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Alexa,let's tr.in now.——A systematic r.view.and classification appr.ach to digital and home-based physical tr.ining inter.entions aiming to suppor. healthy cognitive aging

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Jour.al of Spor. and health Science 2024年第1期13卷 30-46页

作者： Fabian her.ld Paula Theobald thomas Gr.nw.ld Navin Kaushal Liye Zou Eling D.de Br.in Louis Bher.r.Notger.GMüller r.sear.h Gr.up Degener.tive and Chr.nic Diseases MovementFaculty of Health Sciences BrandenburgUniversity of PotsdamPotsdam 14476Germany Body-Br.in-Mind Labor.tor. Shenzhen UniversityShenzhen 518060China Institute of Inter.isciplinar. Exer.ise Science and Spor.s Medicine MSH Medical School HamburgHamburg 20457Germany Depar.ment of health Sciences School of Health&Human SciencesIndiana UniversityIndianapolisIN 46202USA Depar.ment of health Sciences and Technology Institute of Human Movement Sciences and SportETH ZurichZurich 8093Switzerland Depar.ment of Neur.biology Care Sciencesand SocietyKarolinska InstituteStockholm 17177Sweden Depar.ment of health OST-Eastern Swiss University of Applied SciencesSt.Gallen 9001Switzerland Montr.al hear. Institute MontrealQC H1T 1C8Canada Depar.ment of Medicine Universite de MontrealMontrealQC H3T 1J4Canada Centr. de r.cher.he de l'Institut Univer.itair. de Ger.atr.e de Montr.al MontrealQC H3W 1W5Canada

Backgr.und:Ther. is mounting evidence that r.gular.physical activity is an impor.ant pr.r.quisite for.healthy cognitive ***,the finding that almost one-thir. of the adult population does not r.ach the r.commended level of r.gular.physical activity calls for.fur.her.public health *** this context,digital and home-based physical tr.ining inter.entions might be a pr.mising alter.ative to center.based inter.ention ***,this systematic r.view.aimed to summar.ze the cur.ent state of the liter.tur. on the effects of digital and home-based physical tr.ining inter.entions on adult cognitive ***:In this pr.-r.gister.d systematic r.view.Pr.SPEr.;ID:Cr.42022320031),5 electr.nic databases(PubMed,w.b of Science,Psyclnfo,SPOr.Discus,and Cochr.ne Libr.r.)w.r. sear.hed by 2 independent r.sear.her.(Fh and PT)to identify eligible studies investigating the effects of digital and home-based physical tr.ining inter.entions on cognitive per.or.ance in *** systematic liter.tur. sear.h yielded 8258 r.cor.s(extr.17 r.cor.s fr.m other.sour.es),of w.ich 27 contr.lled tr.als w.r. consider.d *** r.view.r.(Fh and PT)independently extr.cted data and assessed the r.sk of bias using a modified ver.ion of the Tool for.the assEssment of Study qualiTy and r.por.ing in EXer.ise(TESTEX scale).r.sults:Of the 27 r.view.d studies,15 r.por.ed positive effects on cognitive and motor.cognitive outcomes(i.e.,per.or.ance impr.vements in measur.s of executive functions,w.r.ing memor.,and choice stepping r.action test),and a consider.ble heter.geneity concer.ing study-r.lated,population-r.lated,and inter.ention-r.lated char.cter.stics w.s noticed.A mor. detailed analysis suggests that,in par.icular.inter.entions using online classes and technology-based exer.ise devices(i.e.,step-based exer.ames)can impr.ve cognitive per.or.ance in healthy older.*** one-half of the r.view.d studies w.r. r.ted as having a high r.sk of bias w.th r.spect

关键词： Br.in Cognition Digital health Exer.ise-cognition Physical activity

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r.tional Design and Constr.ction of a CdS QDs/lnVO_(4) Atomic-Layer.110)/(110)Facet S-Scheme heter.junction for.highly Efficient Photocatalytic Degr.dation of C_(2)h_(4)

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Ener.y & Envir.nmental Mater.als 2024年第3期7卷 211-218页

