简介：AbstractCoronavirus disease 2019 is a major threat to public health globally. Though its pathogenesis has not been fully elucidated, angiotensin-converting enzyme 2 (ACE2) has been recently identified as a receptor for the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the cell. Here, we aimed to clarify the potential role of ACE2 in SARS-CoV-2-induced acute lung injury and its underlying mechanism. As a receptor for coronavirus, ACE2 mediates the entry of SARS-CoV-2 into cells in a similar way as for severe acute respiratory syndrome coronavirus (SARS-CoV). The high binding affinity of SARS-CoV-2 to ACE2 correlates with its efficient spread among humans. On the other hand, ACE2 negatively regulates the renin-angiotensin-aldosterone system (RAAS) primarily by converting angiotensin II to angiotensin 1-7, which exerts a beneficial effect on coronavirus-induced acute lung injury. Human recombinant ACE2 has been considered as a potential therapy for SARS-CoV-2 by blocking virus entry and redressing the imbalance of RAAS in SARS-CoV-2 infection. The level of ACE2 expression can be upregulated by treatment with an ACE inhibitor (ACEI) or angiotensin II type 1 receptor blocker (ARB). To date, no evidence shows that ACEIs or ARBs increase the susceptibility and mortality of patients infected with SARS-CoV-2, and hence, it is not advisable to discontinue such drugs in patients with cardiovascular disease.

简介：BackgroundEssentialhypertension(EH)isconsideredtobeoneofthemostimportantriskfactorofischemicstroke.Studiesaboutriskfactorsinthepatientsaremeaningfulinearlyforecastandeffectivepreventionoftheonsetofstroke.Renin-angiotensin-aldosteronesystemplaysanimportantroleintheregulationofbloodpressureandthedevelopmentofstroke,whilerecentstudieshavefoundthattheangiotensin-convertingenzyme2(ACE2)maybeareversalagentforthedevelopmentandprogressionofischemicstroke.MethodsTheACE2genewasmeasuredin139EHpatientswithischemicstrokeusingpolymerasechainreaction(PCR)andrestrictionfragmentlengthpolymorphism(PCR-RFLP)tests.Detailedandcompleteclinicalandbiochemicaldatawerecollected,includingpulsepressure,hsCRP,IMT,HDL-Canduricacidlevels.Studythecorrelationbetweenangiotensin-convertingenzyme2geneandtheriskfactorforonsetofischemicstrokeinEHpatients.ResultsPulsepressure,hsCRP,IMTanduricacidlevelshadapositivecorrelationwithon-setofischemicstrokeinEHpatients.Amongmalepatients,pulsepressure,hsCRP,IMTandHDL-CwerehigherinpatientscarryingAallelethanBallele(P<0.05).Whilethesefactorsweredifferentinfemalepa-tientscarryingdifferentgenotypesinwhichAAallelewerehighest.Patientswithvariousgenotypesshoweddifferenturicacidlevelsbutshowednosignificantdifference.ConclusionAmongEHpatientswithcomplicatedischemicstroke,thosecarryingtheA/AAalleleshowhighlevelofriskfactorsandislikelytohavethesusceptibilityofrecurrenceofstroke.

简介：AbstractIntroduction:Tripterygium glycosides (TGs) have been widely used in China to treat diabetic nephropathy (DN); however, proof of their use is scarce. The present study aimed to evaluate the effectiveness and safety of adding TGs to angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs).Methods:By searching Embase, MEDLINE, Cochrane Library, SINOMED, China National Knowledge Infrastructure, VIP Information/Chinese Scientific Journals, and WANFANG databases, we identified previous studies that met the specific selection criteria and included them in the meta-analysis. Analyses were performed using Review Manager (version 5.3).Results:Nine randomized controlled trials were included in the final meta-analysis. Patients were compared before and after treatment with ACE inhibitors or ARBs plus TGs, or ACE inhibitors or ARBs alone. The results revealed that treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in 24-h urinary total protein (UTP) levels (trial duration <2 months, mean difference [MD]: -0.25; 95% confidence interval [CI]: -0.32, -0.18; trial duration between 2 and 6 months, MD: -0.39; 95% CI: -0.44, -0.33; trial duration >6 months, MD: -2.09; 95% CI: -2.89, -1.29) compared with treatment using ACE inhibitors or ARBs alone. Additionally, ACE inhibitors or ARBs plus TGs showed better results after longterm administration. Treatment with ACE inhibitors or ARBs plus TGs resulted in significantly greater reductions in serum creatinine (SCr) compared with ACE inhibitors or ARBs alone (MD: -9.87; 95% CI: -13.76, -5.97).Conclusion:In patients with DN, adding TGs to ACE inhibitors or ARBs significantly lowered both the 24-h UTP and SCr levels. Therefore, ACE inhibitors or ARBs plus TGs might improve the treatment of DN in patients.

