简介：Heterogeneousnuclearribonucleoproteins(hnRNPs)arespliceosomalmacromolecularassemblagesandthusactivelyparticipateinpre-mRNAmetabolism.Theyarecomposedofevolutionarilyconservedandtandemlyrepeatedmotifs,wherebothRNA-bindingandprotein-proteinrecognitionoccurtoachievecellularactivities.Byyetunknownmechanisms,theseribonucleoprotein(RNP)particlesaretargetedbyautoantibodiesandhenceplaysignificantroleinavarietyofhumansystemicautoimmunediseases.Thisfeaturemakesthemimportantprognosticmarkersintermsofmolecularepidemiologyandpathogenesisofautoimmunity.SinceRNPdomainisoneofthemostconservedandwidespreadscaffolds,evolutionalysesoftheseRNA-bindingdomainscanprovidefurthercluesondisease-specificepitopeformation.ThestudypresentedhereinrepresentsasequencecomparisonofRNA-recognitionregionsofrecentlyclonedandcharacterizedhumanhnRNPA3withthoseofotherrelevanthnRNPA/B-typeproteins.Theirimplicationsinhumanautoimmunityareparticularlyemphasized.

简介：Inthepost-genomicera,identificationofspecificregulatorymotifsortranscrip-tionfactorbindingsites(TFBSs)innon-codingDNAsequences,whichisessentialtoelucidatetranscriptionalregulatorynetworks,hasemergedasanobstaclethatfrustratesmanyresearchers.Consequently,numerousmotifdiscoverytoolsandcorrelateddatabaseshavebeenappliedtosolvingthisproblem.However,theseexistingmethods,basedondifferentcomputationalalgorithms,showdiversemotifpredictionefficiencyinnon-codingDNAsequences.Therefore,understandingthesimilaritiesanddifferencesofcomputationalalgorithmsandenrichingthemotifdiscoveryliteraturesareimportantforuserstochoosethemostappropriateoneamongtheonlineavailabletools.Moreover,therestilllackscrediblecriteriontoassessmotifdiscoverytoolsandinstructionsforresearcherstochoosethebestaccordingtotheirownprojects.Thusintegrationoftherelatedresourcesmightbeagoodapproachtoimproveaccuracyoftheapplication.Recentstudiesintegrateregulatorymotifdiscoverytoolswithexperimentalmethodstoofferacomplemen-taryapproachforresearchers,andalsoprovideamuch-neededmodelforcurrentresearchesontranscriptionalregulatorynetworks.HerewepresentacomparativeanalysisofregulatorymotifdiscoverytoolsforTFBSs.

简介：Thispresentstudyinvestigatedtheabilityofvarioussoyproteinhydrolysates(SPHs)inbindingcalcium.ItwasdemonstratedthattheamountofCa-bounddependedgreatlyontheSPHsobtainedusingdifferentproteases,whichincluded:neutrase,flavourzyme,proteaseMandpepsin.ThemaximumlevelofCa-bound(66.9mg/g)occurredwhenproteaseMwasusedtohydrolyzesoyprotein.PeptidefragmentsexhibitinghighCa-bindingcapacityhadmolecularweightsofeither14.4or8-9kDa.ThelevelofCa-boundincreasedlinearlywiththeincrementofcarboxylcontentinSPHs,andfurtherdeamidationonSPHsfromproteaseMimprovedCa-bindingofthehydrolysate.

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：AbstractNonalcoholic fatty liver disease (NAFLD) is becoming increasingly common as the global economy grows and living standards improve. Timely and effective preventions and treatments for NAFLD are urgently needed. Retinol-binding protein-4 (RBP4), the protein that transports retinol through the circulation, was found to be positively related to diabetes, obesity, cardiovascular disease, and other metabolic diseases. Observational studies on the association between serum RBP4 level and the prevalence of NAFLD found contradictory results. Some of the underlying mechanisms responsible for this association have been revealed, and the possible clinical implications of treating NAFLD by targeting RBP4 have been demonstrated. Future studies should focus on the predictive value of RBP4 on NAFLD development and its potential as a therapeutic target in NAFLD.