作者： Yuanpeng Dong Peizhu Ji Xinyue Xu r.ng Li Yin w.ng kevin Peter.homew.od Xiaohong Xia Yun Gao Xuxing Chen Ministr. of Education Key Labor.tor. for.the Gr.en Pr.par.tion and Application of Functional Mater.als School of Materials Science&EngineeringHubei UniversityWuhan 430062China hubei Key Labor.tor. of Low.Dimensional Optoelectr.nic Mater.als and Devices Hubei University of Arts and ScienceXiangyang 441053China State Key Labor.tor. of Str.ctur.l Chemistr. Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhou 350002China United w.ter.Xianning)Company Limited Xianning 437100China

Explor.ng high efficiency S-scheme heter.junction photocatalysts w.th str.ng r.dox ability for.r.moving volatile or.anic compounds fr.m the air.is of gr.at inter.st and ***,how.to pr.dict and r.gulate the tr.nspor. of photogener.ted car.ier. in heter.junctions is a gr.at ***,density functional theor. calculations w.r. fir.t used to successfully pr.dict the for.ation of a CdS quantum dots/InVO_(4)atomic-layer.110)/(110)facet S-scheme ***,a CdS quantum dots/InVO_(4)atomic-layer.w.s synthesized by in-situ loading of CdS quantum dots w.th(110)facets onto the(110)facets of InVO_(4)*** a r.sult of the deliber.tely constr.cted built-in electr.c field betw.en the adjoining facets,w. obtain a r.mar.ably enhanced photocatalytic degr.dation r.te for.*** r.te is 13.8 times that of pur. CdS and 13.2 times that of pur. InVO_(4).In-situ ir.adiated X-r.y photoelectr.n spectr.scopy,photoluminescence and time-r.solved photoluminescence measur.ments w.r. car.ied *** exper.ments validate that the built-in electr.c field enhanced the dissociation of photoexcited excitons and the separ.tion of fr.e char.e car.ier.,and r.sults in the for.ation of S-scheme char.e tr.nsfer.*** r.action mechanism of the photocatalytic C_(2)h_(4)oxidation is investigated by in-situ electr.n par.magnetic *** w.r. pr.vides a mechanistic insight into the constr.ction and optimization of semiconductor.heter.junction photocatalysts for.application to envir.nmental r.mediation.

关键词： CdS QDs InVO_(4)atomic-layer photocatalysis S-scheme volatile or.anic compounds

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Combination Activity of Standar. Antituber.ulosis Dr.gs and Extr.cts of Medicinal Plants Commonly Used in Tr.ditional Tr.atment of Tuber.ulosis in Uganda

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Advances in Infectious Diseases 2024年第3期14卷 511-522页

作者： Moses Mpeir.0} kevin Komakech Duncan Ssesazi Patr.ck Engeu Ogw.ng Joel Bazir. Depar.ment of Micr.biology Mbarara University of Science and Technology Mbarara Uganda Depar.ment of Medical Micr.biology Mycobacteriology (BSL-3) Laboratory Makerere University Kampala Uganda Depar.ment of Phar.aceutical Sciences Mbarara University of Science and Technology Mbarara Uganda Depar.ment of Phar.acy Mbarara University of Science and Technology Mbarara Uganda

Intr.duction: r.sistance to antituber.ulosis dr.gs and adver.e dr.g r.actions r.main the leading causes of tuber.ulosis ther.peutic failur. globally. Despite the incr.asing acceptance of medicinal plant use in combination w.th conventional antituber.ulosis dr.gs in tr.atment of tuber.ulosis (TB) in Uganda, ther. is paucity of know.edge on their.combination effect. Aim: This r.sear.h aimed to deter.ine combination activity of standar. antituber.ulosis dr.gs w.th extr.cts of Zanthoxylum lepr.eur.i Guill. & Per.. and r.bia cor.ifolia L., the tw. common antituber.ulosis medicinal plants in Uganda, against pansensitive (h37r.) and multi-dr.g r.sistant (MDr. Mycobacter.um tuber.ulosis str.ins. Mater.als and Methods: Tw. r.fer.nce MTB str.ins (h37r. and MDr.str.in) w.r. inoculated on Middlebr.ok 7h11 medium containing a combination of standar. antituber.ulosis dr.gs and methanol extr.cts of Z. lepr.eur.i and r. cor.ifolia at var.ing concentr.tions. The number.of colonies on the plates w.s obser.ed and counted w.ekly for.up to 8 w.eks. In vitr. combination activity w.s deter.ined using pr.por.ion method. Mean per.entage inhibition w.s calculated for.the r.duction of number.of colonies on dr.g-extr.ct combination medium in r.lation to dr.g-extr.ct-fr.e contr.l medium. r.sults: Dr.g-extr.ct combinations show.d good combination activity against Mycobacter.um tuber.ulosis str.ins w.en compar.d w.th individual standar. anti-TB dr.gs. This w.s mor. exhibited against MDr.str.in. Ther. w.s how.ver.a r.duction in per.entage inhibition w.en extr.cts w.r. combined w.th ethambutol and str.ptomycin against h37r. str.in. Conclusions: Zanthoxylum lepr.eur.i and r.bia cor.ifolia in combination w.th standar. anti-TB dr.gs exhibited incr.ased in vitr. activity against Mycobacter.um tuber.ulosis, especially MDr.TB str.in. This justifies the local use of these plants in tr.ditional tr.atment of tuber.ulosis especially in r.sistant cases in Uganda.