简介：Theangiotensin-convertingenzymegeneisacandidategeneofstroke.Thepresentstudyinvolved62healthyvolunteersand148patientswithmiddlecerebralarterystenosisasconfirmedbybraincolorultrasoundfromaHanpopulationinNorthChina,anddeterminedtheperipheralbloodangiotensin-convertingenzymegenotypeusingPCR-restrictionfragmentlengthpolymorphismanalysis.TheresultsshowedthatthefrequenciesoftheDDgenotypeandDallelewereincreasedinpatientswithmiddlecerebralarterystenosis,butthedifferencewasnotstatisticallysignificantcomparedwithhealthycontrols.ThefindingsofthisstudyontherelationshipbetweenstrokegenesandmiddlecerebralarterystenosisindicatenosignificantcorrelationbetweenthefrequenciesoftheDDgenotypeandDalleleofangiotensin-convertingenzymeandmiddlecerebralarterystenosisinthisHanpopulationfromNorthChina.Inthefuture,studieswillbecarriedouttoinvestigatecorrelationsbetweenmultiplestrokecandidategenesynergyandmiddlecerebralarterystenosistoprovideafoundationforthedevelopmentofgenetherapy.

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简介：Inspiteofrecentadvancesintreatmentandcontrol,theprevalenceofCVDandpulmonaryhypertension(PH)aroundtheworldhasincreasedsignificantly.Webelievethataconceptualbreakthroughisneededandnoveldrugtargetsmustbediscoveredinanattempttocontrolandtreatthem.ACE2,thenewestmemberoftherenin-angiotensinsystem(RAS),appearstoholdthispotential.Ourstudieshaveestablishedanovelconcept:abalancebetweenthevasodeleteriousaxis(ACE/AngⅡ/ATlR)andthevasoprotectiveaxis(ACE2/Ang-1-7/Mas)oftheRASiscriticalinmaintainingnormalCVfunctionsandanyimbalanceinitiatesvasculardysfunctionsleadingtocardiopulmonarydiseases.ThuswehypothesizethatACE2,whichisakeyenzymeindecreasingAngⅡandincreasingAng-1-7,wouldbeanidealforconsiderationasatherapeutictarget.Theobjectiveofmypresentationwillbetopresentevidenceinsupportofthisconcept.ThedatapresentedwilldemonstratethatoverexpressionofACE2bygeneticmeansoritsactivationbenovelACE2activatorsproteststheheartfromhypertension-andMi-inducedcardiacdamage.Also,thisstrategyisextremelyeffectiveinpreventionandreversalofPHandpulmonaryfibrosis.Astructure-baseddrugdiscoveryapproachwillbepresentedtoidentifysmallmoleculeACE2acti-vatorsandtheirpotentialinproducingbeneficialoutcomesonCVDandpulmonaryhypertensionwillbediscussed.

简介：AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused many deaths and contributed to a tremendous public health concern worldwide since 2020. Angiotensin-converting enzyme 2 (ACE2) binds to the SARS-CoV-2 virus as a receptor. The challenge of different nonhuman primate (NHP) species by SARS-CoV-2 virus demonstrated different effects on virus replication and disease pathology. This study characterizes differences between host ACE2 sequences of three NHP species: Macaca mulatta, Macaca fascicularis, and Chlorocebus sabaeus. In addition, the binding affinity between the ACE2 ectodomain and the SARS-CoV-2 S receptor-binding domain (RBD) was analyzed. Variation of ACE2 sequence among NHP species and the binding affinity may account for different susceptibility and responses to SARS-CoV-2 infection.

