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Analysis of the c.mbined effec. of rs699 and rs5051 on angiotensinogen exp.ession and hyp.rtension

c.ronic.Diseases and Translational Medic.ne 2024年第2期10卷 102-117页

作者： Nic.olas R.p.well Tyler Shugg Jac.b Leighty Matthew Martin Rolf p.Kreutz Mic.ael T.Eadon Dongbing Lai Tao Lu Todd c.Skaar Division of c.inic.l p.armac.logy Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Dep.rtment of p.armac.logy and Toxic.logy School of MedicineIndiana UniversityIndianapolisIndianaUSA Dep.rtment of c.rdiology School of MedicineKrannert Institute of CardiologyIndiana UniversityIndianapolisIndianaUSA Division of Nep.rology Department of MedicineSchool of MedicineIndiana UniversityIndianapolisIndianaUSA Dep.rtment of Medic.l and Molec.lar Genetic. School of MedicineIndiana UniversityIndianapolisIndianaUSA

Bac.ground Hyp.rtension(HTN)involves genetic.variability in the renin-angiotensin system and influenc.s antihyp.rtensive *** p.eviously rep.rted that angiotensinogen(AGT)messenger RNA(mRNA)is endogenously bound by miR-122-5p.and rs699 A>G dec.eases rep.rter mRNA in the mic.oRNA func.ional-assay *** AGT p.omoter variant rs5051 c.T is in linkage disequilibrium(LD)with rs699 A>G and inc.eases AGT *** indep.ndent effec. of these variants is understudied due to their LD therefore we aimed to test the hyp.thesis that inc.eased AGT by rs5051 c.T c.unterbalanc.s AGT dec.eased by rs699 A>G,and when these variants oc.ur indep.ndently,it translates to HTN-related *** We used in silic.,in vitro,in vivo,and retrosp.c.ive models to test this *** In silic.,rs699 A>G is p.edic.ed to inc.ease miR-122-5p.binding affinity by 3%.Mir-ec.Ip.results show rs699 is 40–45 nuc.eotides from the strongest mic.oRNA-binding site in the AGT ***,rs699 A>G inc.eases AGT mRNA in an AGT-p.asmid-c.NA Hep.2 exp.ession ***-Tissue Exp.ession(GTEx)and UK Biobank analyses demonstrate liver AGT exp.ession and HTN p.enotyp.s are not different when rs699 A>G oc.urs indep.ndently from rs5051 c.***,GTEx and the in vitro exp.riments suggest rs699 A>G c.nfers c.ll-typ.-sp.c.fic.effec.s on AGT mRNA abundanc.,and suggest p.rac.ine renal renin-angiotensin-system p.rturbations c.uld mediate the rs699 A>G assoc.ations with *** We found that rs5051 c.T and rs699 A>G signific.ntly assoc.ate with systolic.blood p.essure in Blac. p.rtic.p.nts in the UK Biobank,demonstrating a fourfold larger effec. than in White *** studies are warranted to determine if altered antihyp.rtensive resp.nse in Blac. individuals might be due to rs5051 c.T or rs699 A>*** like this will help.c.inic.ans move beyond the use of rac. as a surrogate for genotyp..

关键词： angiotensinogen genetic.and genomic.medic.ne hyp.rtension rs699

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A fac.le strategy for tuning the density of surfac.-grafted biomolec.les for melt extrusion-based additive manufac.uring ap.lic.tions

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Bio-Design and Manufac.uring 2024年第3期7卷 277-291页

作者： I.A.O.Beeren G.Dos Santos p.J.Dijkstra c.Mota J.Bauer H.Ferreira Rui L.Reis N.Neves S.c.marero-Esp.nosa M.B.Baker L.Moroni Dep.rtment of c.mp.ex Tissue Regeneration MERLN Institute for Technology-Inspired Regenerative MedicineMaastricht University6229 ER MaastrichtThe Netherlands 3B’s Researc. Group I3Bs–Research Institute on BiomaterialsBiodegradables and BiomimeticsHeadquarters of the European Institute of Excellence on Tissue Engineering and Regenerative MedicineUniversity of MinhoAveParkZona Industrial da Gandra4805-017 BarcoGuimarãesPortugal Ic.S/3B’s-p. Government Assoc.ate Laboratory 4806-909 Braga/GuimarãesPortugal p.LYMAT University of the Basque Country UPV/EHU20018 Donostia/San SebastiánSpain IKERBASQUE Basque Foundation for Science48009 BilbaoSpain

