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Inhibition of Wnt signaling by Frizzled7 antibody-coated nanoshells sensitizes triple-negative breast cancer cells to the autophagy regulator chloroquine

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Nano Research 2020年第6期13卷 1693-1703页

作者： Jianxin Wang Megan N.Dang emily s.day Department of Biomedical Engineering University of DelawareNewarkDE19716USA Department of Materials science and Engineering University of DelawareNewarkDE19716USA Helen F.Graham Cancer Center&Research Institute NewarkDE19713USA

Nano Research volume 13,pages1693–1703(2020)Cite this article 137 Accesses 6 Altmetric Metrics details Abstract Despite improvements in our understanding of the biology behind triple-negative breast cancer(TNBC),it remains a devastating disease due to lack of an effective targeted *** Wnt signaling is a promising strategy to combat TNBC because Wnt signaling drives TNBC progression,chemoresistance,and ***,Wnt inhibition can lead to upregulation of autophagy,which confers therapeutic *** provides an opportunity for combination therapy,as autophagy inhibitors applied concurrently with Wnt inhibitors could increase treatment ***,we applied the autophagy inhibitor chloroquine(CQ)to TNBC cells in combination with Frizzled7 antibody-coated nanoshells(FZD7-Ns)that suppress Wnt signaling by blocking Wnt ligand/FZD7 receptor interactions,and evaluated this dual treatment in *** found that FZD7-Ns can inhibit Axin2 and CyclinD1,two targets of canonical Wnt signaling,and increase the expression of LC3,an autophagy *** FZD7-Ns and CQ are applied together,they reduce the expression of several stemness genes in TNBC cells,leading to inhibition of TNBC cell migration and ***,co-delivery of FZD7-Ns and CQ is more effective than either therapy alone or the combination of CQ with free FZD7 *** demonstrates that the nanocarrier design is important to its therapeutic ***,these findings indicate that combined regulation of Wnt signaling and autophagy by FZD7-Ns and CQ is a promising strategy to combat TNBC.

关键词： nanomedicine nanoparticles combination therapy antibody delivery cancer stem cells

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Acute and chronic excitotoxicity in ischemic stroke and late-onset Alzheimer's disease

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Neural Regeneration Research 2025年第7期20卷 1981-1988页

作者： shan Ping Yu emily Choi Michael QJiang Ling Wei Department of Anesthesiology Emory University School of MedicineAtlantaGAUSA Center for Visual and Neurocognitive Rehabilitation Atlanta Veterans Affairs Medical CenterDecaturGAUSA

stroke and Alzheimer's disease are common neurological disorders and often occur in the same *** comorbidity of the two neurological disorders represents a grave health threat to older *** review presents a brief background of the development of novel concepts and their clinical *** activity of glutamatergic N-methyl-D-aspartate receptors and N-methyl-D-aspartate receptor-mediated Ca^(2+)influx is critical for neuronal *** ischemic insult induces prompt and excessive glutamate release and drastic increases of intracellular Ca^(2+)mainly via N-methyl-D-aspartate receptors,particularly of those at the extrasynaptic *** Ca^(2+)-evoked neuronal cell death in the ischemic core is dominated by necrosis within a few hours and days known as acute ***,mild but sustained Ca^(2+)increases under neurodegenerative conditions such as in the distant penumbra of the ischemic brain and early stages of Alzheimer's disease are not immediately toxic,but gradually set off deteriorating Ca^(2+)-dependent signals and neuronal cell loss mostly because of activation of programmed cell death *** on the Ca^(2+)hypothesis of Alzheimer's disease and recent advances,this Ca^(2+)-activated“silent”degenerative excitotoxicity evolves from years to decades and is recognized as a unique slow and chronic *** N-methyl-D-aspartate receptor subunit GluN3A,primarily at the extrasynaptic site,serves as a gatekeeper for the N-methyl-D-aspartate receptor activity and is neuroprotective against both acute and chronic *** stroke and Alzheimer's disease,therefore,share an N-methyl-D-aspartate receptor-and Ca^(2+)-mediated mechanism,although with much different time *** is thus proposed that early interventions to control Ca^(2+)homeostasis at the preclinical stage are pivotal for individuals who are susceptible to sporadic late-onset Alzheimer's disease and Alzheimer's disease-related

关键词： Ca^(2+)hypothesis cognitive deficits hyperactivity late-onset Alzheimer's disease neurodegeneration N-methyl-D-aspartate receptors N-methyl-D-aspartate receptor subunits pathogenesis preventive treatment

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Excess non-COVID-19-related mortality among inflammatory bowel disease decedents during the COVID-19 pandemic

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World Journal of Gastroenterology 2024年第20期30卷 2677-2688页