简介：ObjectivesToexamineinvivointeractionsbetweenangiotensinⅡ(AngⅡ)AT1areceptor(AT1aR),angiotensin-convertingenzymes(ACE)andACE2usingsmallhairpinRNA(shRNA)gene-silencingmethodsinmicebrainstemnucleustractussolitarius(NTS).MethodsC57BLmice(n=8)wereusedasanimalmodel.MethodofmicroinjectioninthenucleusofNTSwasadopted.Aftertendays,micewerekilledandtheirbraintissuewerefixedandsectioned.TheexpressionlevelsofAT1aR,ACEandACE2mRNAatbothsidesofNTSwereexaminedbyinsituhybridization.Basedoncomparedt-test,thechangingformRNAexpressionwasexamined.ResultsAftertheexpressionofAT1aRmRNAwassignificantlyinhibited(61.6%±6.8%)byAT1aR-shRNA,itwasassociatedwithdecreasesinACE2mRNAexpressionfrom(1.05±0.12)μCi/mgto(0.74±0.09)μCi/mg(29.0%±14.5%,P<0.01)onthesamesideofthebrainstem.ACEmRNAexpressionwasconsistentatbothsides(0.50μCi/mg±0.09μCi/mgand0.53μCi/mg±0.08μCi/mg),withinsignificantdifference(P>0.05).ConclusionsThegenesilencingresultshowedthattherewereinteractionsbetweenbrainstemAT1aRandACE2.ACEmRNAexpressionwasnotalteredbyRNAinterferencetreatmentatAT1aR.

简介：AbstractBackground:Since 2019, a novel coronavirus named 2019 novel coronavirus (2019-nCoV) has emerged worldwide. Apart from fever and respiratory complications, acute kidney injury has been observed in a few patients with coronavirus disease 2019. Furthermore, according to recent findings, the virus has been detected in urine. Angiotensin-converting enzyme II (ACE2) has been proposed to serve as the receptor for the entry of 2019-nCoV, which is the same as that for the severe acute respiratory syndrome. This study aimed to investigate the possible cause of kidney damage and the potential route of 2019-nCoV infection in the urinary system.Methods:We used both published kidney and bladder cell atlas data and new independent kidney single-cell RNA sequencing data generated in-house to evaluate ACE2 gene expression in all cell types in healthy kidneys and bladders. The Pearson correlation coefficients between ACE2 and all other genes were first generated. Then, genes with r values larger than 0.1 and P values smaller than 0.01 were deemed significant co-expression genes with ACE2.Results:Our results showed the enriched expression of ACE2 in all subtypes of proximal tubule (PT) cells of the kidney. ACE2 expression was found in 5.12%, 5.80%, and 14.38% of the proximal convoluted tubule cells, PT cells, and proximal straight tubule cells, respectively, in three published kidney cell atlas datasets. In addition, ACE2 expression was also confirmed in 12.05%, 6.80%, and 10.20% of cells of the proximal convoluted tubule, PT, and proximal straight tubule, respectively, in our own two healthy kidney samples. For the analysis of public data from three bladder samples, ACE2 expression was low but detectable in bladder epithelial cells. Only 0.25% and 1.28% of intermediate cells and umbrella cells, respectively, had ACE2 expression.Conclusion:This study has provided bioinformatics evidence of the potential route of 2019-nCoV infection in the urinary system.

