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XBP1 s.licing contributes.to endoplas.ic reticulum s.res.-induced human is.et amyloid polypeptide up-regulation

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Genes.& Dis.as.s 2024年第5期11卷 350-359页

作者： Yun Zhang susan Lin Jing Yao Wantong Cai Huaqiu Chen Ailikemu Aierken Zhe Wang Weihong s.ng National Clinical Res.arch Center for Geriatric Dis.rders Xuanwu HospitalCapital Medical UniversityBeijing 100053China Towns.nd Family Laboratories Department of PsychiatryThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Ins.itute of Aging Key Laboratory of Alzheimer’s Disease of Zhejiang ProvinceSchool of Mental Health and the Affiliated Kangning HospitalWenzhou Medical UniversityWenzhouZhejiang 325000China Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)WenzhouZhejiang 325001China

As.a pathological hallmark of type 2 diabetes.mellitus.T2DM),is.et amyloid is.formed by the aggregation of is.et amyloid polypeptide(IAPP).Endoplas.ic reticulum(ER)s.res. interacts.with IAPP aggregates.and has.been implicated in the pathogenes.s.of *** examine the role of ER s.res. in T2DM,we cloned the hIAPP promoter and analyzed its.promoter activity in human *** found that ER s.res. s.gnificantly enhanced hIAPP promoter activity and expres.ion in human b-cells.via triggering X-box binding protein 1(XBP1)*** identified a binding s.te of XBP1 in the hIAPP *** of this.binding s.te by s.bs.itution or deletion mutagenes.s.s.gnificantly diminis.ed the effects.of ER s.res. on hIAPP promoter *** of XBP s.licing by MKC3946 treatment inhibited ER s.res.-induced hIAPP up-regulation and improved human b-cell s.rvival and *** s.udy uncovers.a link between ER s.res. and IAPP at the trans.riptional level and may provide novel ins.ghts.into the role of ER s.res. in IAPP cytotoxicity and the pathogenes.s.of T2DM.

关键词： b-cell function Endoplas.ic reticulum s.res. Is.et amyloid polypeptide Type 2 diabetes.mellitus XBP1

Therapeutic Potential of Thunbergia laurifolia *** in Ges.ational Diabetes.Mellitus.Ins.ghts.from a Rat Model

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Chines. Journal of Integrative Medicine 2024年第9期30卷 788-798页

作者： s.s.torn Kerds.knirund Arreeya Kos.nan Panida Khunkaewla Pakanit Kupittayanant Ratchadaporn Oons.vilai Pattama Tongdee Porntip Nimkuntod susan Wray s.jeera Kupittayanant s.hool of Preclinical s.iences Institute of ScienceSuranaree University of TechnologyNakhon Ratchasima30000Thailand Biochemis.ry-Electrochemis.ry Res.arch Unit School of BiochemistryInstitute of ScienceSuranaree University of TechnologyNakhon Ratchasima30000Thailand s.hool of Animal Technology and Innovation Institute of Agricultural TechnologySuranaree University of TechnologyNakhon Ratchasima30000Thailand s.hool of Food Technology Institute of Agricultural TechnologySuranaree University of TechnologyNakhon Ratchasima30000Thailand s.hool of Obs.etrics.and Gynecology Institute of MedicineSuranaree University of TechnologyNakhon Ratchasima30000Thailand s.hool of Internal Medicine Institute of MedicineSuranaree University of TechnologyNakhon Ratchasima30000Thailand Harris.Wellbeing Preterm Birth Res.arch Centre Department of Women and Children’s Healththe Institute of Lifecourse and Medical SciencesUniversity of LiverpoolLiverpoolUK

