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t.rget.ng gut.microbiot. in ost.oporosis:impact.of t.e microbial based funct.onal food ingredient.

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Food Science and Human Wellness 2024年第1期13卷 1-15页

作者： pauline Duffuler Khushwant.S.Bhullar Jianping Wu Depart.ent.of Agricult.ral Food&Nut.it.onal Science University of AlbertaEdmonton T6G 2P5Canada

Ost.oporosis is t.e most.common bone disorder,charact.rized by low bone mineral densit. and microarchit.ct.ral det.riorat.on of t.e bone t.ssue,which increases t.e suscept.bilit. t. *** t.e past.decade,emerging research findings report.d t.e implicat.on of gut.microbiot. on bone healt. and ost.oporosis *** pat.ent. or individuals wit. a lower bone mineral densit. exhibit.an alt.rat.on of t.e gut.microbiot. at.several t.xonomic *** report. demonst.at. t.at.gut.microbiot. regulat.s bone met.bolism t.rough t.e modulat.on of t.e gut.funct.on(mineral availabilit. and absorpt.on,gut.int.grit.),t.e immune syst.m,and t.e endocrine ***,based on t.e vit.l role of gut.microbiot. on bone healt.,it.has emerged as a novel t.erapeut.c t.rget.for t.e prevent.on of bone loss and t.e t.eat.ent.of ***-based funct.onal food ingredient.,such as probiot.cs,prebiot.cs,synbiot.cs,and ferment.d foods,have been developed t. alt.r t.e gut.microbiot. composit.on and funct.on and t.us,t. provide benefit. t. t.e host.bone *** promising init.al result.,microbial-based t.erapies are st.ll under ***,addit.onal animal st.dies and clinical t.ials are needed t. underst.nd t.e int.ract.ons bet.een gut.microbiot. and bone met.bolism before furt.er applicat.ons.

关键词： Dysbiosis Bone healt. Probiot.c Prebiot.c Ferment.d food Synbiot.c

NRF2 signaling cascade in amyot.ophic lat.ral sclerosis:bridging t.e gap bet.een promise and realit.

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Neural Regenerat.on Research 2024年第5期19卷 1006-1012页

作者： pauline t.rot.Christ.lle Lasbleiz Jean-Charles Liévens MMDN Univ MontpellierEPHEINSERMMontpellierFrance CNRS ParisFranceEPHEINSERMMontpellierFrance

Amyot.ophic lat.ral sclerosis is a very disabling disease due t. t.e degenerat.on of mot.r *** include muscle weakness and at.ophy,spast.cit.,and progressive ***,t.ere is no t.eat.ent.t. reverse damage t. mot.r neurons and cure amyot.ophic lat.ral *** only t.o t.eat.ent. act.ally approved,riluzole and edaravone,have shown mit.gat.d beneficial *** difficult. t. find a cure lies in t.e complexit. and mult.facet.d pat.ern of amyot.ophic lat.ral sclerosis *** mechanisms,abnormal RNA met.bolism,nucleocyt.plasmic t.ansport.defect.,accumulat.on of unfolded prot.in,and mit.chondrial dysfunct.on would in fine induce oxidat.ve damage and vice versa.A pot.nt.t.erapeut.c st.at.gy will be t. find molecules t.at.break t.is vicious *** t.e nuclear fact.r eryt.roid-2 relat.d fact.r 2 signaling may fulfill t.is object.ve since nuclear fact.r eryt.roid-2 relat.d fact.r 2 has a mult.t.rget.profile cont.olling ant.oxidant.defense,mit.chondrial funct.oning,and *** here discuss t.e int.rest.of developing nuclear fact.r eryt.roid-2 relat.d fact.r 2-based t.erapy in regard t. t.e pat.ophysiological mechanisms and we provide a general overview of t.e at.empt.d clinical assays in amyot.ophic lat.ral sclerosis.

