasperformedintheCentralLaboratoryofChinaMedicalUniversityfromSeptember2006toMarch2007.Ratfemoralandtibialbonemarrowwascollectedforseparationandprimarycultureofbonemarrowmesenchymalstemcells.Bonemarrowmesenchymalstemcellculturesweredividedinto5groups:controlgroup,non-activatedgroup,aswellaslow-,medium-,andhigh-doseLPSgroups.Inthecontrolgroup,bonemarrowmesenchymalstemcellswereculturedwithDulbecco’smodifiedEagle’smedium(DMEM)supplementedwithfetalbovineserum(volumefraction0.1).Inthenon-activatedgroup,bonemarrowmesenchymalstemcellswereincubatedwithnon-activatedBV2supernatant.Inthelow-,medium-,andhigh-doseLPSgroups,bonemarrowmesenchymalstemcellswereincubatedwithLPS(0.01,0.1and1μg/L,respectively)-activatedBV2supernatant.MAIN

简介：Objective:ToexploretheeffectsofnuclearM-CSFontheprocessoftumorigenesis.Methods:FunctionalpartofM-CSFcDNAwasinsertedintoaneukaryoticexpressionplasmidpCMV/myc/nuc,whichcanaddthreeNLStotheC-terminaloftheexpressedproteinanddirecttheproteinintothecellnuclei.TheconstructedplasmidwastransferredintoNIH3T3cellsandthecellcloneswereselectedbyG-418selection.CellclonesstableexpressingtargetproteinwereidentifiedbyRT-PCR,ABCimmunohistochemistryassayandWesternblot.Cellgrowthkineticsanalysesthroughgrowthcurves,celldoublingtime,MTTtestandanti-senseoligodeoxynucleotide(ASODN)inhibitingcellgrowthtestwereperformedtoidentifycellsproliferationpotential.Results:Thetransfectedcellsshowedelevatedproliferationpotentialoverthecontrolcells.Conclusion:AbnormalappearanceofM-CSFinnucleuscouldenhancecellproliferation,whichsuggeststhatcytokineisoformswithincellnucleusmightplaytranscriptionfactor-likerole.

简介：Objective:ToconstructamutantpEGFP-hTERTexpressionvector,toobserveitssteadyexpressionintransfectedhumanbladdercarcinomacelllineT24anditsroleinmolecularregulatorymechanismsoftelomerase,andtoprovideanewtargetgeneforbladdercancer.Methods:PCRamplificationwasperformedbyusingprimersbasedontheknowngenesequenceofhTERT.PCRproductionwasclonedintoplasmidpGEMT-TeasyandthesequenceofmutanthTERTgenewasanalyzed.ArecombinantmutanthTERTvector(pEGFP-hTERT)wasconstructedattheEcoRIandSalIsitesofthepEGFP-C1vector.AftertransfectingthefusiongeneintobladdercarcinomacelllineT24bycalciumphosphate-DNAcoprecipitation,thesteadyexpressionofGFP-hTERTfusionproteinwastestedbyfluorescentlightmicroscopy.TheproliferationchangesofbladdercarcinomacelllineT24weredetectedbylightmicroscopyandsenescencecorrelatedβ-galactosidasestaining.Results:IdentificationofpEGFP-hTERTbyenzymedigestionshowedthatmutanthTERTfragmenthadbeenclonedintoEcoRIandSalIsitesofthepEGFP-C1vector.ThesteadyexpressionofGFP-hTERTfusionproteinwaslocalizedinthenucleusoftransfectedcells.Expressionofsenescence-associatedβ-galactosidaseintransfectedcellsgraduallyincreasedwithextendedculturedtimeandcellgrowthwassuppressed.Conclusion:Themutant-typehTERTgenesuppressestheproliferationofbladdercarcinomacelllineT24bycompetitiveeffectontelomeraseactivity.ThissuggeststhathTERTgenemightbeasuitablegenetargetforbladdercancertherapy.

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简介：Radiotherapy,astandardadjuvanttosurgery,improvessurvivalratesinpatients,butresistancetotreatmentbysomegliomaslimitsthesuccessofclinicalapplication.Emergingevidenceindicatesthatthetumormicroenvironmentcontributestoradiationresistancebyregulatingthelevelsofcytokinesandgrowthfactors[1;2].