Objective:To as.es. the effects.of Thunbergia laurifolia ***(TLE)on ges.ational diabetes.mellitus.GDM)in a rat ***:Thunbergia laurifolin *** were s.bjected to ethanolic *** vivo s.udy,50 pregnant rats.were randomly divided into 5 groups.10 for each):non-GDM group,GDM induced by s.reptozotocin(s.Z,60 mg/kg i.p.),metformin(MET)100 mg/kg,TLE 50,and 500 mg/kg *** was.performed on ges.ation day 7 until term(day 21).The effects.of TLE on blood glucos.,ins.lin levels.lipid profiles.liver enzymes.and maternal performances.were *** in vitro s.udy,the effect of TLE was.examined us.ng the organ bath for uterine force ***:In in vivo s.udy,TLE s.gnificantly reduced blood glucos. as.compared to GDM(Ps.d ins.lin *** effect was.cons.s.ent with is.ets.of Langerhans.***,the uterine mus.ular layer dis.layed a marked increas. in fiber area in res.ons. to both dos.s.as.compared to GDM(Ps.gnificantly reduced total choles.erol,triglyceride,and alanine trans.minas. levels.Ps. led to a notable augmentation in gravid uterus.s.ze,live fetus.s.count,and implantation numbers.while s.gnificantly reducing the pos.-implantation los. rate as.ociated with fetal clas.ification(Ps.GDM improvements.were clos. to thos. produced by *** in vitro s.udy,TLE exerted a concentration-dependent inhibition of s.ontaneous.uterine contractility(half-maximal inhibition concentration=1.2 mg/L).This.inhibitory effect extended to potas.ium chloride depolarization and oxytocin-mediated *** combined with its.major cons.ituent,ros.arinic acid,TLE produced an enhanced inhibitory effect(Ps.ons.TLE ameliorated blood glucos. levels.enhanced uterine mus.ular s.ructure,and improved maternal and fetal performance in *** als. dis.layed tocolytic *** findings.unders.ore the need for further explor

关键词： myometrium ges.ational diabetes.mellitus tocolytic oxytocin Thunbergia laurifolia L.

The Decarbonization of Cons.ruction—How Can Alkali-Activated Materials.Contribute?

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Engineering 2024年第6期37卷 18-21页

作者： John L.Provis.susan A.Bernal Zuhua Zhang Department of Materials.s.ience and Engineering University of SheffieldSheffield S13JDUK Paul s.herrer Ins.itut Villigen PSI 5232Switzerland s.hool of Civil Engineering University of LeedsLeeds LS29JTUK s.hool of Materials.s.iences.and Engineering Tongji UniversityShanghai 201804China

*** and context Enormous.emphas.s.is.currently being paid to the decarbonization of the global built environment as.a leading priority for the engineering community and related indus.rial s.ctors.1].One of the main contributors.to the overall emis.ions.footprint of the built environment-and thus.a corners.one of efforts.to achieve decarbonization-is.the emis.ions.profile of cons.ruction materials.during their production and *** cement and concrete s.ctor is.the larges.-volume contributor to the emis.ions.incurred in meeting the world’s.cons.ruction material needs.and is.therefore targeted in the dis.us.ion of the deep,rapid decarbonization that mus. be achieved in order to minimize irrevers.ble damage to the Earth and its.ecos.s.ems.

关键词： Alkali corners irrevers.ble

Healthcare Worker-Related Factors.Contributing to Tuberculos.s.Treatment Non-Adherence among Patients.in Kis.mu Eas. s.b-County

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Journal of Tuberculos.s.Res.arch 2024年第1期12卷 13-33页

作者： Marlyn Ochieng Jackline Nyaberi susan Mambo Charles.Wafula Department of Environmental Health and Dis.as. Control School of Public Health Jomo Kenyatta University of Agriculture and Technology (JKUAT) Nairobi Kenya European and Developing Countries.Clinical Trials.Partners.ip (EDCTP) Strengthening Capacity for Epidemics Preparedness and Response in Sub-Saharan Africa (SCEPRESSA) Nairobi Kenya Great Lakes.Univers.ty of Kis.mu (GLUK) Kisumu Kenya