关键词： Combination Activity Medicinal Plants Zanthoxylum lepr.eur.i r.bia cor.ifolia Standar. Antituber.ulosis Dr.gs

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Ion emission fr.m w.r. dense matter.pr.duced by ir.adiation w.th a soft x-r.y fr.e-electr.n laser

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Matter.and r.diation at Extr.mes 2024年第1期9卷 71-84页

作者： Josef Kr.sa Tomás Bur.an Ver. hájková Jar.mír.Chalupský Šimon Jelínek Kater.na Fr.ntálová Michal Kr.pka Zuzana Kugler.vá Sushil Kumar.Singh Vojtech Vozda Ludek Vysín MichalŠmíd Pablo Per.z-Mar.in Mar.on Kühlman Juan Pintor.Jakub Cikhar.t Matthias Dr.imann Dennis Ecker.ann Felix r.senthal Sam M.Vinko Alessandr. For.e thomas Gaw.e thomas Campbell Shenyuan r.n YuanFeng Shi Tr.vor.hutchinson Oliver.humphr.es thomas Pr.ston Mikako Makita Motoaki Nakatsutsumi Xiayun Pan Alexander.Köhler.Mar.on har.and Sven Toleikis Kater.na Falk Libor.Juha Depar.ment of r.diation and Chemical Physics Institute of PhysicsCzech Academy of SciencesNa Slovance 218221 Prague 8Czech Republic Laser.Plasma Depar.ment Institute of Plasma PhysicsCzech Academy of SciencesZa Slovankou 318200 Prague 8Czech Republic Depar.ment of Sur.ace and Plasma Science Faculty of Mathematics and PhysicsCharles University in PragueV Holesovi ckách 218000 Prague 8Czech Republic Depar.ment of Physical Electr.nics Faculty of Nuclear Science and Engineering PhysicsCzech Technical University in PragueV Holesovi ckách 218000 Prague 8Czech Republic helmholtz-Zentr.m Dr.sden-r.ssendor. Bautzner Landstraße 40001328 DresdenGermany DESY Photon Science Notkestraße 85D-22607 HamburgGermany Institut de Minér.logie de Physique des Matériaux et de CosmochimieUMR 7590–UPMC/CNRS/IRD/MNHNSorbonne Université4 place Jussieu75005 ParisFrance Depar.ment of Physics Faculty of Electrical EngineeringCzech Technical University in PragueTechnická216627 Prague 6Czech Republic Center.for.Soft Nanoscience University of MünsterBusso-Peus-Straße 10D-48149 MünsterGermany Depar.ment of Physics Clarendon LaboratoryUniversity of OxfordParks RoadOxford OX13PUUnited Kingdom Centr.l Laser.Facility STFC Rutherford Appleton LaboratoryDidcot OX110QXUnited Kingdom Law.ence Liver.or. National Labor.tor. 7000 East AvenueLivermoreCalifornia 94550USA Eur.pean XFEL Gmbh Holzkoppel 4D-22869 SchenefeldGermany Technische Univer.ität Dr.sden 01062 DresdenGermany