简介：β的识别；由dectin-1的-glucans被显示了调停房间激活，cytokine生产和许多抗真菌的回答。这里，我们报导在到Candidaalbicans的mucosal免疫的dectin-1的功能的活动被主人的基因背景影响。Dectin-1在C57BL/6，然而并非BALB/c老鼠为胃肠、阴道的candidiasis的合适的控制被要求；事实上，后者当dectin-1不在时显示出增加的抵抗。到感染的dectin-1-deficientC57BL/6老鼠的危险性在IL-17A和芳基烃受体依赖者IL-22生产并且在适应Th1回答与缺点被联系。相反，dectin-1-deficientBALB/c鼠标的抵抗与增加的IL-17A和IL-22生产并且向提供免疫学的存储器的Th1/Treg有免疫力的回答扭曲被联系。迥异的正规/不在经典中的NF-κ；dectin-1下游地表明小径的B在二不同老鼠紧张被激活。因此，在抗真菌的mucosal免疫的dectin-1的网活动依赖于主人的基因背景，它在dectin-1发信号之上影响天生的cytokine生产和适应Th1/Th17房间激活。

简介：Purpose:Anumberofdifferentclinicalcharacteristicshavebeenreportedtosinglycorrelatewiththerapeuticactivityofepidermalgrowthfactorreceptor(EGFR)tyrosinekinaseinhibitors(TKIs)inadvancednon-small-celllungcancer(NSCLC).Thisstudyaimedtoidentifypredictivefactorsassociatedwithprognosticbenefitsofgefitinib.Patientsandmethods:EGFRgenetypingin33advancedNSCLCpatientsreceivedgefitinib(250mg/day)wereanalyzedwithmutant-enrichedPCRassay.Gefitinibresponsewasevaluatedwithpotentialpredictivefactorsretrospectively.Results:Theoverallobjectiveresponserate(ORR)andmedianprogression-freesurvival(PFS)inthe33patientstreatedbygefitinibwere45.5%and3.0(2.0-4.0)months.TheORRandmedianPFSinEGFRgenemutationpatientsweresignificantlyhigher/longerthanthoseinEGFRgenewild-typepatients(P<0.01).Similarly,theORRandmedianPFSinnon-smokerpatientsweresignificantlyhigher/longerthanthoseinsmokerpatients(P<0.05,P<0.01,respectively).However,nodifferenceforORRandmedianPFSoccurredbetweenmaleandfemalepatients.LogisticmultivariateanalysisshowedthatonlyEGFRmutatedgenewassignificantlyassociatedwiththeORR(P<0.01).BothEGFRmutatedgeneandnon-smokerwerethemajorfactorsthatcontributedtoPFS(P<0.05).Conclusions:EGFRmutatedgeneandnon-smokerstatusarepotentialpredictorsforgefitinibresponseinNSCLCpatients.

简介：瞄准：由一个树枝状的房间(DC)调查反肿瘤免疫鼠科的前列腺癌症上的疫苗的编码第二等的淋巴的chemokine基因和肿瘤lysate。方法：从C57BL/6的骨头髓的DC是有表示第二等的淋巴的chemokine(SLC)的原生质标志向量的transfected由Lipofectamine2000的cDNA脂肪的一些和肿瘤lysate。从SLC+lysateDC提取的全部的RNA被用来由反向的transcriptase聚合酶链反应(RT-PCR)验证SLC的表示。免疫在鼠科的前列腺癌症上疫苗的DC的治疗学的效果被估计。结果：当与SLC相比DC，lysateDC，DC或磷酸盐缓冲答案(PBS)时，我们发现在C57BL/6鼠标的前列腺肿瘤模型，SLC+lysateDC的adminstration最显著地禁止了肿瘤生长对应物(P<0.01)。荧光灯的染色分析显示出的Immunohistochemical在确定的肿瘤以内的更多的CD4+,CD8+T房间和CD11c+DC的渗入由比另外的DC疫苗疫苗的SLC+lysateDC对待(P<0.01)。结论：编码第二等的淋巴的chemokine和肿瘤lysate的DC疫苗能由CD4+,CD8+T房间和DC的渗入得到重要的反肿瘤免疫，它可能为前列腺癌症提供一个潜在的免疫疗法方法。