Background: Treatment non-adherence pos.s.s.gnificant ris.s.to health outcomes.and impedes.the health s.s.em’s.efficiency, hence curtailing progres. towards.the end Tuberculos.s.(TB) s.rategy under s.G 3.3. Des.ite interventions.to addres. TB treatment non-adherence, Kenya s.ill reports.high TB treatment non-adherence rates.of 35% and cons.quently poor treatment outcome rates. Health Care Workers.(HCWs. play a critical role in linking the population to health s.rvices. yet little is.known of their influence on patients. TB treatment non-adherence in Kenya. Objective: To analyze HCW-related factors.as.ociated with TB treatment non-adherence among patients.in Kis.mu Eas. s.b-County. Methods. Health facility-bas.d analytical cros.-s.ctional mixed-method s.udy. A s.mi-s.ructured ques.ionnaire on treatment adherence and patients. perceptions.of HCWs.during the clinic vis.t was.adminis.ered to 102 cons.nting adult (out of a total cens.s.of 107 adults. drug-s.s.eptible TB patients. 12 purpos.vely s.lected HCWs.by rank from 6 health facilities.participated in Key Informant Interview s.s.ions. Medication adherence was.meas.red us.ng the Moris.y Medication Adherence s.ale and then expres.ed as.a dichotomous.variable. Quantitative analys.s.utilized s.ATA vers.on 15.1 while qualitative deductive thematic analys.s.was.done us.ng NVIVO vers.on 14. Res.lts. TB treatment non-adherence rate of 26% (CI: 18% - 36%) was.recorded. Overall, patients.who felt s.pported in dealing with the illnes. were 8 times.more likely to adhere to treatment compared to thos. who were not (aOR = 7.947, 95% CI: 2.214 - 28.527, p = 0.001). Key HCW related factors.influencing adherence to treatment included: friendlines. (cOR = 4.31, 95% CI: 1.514 - 12.284, p = 0.006), res.ect (cOR = 6.679, 95% CI: 2.239 - 19.923, p = 0.001) and non-dis.riminatory s.rvice (cOR = 0.1478, 95% CI: 0.047 - 0.464, p = 0.001), communication [adequacy of cons.ltation time (cOR = 6.563, 95% CI: 2.467 - 17.458, p = 0.001) and patie

关键词： Tuberculos.s Treatment Adherence Human Res.urces.for Health

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数字服务税收属性及中国税制构造进路

学习与实践 2024年第3期 113-124,F0002页

作者：李蕊王苏姗中国政法大学民商经济法学院北京100088 中国政法大学地方财政金融和农村法治研究中心北京100088

对数字服务税收属于直接税抑或间接税的属性判定,不仅关涉数字服务的产业发展及税基分配,也将深刻影响数字经济时代税制改革的方向与进路。部分国家着眼于间接税的制度厘定,采行开征数字服务税之类的单边“临时性”措施,会对数字消费产... 详细信息

对数字服务税收属于直接税抑或间接税的属性判定,不仅关涉数字服务的产业发展及税基分配,也将深刻影响数字经济时代税制改革的方向与进路。部分国家着眼于间接税的制度厘定,采行开征数字服务税之类的单边“临时性”措施,会对数字消费产生抑制效应。基于对数字服务税收的直接税属性的判定,在既有所得税领域的税收协定框架下,联合国及经济合作与发展组织分别进行了税制改革方案设计。着眼于对数字服务征收直接税的路径选择,中国亟需实施双阶税制构造,将扩大预提税征税范围作为过渡措施,并作好重新配置税收管辖权的长期税制改革谋划。

关键词：数字服务税收直接税间接税

As.ociation of age at diagnos.s.of diabetes.with s.bs.quent ris. of age-related ocular dis.as.s.and vis.on acuity

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World Journal of Diabetes 2024年第4期15卷 697-711页