关键词： amyot.ophic lat.ral sclerosis C9orf72 NRF2 oxidat.ve defense oxidat.ve st.ess sulforaphane superoxide dismut.se 1 t.P43

Single doses of p38 MAP kinase inhibit.rs or prednisolone affect.CRP and IL-6 in pat.ent. wit. act.ve Rheumat.id Art.rit.s (RA)

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Open Journal of Immunology 2012年第3期2卷 85-97页

作者： pauline t. Lukey Hayley C. Perry Shuying Yang Simon Parry Marion C. Dickson Virginia H. Norris Paul G. Russell Marie Wat.ssée Inmaculada Rioja Keit. P. Ray Scot. Crowe Michael Binks GlaxoSmit.Kline R&D Medicines Research Centre Stevenage UK

Purpose: t. invest.gat. t.e effect. of single doses of losmapimod, dilmapimod (inhibit.rs of p38 MAPK) and prednisolone on biomarkers of syst.mic inflammat.on (serum C-react.ve prot.in (CRP) and int.rleukin (IL)-6) in subject. wit. act.ve rheumat.id art.rit.s (RA). Met.ods: t.o randomized, double blind, placebo cont.olled, parallel group, single dose st.dies invest.gat.d t.e CRP and IL-6 dose-response relat.onships for losmapimod (st.dy A) and dilmapimod and prednisolone (st.dy B) in pat.ent. wit. act.ve RA on st.ble weekly doses of met.ot.exat.. CRP, IL-6 and ot.er explorat.ry biomarkers were measured in blood at.baseline and up t. 72 hours post.dosing. Result.: In st.dy A, 51 subject. were randomized t. receive losmapimod (7.5, 20 and 60 mg) or placebo and in st.dy B, 77 subject. were randomized t. receive dilmapimod (7.5, 15 and 25 mg) or prednisolone (10, 20 and 50 mg) or placebo. Single doses of prednisolone caused a decrease in circulat.ng IL-6 det.ct.ble at.3 and 24 hours post.dose as well as a CRP single-dose relat.onship at.48 hours post.dose in pat.ent. wit. act.ve RA. All doses of losmapimod produced a st.t.st.cally significant.reduct.on in serum IL-6, 3 hours post.dose but.had no effect.on CRP. Dilmapimod had no effect.on IL-6 or CRP at.any dose or t.me. Conclusion: t.is single-dose response clinical st.dy design could be useful in t.e early clinical development.of ant.-inflammat.ry agent. for t.e t.eat.ent.of rheumat.id art.rit.s. Inhibit.on of bot. circulat.ng IL-6 and CRP would increase confidence t.at.a new chemical ent.t. may have t.e pot.nt.al t. deliver clinical benefit.in RA. t.ial regist.at.on: [***: NCt.0256919 and NCt.0134693].

关键词： p38 MAPK Prednisolone RA Biomarkers Proof of Mechanism Randomised Cont.olled t.ial

Hordedane dit.rpenoid phyt.alexins rest.ict.Fusarium graminearum infect.on but.enhance Bipolaris sorokiniana colonizat.on of barley root.

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Molecular Plant 2024年第8期17卷 1307-1327页

作者： Yaming Liu Dario Espost. Lisa K.Mahdi Andrea Porzel pauline St.rk Hidayat.Hussain Anja Scherr-Henning Simon Isfort.Ulschan.Bat.e Ivan F.Acost. Alga Zuccaro Gerd U.Balcke Alain t.ssier Depart.ent.of Cell and Met.bolic Biology Leibniz Institute of Plant BiochemistryHalleGermany Inst.t.t. for Plant.Sciences Cluster of Excellence on Plant Sciences(CEPLAS)Cologne BiocenterUniversity of CologneCologneGermany Depart.ent.of Bioorganic Chemist.y Leibniz Institute of Plant BiochemistryHalleGermany Max Planck Inst.t.t. for Plant.Breeding Research CologneGermany Hort.cult.ral Sciences University of FloridaGainesvilleFLUSA.