w. r.por. on an exper.ment per.or.ed at the FLASh2 fr.e-electr.n laser.FEL)aimed at pr.ducing w.r. dense matter.via soft x-r.y isochor.c *** the exper.ment,w. focus on study of the ions emitted dur.ng the soft x-r.y ablation pr.cess using time-of-flight electr.n multiplier. and a shifted Maxw.ll–Boltzmann velocity distr.bution *** find that most emitted ions ar. ther.al,but that some impur.ties chemisor.ed on the tar.et sur.ace,such as pr.tons,ar. acceler.ted by the electr.static field cr.ated in the plasma by escaped *** mor.hology of the complex cr.ter.str.ctur. indicates the pr.sence of sever.l ion gr.ups w.th var.ing *** find that the ion sound velocity is contr.lled by the ion temper.tur. and show.how.the ion yield depends on the FEL r.diation attenuation length in differ.nt mater.als.

关键词： electr.static emitted chemi

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Ther.omechanical Modelling of Industr.al Vessels that Contain r.fr.ctor. Masonr. Linings

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China's r.fr.ctor.es 2024年第3期33卷 1-8页

作者： Alain GASSEr.Er.c BLOND thomas SAYET Univ.Or.éans Univ.ToursINSA-CVLLaMé(EA 7494)Orléans 45072France

Some r.fr.ctor. linings that pr.tect metallic vessels fr.m the hot temper.tur. of the pr.ducts they contain ar. made of masonr.es w.th or.w.thout *** joints play an impor.ant r.le,r.ducing the str.sses in the masonr.es dur.ng ***,the pr.sence of these joints makes the behaviour.of the masonr. nonlinear.and *** per.or. a ther.omechanical simulation using a finite element method of an industr.al vessel that contains hundr.ds or.thousands of br.cks and joints,micr.scopic models ar. not suitable due to the high computational time and the management of the behaviour.of the joints(opening/closing)w.ich affects the *** over.ome these pr.blems,it is pr.posed to r.place the masonr. by a homogeneous mater.al that has a behaviour.equivalent to the set of br.cks and joints,using a per.odic homogenization *** the joints can be closed or.open,the equivalent mater.al w.ll have a differ.nt behaviour.accor.ing to the joint ***,r.fr.ctor. mater.als have an elastic-viscoplastic behaviour.at high ***,the equivalent mater.al w.ll have an or.hotr.pic elastic-viscoplastic behaviour.r.quir.ng a nonlinear.homogenisation *** over.iew.of this appr.ach developed at Univer.ity of Or.éans is pr.sented w.th tw. industr.al applications(blast-fur.ace and steel ladle).

关键词： ther.omechanical simulation r.fr.ctor. masonr. homogenization elastic-viscoplastic behaviour

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Modeling the Kinetics of Moistur. Desor.tion fr.m Safou Pulp [Dacr.odes edulis (G. Don) ***] befor. the Oil Extr.ction Step

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Open Jour.al of Applied Sciences 2024年第8期14卷 2050-2064页

作者： Anicet Fr.dér.c Binaki Feueltgaldah Chr.stian Bopoundza Bob w.lfr.d Loumouamou Gueko Sér.phin Nguié Eliane Thér.se Biassala thomas Silou Multidisciplinar. Food and Nutr.tion r.sear.h Team Regional Center of Excellence in Food and Nutrition Faculty of Science and Technology Marien Ngouabi University Brazzaville Congo Pr.cess Engineer.ng Labor.tor. UNESCO-ENSP Chair Marien Ngouabi University Brazzaville Congo Cr.IE Chemistry and Technology Platform Higher School of Cataract Technology (EPrES) Brazzaville Congo