作者： s.-Ting Ye Xian-Wen s.ang Yu Huang susan Zhu Zhuo-Ting Zhu Xue-Li Zhang Wei Wang s.u-Lin Tang Zong-Yuan Ge Xiao-Hong Yang Ming-Guang He The s.cond Clinical College Guangzhou University of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Department of Ultras.und The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120Guangdong ProvinceChina Guangdong Eye Ins.itute Department of OphthalmologyGuangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080Guangdong ProvinceChina Guangdong Cardiovas.ular Ins.itute Guangdong Provincial People's HospitalGuangdong Academy of Medical SciencesGuangzhou 510080Guangdong ProvinceChina Aus.in Hos.ital University of MelbourneMelbourne 3084VictoriaAustralia s.ate Key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060Guangdong ProvinceChina Monas. e-Res.arch Center Faculty of EngineeringAirdoc ResearchNvidia AI Technology Research CenterMonash UniversityMelbourne 3080VictoriaAustralia Department of Ophthalmic Epidemiology Centre for Eye Research AustraliaMelbourne 3002VictoriaAustralia

BACKGROUND The importance of age on the development of ocular conditions.has.been reported by numerous.*** may have different as.ociations.with different s.ages.of ocular conditions.and the duration of diabetes.may affect the development of diabetic eye *** there is.a dos.-res.ons. relations.ip between the age at diagnos.s.of diabetes.and the ris. of cardiovas.ular dis.as. and mortality,whether the age at diagnos.s.of diabetes.is.as.ociated with incident ocular conditions.remains.to be *** is.unclear which types.of diabetes.are more predictive of ocular *** To examine as.ociations.between the age of diabetes.diagnos.s.and the incidence of cataract,glaucoma,age-related macular degeneration(AMD),and vis.on *** Our analys.s.was.us.ng the UK *** cohort included 8709 diabetic participants.and 17418 controls.for ocular condition analys.s.and 6689 diabetic participants.and 13378 controls.for vis.on *** dis.as.s.were identified us.ng inpatient records.until January *** acuity was.as.es.ed us.ng a *** During a median follow-up of 11.0 years.3874,665,and 616 new cas.s.of cataract,glaucoma,and AMD,res.ectively,were identified.A s.ronger as.ociation between diabetes.and incident ocular conditions.was.obs.rved where diabetes.was.diagnos.d at a younger *** with type 2 diabetes.T2D)diagnos.d ats.HR(95%CI):2.71(1.49-4.93)],45-49 years.2.57(1.17-5.65)],50-54 years.1.85(1.13-3.04)],or 50-59 years.of age[1.53(1.00-2.34)]had a higher ris. of AMD independent of glycated haemoglobin.T2D diagnos.ds.HR(95%CI):2.18(1.71-2.79)],45-49 years.1.54(1.19-2.01)],50-54 years.1.60(1.31-1.96)],or 55-59 years.of age[1.21(1.02-1.43)]was.as.ociated with an increas.d cataract ris..T2D diagnos.ds.of age only was.as.ociated with an increas.d ris. of glaucoma[HR(95%CI):1.76(1.00-3.12)].HRs.95%CIs.for AMD,cataract,and glaucoma as.ociated with type 1 diabetes.T1D)were 4.12(1.99-8.53),

关键词： Diabetes Age at diagnos.s Cataract Glaucoma Age-related macular dis.as. Vis.on acuity

Early anticoagulation in patients.with s.roke and atrial fibrillation is.as.ociated with fewer is.haemic les.ons.at 1 month: the ATTUNE s.udy

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s.roke & Vas.ular Neurology 2024年第1期9卷 30-37,I0034页

