简介：Humanendogenousretroviruses(HERVs)areretrovirusesthatinfectedhumangenomemillionsofyearsagoandhavepersistedthroughouthumanevolution.About8%ofourgenomeiscomposedofHERVs,mostofwhicharenonfunctionalbecauseofepigeneticcontrolordeactivatingmutations.However,acorrelationbetweenHERVsandhumancancerhasbeendescribedandmanytumors,suchasmelanoma,breastcancer,germcelltumors,renalcancerorovariancancer,expressHERVproteins,mainlyHERV-K(HML6)andHERV-K(HML2).AlthoughthecausativeroleofHERVsincanceriscontroversial,datafromanimalmodelsdemonstratedthatendogenousretrovirusesarepotentiallyoncogenic.HERVproteinexpressioninhumancellsgeneratesanimmuneresponsebyactivatinginnateandadaptiveimmunities.SomeHERV-derivedpeptideshaveantigenicproperties.Forexample,HERV-K(HML-6)encodestheHER-KMELpeptiderecognizedbyCD8+lymphocytes.Inaddition,HERVsaretwoedgedimmunomodulators.HERVsshowimmunosuppressiveactivity.Thepresenceofgenomicretroviralelementsinhost-cellcytosolmayactivateaninterferontypeIresponse.Therefore,targetingHERVsthroughcellularvaccinesorimmunomodulatorydrugscombinedwithcheckpointinhibitorsisattractinginterestbecausetheycouldbeactiveinhumantumors.

简介：Thispaperadoptstherealoptionsapproachtostudythedecision-makingofcorporateendogenousbankruptcyanddebtreorganizationinarisk-neutralframework,whileunderstandingcorporatebankruptcyanddebtreorganizationastheoptionsheldbyequityholdersandthecreditor.Afterobtainingthevaluesofcontingentclaimsonthecorporateassets,thepaperanalyzesthebankruptcydecisionsofdifferentleveredcorporate.Withstandarddebtcontractandunderabsolutepriorityrule,thebankruptcytimesmaximizingtheequityvaluearenotconsistentwiththosemaximizingthecorporatevalue:thehighleveredcorporatewillinefficientlybankruptearlywhilethelowleveredcorporatewillinefficientlybankruptlate.Ifdebtreorganizationorcreditorconcessionisn'tallowed,liquidationoftenleadstothelossinvalue.Butifstrategicdefaultordeviationfromabsolutepriorityruleisallowed,thedecisionmaximizingtheequityvaluewillbeconsistentwiththatmaximizingthecorporatevalue.Debtreorganizationhassignificanteconomicimplication:forhighleveredcorporateorlowleveredcorporate,withdebtreorganizationordeviationoftheabsolutepriorityrulepermitted,postponedorhastenedbankruptcycanbeavoided,hence,thebankruptcytriggerchosenbyequityholderstomaximizetheequityvalueisefficientdecisionwithoutvaluelosses.

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简介：IAPs(inhibitorsofapoptosis)areafamilyofproteinscontainingoneormorecharacteristicBIRdomains.Theseproteinshavemultiplebiologicalactivitiesthatincludebindingandinhibitingcaspases,regulatingcellcycleprogression,andmodulatingreceptor-mediatedsignaltransduction.OurrecentstudiesfoundtheIAPfamilymembersXIAPandc-IAP1areubiquitinatedanddegradedinproteasomesinresponsetoapoptoticstimuliinTcells,andtheirdegradationappearstobeimportantforTcellstocommittodeath.InadditiontothreeBIRdomains,eachoftheseIAPsalsocontainsaRINGfingerdomain.Wefoundthisregionconfersubiquitinproteaseligase(E3)activitytoIAPs,andisresponsiblefortheauto-ubiquitinationanddegradationofIAPsafteranapoptoticstimulus.GiventhefactthatIAPscanbindavarietyofproteins,suchascaspasesandTRAFs,itwillbeofinteresttocharacterizepotentialsubstratesoftheE3activityofIAPsandtheeffectsofubiquitinationbyIAPsonsignaltransduction,cellcycle,andapoptosis.