简介：Objective:TodetecttheeffectofarsenictrioxideorATRAonAPLcellsorHL-60cellsandtoinvestigatethemechanismofthehyperleukocytosisanddetectthecrossresistancebetweenATRAandarsenictrioxide.Methods:Thenumberofpromyelocytesormorematuredgranulocyteswerecountedbyregularmethod,MTTtestwasusedtomeasuretheproliferationofHL-60cellsorAPLcells,flowcytometryanalysistomeasuretheapoptosis,NBTmethodtodetectthedifferentiationofHL-60cellsorAPLcells.Results:TheproliferationofprimaryAPLcellsorHL-60cellscouldbeinhibitedinvitrobyeitherarsenictrioxideorATRA,whichcouldinduceobviousapoptosisorobviousdifferentiationofprimaryAPLcellsorHL-60cells.InhibitionofproliferationorapoptosisofATRAresistantHL-60cellswereachievedbyexposuretoarsenictrioxideinvitro.Ontheotherhand,theresultsofinvivotreatmentshowedthatarsenictrioxidealsoinduceofhyperleukocytosis.Conclusion:TheresultsindicatedthatthehyperleukocytosisinducedbyATRAisnotcontributedtothemechanismofmoredifferentiationthanapoptosis,therewasnotcrossresistancebetweenATRAandarsenictrioxide.

简介：Thispaperdescribesthedesignandfabricationofarangeof‘gascell'microtargetsproducedbytheTargetFabricationGroupintheCentralLaserFacility(CLF)foracademicaccessexperimentsontheOrionlaserfacilityattheAtomicWeaponsEstablishment(AWE).TheexperimentswerecarriedoutbyanacademicconsortiumledbyImperialCollegeLondon.Theunderlyingtargetmethodologywasanevolutionofarangeoftargetsusedforexperimentsonradiativeshocksandinvolvedthefabricationofaprecisionmachinedcellcontaininganumberofaperturesforinteractionfoilsordiagnosticwindows.Theinteriorofthecellwasgas-filledbeforelaserirradiation.Thispaperdetailstheassemblyprocesses,thinfilmrequirementsandmicro-machiningprocessesneededtoproducethetargets.Alsodescribedistheimplementationofagas-fillsystemtoproducetargetsthatarefilledtoapressureof0.1–1bar.Thepaperdiscussesthechallengesthatareposedbysuchatarget.

简介：Objective:TostudytheeffectoftraditionalChinesemedicineantiviralcapsulesinthetreatmentofgenitalherpes.Methods:Usingfemaleguineapiggenitalherpesastheanimalmodel,thisstudyusedoraladministrationoftwoformulationsofantiviralcapsules(AC)andobservedtheeffectonvaginalHSV-2titersandvulvarsymptoms.CellcultureswerealsousedtoexaminethedirectinactivationofHSV-2bytheantiviralcapsulesandthesuppressionofHSV-2viathreedrugadministrationmethods.Results:Therewasnosignificantdifferenceofmeanvaginalvirustitersbetweentheantiviralcapsulegroupsandthatofthepositiveacyclovir(ACV)control(P>0.05).Meanvulvarsymptomscoresofthetwoantiviralcapsulegroupswerealsosignificantlylowerthanthatofthesalinenegativecontrolgroupondays2,3,5,7and8(P<0.05)andsimilartothatoftheACVcontrol(P>0.05).CellcultureshowedtheminimuminhibitoryconcentrationsofantiviralcapsulesNo.1andNo.2were0.390625mg/mland1.5625mg/ml,respectively.Conclusion:ThetraditionalChinesemedicineantiviralcapsuleshadsuppressiveeffectsonHSV-2inbothanimalmodelGHandinvitrocellculture.

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简介：Wedevelopadualporous(DP)TiO_2filmfortheelectrontransportinglayer(ETL)incarboncathodebasedperovskitesolarcells(C-PSCs).TheDPTiO_2filmwassynthesizedviaafacilePS-templatedmethodwiththethicknessbeingcontrolledbythespin-coatingspeed.ItwasfoundthatthereisanoptimumDPTiO_2filmthicknessforachievinganeffectiveETL,asuitableperovskite/TiO_2interface,anefficientlightharvesterandthusahighperformanceC-PSC.Inparticular,suchaDPTiO_2filmcanactasascaffoldforcomplete-fillingoftheporeswithperovskiteandforforminghigh-qualityperovskitecrystalsthatareseamlesslyinterfacedwithTi_O2toenhanceinterfacialchargeinjection.LeveragingtheuniqueadvantagesofDPTiO2ETL,togetherwithadense-packedandpinhole-freeTiO_2compactlayer,PCEoftheC-PSCshasreached9.81%withgoodstability.