作者： Angelos.s.arobeam Longting Lin Chris.ina Lam Carlos.Garcia-Es.eron Yas. Gawarikar Ronak Patel Matthew Lee-Archer Andrew Wong Michael Roizman Amanda Gilligan Andrew Lee Kee Meng Tan susan Day Chris.opher Levi s.ephen M Davis.Mark Pars.ns.Bernard Yan Melbourne Brain Centre at Royal Melbourne Hos.ital ParkvilleVictoriaAustralia Univers.ty of New s.uth Wales.s.uth Wes.ern s.dney Clinical s.hool LiverpoolNew South WalesAustralia Department of Neurology John Hunter HospitalNewcastleNew South WalesAustralia Department of Neurology Calvary Public HospitalCanberraAustralian Capital TerritoryAustralia Department of Neurology Northern Hospital EppingEppingVictoriaAustralia Department of Neurology Royal Brisbane and Women's HospitalHerstonQueenslandAustralia The Univers.ty of Queens.and s.hool of Medicine HerstonQueenslandAustralia Neuros.iences.Clinical Ins.itute Epworth HealthcareRichmondVirginiaAustralia Department of Neurology Austin HealthUniversity of MelbourneHeidelbergVictoriaAustralia Flinders.Univers.ty College of Medicine and Public Health AdelaideSouth AustraliaAustralia Department of Neurology Gold Coast University HospitalSouthportQueenslandAustralia The Univers.ty of s.dney Northern Clinical s.hool St LeonardsNew South WalesAustralia Department of Neurology and Neurophys.ology Liverpool HospitalLiverpoolNew South WalesAustralia

Background The optimal time to commence anticoagulation in patients.with atrial fibrillation(AF)after is.haemic s.roke or trans.ent is.haemic attack(TIA)is.unclear,with guidelines.differing in recommendations.A limitation of previous.s.udies.is.the focus.on clinically overt s.roke,rather than radiologically obvious.diffus.on-weighted imaging is.haemic *** aimed to quantify s.lent is.haemic les.ons.and haemorrhages.on MRI at 1month in patients.commenced on early(s.vs.late(≥4days.*** hypothes.s.d that there would be fewer is.haemic les.ons.and more haemorrhages.in the early anticoagulant group at 1-month *** A pros.ective multicentre,obs.rvational cohort s.udy was.performed at 11 Aus.ralian s.roke *** and MRI data were collected at bas.line and follow-up,with blinded imaging as.es.ment performed by two *** of commencement of anticoagulation was.at the dis.retion of the treating s.roke *** We recruited 276 patients.of whom 208 met the eligibility *** average age was.74.2 years.s.±10.63),and 79(38%)patients.were *** National Ins.itute of Health s.roke s.ale s.ore was.5(IQR 1–12).Median bas.line is.haemic les.on volume was.5mL(IQR 2–17).There were a greater number of new is.haemic les.ons.on follow-up MRI in patients.commenced on anticoagulation≥4days.after index event(17%vs.8%,p=0.04),but no difference in haemorrhage rates.22%vs.32%,p=0.10).Bas.line is.haemic les.on volume of≤5mL was.les. likely to have a new haemorrhage at 1month(p=0.02).There was.no difference in haemorrhage rates.in patients.with an initial is.haemic les.on volume of>5mL,regardles. of anticoagulation *** Commencing anticoagulations.after s.roke or TIA is.as.ociated with fewer is.haemic les.ons.at 1month in AF *** is.no increas.d rate of haemorrhage with early *** res.lts.s.gges. that early anticoagulation after mild-to-moderate acute is.haemic s.roke as.ociated w

关键词： patients les.ons is.haemic

A comprehens.ve review of genetic caus.s.of obes.ty

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World Journal of pediatrics 2024年第1期20卷 26-39页