简介：Withvillageeliteflowastheclues,thisstudymainlydescribesthedevelopmentoftheHongqivillagecooperativeorganization.Throughanalyzingtheflowconditionindevelopmentprocessofthevillageelitepersonnelinthevillagecooperatives,thispaperexploresthestruggleandcooperationbetweenthedevelopmentsofcooperativesofendogenousforceinruralstructure.Thestudyfoundthatunderthelimitedsituationofruralelitecapacity,asanembeddedbasevillagebottom-upformationofcooperatives,theinternalforcesareconstantlyinatensionstructure,thevariousforcesinthedifferentdevelopmentperiodareconversionbetweenthesymbioticandopposition;Combination,differentiation,struggleofvariousforceswithinthecooperativearesupportedbytheirownwealth,genetic,factionalsocialcapital;thesplitsandrealignmentsofmalignantcompetitionforcescausedbyinternalcooperativesarethekeypowertorestrictthedevelopmentofvillagecooperatives.Thebase-levelcountrysideandcooperativesneedslimitedeliteunityandequilibriumofinternalforcestoobtaineffectivegovernanceandlong-termdevelopment.

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简介：Traumaticbraininjury(TBI)istheleadingcauseofdeathanddisabilityofpersonsunder45yearsoldintheUnitedStates,affectingover1.5millionindividualseachyear.Ithadbeenthoughtthatrecoveryfromsuchinjuriesisseverelylimitedduetotheinabilityoftheadultbraintoreplacedamagedneurons.However,recentstudiesindicatethatthematuremammaliancentralnervoussystem(CNS)hasthepotentialtoreplenishdamagedneuronsbyproliferationandneuronaldifferentiationofadultneuralstem/progenitorcellsresidingintheneurogenicregionsinthebrain.Furthermore,increasingevidenceindicatesthattheseendogenousstem/progenitorcellsmayplayregenerativeandreparativerolesinresponsetoCNSinjuriesordiseases.Insupportofthisnotion,heightenedlevelsofcellproliferationandneurogenesishavebeenobservedinresponsetobraintraumaorinsultssuggestingthatthebrainhastheinherentpotentialtorestorepopulationsofdamagedordestroyedneurons.Thisreviewwilldiscussthepotentialfunctionsofadultneurogenesisandrecentdevelopmentofstrategiesaimingatharnessingthisneurogeniccapacityinordertorepopulateandrepairtheinjuredbrain.

简介：Ciliaryneurotrophicfactoristheonlyknownneurotrophicfactorthatcanpromotedifferentiationofhippocampalneuralprogenitorcellstoglialcellsandneuronsinadultrats.Thisprocessissimilartospontaneousdifferentiation.Therefore,ciliaryneurotrophicfactormaybeinvolvedinspontaneousdifferentiationofneuralstemcells.Toverifythishypothesis,thepresentstudyisolatedneuralprogenitorcellsfromadultmaleratsandculturedtheminvitro.Resultsshowedthatwhenneuralprogenitorcellswereculturedintheabsenceofmitogenfibroblastgrowthfactor-2orepidermalgrowthfactor,theyunderwentspontaneousdifferentiationintoneuronsandglialcells.Westernblotandimmunocytochemicalstainingshowedthatexogenousciliaryneurotrophicfactorstronglyinducedadulthippocampalprogenitorcellstodifferentiateintoneuronsandglialcells.Moreover,passage4adulthippocampalprogenitorcellsexpressedhighlevelsofendogenousciliaryneurotrophicfactor,andaneutralizingantibodyagainstciliaryneurotrophicfactorpreventedthespontaneousneuronalandglialdifferentiationofadulthippocampalprogenitorcells.Theseresultssuggestthatthespontaneousdifferentiationofadulthippocampalprogenitorcellsismediatedpartiallybyendogenousciliaryneurotrophicfactor.

