简介：AIMToexploretheprotectiveeffectsandunderlyingmechanismsoftotalpolysaccharidesoftheSijunzidecoction(TPSJ)ontheepithelialbarriersinvitro.METHODSCaco-2cellmonolayersweretreatedwithorwithoutTPSJinthepresenceorabsenceofTNF-α,andparacellularpermeabilityandtransepithelialelectricalresistance(TEER)weremeasuredtoevaluatetheepithelialbarrierfunction.Immunofluorescenceandwesternblottingwererespectivelyusedtoevaluatethedistributionandexpressionofthetightjunctionproteinsclaudin1,claudin2,zo3,andoccludininCaco-2cells.Westernblottingwasalsousedtoevaluatethecellularexpressionofmyosinlightchain(MLC),phosphorylatedMLC(pMLC),MLCkinase(MLCK),andnuclearfactor(NF)-κBp65.RESULTSTPSJpromotedtheproliferationofCaco-2cellsandinhibitedTNF-α-inducedsecretionofpro-inflammatorycytokines.Furthermore,TPSJsignificantlyamelioratedboththereductionofTEERandtheincreasedparacellularpermeabilityobservedintumornecrosisfactor(TNF)-α-damagedCaco-2monolayers.Furthermore,TPSJremarkablyattenuatedTNF-α-inducedmorphologicalchanges,downregulatedtheexpressionofclaudin1,claudin2,zo3,andoccludin,andmarkedlysuppressedTNF-α-mediatedupregulationofp-MLCandMLCKexpression.Finally,TPSJinhibitedtheactivationandexpressionofNF-κBp65.CONCLUSIONOurresultsdemonstratethatTPSJalleviatestheTNF-α-inducedimpairmentoftheintestinalepithelialcellbarrierfunctionbysuppressingNF-κBp65-mediatedphosphorylationofMLCKandMLC.

简介：AbstractBackground:Dysuria is one of the main symptoms of genitourinary syndrome of menopause, which causes serious disruption to the normal life of peri-menopausal women. Studies have shown that it is related to decrease of detrusor contractile function, but the exact mechanism is still poorly understood. Previous results have suggested that the sphingosine-1-phosphate (S1P) pathway can regulate detrusor contraction, and this pathway is affected by estrogen in various tissues. However, how estrogen affects this pathway in the detrusor has not been investigated. In this study, we detected changes of the S1P/RhoA/Rho associated kinases (ROCK)/myosin light chain (MLC) pathway in the detrusor of ovariectomized rats in order to explore the underlying mechanism of dysuria during peri-menopause.Methods:Thirty-six female Sprague-Dawley rats were randomly divided into SHAM (sham operation), OVX (ovariectomy), and E groups (ovariectomy + estrogen), with 12 rats in each group. We obtained bladder detrusor tissues from each group and examined the mRNA and protein levels of the major components of the S1P/RhoA/ROCK/MLC pathway using quantitative real-time polymerase chain reaction and Western blotting, respectively. We also quantified the content of S1P in the detrusor using an enzyme linked immunosorbent assay. Finally, we compared results between the groups with one-way analysis of variance.Results:The components of the S1P pathway and the RhoA/ROCK/MLC pathway of the OVX group were significantly decreased, as compared with SHAM group. The percent decreases of the components in the S1P pathway were as follows: sphingosine kinase 1 (mRNA: 39%, protein: 45%) (both P < 0.05), S1P (21.73 ± 1.09 nmol/g vs. 18.86 ± 0.69 nmol/g) (P < 0.05), and S1P receptor 2/3 (S1PR2/3) (mRNA: 25%, 27%, respectively) (P < 0.05). However, the protein expression levels of S1PR2/3 and the protein and mRNA levels of SphK2 and S1PR1 did not show significant differences between groups (P > 0.05). The percent decreases of the components in the RhoA/ROCK/MLC pathway were as follows: ROCK2 (protein: 41%, mRNA: 36%) (both P < 0.05), p-MYPT1 (protein: 54%) (P < 0.05), and p-MLC20 (protein: 47%) (P < 0.05), but there were no significant differences in the mRNA and protein levels of RhoA, ROCK1, MYPT1, and MLC20 (all P > 0.05). In addition, all of the above-mentioned decreases could be reversed after estrogen supplementation (E group vs. SHAM group) (all P > 0.05).Conclusion:In this study, we confirmed that ovariectomy is closely associated with the down-regulation of the S1P/RhoA/ROCK/MLC pathway in the rat detrusor, which may be one mechanism of dysuria caused by decreased contractile function of the female detrusor during peri-menopause.