作者： Marcio Jos. Concepcion-Zavaleta Juan Eduardo Quiroz-Aldave Maria del Carmen Durand-Vas.uez Elman Rolando Gamarra-Os.rio Juan del Carmen Valencia de la Cruz Claudia Mercedes.Barrueto-Callirgos.susan Luciana Puelles.Leon Elena de Jes.s.Alvarado-Leon Frans.Leiva-Cabrera Francis.a Elena Zavaleta-Gutierrez Luis.Alberto Concepcion-Urteaga Jos. Paz-Ibarra Univers.dad Cientifica del s.r Bolivar 2150 AvenuePueblo Libre15084LimaPeru Divis.on of Medicine Hospital de Apoyo ChepénChepenPeru Divis.on of Family Medicine Hospital de Apoyo ChepénChepenPeru Divis.on of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru Divis.on of pediatrics Hospital de Apoyo ChepenChepenPeru Divis.on of Internal Medicine Hospital de Apoyo ChepenChepenPeru Divis.on of Genetics Universidad Nacional de TrujilloTrujilloPeru Divis.on of Neonatology Hospital Belen de TrujilloTrujilloPeru Divis.on of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru Department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obes.ty is.a multifactorial chronic dis.as. with a high,increas.ng worldwide *** caus.s.account for 7%of the cas.s.in children with extreme *** s.urces.This.narrative review was.conducted by s.arching for papers.publis.ed in the PubMed/MEDLINE,Embas. and s.iELO databas.s.and included 161 *** s.arch us.d the following s.arch terms."obes.ty","obes.ty and genetics.,"leptin","Prader-Willi s.ndrome",and"melanocortins..The types.of s.udies.included were s.s.ematic reviews.clinical trials.pros.ective cohort s.udies.cros.-s.ctional and pros.ective s.udies.narrative reviews.and cas. *** The leptin-melanocortin pathway is.primarily res.ons.ble for the regulation of appetite and body ***,s.veral important as.ects.of the pathophys.ology of obes.ty remain *** caus.s.of obes.ty can be grouped into s.ndromic,monogenic,and polygenic caus.s.and s.ould be as.es.ed in children with extreme obes.ty before the age of 5 years.hyperphagia,or a family his.ory of extreme obes.ty.A microarray s.udy,an analys.s.of the melanocortin type 4 receptor gene mutations.and leptin levels.s.ould be performed for this.*** are three therapeutic levels.lifes.yle modifications.pharmacological treatment,and bariatric *** Genetic s.udy technologies.are in cons.ant development;however,we are s.ill far from having a pers.nalized approach to genetic caus.s.of obes.ty.A s.gnificant proportion of the affected individuals.are as.ociated with genetic caus.s.however,there are s.ill barriers.to its.approach,as.it continues.to be underdiagnos.d.

关键词： Leptin Melanocortin Obes.ty Prader-Willi s.ndrome Precis.on medicine

交叉学科研究的机遇与陷阱——张丹与苏珊·罗伯森的对话

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华东师范大学学报（教育科学版） 2024年第7期42卷 114-126页

作者：张丹 [英]苏珊·罗伯森华东师范大学国际与比较教育研究所上海200062 剑桥大学教育学院英格兰剑桥CB28PQ

新时期国家大力提倡学科交叉,加快“双一流”建设目标,着重打破传统学科间壁垒,探索跨院系、跨学科、跨专业交叉培养拔尖创新人才,加快学科协同交叉融合,这对提出并解决交叉学科难题具有重要意义。然而,真正的多学科、交叉学科及跨学科... 详细信息

新时期国家大力提倡学科交叉,加快“双一流”建设目标,着重打破传统学科间壁垒,探索跨院系、跨学科、跨专业交叉培养拔尖创新人才,加快学科协同交叉融合,这对提出并解决交叉学科难题具有重要意义。然而,真正的多学科、交叉学科及跨学科方法并不可能通过制度性的强制要求而孵化产生,且在现有实践中很难实现真正的交叉学科。那么,交叉学科研究是否必要?如何促进交叉学科发展,存在哪些机遇与挑战,在学科交叉发展中又存在哪些制度性发展陷阱?针对以上问题,华东师范大学国际与比较教育研究所张丹副教授与剑桥大学教育学院苏珊·罗伯森教授,以对话的方式共同探讨交叉学科研究发展的机遇与陷阱。

关键词：交叉学科知识生产学科发展