简介：AbstractAspirin-exacerbated respiratory disease (AERD) is characterized by the triad of chronic rhinosinusitis with nasal polyposis, adult-onset asthma and non-IgE mediated reactions to aspirin and other cyclooxygenase-1 (COX-1) inhibitors. Patients with AERD are dependent on COX-1 activity to maintain production of prostaglandin (PG) species, such as PGE2, which maintain physiologic levels of inflammation and limit the production of pro-inflammatory cysteinyl leukotrienes. The endogenous cannabinoid system is a family of immunomodulatory lipids and their innate g-protein coupled receptors that are closely related to arachidonic acid and may modulate inflammation via several pathways, including the direct production of metabolically active prostaglandin glycerol-esters. A recent pilot study has identified the significant up-regulation of the peripherally expressed, type-2 cannabinoid receptor (CB2) in AERD nasal polyps versus control tissues from patients with either allergic fungal rhinosinusitis or no history of chronic sinonasal inflammation. These early findings suggest the involvement of increased endogenous cannabinoid activity in prostaglandin deficient states such as AERD. Future study is needed to explore the significance of these findings, with specific investigation of the impact of CB2 activation on markers of airway inflammation, as well as the potential to measure CB2 expression as a screening biomarker for the evaluation of unrecognized disease.

简介：Thetraditionalevaluationofenergyconsumptionmostlyintroducespollutantsasanegativeeconomicoutputintoevaluatingmodel,ignoringtheconfigurationrelationshipamongtheenergyinput,pollutantsaswellaseconomicoutput.Thispaperconsiderstheoverallprocessofenergyconsumptionandconstructsanevaluationindicationsystemofenergyconsumptionlevelcombinedwithendogenouspollutantsbasedonentropytopsismethod,thenmakesempiricalresearch.TheresultsshowthatChina'senergyconsumptionlevelpresentsafluctuantriseinthepremiseofemission.Energyconsumptionleveldependsontherelationshipamongenergyinput,pollutantsandeconomicoutput.Theraiseofenergyconsumptionlevelshouldnotincreaseeconomicoutputandreducepollutantemissionattheexpenseofenvironment.Finally,thewholepaperputsforwardthecountermeasurestoimprovetheoveralllevelofenergyconsumption.

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简介：Humanμ-opioidreceptor(HμOR)withatagofsixconsecutivehistidinesatitscarboxylterminushasbeenexpressedinrecombinantbaculovirusinfectedSf9insectcells.Themaximalbindingcapacityforthe[^3H]diprenorphineand[^3H]ohmefentanyl(Ohm)were9.1±0.7and6.52±0.23nmol/gprotein,respectively.The[^3H]diprenorphineor[^3H]OhmbindingtothereceptorexpressedinSf9cellswasstronglyinhibitedbyμ-selectiveagonists[D-Ala^2,N-methyl-Phe^4,glyol^5]enkephalin(DAGO),Ohm,andmorphine,butneitherbyδnorbyκselectiveagonist.Na^+(100mM)andGTP(50μM)couldreduceHμORagonistsetorphineandOhmaffinitybindingtotheoverexpressedHμOR.μ-selectiveagonistsDAGOandOhmeffectivelystimulated[^35S]GTPγSbinding(EC50=2.7nMand6.9nM)andinhibitedforskolin-stimulatedcAMPaccumulation(IC50=0.9nMand0.3nM).Theagonist-dependenteffectscouldbeblockedbyopioidantagonistnaloxoneorbypretreatmentofcellswithpertussistoxin(PTX).TheseresultsdemonstratedthatHμORoverexpressedinSf9insectcellsfunctionallycoupledtoendogenousCi/oproteins.