简介：Objective:ToinvestigatetheeffectsofCAL-101,particularlywhencombinedwithbortezomib(BTZ)onmantlecelllymphoma(MCL)cells,andtoexploreitsrelativemechanisms.Methods:MTTassaywasappliedtodetecttheinhibitoryeffectsofdifferentconcentrationsofCAL-101.MCLcellsweredividedintofourgroups:controlgroup,CAL-101group,BTZgroup,andCAL-101/BTZgroup.TheexpressionofPI3K-p110σ,AKT,ERK,p-AKTandp-ERKweredetectedbyWesternblot.TheapoptosisratesofCAL-101group,BTZgroup,andcombinationgroupweredetectedbyflowcytometry.Thelocationchangesofnuclearfactorkappa-B(NF-κB)of4groupswasinvestigatedbyNF-κBKitexploring.Westernblotwasappliedtodetectthelevelsofcaspase-3andthephosphorylationofAKTindifferentgroups.Results:CAL-101dose-andtime-dependentlyinducedreductioninMCLcellviability.CAL-101combinedwithBTZenhancedthereductionincellviabilityandapoptosis.WesternblotanalysisshowedthatCAL-101significantlyblockedthePI3K/AKTandERKsignalingpathwayinMCLcells.ThecombinationtherapycontributedtotheinactivationofNF-κBandAKTinMCLcelllines.However,cleavedcaspase-3wasup-regulatedaftercombinedtreatment.Conclusion:OurstudyshowedthatPI3K/p110σisanoveltherapeutictargetinMCL,andtheunderlyingmechanismcouldbetheblockingofthePI3K/AKTandERKsignalingpathways.ThesefindingsprovidedabasisforclinicalevaluationofCAL-101andarationaleforitsapplicationincombinationtherapy,particularlywithBTZ.

简介：Inwirelesscellularnetworks,theinterferencealignment(IA)isapromisingtechniqueforinterferencemanagement.AnewIAschemefordownlinkcellularnetworkwithmulti-cellandmulti-userwasproposed.Intheproposedscheme,theinterferenceinthenetworksisdividedintointer-cellinterference(ICI)amongcellsandinter-userinterference(IUI)ineachcell.TheICIisalignedontoamulti-dimensionalsubspacebymultiplyingtheICIalignmentprecodingmatrixwhichisdesignedbythesingularvaluedecomposition(SVD)schemeatthebasestation(BS)side.ThealignedICIiseliminatedbytimingtheinterferencesuppressionmatrixwhichisdesignedbyzero-forcing(ZF)schemeattheuserequipment(UE)side.Meanwhile,theIUIisalignedbymultiplyingtheIUIalignmentprecodingmatrixwhichisdesignedbasedonNashbargainingsolution(NBS)ingametheory.TheNBSissolvedbytheparticleswarmoptimization(PSO)method.Simulationsshowthat,comparedwiththetraditionalZFIAscheme,theproposedschemecanobtainhigherdatarateandguaranteethedataratefairnessofUEswithlittleadditionalcomplexity.

简介：AbstractLike antibody evaluation, using an effective antigen-specific T-cell immunity assessment method in coronavirus disease 2019 (COVID-19) patients, survivors and vaccinees is crucial for understanding the immune persistence, prognosis assessment, and vaccine development for COVID-19. This study evaluated an empirically adjusted enzyme-linked immunospot assay for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T-cell immunity in 175 peripheral blood samples from COVID-19 convalescents and healthy individuals. Results of viral nucleic acid were used as the gold standard of infection confirmation. The SARS-CoV-2M peptide pool had higher sensitivity of 85% and specificity of 71% for the single peptide pool. For combined peptide pools, the parallel evaluation (at least one of the peptide pools is positive) of total peptide pools (S1&S2&M&N) had higher sensitivity (up to 93%), and the serial evaluation (all peptide pools are positive) of total peptide pools had higher specificity (up to 100%). The result of the serial evaluation was better than that of the parallel evaluation as a whole. The detection efficiency of M and N peptide pool serial evaluation appeared the highest, with a sensitivity of 80% and specificity of 93%. This T-cell immunity detection assay introduced in this report can achieve high operability and applicability. Therefore, it can be an effective SARS-CoV-2-specific cellular immune function evaluation method.