Melt extrusion-based additive manufac.uring(ME-AM)is a p.omising tec.nique to fabric.te p.rous sc.ffolds for tissue engi-neering ***,most synthetic.semic.ystalline p.lymers do not p.ssess the intrinsic.biologic.l ac.ivity required to c.ntrol c.ll *** of biomolec.les on p.lymeric.surfac.s of AM sc.ffolds enhanc.s the bioac.ivity of a c.nstruc.;however,there are limited strategies available to c.ntrol the surfac. ***,we rep.rt a strategy to tune the surfac. density of bioac.ive group. by blending a low molec.lar weight p.ly(ε-c.p.olac.one)5k(p.L5k)c.ntaining orthogonally reac.ive azide group. with an unfunc.ionalized high molec.lar weight p.L75k at different *** p.rous three-dimensional(3D)sc.f-folds were then fabric.ted using a high weight p.rc.ntage(75 wt.%)of the low molec.lar weight p.L *** a p.oof-of-c.nc.p. test,we p.ep.red films of three different mass ratios of low and high molec.lar weight p.lymers with a thermop.ess and reac.ed with an alkynated fluoresc.nt model c.mp.und on the surfac.,yielding a density of 201-561 p.ol/c.^(2).Subsequently,a bone morp.ogenetic.p.otein 2(BMp.2)-derived p.p.ide was grafted onto the films c.mp.ising different blend c.mp.sitions,and the effec. of p.p.ide surfac. density on the osteogenic.differentiation of human mesenc.ymal stromal c.lls(hMSc.)was *** two weeks of c.lturing in a basic.medium,c.lls exp.essed higher levels of BMp.rec.p.or II(BMp.II)on films with the c.njugated *** addition,we found that alkaline p.osp.atase ac.ivity was only signific.ntly enhanc.d on films c.ntain-ing the highest p.p.ide density(i.e.,561 p.ol/c.^(2)),indic.ting the imp.rtanc. of the surfac. *** together,these results emp.asize that the density of surfac. p.p.ides on c.ll differentiation must be c.nsidered at the c.ll-material ***,we have p.esented a viable strategy for ME-AM c.mmunity that desires to tune the bulk and surfac. func.ionality via blending of(m

关键词： Additive manufac.uring Blending Surfac. func.ionalization Surfac. density c.ic. c.emistry Human

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Synthesis of c.ral-like struc.ures of p.-Yb c.-dop.d YIG: Struc.ural,op.ic.l, magnetic.and antimic.obial p.op.rties

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Journal of Rare Earths 2024年第3期42卷 543-554,I0004页

作者： A.Fernandez Franc.sc. p.Araujo Y.Guerra S.c.stro-Lop.s J.Matilla-Arias Idglan S.de Lima Edson c.Silva-Filho Josy A.Osajima F.Guerrero R.p.na-Garc.a Federal University of p.au Graduate Program in Materials Science and EngineeringTeresinaPIBrazil Federal Rural University of p.rnambuc. Academic Unit of Cabo de Santo AgostinhoCabo de Santo AgostinhoPEBrazil Federal University of p.aui Department of PhysicTeresinaPBrazil Federal University of p.rnambuc. Graduate Program in Materials ScienceRecifePEBrazil University of Granma Departmentof Basic Sciences and Applied InformaticsFaculty of Technical SciencesBayamoCuba Federal University of Amazonas Department of PhysicManausAMBrazil Federal University of p.rnambuc. Department of PhysicRecifePEBrazil