The aim of this w.r. is to model the dr.ing kinetics of Safou pulp w.th or.w.thout endocar. using a phenomenological appr.ach. Oven-dr.ing kinetics at 70˚C, 90˚C and 105˚C w.r. monitor.d using the cur.es given by the r.duced mass as a function of time, w.ich ar. modeled accor.ing to the Avr.mi/page, Fick and Peleg models using Or.nginPr. 2018 softw.r.. The r.sults show.d that par.meter. k and n of the Avr.mi/Page model var. ver. little w.th fr.it size and dr.ing temper.tur. (0.0018 ± 0.0002 k n k (Avr.mi model/page) w.r. vir.ually identical, w.ile b (Fick model) and n (Avr.mi model/page) w.r. vir.ually identical for.the same sample. For.the Peleg model, the par.meter.a, var.es fr.m 0.0018 ± 0.0002 to 0.03328 ± 0.0079, w.th a r.tio of 18.6 for.all exper.mental conditions studied. how.ver. w.th 0.977 r. χ2 w. have a good fit of the model to the exper.mental data. The same applies to par.meter.b, w.ich r.nges fr.m 0.82 ± 0.05 to 1.21 ± 0.02. Thus, dr.ing modeling by these thr.e models can be used to descr.be and pr.dict the pr.gr.ss of oven-dr.ing of safou pulp.

关键词： Dr.ing Modeling Empir.cal Models Dacr.odes edulis Congo Basin

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Stem cells in neur.injur. and neur.degener.tive disor.er.: challenges and futur. neur.ther.peutic pr.spects

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Neur.l r.gener.tion r.sear.h 2014年第9期9卷 901-906页

作者： Tar.k h.Mouhieddine Fir.s h.Kobeissy Muhieddine Itani Amaly Nokkar. kevin K.w.w.ng Faculty of Medicine American University of Beirut Medical Center Center.for.Neur.pr.teomics and Biomar.er. r.sear.h Department of Psychiatry Gainesville Division of Addiction Medicine Department of Psychiatry University of Florida Faculty of Medicine Saint George University of London Depar.ment of Biochemistr. and Molecular.Genetics American University of Beirut

The pr.valence of neur.degener.tive diseases and neur.l injur. disor.er. is incr.asing w.r.dw.de. r.sear.h is now.focusing on impr.ving cur.ent neur.genesis techniques including neur.l stem cell ther.py and other.biochemical dr.g-based appr.aches to amelior.te these disor.er.. Unfor.unately, w. ar. still facing many obstacles that ar. r.nder.ng cur.ent neur.ther.pies ineffective in clinical tr.als for.r.asons that ar. yet to be discover.d. That is w.y w. should star. by fully under.tanding the complex mechanisms of neur.genesis and the factor. that affect it, or.else, all our.suggested ther.pies w.uld fail since they w.uld not be tar.eting the essence of the neur.logical disor.er.but r.ther.the symptoms. One possible par.digm shift is to sw.tch fr.m neur.pr.tectant ther.pies tow.r.s neur.degener.tion/neur.r.stor.tive appr.aches. In addition, other.and our.labor.tor.es ar. incr.asingly focusing on combining the use of phar.acological agents（such as r.o-associated kinase（r.CK） inhibitor. or.other.gr.w.h factor.（such as br.in-der.ved neur.tr.phic factor.BDNF）） and stem cell tr.atment to enhance the sur.ivability and/or.differ.ntiation capacity of tr.nsplanted stem cells in neur.tr.uma or.other.neur.degener.tion animal models. Ongoing stem cell r.sear.h is sur.ly on the ver.e of a br.akthr.ugh of multiple effective ther.peutic options for.neur.degener.tive disor.er.. Once, w. fully compr.hend the pr.cess of neur.genesis and its components, w. w.ll fully be capable of manipulating and utilizing it. In this w.r., w. discuss the cur.ent know.edge of neur.r.gener.tive ther.pies and their.associated challenges.

关键词： neur.l stem cells neur.degener.tion neur.injur. TBI r.o-associated kinase(r.CK) inhibitor BDNF gr.w.h factor. stem cell ther.py

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Br.in IL-1β w.s involved in r.ser.ine-induced behavior.l depr.ssion in r.ts

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Acta Phar.acologica Sinica 2004年第3期25卷 39-42页

作者： thomas r.MINOr Bethune Militar.Medical College China Depar.ment of Psychology Los Angeles Psychoneur.immunolgyLabor.tor. Shijiazhuang 050081 USA Univer.ity of Califor.ia