作者： sarah Rotondo-Trivette Xin-Yuan He Jamil s samaan Fan Lv emily Truong Michaela Juels Anthony Nguyen Xu Gao Jian Zu Yee Hui Yeo Fan-Pu Ji Gil Y Melmed Department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States Department of Infectious Disease The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Karsh Division of Gastroenterology and Hepatology Department of Medicine Cedars-Sinai Medical CenterLos AngelesCA 90048United States school of Mathematics and statistics Xi’an Jiaotong UniversityXi’an 710049Shaanxi ProvinceChina David Geffen school of Medicine University of CaliforniaLos AngelesLos AngelesCA 90095United States Division of Gastroenterology The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina National and Local Joint Engineering Research Center of Biodiagnosis and Biotherapy The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina Key Laboratory of surgical Critical Care and Life support(Xi’an Jiaotong University) Ministry of EducationXi’an 710004Shaanxi ProvinceChina

BACKGROUND The coronavirus disease 2019(COVID-19)pandemic disrupted healthcare in the United *** To investigate COVID-19-related and non-COVID-19-related death and characteristics associated with excess death among inflammatory bowel disease(IBD)*** We performed a register-based study using data from the National Vital statistics system,which reports death data from over 99%of the United states population,from January 1,2006 through December 31,***-related deaths among adults 25 years and older were stratified by age,sex,race/ethnicity,place of death,and primary cause of *** and actual age-standardized mortality rates(AsMRs)per 100000 persons were *** 49782 IBD-related deaths occurred during the study ***-COVID-19-related deaths increased by 13.14%in 2020 and 18.12%in 2021[2020 AsMR:1.55 actual vs 1.37 predicted,95%confidence interval(CI):1.26-1.49;2021 AsMR:1.63 actual vs 1.38 predicted,95%CI:1.26-1.49].In 2020,non-COVID-19-related mortality increased by 17.65%in ulcerative colitis(UC)patients between the ages of 25 and 65 and 36.36%in non-Hispanic black(NHB)Crohn’s disease(CD)*** the pandemic,deaths at home or on arrival and at medical facilities as well as deaths due to neoplasms also *** IBD patients suffered excess non-COVID-19-related death during the *** death was associated with younger age among UC patients,and with NHB race among CD *** death at home or on arrival and due to neoplasms suggests that delayed presentation and difficulty accessing healthcare may have led to increased IBD mortality.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease COVID-19 Excess death Race sex Disparities

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Long-term follow-up of kidney transplant recipients admitted to a tertiary care transplant center with sARs-CoV-2

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World Journal of Virology 2024年第2期13卷 87-95页

作者： emily E Zona Mina L Gibes Asha s Jain Jeannina A smith Jacqueline M Garonzik-Wang Didier A Mandelbrot sandesh Parajuli Division of Nephrology Department of MedicineUniversity of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States Department of Infectious Disease University of Wisconsin Hospital and ClinicsMadisonWI 53705United States Department of surgery University of WisconsinMadisonWI 53705United States Department of Medicine University of Wisconsin School of Medicine and Public HealthMadisonWI 53705United States Department of Medicine University of Wisconsin School of Medicine and Public HealthUniversity of Wisconsin MadisonMadisonWI 53705United States

BACKGROUND Kidney transplant recipients(KTR)are at risk of severe coronavirus disease 2019(COVID-19)disease and mortality after severe acute respiratory syndrome coronavirus 2(sARs-CoV-2)*** predicted that hospitalization for COVID-19 and subsequent admission to the intensive care unit(ICU)would yield worse outcomes in *** was stratified by ICU *** of interest included risk factors for ICU admission and mortality,length of stay(LOs),respiratory symptoms at admission,all-cause graft failure at the last follow-up,and death related to *** 96 KTRs were hospitalized for sARs-COV-2 infection.21(22%)required ICU *** ICU group had longer hospital LOs(21.8 vs 8.6 days,Ps 31%,Pse admitted to the ICU,76%had death at last-follow up,and 71%had death related to *** factors for ICU admission included male sex(aHR:3.11,95%CI:1.04-9.34;P=0.04).Risk factors for all-cause mortality and COVID-19-related mortality included ICU admission and advanced age at sARs-CoV-2 *** was highest within a month of COVID-19 diagnosis,with the ICU group having increased risk of all-cause(aHR:11.2,95%CI:5.11-24.5;PsION ICU admission conferred an increased risk of mortality,graft failure,and longer ***-fifth of those hospit-alized died of COVID-19,reflecting the impact of COVID-19-related morbidity and mortality among KTRs.

关键词： Kidney transplants sARs-CoV-2 Intensive care unit admission Outcomes Graft failure

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Advances in targeted nanotherapeutics： From bioconjugation to biomimicry

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Nano Research 2018年第10期11卷 4999-5016页