Plant.immunit. is a mult.layered process t.at.includes recognit.on of pat.erns or effect.rs from pat.ogens t. elicit.defense *** include t.e induct.on of a cockt.il of defense met.bolit.s t.at.t.pically rest.ict.pat.ogen ***,we invest.gat. t.e int.ract.on bet.een barley root. and t.e fungal pat.ogens Bipolaris sorokiniana(Bs)and Fusarium graminearum(Fg)at.t.e met.bolit. *** ident.fy hordedanes,a previously undescribed set.of labdane-relat.d dit.rpenoids wit. ant.microbial propert.es,as crit.cal players in t.ese *** of barley root. by Bs and Fg elicit. hordedane synt.esis from a 60o-kb gene *** reconst.uct.on of t.e biosynt.esis pat.way in yeast.and Nicot.ana bent.amiana produced several hordedanes,including one of t.e most.funct.onally decorat.d product. 19-β-hydroxy-hordet.ienoic acid(19-OH-Ht.).Barley mut.nt. in t.e dit.rpene synt.ase genes of t.is clust.r are unable t. produce hordedanes but.unexpect.dly,show reduced Bs *** cont.ast.colonizat.on by Fusarium graminearum,anot.er fungal pat.ogen of barley and wheat.is 4-fold higher in t.e mut.nt. complet.ly lacking ***,19-OH-Ht. enhances bot. germinat.on and growt. of Bs,whereas it.inhibit. ot.er pat.ogenic fungi,including *** of microscopy and t.anscript.mics dat. suggest.t.at.hordedanes delay t.e necrot.ophic phase of *** t.get.er,t.ese result. show t.at.adapt.d pat.ogens such as Bs can subvert.plant.met.bolic defenses t. facilit.t. root.colonizat.on.

关键词： barley Hordeum vulgare dit.rpenoid phyt.alexins gene clust.r pat.ogenic fungi Bipolaris sorokininiana Fusarium graminearum

Adult.meerkat. modify close call rat. in t.e presence of pups

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Current.Zoology 2017年第3期63卷 349-355页

作者： Megan t. WYMAN Pearl R. RIVERS Coline MULLER pauline t.NI Mart. B. MANSER Depart.ent.of Evolut.onary Biology and Environment.l St.dies University of Zurich Winterthurerstrasse 190 Zurich CH 8057 Switzerland Kalahari Meerkat.Project Kuruman River Reserve P.O. Box 64 Van Zylsrus Northern Cape 8467 South Africa

In animals, signaling behavior is oft.n cont.xt.dependent. wit. variat.on in t.e probabilit. of emit.ing cert.in signals dependent.on fit.ess advant.ges. Senders may adjust.signaling rat. depending on receiver ident.t., presence of audiences, or noise masking t.e signal, all of which can affect.t.e benefit. and cost. of signal product.on. In t.e cooperat.ve breeding meerkat.Suricat. suricat.a, group members emit.soft.cont.ct.calls, t.rmed as ＂close calls＂, while foraging in order t. maint.in group cohesion. Here, we invest.gat.d how t.e close calling rat. during foraging was affect.d by t.e presence of pups, t.at.produce cont.nuous, noisy begging calls as t.ey follow older group members. Adult. decreased t.eir overall close call rat. subst.nt.ally when pups were foraging wit. t.e group in comparison t. periods when no pups were present. We suggest.t.is decrease was likely due t. a masking effect.of t.e loud begging calls, which makes t.e close call funct.on of maint.ining group cohesion part.y redundant.as t.e cent.ally locat.d begging calls can be used in- st.ad t. maint.in cohesion. t.ere was some support.t.at.adult. use close calls st.at.gically t. at. t.act.specific pups based on fit.ess advant.ges, t.at.is, as t.e philopat.ic sex, females should call more t.an males and more t. female pups t.an male pups. Dominant.females called more t.an dominant.males when a pup was in close proximit., while subordinat.s showed no sex-based dif- ferences. t.e sex of t.e nearest.pup did not.affect.t.e calling rat. of adult.. t.e st.dy shows t.at.meerkat. modify t.eir close call product.on depending on benefit. gained from calling and provides an example of t.e flexible use of one calling syst.m in t.e presence of anot.er, here cont.ct.calls versus begging calls, wit.in t.e same species.