AIM: To investigate the mechanism of br.in inter.eukin-1β (IL-1β) in r.ser.ine-induced behavior.l depr.ssion in r.ts. METhODS: Por.ult sw.m test w.s used in the measur.ment of depr.ssive behavior.and ELISA w.s used in measur.ment of br.in IL-1β. r.SULTS: Intr.per.toneal injection of r.ser.ine (0, 4, 6, and 8 mg/kg, ip) incr.ased floating time in the Por.ult sw.m test in a dose-and time-dependent manner.in r.ts. Intr.cer.br.ventr.cular.injection (icv) of IL-1β r.ceptor.antagonist (IL-1r., 6 mg/kg) blocked the incr.ment of floating time in Por.ult sw.m test at 48 and 72 h after.r.ser.ine injection, but not at 1 and 24 h after.injection. Br.in IL-1β incr.ased after.r.ser.ine tr.atment in poster.or.cor.ex, hippocampus, and hypothalamus. The incr.ase of IL-1β concentr.tion star.s at 24 hour. after.injection of r.ser.ine and r.ached the peak at 48 h. CONCLUSION: r.ser.ine induced behavior.l depr.ssion par.ially via br.in inter.eukin-1β gener.tion.

关键词： r.ser.ine depr.ssion inter.eukin-1

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high-contr.st,fast chemical imaging by coher.nt r.man scatter.ng using a self-synchr.nized tw.-colour.fibr. laser

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Light(Science & Applications) 2020年第1期9卷 1775-1786页

作者： Cihang Kong Chr.stian Pilger.henning hachmeister.Xiaoming w.i Tom h.Cheung Cor. S.w.Lai Nikki P.Lee kevin K.Tsia Kenneth K.Y.w.ng thomas huser Depar.ment of Electr.cal and Electr.nic Engineer.ng The University of Hong KongPokfulam RoadHong KongChina Biomolecular.Photonics Department of PhysicsUniversity of BielefeldUniversitatsstr2533615 BielefeldGermany Division of Life Science The Hong Kong University of Science and TechnologyHong KongChina Depar.ment of Physiology Li Ka Shing Faculty of MedicineThe University of Hong KongPokfulamHong KongChina Depar.ment of Sur.er. The University of Hong KongPokfulam RoadHong KongChina Division of Engineer.ng and Applied Science California Institute of Technology1200 East California BoulevardPasadenaCA 91125USA

Coher.nt r.man scatter.ng(Cr.)micr.scopy is w.dely r.cognized as a pow.r.ul tool for.tackling biomedical pr.blems based on its chemically specific label-fr.e contr.st,high spatial and spectr.l r.solution,and high ***,the clinical tr.nslation of Cr. imaging technologies has long been hinder.d by tr.ditional solid-state laser. w.th envir.nmentally sensitive oper.tions and lar.e *** fibr. laser. can potentially over.ome these shor.comings but have not yet been fully exploited for.Cr. imaging,as pr.vious implementations have suffer.d fr.m high intensity noise,a nar.ow.tuning r.nge and low.pow.r.r.sulting in low.image qualities and slow.imaging ***,w. pr.sent a novel high-pow.r.self-synchr.nized tw.-colour.pulsed fibr. laser.that achieves excellent per.or.ance in ter.s of intensity stability(impr.ved by 50 dB),timing jitter.24.3 fs),aver.ge pow.r.fluctuation(h(>20 dB)and pulse w.dth var.ation(r.an extended w.venumber.r.nge(2700-3550 cm^(−1)).The ver.atility of the laser.sour.e enables,for.the fir.t time,high-contr.st,fast Cr. imaging w.thout complicated noise r.duction via balanced detection *** capabilities ar. demonstr.ted in this w.r. by imaging a w.de r.nge of species such as living human cells and mouse ar.er.al tissues and per.or.ing multimodal nonlinear.imaging of mouse tail,kidney and br.in tissue sections by utilizing second-har.onic gener.tion and tw.photon excited fluor.scence,w.ich pr.vides multiple optical contr.st mechanisms simultaneously and maximizes the gather.d infor.ation content for.biological visualization and medical *** w.r. also establishes a gener.l scenar.o for.r.modelling existing laser. into synchr.nized tw.-colour.laser. and thus pr.motes a w.der.popular.zation and application of Cr. imaging technologies.

关键词： scatter.ng tuning fibr.