简介：Toobtainthemaximumangiotensin-Iconvertingenzyme(ACE)inhibitoryactivity,theproteinhydrolysisconditionsofthejellyfishRhopilemahispidumwereoptimizedusingresponsesurfacemethodology(RSM).TrypsinwasselectedtoproduceR.hispidumproteinhydrolysates(RPH)withACEinhibitoryactivity.TheoptimalparametersforproducingproteinhydrolysateswiththehighestACEinhibitoryactivitywereasfollows:hydrolysistime5h,hydrolysistemperature50℃,andtheenzyme-to-substrateratio6%.Undertheseconditions,theACEinhibitoryrateofRPHcouldreach64.28%±5.72%.Inaddition,RPHcontainedhighlevelsofGly,Glu,Pro,Ala,AspandArg,withamolecularweightdistributionrangeof0.32–6.84kDa.ThefollowingthreenovelACEinhibitorypeptideswereisolatedandidentified:Ile-Gly-Glu-Thr-Gly-Pro,Gly-Ala-Thr-Gly-Pro-Ala-Gly-Tyr-ValandGly-Ala-Phe-Gly-Pro-Gly-Gly-Leu-Val-Gly-Arg-Pro.TheIC50valuesoftheACEinhibitoryactivityofthesethreepurifiedpeptideswere19.07,27.42and31.26μmolL^-1,respectively.TheseresultssuggestedthatproteinsandpeptidesisolatedfromR.hispidumcouldbeutilizedasantihypertensivefunctionalfoodsources.

简介：Shortpeptidesbasedonthetripeptides,Leu-Arg-ProandLeu-Lys-Pro,weresynthesizedbymicrowaveassistedsolid-phasesynthesismethod,inordertomakeasearchforpotentialinhibitorsforangiotensinI-convertingenzyme(ACE)withminimumsideeffectsinthetreatmentofhypertension.OnepeptidewiththesequenceLeu-Arg-Pro-Phe-PheshowsthestrongestinhibitiontowardsACEwithanIC50valueof0.26μmol/Linvitro.Thestudyofstructure-activityrelationshipshowsthattheintroductionofabulkygroupintotheN-terminalofthisseriesofinhibitorsmayenlargesterichindrance,resultinginthepoorinhibitoryactivitytowardsACE.TheinhibitoryactivitydecreasedinturnwhenL-Pro,D-ProorAc6cwasattheC-terminalrespectively.ThebindinginteractionbetweeneachoftheseinhibitorsandtesticularACE(tACE)wasperformedbymoleculardocking.TheresultssuggestthatLeu-Arg-Pro-Phe-PhemainlyoccupiedtheS1subsiteoftACE,andmadecontactwithtACEviasevenH-bonds.ItappearedthatthesiteonthepeptidethatboundwithtACEwasinfluencedbytheconfigurationoftheaminoacid,LorD-form,attheC-terminalofthepeptide.

简介：BackgroundAngiotensinⅡtype1receptor(ATR1)/AngiotensinⅡtype2receptor(ATR2)usuallyinteractwitheachotherintheirexpressionandphysiologicalfunctions,andnitricoxide(NO)isalwaysinvolvedinATR1/ATR2regulationinvivo.Endothelialcellsplayacrucialroleinthemaintenanceofvascularfunctionandinthepreventionofcardiovasculardiseases.ObjectivesToinvestigatetheeffectsofangiotensinⅡ(AngⅡ)andATR1blockervalsartanonATR1,ATR2expressionandtheirrelationwithendothelialnitricoxidesynthase(eNOS)expression,andNOproductioninculturedvascularendothelialcells.MethodsHumanumbilicalveinendothelialcellline(HUVEC)andbovineaorticendothelialcell(BAEC)wereused.BAECwereisolatedfromaortaofnewborncalfbyenzymedigestionandcellsof3-5passageswereused.Cellswereincubatedwithvehicle,AngⅡ,valsartan,orAngⅡplusvalsartanrespectivelyforvariousperiods.ATR1,ATR2,eNOSexpressionandNOproductionweredetected.ResultsIncubationwithAngⅡorvalsartanapparentlydownregulatedATR1mRNAandproteinexpressioninvascularendothelialcells,andthecombinationeffectofthetwodrugsweremoreapparent.AngⅡshowedatransientslightlypromotiveeffectoneNOSandNOgenerationinBAECandanapparentlyinhibitoryeffectwithprolongedincubation,whilevalsartancanapparentlyreversethoseeffects.ConclusionsBothAngⅡandvalsartandownregulatedtheexpressionofATR1invascularendothelialcells.Thesynergisticeffectofthetwodrugswasmoreapparent.ProlongedincubationwithAngⅡcanapparentlyinhibiteNOSexpressionandNOproductioninendothelialcells,whilevalsartancanapparentlyreversethatinhibitoryeffect.