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简介：AbstractBackground:Pancreatic cancer (PC) is a highly deadly malignancy with few effective therapies. We aimed to unmask the role that long non-coding RNA small nucleolar RNA host gene 6 (SNHG6) plays in PC cells by targeting far upstream element binding protein 1 (FUBP1) via microRNA-26a-5p (miR-26a-5p).Methods:SNHG6 expression was predicted by bioinformatics, followed by verification via reverse transcription quantitative polymerase chain reaction. Then, the interactions among SNHG6, miR-26a-5p, and FUBP1 were detected through online software analysis, dual luciferase reporter assay and RNA pull-down. After that, cells were treated with different small interfering RNAs and/or mimic to determine the interactions among SNHG6, miR-26a-5p, and FUBP1 and their roles in PC cells. Finally, the role of SNHG6 in tumor growth in vivo was evaluated by measuring the growth and weight of transplanted tumors in nude mice. A t-test, one-way and two-way analysis of variance were used for data analysis.Results:Compared with that in normal tissues, SNHG6 was highly expressed in PC tissues (1.00 ± 0.05 vs. 1.56 ± 0.06, t= 16.03, P < 0.001). Compared with that in human pancreatic duct epithelial cells (HPDE6-C7), SNHG6 showed the highest expression in PANC-1 cells (1.00 ± 0.06 vs. 3.87 ± 0.13, t= 34.72, P < 0.001) and the lowest expression in human pancreatic cancer cells (MIAPaCa-2) (1.00 ± 0.06 vs. 1.41 ± 0.07, t= 7.70, P= 0.0015). Compared with the levels in the si-negative control group, SNHG6 (0.97 ± 0.05 vs. 0.21 ± 0.06, t = 16.85, P < 0.001), N-cadherin (0.74 ± 0.05 vs. 0.41 ± 0.04, t= 8.93, P < 0.001), Vimentin (0.55 ± 0.04 vs. 0.25 ± 0.03, t= 10.39, P < 0.001), and β-catenin (0.62 ± 0.05 vs . 0.32 ± 0.03, t= 8.91, P < 0.001) were decreased, while E-cadherin (0.65 ± 0.06 vs. 1.36 ± 0.07, t= 13.34, P < 0.001) was increased after SNHG6 knockdown or miR-26a-5p overexpression, accompanied by inhibited cell proliferation, migration, and invasion. SNHG6 overexpression exerted the opposite effects. SNHG6 upregulated FUBP1 expression by sponging miR-26a-5p. Silencing SNHG6 blocked the growth of PC in vivo.Conclusion:Silencing SNHG6 might ameliorate PC through inhibition of FUBP1 by sponging miR-26a-5p, thus providing further supporting evidence for its use in PC treatment.

简介：BACKGROUND:Highincidenceofstrokeatinterchangeperiodofautumnandwinterwasdemonstratedbyepidemiologicalsurvey,andthespecificcausesshouldbefurtherinvestigated.OBJECTIVE:Toinvestigatetheinfluenceofartificialcoldexposureontheincidenceofstrokeinrenovascularhypertensiverats(RHR),andanalyzetheassociationwithbloodpressureandcold-inducibleRNAbindingprotein(CIRP)mRNAexpressioninbraintissue.DESIGN:Acompletelyrandomizedgroupingdesign,arandomizedcontrolanimaltrial.SETTINGS:LabofNeurology,theFirstAffiliatedHospitalofSunYat-senUniversity;DepartmentofChemistry,OpenlaboratoryofChemicalBiology,InstituteofMolecularTechnologyforDrugDiscoveryandSynthesis,UniversityofHongKong.MATERIALS:MaleSDrats(n=460),weighing80-100gwereobtainedfromGuangdongProvinceHealthAnimalUnit.AmodifiedRXZ-300Aintelligentartificialclimatecabinet(NingboJiangnanInstrumentCo.,Ltd.,China).METHODS:TheexperimentwereprocessedintheLabofNeurology,theFirstAffiliatedHospitalofSunYat-senUniversityandtheOpenLaboratoryofChemicalBiology,InstituteofMolecularTechnologyforDrugDiscoveryandSynthesis,UniversityofHongKongfromOctober2004toNovember2005.Rats(n=400)wereoperatedtoestablish2-kidney2-clipRHRmodelasdescribedpreviously.Thesham-operatedrats(n=60)servedasnormotensivecontrols.Eightweekslater,300ofRHRwererandomlyselectedaccordingtotheirsystolicbloodpressure(SBP)anddividedinto3sub-groups(n=100pergroup):mildhypertensivegroup(SBPof160-200mmHg),moderatehypertensivegroup(SBPof200-220mmHg)andseverehypertensivegroup(SBP>220mmHg).Eachgroupwasfurtherdividedintotwogroups(n=50)underACEandnon-ACE.Normalsham-operatedSDrats(n=60),SBP<140mmHg,wererandomlydividedintotwogroups:Sham-operatedcontrolgroup(n=30)underACEandnon-ACE.ToestablishtheACEandnon-ACEtreatment,ratswerehousedindividuallyinartifici

简介：Direct-methodphaseextensionhasbeenappliedtotwo-dimensionalelectrondiffractiondataoftheproteinstreptavidin.Structure-factoramplitudesfromelectrondiffractionwerecombinedwithphasesfromthecorrespondingelectronmicrographs.Maximum-entropydiscriminationandclusteranalysiswereusedtoderiveasolutionfromalargenumberofrandomtrials.Thephaseextensionfrom0.3to0.25nmledtosubstantialimprovementofthereconstructedprojectionimagequality.