简介：AIM:Toinvestigatetheassociationbetweenendogenousgeneexpressionandgrowthregulationincludingproliferationandapoptosisinducedbytransforminggrowthfactor-β1(TGF-β1)inhumangastriccancer(GC)cells.METHODS:Reversetranscriptionpolymerasechainreaction(RT-PCR)wasperformedtodetectthemaincomponentsoftheTGF-β1/SmadssignalpathwayinhumanpoorlydifferentiatedGCcelllineBGC-823.LocalizationofSmadproteinswasalsodeterminedusingimmunofluorescence.Then,theBGC-823cellswereculturedinthepresenceorabsenceofTGF-β1(10ng/mL)for24and48h,andtheeffectsofTGF-β1onproliferationandapoptosisweremeasuredbycellgrowthcurveandflowcytometry(FCM)analysis.TheultrastructuralfeaturesofBGC-823cellswithorwithoutTGF-β1treatmentwereobservedundertransmissionelectronmicroscope.Theapoptoticcellswerevisualizedbymeansoftheterminaldeoxynucleotidyltransferase(TdT)-mediateddTUPinsitunickend-labeling(TUNEL)method.Meanwhile,theexpressionlevelsofendogenousp15,p21andSmad7mRNAandthecorrespondingproteinsinthecellsweredetectedat1,2and3haftercultureinthepresenceorabsenceofTGF-β1(10ng/mL)bysemi-quantitativeRT-PCRandWesternblot,respectively.RESULTS:TheTGF-β1/SmadsignalingwasfoundtobeintactandfunctionalinBGC-823cells.ThegrowthcurverevealedthemostevidentinhibitionofcellproliferationbyTGF-β1at48h,andFCMassayshowedG1arrestaccompaniedwithapoptosisinducedbyTGF-β1.ThetypicalmorphologicalchangesofapoptosiswereobservedincellsexposedtoTGF-β1.Theapoptosisindex(AI)inTGF-β1-treatedcellswassignificantlyhigherthanthatintheuntreatedcontrols(10.7±1.3%vs0.32±0.06%,P＜0.01).Thelevelsofp15,p21andSmad7mRNAandcorrespondingproteinsincellsweresignificantlyup-regulatedat1h,butgraduallyreturnedtobasallevelsat3hfollowingTGF-β1(10ng/mL)treatment.CONCLUSION:TGF-β1affectsbothproliferationandapoptosisofGCcellsth

简介：Amajorprobleminhybridriceproductionistheoccurrenceofleafsenescenceduringthegrainfillingstagethatcanresultinreductionofyield.Changesincontentsofseveralendogenoushormonesarerelatedtoleafsenescence.TherelationshipbetweenendogenoushormonesandleafsenescenceinthericehybridTiyou418anditsparentsTijinandC418,wasundertakenforinvestigation.Indicatorsofleafsenescence,includingsuperoxidedismutase(SOD)activity,malondialdehyde(MDA)accumulationandchlorophyllcontent,aswellasthecontentsofabscisicacid(ABA),zeatinriboside(ZR),gibberellin(GA1/3)andauxin(IAA)intheleavesweredetermined.Differentratesofleafsenescencewereobservedinthethreematerials.SenescenceoccurredearliestandfastestinTijin,followedbyTiyou418andthenC418.AsimilartrendwasrecordedinABA,ZR,andIAAcontentsduringthegrainfillingstageinthethreematerials.Changesin(GA1/3+ZR+IAA)/ABAratioswerealsosimilar,beingquitestableduringtheearlystageofleafsenescence,anddecreasingmarkedlyduringthelatestage.TheratiodeclinedmoredramaticallyinTijin,inaccordancewithitsfasterleafsenescence.Theresultssuggestthattheratioof(GA1/3+ZR+IAA)/ABAregulateschlorophyllcontent,SODactivity,MDAcontentandmembranelipidperoxidation.Itispostulatedthatendogenoushormonesmayplayaroleintheregulationofleafsenescenceinasystematicway.

简介：Objective:Fusogenicendogenousretroviralsyncytinplaysanimportantroleintheformationofsyncytiotrophoblastsinhumanplacenta.Apartfromitsexpressioninplacenta,brainandtestis,syncytinhasalsobeenfoundinmanycancers.Althoughsyncytinhasbeenproposedtoserveasapositiveprognosticmarkerinsomecancers,theunderlyingmechanismisunclear.Theaimofthisstudyistoevaluatetheeffectsofsyncytinexpressionontheinvasivephenotypeofmelanomacells.Methods:Theeukaryoticexpressionplasmidforsyncytin-EGFPwasconstructedandtransfectedintoB16F10melanomacells.TheeffectofsyncytinontheinvasionpotentialoftumorcellswasevaluatedinB16F10sublinecellsthatstablyexpressedsyncytin-EGFPfusionproteinorEGFPalone.Results:TheB16F10sublinesthatstablyexpressedsyncytin-EGFPorEGFPalonewereestablishedrespectivelyandconfirmedbyimmunofluorescentandimmunoblottingassay.SyncytinexpressioninB16F10cellswasassociatedwithdecreasedcellproliferation,migrationandinvasion.Multinucleatedgiantcellsthatcontainedasmanyasfivenucleiwereinducedinsyncytin-expressingcells.Inaddition,syncytinexpressiondidnotalterthesensitivityofB16F10cellstotrichosanthin,atoxinthatdamagessyncytiotrophoblastsmoreefficientlythanothertissues.Conclusions:Theseresultssuggestthatsyncytinexpressioninsomecancersmayconfinetheirinvasionpotentialandthusserveasapositiveprognosticfactor.更多还原