简介：ThethermalstabilityofNewZealandculturerabbitmusclealdolasewasinvestigatedbydifferentialscanningcalorimetryinthewatercontentrange0.23-3.70gwaterpergprotein.Theexperimentalresultsshowedthatatwatercontentsbelow0.47g/g,anendothermicpeakwasobservedandatwatercontentsabove0.57g/g,anendothermicandanexothermicpeakwerebothobservedonDSCthermogram.Thermaldenaturationresultoftheenzymeandtherelationshipbetweentwotransitiontemperaturesandwatercontentswerefirstreportedinthispaper.Uptonowwehavenotseenanysimilarreportsconcerningtheexothermictransition.

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简介：在变换模拟调查和传统的靠近的范围摄影测量学的地里，由商业数字照相机调查目标到目前为止被开发了，这种技术在生产的每部分广泛地被使用。以便得到目标的三维的信息，商业数字照相机必须被检验。很长时间，数字照相机被DLT检验了。当时，一定有高精确的控制域。为没有控制点，认识到调查，为自我刻度的一个方法被建议。

简介：Smallubiquitin-likemodifier(SUMO)-conjugatingenzymesareinvolvedinpost-translationalregulatoryprocessesineukaryotes,includingtheconjugationofSUMOpeptidestoproteinsubstrate(SUMOylation).SUMOylationplaysanimportantroleinimprovingplanttolerancetoabioticstresssuchassalt,drought,heatandcold.Herein,wereportedtheisolationofOsSCE1(LOC_Os10g39120)geneencodingaSUMO-conjugatingenzymefromrice(Oryzasativacv.Nipponbare)anditsfunctionalvalidationinresponsetodroughtstress.TheE2enzyme,OsSCE1,isoneofthreekeyenzymesinvolvedintheconjugationofSUMOtoitstargetproteins.ActivatedSUMOistransferredtothecysteineofanE2enzymeandthentothetargetlysineresidueofthesubstrate,withorwithoutthehelpofanE3SUMOligase.ExpressionofOsSCE1wasstronglyinducedbypolyethyleneglycol6000(PEG6000)treatment,whichsuggestedOsSCE1maybeinvolvedinthedroughtstressresponse.OverexpressionofOsSCE1(OsSCE1-OX)inNipponbarereducedthetolerancetodroughtstress.Conversely,thedroughttolerancewasslightlyimprovedbytheknockdownofOsSCE1(OsSCE1-KD).TheseresultswerefurthersupportedbymeasurementofprolinecontentinOsSCE1-OXandOsSCE1-KDtransgeniclinesunderinduceddroughtstress,whichshowedOsSCE1-KDtransgeniclinesaccumulatedhigherprolinecontentthanthewildtype,whereasOsSCE1-OXlinehadlowerprolinecontentthanthewildtype.ThesefindingssuggestedOsSCE1mayplayaroleasanegativeregulatorinresponsetodroughtstressinrice.

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简介：在allosteric酶和底层之间的有约束力的过程上的使活跃之物分子和压抑的分子的效果被考虑绑在allosteric酶的调整分子的heterotropic效果讨论。有heterotropic效果的allosteric酶的一个模型被介绍。在规定过程的cooperativity和anticooperativity被学习。

简介：Themaingoalofthispaperistostudythefollowingcombinatorialproblem.givenafinitesetE={e1,e2,…em}andasubsetfamillyσ={S1,S2,…,Sn}ofE,doesthereexistatreeTwiththeedgesetEsuchthateachinducedsubgraphT[Si]ofSiispreciselyapath(1≤i≤k)?