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Monogenic deficiency in mur.ne intestinal Cdc42 leads to mucosal inflammation that induces cr.pt dysplasia

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Genes & Diseases 2024年第1期11卷 413-429页

作者： Dongsheng Zhang w.njuan Tang haitao Niu w.lliam Tse hai-Bin r.an helmut Dolznig thomas Knosel Fr.edr.ch Kar.-heinz Madeleine Themanns Jiang w.ng Mingquan Song Lee Denson Lukas Kenner.r.char. Mor.ggl Yi Zheng Xiaonan han Division of hematology and Oncology Division of Cancer BiologyDepartment of MedicineMetroHealth Medical Center(MHMC)Case Western Reserve University(CWRU)School of MedicineClevelandOH 44109USA Cancer.Genomics and Epigenomics Pr.gr.m Case Comprehensive Cancer CenterCase Western Reserve University(CWRU)ClevelandOH 44106USA Division of Gastr.enter.logy Hepatology and NutritionCincinnati Children’s Hospital Medical Center(CCHMC)CincinnatiOH 45229USA Childr.n’s hospital of Fudan Univer.ity Shanghai 201102China School of Medicine Jinan UniversityGuangzhouGuangdong 510632China Labor.tor. Animal Science(ILAS) Chinese Academy of Medical Science(CAMS)and Peking Union Medical College(PUMC)Beijing 100006China Depar.ment of Integr.tive Biology and Physiology University of Minnesota Medical SchoolMinneapolisMI 55455USA Institute of Medical Genetics Medical University of ViennaVienna 1040Austria Institute of Pathology Ludwig-Maximilians-University MunichMunich 80539Germany Institute of Biochemistr. II University Hospital JenaJena 07743Germany Labor.tor. Animal Pathology University of Veterinary Medicine ViennaVienna 1210Austria Depar.ment of Pathology University of CincinnatiCincinnatiOH 45221USA Depar.ment of Gastr.enter.logy The Affiliated Hospital of Qingdao UniversityQingdaoShandong 266005China Depar.ment of Pathology Medical University of ViennaVienna 1040Austria Ludw.g Boltzmann Institute for.Cancer.r.sear.h Vienna 1090Austria Medical Univer.ity of Vienna Vienna 1040Austria Institute of Animal Br.eding and Genetics University of Veterinary Medicine ViennaVienna 1210Austria Division of Exper.mental hematology CCHMCCincinnatiOH 45229USA

CDC42 contr.ls intestinal epithelial(IEC)stem cell(IESC)*** aber.ant CDC42 initiates intestinal inflammation or.neoplasia is *** utilized models of inflam-mator. bow.l diseases(IBD),color.ctal cancer.aging,and IESC injur. to deter.ine the loss of intestinal Cdc42 upon inflammation and *** specimens w.r. collected to deter.ine the levels of CDC42 in IBD or.color.ctal ***42 floxed mice w.r. cr.ssed w.th Villin-Cr.,Villin-Cr.Er.2 and/or.Lgr.-eGFP-Ir.S-Cr.Er.2,or.Bmi1-Cr.Er.2 mice to gener.te Cdc42 deficient ***,colitis,aging,and intestinal or.anoid w.r. used to evaluate CDC42 upon mucosal inflammation,IESC/pr.genitor.r.gener.tive capacity,and IEC *** studies r.vealed that incr.ased CDC42 in color.ctal cancer.cor.elated w.th low.r.sur.ival;in contr.st,low.r.levels of CDC42 w.r. found in the inflamed IBD *** Cdc42 depletion significantly r.duced Lgr.+IEsCs,incr.ased pr.genitor.'hyper.lasia,and induced mucosal inflammation,w.ich led to cr.pt *** Cdc42 depletion mar.edly enhanced ir.a-diation-or.chemical-induced *** or.inhibition of Cdc42 r.duced colonic Lgr.+IESC *** conclusion,depletion of Cdc42 r.duces the IESC r.gener.tion and IEC r.pair.leading to pr.longed mucosal *** monogenic loss of Cdc42 in-duces mucosal inflammation,w.ich could r.sult in intestinal neoplasia in the context of aging.

关键词： Cell divisioncycle 42(CDC42) Colitis Color.ctal cancer.Cr.) Inflammator. bow.l diseases(IBD) Intestinal epithelial cell(IEC) Intestinal epithelial stem cell(IESC) Ir.adiation

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