简介：CREB有约束力的蛋白质(CBP)和它的相当或相同事物p300是涉及细胞的活动的一个宽数组的各种各样的顺序特定的抄写因素的transcriptionalco使活跃之物，例如脱氧核糖核酸修理，房间生长，区别和apoptosis。Severalstudies建议了CBP和p300可能被看作瘤压制ors，与他们是的突出的角色响应各种各样的刺激的不同基因表示模式的跨coupling。他们主要经由乙酰化施加行动嘘和另外的规章的蛋白质(例如p53)。在CBP/p300功能的主要悖论是他们似乎能够贡献各种各样的反对细胞的进程。呼吸上皮tumorigenesis代表一个范围的多步累积的一个复杂过程基因并且epigenetic错误。通过激活和压抑的建筑群的交替的形成的Transcriptionmodulation是这些精神错乱的最终的收敛点，并且CBP/p300在这相互影响代表关键参加者。因此，他们的分子的行动和相互作用的照明能在呼吸上皮carcinogenesis为药理学干预揭示新潜在的目标。

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简介：AbstractBackground:Arteriosclerosis obliterans (ASO) is a major cause of adult limb loss worldwide. Autophagy of vascular endothelial cell (VEC) contributes to the ASO progression. However, the molecular mechanism that controls VEC autophagy remains unclear. In this study, we aimed to explore the role of the GRB2 associated binding protein 1 (GAB1) in regulating VEC autophagy.Methods:In vivo and in vitro studies were applied to determine the loss of adapt protein GAB1 in association with ASO progression. Histological GAB1 expression was measured in sclerotic vascular intima and normal vascular intima. Gain- and loss-of-function of GAB1 were applied in VEC to determine the effect and potential downstream signaling of GAB1.Results:The autophagy repressor p62 was significantly downregulated in ASO intima as compared to that in healthy donor (0.80 vs. 0.20, t= 6.43, P < 0.05). The expression level of GAB1 mRNA (1.00 vs. 0.24, t= 7.41, P < 0.05) and protein (0.72 vs. 0.21, t = 5.97, P < 0.05) was significantly decreased in ASO group as compared with the control group. Loss of GAB1 led to a remarkable decrease in LC3II (1.19 vs. 0.68, t = 5.99, P < 0.05), whereas overexpression of GAB1 significantly led to a decrease in LC3II level (0.41 vs. 0.93, t= 7.12, P < 0.05). Phosphorylation levels of JNK and p38 were significantly associated with gain- and loss-of-function of GAB1 protein.Conclusion:Loss of GAB1 promotes VEC autophagy which is associated with ASO. GAB1 and its downstream signaling might be potential therapeutic targets for ASO treatment.

简介：AbstractThe present pandemic has posed a crisis to the economy of the world and the health sector. Therefore, the race to expand research to understand some good molecular targets for vaccine and therapeutic development for SARS-CoV-2 is inevitable. The newly discovered coronavirus 2019 (COVID-19) is a positive sense, single-stranded RNA, and enveloped virus, assigned to the beta CoV genus. The virus (SARS-CoV-2) is more infectious than the previously detected coronaviruses (MERS and SARS). Findings from many studies have revealed that S protein and RdRp are good targets for drug repositioning, novel therapeutic development (antibodies and small molecule drugs), and vaccine discovery. Therapeutics such as chloroquine, convalescent plasma, monoclonal antibodies, spike binding peptides, and small molecules could alter the ability of S protein to bind to the ACE-2 receptor, and drugs such as remdesivir (targeting SARS-CoV-2 RdRp), favipir, and emetine could prevent SASR-CoV-2 RNA synthesis. The novel vaccines such as mRNA1273 (Moderna), 3LNP-mRNAs (Pfizer/BioNTech), and ChAdOx1-S (University of Oxford/Astra Zeneca) targeting S protein have proven to be effective in combating the present pandemic. Further exploration of the potential of S protein and RdRp is crucial in fighting the present pandemic.