简介：AbstractBackground:Accumulating evidence suggests that lithium influences mesenchymal stem cell (MSC) proliferation and osteogenic differentiation. As decreased bone formation in femoral heads is induced by glucocorticoids (GCs), we hypothesized that lithium has a protective effect on GC-induced osteonecrosis of femoral heads (ONFH).Methods:A rat ONFH model was induced by methylprednisolone (MP) and the effect of lithium chloride on the models was evaluated. Micro-computed tomography (CT)-based angiography and bone scanning were performed to analyze the vessels and bone structure in the femoral heads. Hematoxylin and eosin and immunohistochemical staining were performed to evaluate the trabecular structure and osteocalcin (OCN) expression, respectively. Bone marrow-derived MSCs were isolated from the models, and their proliferative and osteogenic ability was evaluated. Western blotting and quantitative real-time polymerase chain reaction were performed to detect osteogenic-related proteins including Runx2, alkaline phosphatase, and Collagen I.Results:Micro-CT analysis showed a high degree of osteonecrotic changes in the rats that received only MP injection. Treatment with lithium reduced this significantly in rats that received lithium (MP + Li group); while 18/20 of the femoral heads in the MP showed severe osteonecrosis, only 5/20 in the MP + Li showed mild osteonecrotic changes. The MP + Li group also displayed a higher vessel volume than the MP group (0.2193 mm3vs. 0.0811 mm3, P < 0.05), shown by micro-CT-based angiography. Furthermore, histological analysis showed better trabecular structures and more OCN expression in the femoral heads of the MP + Li group compared with the MP group. The ex vivo investigation indicated higher proliferative and osteogenic ability and upregulated osteogenic-related proteins in MSCs extracted from rats in the MP + Li group than that in the MP group.Conclusions:We concluded that lithium chloride has a significant protective effect on GC-induced ONFH in rats and that lithium also enhances MSC proliferation and osteogenic differentiation in rats after GC administration.

简介：AbstractIntroduction:Primary central nervous system lymphoma (PCNSL) is extremely rare in pediatric population. We reported a case of PCNSL in a 3-year-old girl and reviewed the literature in the past three decades.Case presentation:A 3-year-old girl presented with gait disturbance. A contrast-enhanced magnetic resonance image of the brain showed a solitary bulky mass in the left cerebellar hemisphere, hydrocephalus and cerebellar tonsillar hernia. Surgical resection was performed and the patient was diagnosed with primary central nervous system lymphoblastic B cell lymphoma. Then the patient received regular chemotherapy, including 6 cycles of chemotherapy containing high-dose methotrexate (HD-MTX). The patient remains alive 15 months after the diagnosis with no evidence of active disease, but suffered twice chronic subdural hematoma, which was treated by burr hole drainage.Conclusion:Lymphoblastic B cell lymphoma is a rare histologic subtype of pediatric PCNSL. Chemotherapy containing HD-MTX remains the most effective treatment. The patient should avoid head impact after surgical resection of the tumor to prevent chronic subdural hematoma.

简介：ActivinA,amemberofthetransforminggrowthfactor-betasuperfamily,playsaneuroprotectiveroleinmultipleneurologicaldiseases.Endoplasmicreticulum(ER)stress-mediatedapoptoticandautophagiccelldeathisimplicatedinawiderangeofdiseases,includingcerebralischemiaandneurodegenerativediseases.ThapsigarginwasusedtoinducePC12celldeath,andActivinAwasusedforintervention.OurresultsshowedthatActivinAsignificantlyinhibitedmorphologicalchangesinthapsigargin-inducedapoptoticcells,andtheexpressionofapoptosis-associatedproteins[cleaved-caspase-12,C/EBPhomologousprotein(CHOP)andcleaved-caspase-3]andbiomarkersofautophagy(Beclin-1andlightchain3),anddownregulatedtheexpressionofthapsigargin-inducedERstress-associatedproteins[inositolrequiringenzyme-1(IRE1),tumornecrosisfactorreceptor-associatedfactor2(TRAF2),apoptosissignal-regulatingkinase1(ASK1),c-JunN-terminalkinase(JNK)andp38].Theinhibitionofthapsigargin-inducedcelldeathwasconcentration-dependent.ThesefindingssuggestthatadministrationofActivinAprotectsPC12cellsagainstERstress-mediatedapoptoticandautophagiccelldeathbyinhibitingtheactivationoftheIRE1-TRAF2-ASK1-JNK/p38cascade.