c.ral-like struc.ures of the Y_(3-x)p._(x)Fe_(5-y)Yb_(y)O_(12),(0.00 ≤ x ≤ 0.04, 0.00 ≤ y ≤ 0.02) c.mp.und were synthesized using the sol-gel method. Struc.ural investigation c.rtified the YIG c.bic.c.ystal struc.ure formation, without any sec.ndary p.ase. It is shown that, the relatively large ionic.radius of the dop.nt c.tions results in an exp.nsion of the lattic. p.rameter, variations in the Iona-O-Iondangle, Iona-O,Iond-O and Ionc.O bond distanc.s and dec.ease in the average c.ystallite size. Fourier transform infrared(FTIR) and Raman measurements are essential to testify the single-p.ase formation of YIG c.ystal struc.ure and are observed c.anges in the stretc.ing and vibrational modes, resp.c.ively. The morp.ologic.l study, energy disp.rsive sp.c.rosc.p.(EDS) sp.c.ra and textural p.op.rties show c.rallike struc.ures, p.aks assoc.ated with p.^(3+) and Yb^(3+) atoms and the effec. of dop.nts on surfac. area,diameter, and p.re volume, resp.c.ively. The op.ic.l analysis from diffuse reflec.anc. sp.c.ra witnessed an inc.ease in the op.ic.l gap.band, a dec.ease in Urbac. energy and blue shift in the c.arge transfer,c.rrelated with the exp.nsion of the unit c.ll due to the dop.nt's insertion in the YIG struc.ure. A typ.c.l ferrimagnetic.behavior is exhibited by the Y_(3-x)p._(x)Fe_(5-y)Yb_(y)O_(12)c.mp.und. The saturation magnetization(M_(s)), c.bic.anisotrop. c.nstant(K_(1)) and c.erc.ve field(H_(c.) inc.ease with the p.^(3+)c.tions c.ntent, as c.nsequenc. of their magnetic.nature and distribution around of Fe^(3+)ions due to the c.existenc. with the Yb^(3+). Finally, for the first time, antibac.erial tests by mean of the direc. c.ntac. method were p.rformed for YIG c.-dop.d with p.^(3+)and Yb^(3+)and it is shown that, relatively high dosages of p.^(3+) c.tions favored the ac.ivity against S. aureus, therefore, a new biologic.l p.op.rty for YIG dop.d with rare earths is p.esented.

关键词： Yttrium iron garnet(YIG) c.ral-like struc.ures Rare earths Band gap.energy Magnetic.p.op.rties Antimic.obial p.op.rties

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Molec.lar Frame p.otoemission： p.obe of the p.otoionization Dynamic. for Molec.les in the Gas p.ase

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c.inese Journal of c.emic.l p.ysic. 2009年第2期22卷 178-186页

作者： D. Dowek Y. J. p.c.rd p. Billaud c. Elkharrat J. c. Houver Université p.ris-Sud 11 UMR 8625 Laboratoire des Collisions Atomiques et Moléculaires Bat. 351 Université Paris-Sud 91405 Orsay France c.RS UMR 8625 Laboratoire des Collisions Atomiques et Moléculaires Bat. 351 Université Paris-5ud 91405 Orsay France

Molec.lar frame p.otoemission is a very sensitive p.obe of the p.otoionization （p.） dynamic. of molec.les. This p.p.r rep.rts a c.mp.rative study of non-resonant and resonant p.otoionization of D2 induc.d by VUV c.rc.larly p.larized sync.rotron radiation at SOLEIL at the level of the molec.lar frame p.otoelec.ron angular distributions （MFp.Ds）. We use the vec.or c.rrelation method whic. c.mbines imaging and time-of-flight resolved elec.ron-ion c.inc.denc. tec.niques, and a generalized formalism for the exp.ession of the Ⅰ（χ, θe, Фe） MFp.Ds, where χ is the orientation of the molec.lar axis with resp.c. to the light quantization axis and （θe, Фe） the elec.ron emission direc.ion in the molec.lar frame. Selec.ed MFp.Ds for a molec.le aligned p.rallel or p.rp.ndic.lar to linearly p.larized light, or p.rp.ndic.lar to the p.op.gation axis of c.rc.larly p.larized light, are p.esented for dissoc.ative p.otoionization （Dp.） of D2 at two p.oton exc.tation energies, hv=19 eV, where direc. p. is the only c.annel op.ned, and hv=32.5 eV, i.e. in the region involving resonant exc.tation of Q1 and Q2 doubly exc.ted state series. We disc.ss in p.rtic.lar the p.op.rties of the c.rc.lar dic.roism c.arac.erizing p.otoemission in the molec.lar frame for direc. and resonant p.. In the latter c.se, a remarkable behavior is observed whic. may be attributed to the interferenc. oc.urring between undistinguishable autoionization dec.y c.annels.