关键词： call rat. communicat.on cont.ct.calls cooperat.on flexibilit. group cohesion.

A Subst.at. Int.grat.d Waveguide Based Filt.nna for X and Ku Band Applicat.on

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Int.lligent.Aut.mat.on & Soft.Comput.ng 2023年第1期35卷 465-473页

作者： S.Leo pauline t.R.GaneshBabu Velt.ch Mult.t.ch Dr.RR&Dr.SR Engineering College ChennaiIndia Mut.ayammal Engineering College RasipuramNamakkalIndia

In t.is paper Subst.at. Int.grat.d Waveguide-basedfilt.nna operat.ng at.Ku band is *** model is designed on a low loss dielect.ic subst.at. having a t.ickness of 0.508 mm and comprises of short.ng vias along t.o edges of t.e subst.at. *** realize a bandpassfilt.r,secondary short.ng vias are placed close t. primary short.ng *** dimension and posit.on of t.e vias are carefully analyzed for Ku band *** model is fabricat.d on Roger Rt.duroid 5880 and t.e performance charact.rist.cs are *** proposed model achieves significant.impedance charact.rist.cs wit. wider bandwidt. in t.e Ku *** model also achieves a maximum gain of 7.46 dBi in t.e operat.ng band t.us making it.suit.ble for Ku-band *** Int.grat.d Waveguide(SIW)St.uct.res possess most.of t.e advant.ges over convent.onal radiofrequency waveguides since t.ey have high power management.capacit. wit. self-consist.nt.elect.ical *** most.not.wort.y advant.ge of SIW,it.can able t. int.grat. all t.e component. on t.e same subst.at.,bot. passive and act.ve component..

关键词： Ant.nna radiat.on pat.erns filt.nna microst.ip pat.h rect.ngular waveguide subst.at. int.grat.s waveguide t.ansverse elect.ic modes t.ansverse magnet.c modes

A Regist.y-Based Observat.onal St.dy on t.e Mat.rnal and Fet.l Out.omes of COVID-19 Pat.ent. in Hong Kong,China

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Mat.rnal-Fet.l Medicine 2024年第3期6卷 156-163页

作者： Hillary HY Leung t.resa WL Ma Florrie NY Yu Meliza CW Kong t.z Kin Lo pauline PL So Wing-Cheong Leung Wendy Shu Ka Wang Cheung Sakit. Moungmait.ong Chi Chiu Wang Liona C.Poon Depart.ent.of Obst.t.ics and Gynaecology The Chinese University of HongKongHong Kong 999077China Depart.ent.of Obst.t.ics and Gynaecology Queen Elizabeth HospitalHong Kong 999077China Depart.ent.of Obst.t.ics and Gynaecology United Christian HospitalHong Kong 999077China Depart.ent.of Obst.t.ics and Gynaecology Princess Margaret HospitalHong Kong 999077China Depart.ent.of Obst.t.ics and Gynaecology Tuen Mun HospitalHong Kong 999077China Depart.ent.of Obst.t.ics and Gynaecology Kwong Wah HospitalHong Kong 999077China Depart.ent.of Obst.t.ics and Gynaecology Pamela Youde Nethersole Eastern HospitalHong Kong 999077China Depart.ent.of Obst.t.ics and Gynaecology Queen Mary HospitalHong Kong 999077China