简介：AbstractMyosins comprise a large superfamily of adenosine triphosphatases (ATPases) that interact with actin filaments to generate motility or force. Unconventional myosins are implicated in diverse cellular processes including organelle trafficking, F-actin organization and cell movement. The unconventional myosin, myosin XVA (MYO15A), is localized at the tips of stereocilia in the inner ear hair cells and plays important roles in the development and maintenance of stereocilia. Mutations in MYO15A/Myo15a genes are responsible for hearing loss DFNB3 and shaker-2 in human and mice, respectively. In the present review, we will discuss the expression and alternative splicing of the MYO15A gene, the biochemical properties of the MYO15A protein and the association of MYO15A mutations with hearing loss. We will also discuss the recent investigations into the mechanism of how MYO15A regulates stereocilia development and maintenance. At present we are just beginning to appreciate the important roles of MYO15A in stereocilia, and further investigations are warranted to fully understand them.

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简介：火的出现，让人类拥有了对抗黑夜的法宝。最初，原始人把动物脂肪或者蜡一类的东西涂抹在木棍上，做成照明用的火把。

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简介：TheauthorpresentssomestraightforwardproofsfortwocomparisontheoremsforGreenfunctionsofMarkovchains,whichslightlyimprovethepreviousresultsbyVaropoulos,DurrettandYanandChen.ArecentresultbyRogersandWilliamsaboutinstantaneousMarkovchainsisalsoimprovedbyusingthesameidea.

简介：Informationsharinginprocurementoccursinrichandvariedindustrycontextsinwhichmanagerialdecisionsaremadeandorganizationalstrategyisformulated.Weexplorehowinformationsharingoughttoworkinprocurementcontextsmatinvolveinvestmentsininter-organizationalinformationsystems(IOS)andcollaborativeplanning,forecastingandreplenishment(CPFR)practices.Howandunderwhatcircumstancesdoesafirmthatplaystheroleofasupplychainbuyerdecidetoshareinformationonkeyvariables,suchaspoint-of-saleconsumerdemanddatawithitssupplier,upthesupplychain?Thisisakeyissuethatcrossestheboundarybetweensupplychainmanagementandinformationsystems(IS)management.Theanswersthatweprovidearebasedonouruseofagame-theoreticsignalingmodelofbuyerandsupplierstrategyinthepresenceofuncertaintiesaboutfinalconsumerdemand.Wealsoexploretheconnectionbetweenoperationalcoststhatareassociatedwiththefirm'sinformationsharingandinformationwithholdingstrategies.Ourresultsprovidenormativeguidancetosupplychainbuyersabouthowtointerpretdifferentdemanduncertaintyscenariostoimprovetheirdecisionsandgeneratehighvalue.FromtheISmanagementperspective,weshowtheimpactsonthefirmofdifferentinformationsharingapproachesthataremadepossiblebypresentdaytechnologies.