关键词： Dissoc.ative p.otoionization Molec.lar frame p.otoemission c.rc.lar dic.roism in p.otoemission Autoionization dynamic. Sync.rotron radiation Vec.or c.rrelation

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Influenc. of wall slip.on the hydrodynamic.behavior of a two-dimensional slider bearing

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Ac.a Mec.anic. Sinic. 2007年第6期23卷 655-661页

作者： G. J. Ma c. W. Wu p. Zhou State Key Laboratory of Struc.ural Analysis for Industrial Equip.ent Department of Engineering Mechanics Dalian University of Technology Dalian 116024 China

In the p.esent p.p.r, a multi-linearity method is used to address the nonlinear slip.c.ntrol equation for the hydrodynamic.analysis of a two-dimensional （2-D） slip.gap.flow. Numeric.l analysis of a finite length slider bearing with wall slip.shows that the surfac. limiting shear stress exerts c.mp.ic.ted influenc.s on the hydrodynamic.behavior of the gap.flow. If the slip.oc.urs at either the stationary surfac. or the moving surfac. （esp.c.ally at the stationary surfac.）, there is a transition p.int in the initial limiting shear stress for the p.op.rtional c.effic.ent to affec. the hydrodynamic.load sup.ort in two op.osite ways： it inc.eases the hydrodynamic.load sup.ort at higher initial limiting shear stresses, but dec.eases the hydrodynamic.load sup.ort at lower initial limiting shear stresses. If the slip.oc.urs at the moving surfac. only, no fluid p.essure is generated in the c.se of null initial limiting shear stress. If the slip.oc.urs at both the surfac.s with the same slip.p.op.rty, the hydrodynamic.load sup.ort goes off after a c.itic.l sliding sp.ed is reac.ed. A small initial limiting shear stress and a small p.op.rtionality c.effic.ent always give rise to a low fric.ion drag.

关键词： Wall slip Slider beating Multi-linearity method Quadratic.p.ogramming

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p.edic.ors of survival in autoimmune liver disease overlap.syndromes

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World Journal of Hep.tology 2024年第9期16卷 1269-1277页

作者： Dujinthan Jayabalan Yi Huang Luis c.lzadilla-Bertot Malik Janjua Bastiaan de Boer John Josep. Wendy c.eng Simon Hazeldine Briohny W Smith Gerry c.Mac.uillan Mic.ael c.Wallac. George Garas Leon A Adams Gary p.Jeffrey Medic.l Sc.ool University of Western AustraliaNed-lands 6009Western AustraliaAustralia Dep.rtment of Hep.tology Sir Charles Gairdner HospitalNedlands 6009Western AustraliaAustralia Dep.rtment of Anatomic.l p.thology PathWest Laboratory MedicineNedlands 6009Western AustraliaAustralia Dep.rtment of Gastroenterology and Hep.tology Royal Perth HospitalPerth 6000Western AustraliaAustralia Dep.rtment of Gastroenterology and Hep.tology Fiona Stanley HospitalMurdoch 6150Western AustraliaAustralia Medic.l Sc.ool University of Western AustraliaNedl-ands 6009Western AustraliaAustralia

BAc.GROUND Survival in p.tients with autoimmune liver disease overlap.syndromes(AILDOS)c.mp.red to those with single autoimmune liver disease is *** To investigate the survival of p.tients with AILDOS and assess the ac.urac. of non-invasive serum models for p.edic.ing liver-related *** p.tients with AILDOS were defined as either autoimmune hep.titis and p.imary biliary c.olangitis overlap.AIH-p.c.or autoimmune hep.titis and p.imary sc.erosing c.olangitis overlap.AIH-p.c.and were identified from three tertiary c.ntres for this c.hort ***-related death or transp.antation(liver-related mortality)was determined using a p.p.lation-based data linkage *** sc.res for liver-related death were c.mp.red for ac.urac.[inc.uding liver outc.me sc.re(LOS),Hep.sc.re,Mayo Sc.re,model for end-stage liver disease(MELD)sc.re and MELD inc.rp.rated with serum sodium(MELD-Na)sc.re].RESULTS Twenty-two AILDOS p.tients were followed for a median of 3.1 years(range,0.35-7.7).Fourteen were female,the median age was 46.7 years(range,17.8 to 82.1)and median Hep.sc.re was 1(range,0.07-1).At five years p.st enrolment,57%of p.tients remained free from liver-related mortality(74%AIH-p.c.27%AIH-p.c..There was no signific.nt differenc. in survival between AIH-p.c.and *** was a signific.nt p.edic.or of liver-related mortality(p.0.05)in p.tients with AIH-p.c.n=14)but not AIH-p.c.n=8).A LOS c.t-p.int of 6 disc.iminated liver-related mortality in AIH-p.c.p.tients(p.0.012,log-rank test,100%sensitivity,77.8%sp.c.fic.ty)(Harrell's c.statistic.0.867).The MELD sc.re,MELD-Na sc.re and Mayo Sc.re were not p.edic.ive of liver-related mortality in any *** Survival in the rare,AILDOS is *** c.rrent study sup.orts the LOS as a p.edic.or of liver-related mortality in AIH-p.c.*** trials investigating p.edic.ors of survival in AILDOS are required.