Object.ve:t. report.t.e clinical mat.rnal and fet.l out.omes of pregnant.women wit. coronavirus disease 2019(COVID-19),along wit. any associat.d pregnancy complicat.ons,in Hong Kong,China,and t. assess t.e impact.of COVID-19 vaccinat.on on t.ese ***:t.is prospect.ve regist.y-based observat.onal st.dy included pregnant.women who were recruit.d t.rough convenient.sampling and had a laborat.ry-confirmed severe acut. respirat.ry syndrome coronavirus 2 infect.on wit. a cycle t.reshold(Ct.value result.available on admission t. eight.local hospit.ls in Hong Kong,*** on clinical sympt.ms,laborat.ry result.,medical t.eat.ent.,delivery t.ming and mode,and pregnancy complicat.ons were ext.act.d from t.e Hospit.l Aut.orit.’s elect.onic medical record ***,fet.l,and pregnancy out.omes were compared bet.een unvaccinat.d pregnant.women wit. COVID-19 and t.ose who had received at.least.one dose of COVID-19 vaccine before *** cont.nuous variables and cat.gorical variables were analyzed using t.e Mann-Whit.ey U t.st.and t.e Pearson’s chi-squared t.st.respect.vely.A P value less t.an 0.05 was considered st.t.st.cally ***:A t.t.l of 164 pregnant.women were included,of whom 78(47.56%)were ***-19 was diagnosed before 28 weeks’gest.t.on in 30(18.29%),while 134(81.71%)were diagnosed at.or aft.r 28 weeks’***-t.o(37.80%)women received at.least.one dose of COVID-19 *** were no significant.differences bet.een vaccinat.d and unvaccinat.d groups in t.e t.me int.rval bet.een COVID-19 diagnosis and delivery,t.e Ct.value,and t.e gest.t.onal age at.infect.on onset.or delivery(P>0.05).t.e majorit. of women were sympt.mat.c at.diagnosis regardless of vaccinat.on st.t.s 55(88.71%)in vaccinat.d group vs.78(76.47%)in unvaccinat.d group(P=0.052).Sympt.ms did not.significant.y differ bet.een groups except.for cough(62.90%vs.47.06%,P=0.049).t.e overall rat. of severe COVID-19 in pregnant.women was *** t

关键词： COVID-19 Mat.rnal out.omes Fet.l out.omes Pregnancy complicat.ons Severe COVID-19

Have pat.ent. wit. esophagit.s got.an increased risk of adenocarcinoma? Result. from a populat.on-based st.dy

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World Journal of Gast.oent.rology 2005年第46期11卷 7290-7295页

作者： Seamus J Murphy Lesley A Anderson Brian t.Johnst.n Deirdre A Fit.pat.ick Pet.r RG Wat.on pauline Monaghan Liam J Murray BSc MB BCh MRCPResearch Regist.ar in Gast.oent.rology Northern Ireland Cancer Registry (NICR)Northern Ireland PhDResearch assist.nt NICRNorthern Ireland MD MRCPRoyal Vict.ria Hospit.l Grosvenor RoadBelfast BT12 6BANorthern Ireland Biost.t.st.ciansNICR Northern Ireland MD FRCPConsult.nt.Gast.oent.rologist. Royal Victoria HospitalGrosvenor RoadBelfast BT12 6BANorthern Ireland MBMFPHM Consultant/Senior lecturer in EpidemiologyDepartment of Epidemiology and Public HealthMulhouse BuildingGrosvenor RoadBelfast BT12 6BJNorthern Ireland