简介：ToexploretherelationshipbetweensubstanceP(SP)releasedfromperipheralnerveendingsandtheexpressionofepidermalgrowthfactor(EGF)andepidermalgrowthfactorreceptor(EGFR)duringwoundhealing.Methods:FiftyWistarratswererandomlydividedinto2groups,injurygroupandcapsaicingroup.Intheinjurygroup,afull-thicknessskinwoundonthebackoftheratwastaken.Thewoundedgeandgranulationtissuesweretakenonthe1st,3rd,6th,9th,12thdaysafterinjury,respectively.Inthecapsaicingroup,capsaicinwasinjectedsubcutaneouslyonthebackoftheratstodestroythesensorynervetopreventthesecretionofSP,thenawoundandsamplewasmadeinthesameway.ImmunohistochemistryandinsituhybridizationwereemployedtodetecttheexpressionofSP,EGF/EGFR,andEGFmRNA/EGFRmRNAinthegranulationtissues.Results:Intheinjurygroup,immunohistochemicalstainofSPandEGF/EGFRwaslocatedonthehairfolliclesandsebaceousglandsatthe1stday.AndthestainofSPwasobviousatthe3rddayinthegranulationtissues,thendecreasedgradually.EGF/EGFRwasatlowlevelatthe3rdday,thenincreasedgraduallyandreachedthepeakatthe9thday,thendeclined.Inthecapsaicingroup,theimmunohistochemicalstainofSPandEGF/EGFRwasfaintandwithoutobviouschangeduringthewoundhealingprocess.ThetendencyoftheEGFmRNA/EGFRmRNAexpressionwassimilartothatofEGF/EGFR.Conclusions:Duringwoundhealing,SPmaypromotethehealingprocessbyaffectingtheexpressionofEGF/EGFRinthegranuationtissues.

简介：在地域社会所展开的社会调查,应避免过度的买用主义的强调,同时应有对量·质两方面内容的关注,尤其是质性调查研究于地域社会主体性的捕捉十分有效.在发展实践中常常会因为地域主体的呈现不足,而导致发展计划及其实施偏离地域社会的内在文化脉络.90年代后,诸多含茂县在内的羌族地区的发展规划都因为过于倚重量化数据,缺失了对发展主体的传统文化的考量.而在本世纪启动的茂县经济社会大调查中,因注意到了质性材料的搜集、整理,因此能够结合参与式发展、立场强化（empowerment）、创新、协调、绿色、开放、共享”发展理念来思考茂县的发展.5.12汶川大地震的灾后重建中,举国体制的支援与山西省对口支援取得了很好的实效,山西省对口支援的长效性的强调,也使得茂县今后的发展可以以共发式发展（Neo-EndogenousDevelopment）的理论视角来加以探讨.

简介：AbstractBackground:Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process.Methods:We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A P < 0.05 was considered statistically significant.Results:MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007 ± 0.215 vs. 75.213 ± 18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894 ± 0.684 vs. 1.586 ± 0.398, t= 16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33% ± 5.13% vs. 41.33% ± 3.51%, t= 8.913, P < 0.001), migration (102 ± 8 cells vs. 46 ± 8 cells, t= 8.681, P < 0.001), invasion (59 ± 7 cells vs. 28 ± 2 cells, t = 8.034, P < 0.01), and suppressed apoptosis (22.64% ± 6.97% vs. 36.33% ± 3.96%, t = 2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level.Conclusions:Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.