关键词： Autoimmune liver disease overlap.syndromes Liver outc.me sc.re Liver-related death Hep.sc.re Autoimmune hep.titis p.imary biliary c.olangitis p.imary sc.erosing c.olangitis

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On the analytic.l solution of transient fric.ion in c.annel flows

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Ap.lied Mathematic. and Mec.anic.(English Edition) 2024年第8期45卷 1447-1466页

作者： F.J.GARc.A-GARc.A p.FARINAS-ALVARINO Dep.rtment of Naval&Industrial Engineering Polytechnic School of EngineeringUniversity of A CorunaCampus Industrial de FerrolFerrol 15403A CorunaSpain Integrac.ones Téc.ic.s de Seguridad S.A.Pol.Ind.Espiritu SantoC/Nobel15Cambre 15650A CorunaSpain

The transient fric.ion in c.annel mean flows is the sum of two c.ntributions,i.e.,the underlying laminar flow(ULF)and the p.rely turbulent c.mp.nent(p.c.,and the c.ntributions are analyzed sep.rately by theoretic.l *** is found that,the transient fric.ion may be higher or remarkably lower than that in equal-Reynolds number steady-state *** universal time c.nstant for p.ane-p.rallel laminar flows is rep.rted,and the role of the time c.nstant in a turbulent mean flow is *** is shown that the time c.nstant is related to the turbulenc.'s frozen ***,a study of the logarithmic.layer during the transient flow is ac.omp.ished,whic. shows that the logarithmic.layer is destroyed.

关键词： transient fric.ion transient flow unsteady c.annel flow

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Amino Ac.d Sequenc. of an Exc.tatory Insec.-selec.ive Toxin (BmK IT) From Venom of the Sc.rp.on Buthus martensi Karsc.

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Sc.enc. c.ina c.emistry 1994年第1期37卷 42-49页

作者：吉永华 p. Mansuelle 徐科 c. Granier c. Kop.yan S. Terakawa H. Roc.at Shanghai Institute of p.ysiology Academia Sinica Shanghai 200031 PRC Laboratoire de Bioc.emie c.RS URA 1455 INSERM U 172 Fac.lte de Medc.c.ne Sec.eur Nord BdPierre Dramard 13326 Marseille Cedex 15France

The insec.-selec.ive neurotoxin(BmK IT) of sc.rp.on Buthus martensi Karsc. was first reduc.d and S-alkylated, and then digested by Tp.K-tryp.in and Stap.yloc.c.us aureus V-8 p.otease. The enzymatic.p.p.ides were p.rified on TLc.p.astic.sheet and submitted to determine their amino ac.d c.mp.sitions and sequenc.s. The sequenc. of the 70 amino ac.d residues of BmK IT was established with referenc. to the p.imary struc.ure of AaH IT, another exc.tatory insec.-selec.ive toxin from the venom of North Afric.n sc.rp.on Androc.onus australis Hec.or. About 75% of the homologous sequenc. was found in the molec.les of BmK IT and AaH IT. It is obvious that the results c.ntribute toward better understanding of the molec.lar struc.ure c.arac.eristic., struc.ure/ac.ivity relationship.of sc.rp.on insec.-selec.ive toxins, and they c.n serve as the molec.lar basis for utilizing the toxins as a tool to c.arify molec.lar mec.anism involved in c.annel gating, and to infer the p.ssibility of develop.ng them as new selec.ive bioinsec.ic.des.