AIM: t. examine an increased risk of esophageal adenocarcinoma is rest.ict.d t. pat.ent. who develop Barret.'s esophagus or whet.er esophagit.s per se is a risk fact.r for ***: A populat.on-based cohort.of pat.ent. wit. hist.logical evidence of esophagit.s wit.out.Barret.'s esophagus was const.uct.d using elect.onic pat.ology report. relat.ng t. all esophageal biopsies in Nort.ern Ireland bet.een 1993 and 1996. Person-years of followup and incident.cases of esophageal cancer were calculat.d by linking t.e cohort.t. deat. files and t.e Nort.ern Ireland Cancer Regist.y records. St.ndardized incidence rat.os (SIR) were calculat.d for esophageal cancers (adenocarcinoma, squamous cell carcinoma (SCC), and hist.logically unspecified cancers).RESULt.: A t.t.l of 2 013 pat.ent. in t.e cohort.provided 13 559 pat.ent.years of follow-up (mean follow-up 6.7 years). None of t.e pat.ent. developed adenocarcinoma. t.ree pat.ent. developed SCC, and six developed hist.logically unspecified cancers. t.e SIR for all esophageal cancers and for SCC were 2.73 (95%CI 1.25-5.19) and 2.93 (95%CI 0.61-8.59), respect.vely. In a sensit.vit. analysis in which all unspecified esophageal cancers were t.eat.d as adenocarcinomas, t.e SIR for adenocarcinoma was 2.64 (0.97-5.75).CONCLUSION: t.e risk of adenocarcinoma is not.elevat.d in pat.ent. wit. hist.logical evidence of esophagit.s wit.out.Barret.'s esophagus; however, t.ese pat.ent. may have a moderat.ly increased risk of *** st.dies are required t. confirm t.ese findings,which suggest.t.at.Barret.'s esophagus, not.esophagit.s,is t.e key precursor lesion in t.e development.of adenocarcinoma.

关键词： Barret.'s esophagus Esophageal adenocardnoma Esophageal squamous cell carcinoma Esophagit.s Populat.on-based st.dy

Ant. program deat.-1/ant. program deat.-ligand 1 in digest.ve cancers

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World Journal of Gast.oint.st.nal Oncology 2015年第8期7卷 95-101页

作者： Eléonore de Guillebon pauline Roussille Eric Frouin David t.ugeron Medical Oncology Depart.ent Poitiers University Hospital Radiat.on Oncology Depart.ent Poitiers University Hospital Pat.ology Depart.ent Poitiers University Hospital David t.ugeron Laboratory Inflammation Tissus Epithéliaux et Cytokines EA 4331 Poitiers University Gast.oent.rology Depart.ent Poitiers University Hospital

Human t.mors t.nd t. act.vat. t.e immune syst.m regulat.ry checkpoint. as a means of escaping immunosurveillance. For inst.nce, int.ract.on bet.een program deat.-1(PD-1) and program deat.-ligand 1(PD-L1) will lead t.e act.vat.d t.cell t. a st.t. of anergy. PD-L1 is upregulat.d on a wide range of cancer cells. Ant.-PD-1 and ant.-PD-L1 monoclonal ant.bodies(m Abs), called immune checkpoint.inhibit.rs(ICIs), have consequent.y been designed t. rest.re t.cell act.vit.. Accumulat.ng dat. are in favor of an associat.on bet.een PD-L1 expression in t.mors and response t. t.eat.ent. A PD-L1 expression is present.in 30% t. 50% of digest.ve cancers. Mult.ple ant.-PD-1(nivolumab, pembrolizumab) and ant.-PD-L1 m Abs(MPDL3280A, Medi4736) are under evaluat.on in digest.ve cancers. Preliminary result. in met.st.t.c gast.ic cancer wit. pembrolizumab are highly promising and phase Ⅱ will st.rt.soon. In met.st.t.c colorect.l cancer(CRC), a phase Ⅲ t.ial of MPDL3280 A as maint.nance t.erapy will short.y be init.at.d. t.ials are also ongoing in met.st.t.c CRC wit. high immune t.cell infilt.at.on(i.e., microsat.llit. inst.bilit.). Major challenges are ahead in order t. det.rmine how, when and for which pat.ent. we should use t.ese ICIs. New radiologic crit.ria t. evaluat. t.mor response t. ICIs are await.ng prospect.ve validat.on. t.e opt.mal t.erapeut.c sequence and associat.on wit. cyt.t.xic chemot.erapy needs t. be est.blished. Finally, biomarker ident.ficat.on will be crucial t. select.on ofpat.ent. likely t. benefit.from ICIs.

关键词： Program deat.-1 Program deat.-ligand 1 Ant.body Digest.ve cancer