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简介：在脂肪和肌肉房间，刺激胰岛素的葡萄糖举起被葡萄糖transporter主要调停4(GLUT4)，哪个到响应胰岛素刺激的房间表面的从细胞内部的分隔空间的translocates。AS160是Akt的底层之一并且在调整胰岛素的GLUT4translocation起重要作用。在这研究，(RUVBL2)象RuvB一样蛋白质2用与集体spectrometry相结合的哺乳动物的双人脚踏车亲密关系纯化(龙头)作为新AS160有约束力的蛋白质被识别。在3T3-L1adipocytes，RUVBL2高度被表示并且在cytosol主要是分布式的。在adipocytes的RUVBL2的弄空通过减少刺激胰岛素的AS160phosphorylation禁止刺激胰岛素的GLUT4translocation和葡萄糖举起。然而，人的RUVBL2的介绍能颠倒这禁止的效果。这些数据建议RUVBL2通过它和AS160的相互作用在刺激胰岛素的GLUT4translocation起一个重要作用。

简介：松毛虫蛾，Dendrolimusspp。（鳞翅目：Lasiocampidae)，是松的严肃的经济害虫。以前，用不同方法的Dendrolimus的种系发生的分析产出不一致的结果。昆虫的化学感应的系统可以在支持种形成起基本作用。有气味的东西绑定蛋白质(OBP)参予气味察觉的第一步。在密切相关的种类学习OBP的进化可以帮助我们在种形成识别他们的角色。我们识别了三OBP-一pheromone有约束力的蛋白质和二一般有气味的东西绑定蛋白质-从四Dendrolimus种的男天线，D.superans(巴特勒)，D.punctatus(沃克)，D。kikuchiiMatsumura，和D。houiLajonquiere，哪个一直不是的嗅觉的识别系统以前调查了。我们分析了他们的分子的特征并且在DOBP把他们的序列比作那些。tabulaeformisTsaiet刘。在五Dendrolimus种之中的Ka/Ks比率分析显示PBP1基因比GOBP经历了更进化的压力。PBP1和GOBP1的种系发生的关系两个都显示D.houi是基础种类，然后分叉的D.kikuchii，当时D。tabulaeformis，D.punctatus，和D.superans更最近演变。这些关系与在这的性pheromone部件的变化一致五种。Dendrolimustabulaeformis和D.punctatus是密切相关的姐妹种类。然而，在在五Dendrolimus的GOBP2序列之中的距离是很短的，并且D.houi和D.kikuchii的关系不能被解决。以前的研究与那些集成我们的结果，我们假设了那D.kikuchii，因为性pheromone变化和环境压力，从基础祖先发展的D.punctatus和D.superans。

简介：AIM:ToinvestigatethemechanismsbywhichCskbindingprotein(CBP)inhibitstumorprogressioninesophagealcarcinoma.METHODS:ACBPoverexpressingesophagealcarcinomacellline(TE-1)wasestablished.Thegrowth,invasion,andmigrationofCBP-TE-1cells,aswellastheexpressionofSrcwerethendeterminedandcomparedwiththoseinnormalTE-1cells.RESULTS:TheexpressionofSrcwasdecreasedbytheoverexpressionofCBPinTE-1cells.Thegrowth,invasion,andmigrationofTE-1cellsweredecreasedbytheoverexpressionofCBP.CONCLUSION:ThisstudyindicatesthatCBPmaydecreasethemetastasisofesophagealcarcinomabyinhibitingtheactivationofSrc.CBPmaybeapotentialtumorsuppressorandtargetingtheCBPgenemaybeanalternativestrategyforthedevelopmentoftherapiesforesophagealcarcinoma.

简介：AbstractBackground:Circular RNAs (circRNAs) are considered to be important regulators in cancer biology. In this study, we focused on the effect of circRNA baculoviral inhibitor of apoptosis protein (IAP) repeat containing 6 (circBIRC6) on non-small cell lung cancer (NSCLC) progression.Methods:The NSCLC and adjacent non-tumor tissues were collected at Shanghai Ninth People's Hospital. Quantitative real-time polymerase chain reaction was conducted for assessing the levels of circBIRC6, amyloid beta precursor protein binding protein 2 (APPBP2) messenger RNA (mRNA), baculoviral IAP repeat containing 6 mRNA (BIRC6), and microRNA-217 (miR-217). Western blot assay was adopted for measuring the protein levels of APPBP2, E-cadherin, N-cadherin, and vimentin. Colony formation assay, transwell assay, and flow cytometry analysis were utilized for evaluating cell colony formation, metastasis, and apoptosis. Dualluciferase reporter assay and RNA immunoprecipitation assay were carried out to determine the interaction between miR-217 and circBIRC6 and APPBP2 in NSCLC tissues. The murine xenograft model assay was used to investigate the function of circBIRC6 in tumor formation in vivo. Differences were analyzed via Student's t test or one-way analysis of variance. Pearson's correlation coefficient analysis was used to analyze linear correlation.Results:CircBIRC6 was overexpressed in NSCLC tissues and cells. Knockdown of circBIRC6 repressed the colony formation and metastasis and facilitated apoptosis of NSCLC cells in vitro and restrained tumorigenesis in vivo. Mechanically, circBIRC6 functioned as miR-217 sponge to promote APPBP2 expression in NSCLC cells. MiR-217 inhibition rescued circBIRC6 knockdown-mediated effects on NSCLC cell colony formation, metastasis, and apoptosis. Overexpression of miR-217 inhibited the malignant phenotypes of NSCLC cells, while the effects were abrogated by elevating APPBP2.Conclusion:CircBIRC6 aggravated NSCLC cell progression by elevating APPBP2 via sponging miR-217, which might provide a fresh perspective on NSCLC therapy.