关键词： sc.rp.on Buthus martensi Karsc. insec.-selec.ive neurotoxin amino ac.d sequenc. struc.ure/ac.ivity relationship.

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A MULTIp.E INTELLIGENT AGENT SYSTEM FOR c.EDIT RISK p.EDIc.ION VIA AN Op.IMIZATION OF LOc.LIZED GENERALIZATION ERROR WITH DIVERSITY

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Journal of Systems Sc.enc. and Systems Engineering 2007年第2期16卷 166-180页

作者： Daniel S. YEUNG Wing W. Y. NG Aki p. F. c.AN p.tric. p. K. c.AN Mic.ael FIRTH Eric.c. c. TSANG Media and Life Sc.enc. c.mp.ting Laboratory Shenzhen Graduate School Harbin Institute of Technology Shenzhen 518055 China Dep.rtment of c.mp.ting Hong Kong Polytechnic University Hong Kong China Dep.rtment of Financ. and Insuranc. Lingnan University Hong Kong

c.mp.ny bankrup.c.es c.st billions of dollars in losses to banks eac. year. Thus c.edit risk p.edic.ion is a c.itic.l p.rt of a bank＇s loan ap.roval dec.sion p.oc.ss. Traditional financ.al models for c.edit risk p.edic.ion are no longer adequate for desc.ibing today＇s c.mp.ex relationship.between the financ.al health and p.tential bankrup.c. of a c.mp.ny. In this work, a multip.e c.assifier system （embedded in a multip.e intelligent agent system） is p.op.sed to p.edic. the financ.al health of a c.mp.ny. In our model, eac. individual agent （c.assifier） makes a p.edic.ion on the likelihood of c.edit risk based on only p.rtial information of the c.mp.ny. Eac. of the agents is an exp.rt, but has limited knowledge （rep.esented by features） about the c.mp.ny. The dec.sions of all agents are c.mbined together to form a final c.edit risk p.edic.ion. Exp.riments show that our model out-p.rforms other existing methods using the benc.marking c.mp.stat Americ.n c.rp.rations dataset.

关键词： c.edit rating business intelligenc. loc.lized generalization error multip.e c.assifier system feature group.ng

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p.thogenic.and therap.utic.role of exosomes in neurodegenerative disorders

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Neural Regeneration Researc. 2024年第1期19卷 75-79页

作者： c.rista c.Huber Hongmin Wang Division of Basic.Biomedic.l Sc.enc.s Sanford School of MedicineUniversity of South DakotaVermillionSDUSA

Neurodegenerative disorders affec. millions of p.op.e worldwide,and the p.evalenc. of these disorders is only p.ojec.ed to rise as the number of p.op.e over 65 will drastic.lly inc.ease in the c.ming *** therap.es exist to aid in symp.omatic.relief,effec.ive treatments that c.n stop.or reve rse the p.ogress of eac. neurodegenerative disease are ***,researc. on the role of extrac.llular vesic.es as disease markers and therap.utic. has been intensively ***,30-150 nm in diameter,are one typ. of extrac.llular vesic.es fac.litating c.ll-to-c.ll *** are thought to p.ay a role in disease p.op.gation in a variety of neurodegenerative diseases,suc. as Alzheimer's disease,p.rkinson s disease,and amyotrop.ic.lateral ***,the exosomes derived from the p.tients are an invaluable sourc. of disease *** the other hand,exosomes,esp.c.ally those derived from stem c.lls,c.uld serve as a therap.utic.for these disorders,as seen by a rap.d inc.ease in c.inic.l trials investigating the therap.utic.effic.c. of exosomes in different neurologic.l *** review summarizes the p.thologic.l burden and therap.utic.ap.roac. of exosomes in neurodegenerative *** also highlight how heat shoc. inc.eases the yield of exosomes while still maintaining their therap.utic.***,this review c.nc.udes with outstanding questions that remain to be addressed in exosomal researc..

关键词： aging Alzheimer's disease biomarker drug exosome extrac.llular vesic.e neurodegenerative disease p.rkinson's disease therap.

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