简介：就像是drose1和drose1.5一样,在drose2和drose2.5之间也拥有一段密不可分的完美传承。超轻质的SprintWeb材质鞋面在减轻球鞋重量的同时,为双脚提供足够的足部支撑,这样的新式轻质科技鞋面在adiZeroCrazyLight球鞋上首创,经过若干不同球鞋上的实验,在drose2.5上得到更精确的改进,让球鞋更加适合选择他的穿着者——德里克-罗斯。

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简介：ThemuscleproteinmyosinbindingproteinC(MyBPC)isalargemulti-domainproteinwhoseroleinthesarcomereiscomplexandnotyetfullyunderstood.MutationsinMyBPCarestronglyassociatedwiththeheartdiseasefamilialhypertrophiccardiomyopathy(FHC)andtheseexperimentsofnaturehaveprovidedsomeinsightintotheintricateworkingsofthisproteinintheheart.WhilesomeregionsoftheMyBPCmoleculehavebeenassignedafunctionintheregulationofmusclecontraction,theinteractionofotherregionswithvariouspartsofthemyosinmoleculeandthesarcomericproteins,actinandtitin,remainobscure.Inadditicn,severalintra-domaininteractionsbetweenadjacentMyBPCmoleculeshavebeenidentified.Althoughthebasicstructureofthemolecule(aseriesofimmunoglobulinandfibronectindomains)hasbeenelucidated,theassemblyofMyBPCinthesarcomereisatopicfordebate.ByanalysingtheMyBPCsequencewithrespecttoFHC-causingmutationsitispossibletoidentifyindividualresiduesorregionsofeachdomainthatmaybeimportanteitherforbindingorregulation.Thisreviewlooksatthecurrentliterature,inconcertwithalignmentsandthestructuralmodelsofMyBPC,inanattempttounderstandhowFHCmutationsmayleadtothediseasestate.

简介：SupposethatCisafinitecollectionofpatterns.ObserveaMarkovchainuntiloneofthepatternsinCoccursasarun.Thistimeisdenotedbyτ.Inthispaper,weaimtogiveaneasywaytocalculatethemeanwaitingtimeE(τ)andthestoppingprobabilitiesP(τ=τA)withA∈C,whereτAisthewaitingtimeuntilthepatternAappearsasarun.

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简介：Bisphenolscontaininglongaliphatichydrocarbonsidechainsweresynthesizedbythecondensationofphenolwithaldehydeorketoneinthepresenceofheteropolyacid.TheirstructureswerecharacterizedbyIR,1HNMR,13CNMRandelementanalysis.Theexperimentresultsshowthatwhenheteropolyacidwasusedasacatalyst,thesebisphenolswereobtainedinhighselectivityandhighyields.

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简介：Tostudytheeffectofthesugarchainsinglycoalkaloidsagainstcancercells,6-O-sulfatedsolamargineandacid-catalyzedhydrolyticproductsofα-solamargineandα-solasoninewereprepared.ThesulfationatO-6ofsolamarginewasproceededinfivesteps.The6-OHgroupwasfirstselectivelyprotectedwithDMT-Cl,andthenthesecondaryhydroxylgroupsonthesugarringwereacetylated.AftertheprotectivegroupDMTrwasremoved,thefree6-OHgroupwassulfated.Finally,theacetylgroupswereremovedtogive6-O-sulfatedsolamargineinagoodyield.Thehydrolysesofsolamargineandsolasoninewereperformedindilutedhydrogenchlorede.Threeandtwohydrolyzedproductswereobtainedfromsolamargineandsolasonine,respectively.TheantiproliferativeactivitiesagainstHCT-8tumorcellsoftwoglycoalkaloidsandtheirderivatieswereexaminedviaaMTTassay.Theresultsshowthatα-solamargineandα-solasonineexhibitstrongcytotoxicactivitieswithanIC50of10.63and11.97μmol/L,respectively,wherastheirderivatiesseemtobelessactivities.

简介：Athermoelectricitylightsourceinagaseousplasmadischargebetweentwoelectrodesisdescribed,oneofwhichemitselectronsthermoionically.Theanalyticalmodeldescribingbasicphysicalphenomenaisdeveloped.Theresultsareexcellentagreementwithsimulatedtest.

简介：你可能会说，你孤身前行无人可以依靠你的生活岌岌可危，像把上了膛的枪你正在发抖，亲爱的