简介：BACKGROUND:Drugaddictioninvolvestwomaincentralnervoussystems,namelythedopamineandnoradrenalinesystems.Thesesystemsareprimarilydistributedinfivebrainregions:theventraltegmentalarea,thenucleusaccumbens,theprefrontalcortex,thehippocampus,andthelocuscoeruleus.OBJECTIVE:Toinvestigateregionalchangesofguaninenucleotidebindingprotein-inhabitant2(Gi2)indopaminergicandnoradrenergicneuronsinbrainsofmorphine-tolerantand-dependentrats.DESIGN,TIME,ANDSETTING:ArandomizedcontrolstudywasperformedattheDepartmentofNeu-robiologyintheSecondMilitaryMedicalUniversityofChinesePLA(Shanghai,China)betweenSeptember2002andMarch2004.MATERIALS:Thirty-six,healthy,male,Sprague-Dawley(SD)ratswereusedtoestablishmorphine-dependentmodels.MorphinehydrochloridewasaproductofShenyangFirstPharmaceuticalFactory(China);naloxonehydrochloridewasaproductofBeijingFour-RingPharmaceuticalFactory(China);andαsubunitofGi2antibodywasofferedbySantaCruzBiotechnology,Inc(USA).METHODS:Thirty-sixSDratswererandomlydividedintosixgroups(n=6):(1)acutemor-phine-dependentgroup,(2)acuteabstinentgroup,(3)acutecontrolgroup,(4)chronicmorphine-dependentgroup,(5)chronicabstinentgroup,and(6)chroniccontrolgroup.Ratsintheacutemorphine-dependentandtheacutegroupswereinjectedwithmorphine(5mg/kg),oneinjectioneverytwohours,foratotalofeightinjections.Intheacuteandchronicmorphine-dependentratmodels,morphinewithdrawalsyndromewasprecipitatedbyaninjectionofnaloxone(5mg/kg).Ratsintheacutecontrolgroupweregivenaperitonealinjectionofphysiologicalsalineatthesameadministrationtimeastheabovetwogroups.Ratsinthechronicmorphine-dependentandchronicabstinentgroupswereinjectedwithmorphinethreetimesperday.Theadministrationdoseonday1wasinitially5mg/kgat20:00,whichincreasedby5mg/kgat8:00,12:00,and20:00untilday7.Onday

简介：疟蚊属sinensis是主要疟疾向量。昆虫有气味的东西绑定蛋白质(OBP)可以在嗅觉的系统在有气味的东西的接收工作。分类和描述一。sinensisOBP基因系统地没被学习。在这研究，64通常认为的OBP基因在整个染色体的水平被识别一。sinensis基于在OBP之间的比较保存了主题，PBP_GOBP，和种系发生的分析与一。gambiaeOBP。描述一。包括主题保存，基因结构，genomic组织和分类，sinensisOBP被调查。新基因，AsOBP73，属于Plus-C亚科，与抄本和保守主题的支持被识别。这些一。sinensisOBP基因在亚科经典著作与37，15和12基因被分类进三个亚科，不正常并且Plus-C分别地。genomic组织一。sinensisOBP越过九不同脚手架建议聚类的分布。八基因(OBP23-28，OBP63-64)可能至少在疟蚊属，一种蚊虫和豹脚蚊的分叉前通过一系列历史性的复制事件从单个基因发源。microsynteny分析显示很高的synteny在之间一。sinensis并且一。gambiaeOBP。更早在Plus-C下面分类在的OBP70和OBP71一。gambiae作为属于经典亚科的组Obp59a被认出，并且更早在Plus-C下面分类的OBP69在这研究被移动了到不正常的亚科。学习在昆虫以及在为OBP基因的进一步的学习建立了一个基本信息框架一。sinensis。