作者： Danielle M. Valcourt Jenna Harris Rachel s. Riley Megan Dang Jianxin Wang emily s. day 161 Colburn L ab Department of Biomedical Engineering University of Delaware Newark DE 19716 USA 201 DuPont Hall Department of Materials Science & Engineering University o f Delaware Newark DE 79716 USA 4701 Ogletown stanton Road Helen F. Graham Cancer Center & Research Institute Newark DE 19713 USA

since the emergence of cancer nanomedicine, researchers have had intense interest in developing nanoparticles （NPs） that can specifically target diseased sites while avoiding healthy tissue to mitigate the off-target effects seen with conventional treatments like chemotherapy. Initial endeavors focused on the bioconjugation of targeting agents to NPs, and more recently, researchers have begun to develop biomimetic NP platforms that can avoid immune recognition to maximally accumulate in tumors. In this review, we describe the advantages and limitations of each of these targeting strategies. First, we review developments in bioconjugation strategies, where NPs are coated with biomolecules such as antibodies, aptamers, peptides, and small molecules to enable cell-specific binding. While bioconjugated NPs offer many exciting features and have improved pharmacokinetics and biodistribution relative to unmodified NPs, they are still recognized by the body as ＂foreign＂, resulting in their clearance by the mononuclear phagocytic system （MPs）. To overcome this limitation, researchers have recently begun to investigate biomimetic approaches that can hide NPs from immune recognition and reduce clearance by the MPs. These biomimetic NPs fall into two distinct categories： synthetic NPs that present naturally occurring structures, and NPs that are completely disguised by natural structures. Overall bioconjugated and biomimetic NPs have substantial potential to improve upon conventional treatments by reducing off-target effects through site-specific delivery. and they show great promise for future standards of care. Here, we provide a summary of each strategy, discuss considerations for their design moving forward, and highlight their potential clinical impact on cancer therapy.

关键词： targeting nanoparticles cancer biomimicry bioconjugation delivery

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Female Infertility and Obesity across the United states—A Geographic Cross-sectional Analysis

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Advances in Reproductive sciences 2024年第3期12卷 179-189页

作者： Raegan Abadie emily M. Dantes Jennifer H. shaw Dani Zoorob Health sciences Center in shreveport Louisiana State University Shreveport LA USA Department of Biomedical sciences Philadelphia College of Osteopathic Medicine South Georgia Moultrie GA USA Health sciences Center in shreveport Department of Obstetrics and Gynecology Louisiana State University Shreveport LA USA

This cross-sectional study investigates a connection between female infertility and obesity across various regions of the United states, utilizing data from the NIH’s “All of Us” Researcher Workbench. Analysis suggested that the southern region exhibited the highest percentage of concurrently infertile and obese females at 32.3%, in contrast to the lowest in the Western region at 28.7%. The findings underscore the significant regional disparities in obesity-related infertility, particularly in medically underserved areas where healthcare access is limited. The study highlights the urgent need for targeted public health interventions, particularly in the southern United states, to address the rising prevalence of obesity and its impact on infertility. Further, these results advocate for enhanced public health education and policies aimed at improving healthcare accessibility, with the goal of mitigating the adverse effects of obesity on reproductive health.

关键词： Female Infertility Medical Deserts Obesity south

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利用探针跳跃式扫描离子电导显微镜技术揭示结直肠癌单细胞层面对H_(2)O_(2)良性应激的动态响应

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science Bulletin 2024年第12期69卷 1909-1919页

作者：王东 emily Woodcock 杨羲 Hiromi Nishikawa Elena V.sviderskaya Masanobu Oshima Christopher Edwards 张彦军 Yuri Korchev WPI Nano Life science Institute(WPI-Nano LsI) Kanazawa UniversityKanazawa 920-1192Japan Department of Medicine Imperial College LondonLondon W120NNUnited Kingdom Cell Biology Research Centre Molecular and Clinical Sciences Research InstituteSt George’sUniversity of LondonLondon SW170REUnited Kingdom

Colorectal cancer(CRC),a widespread malignancy,is closely associated with tumor microenvironmental hydrogen peroxide(H_(2)O_(2))*** clinical trials targeting H_(2)O_(2)for cancer treatment have revealed its paradoxical role as a promoter of cancer *** the dynamics of cancer cell H_(2)O_(2)eustress at the single–cell level is *** this study,non–contact hopping probe mode scanning ion conductance microscopy(HPICM)with high-sensitive Pt–functionalized nanoelectrodes was employed to measure dynamic extracellular to intracellular H_(2)O_(2)gradients in individual colorectal cancer Caco–*** explored the relationship between cellular mechanical properties and H_(2)O_(2)*** to 0.1 or 1 mmol/L H_(2)O_(2)eustress increased the extracellular to intracellular H_(2)O_(2)gradient from 0.3 to 1.91 or 3.04,***,cellular F–actin–dependent stiffness increased at 0.1 mmol/L but decreased at 1 mmol/L H_(2)O_(2)*** H_(2)O_(2)–induced stiffness modulated AKT activation positively and glutathione peroxidase 2(GPX2)expression *** findings unveil the failure of some H_(2)O_(2)-targeted therapies due to their ineffectiveness in generating H_(2)O_(2),which instead acts eustress to promote cancer cell *** research also reveals the complex interplay between physical properties and biochemical signaling in cancer cells'antioxidant defense,illuminating the exploitation of H_(2)O_(2)eustress for survival at the single–cell *** GPX and/or catalase(CAT)enhances the cytotoxic activity of H_(2)O_(2)eustress against CRC cells,which holds significant promise for developing innovative therapies targeting cancer and other H_(2)O_(2)-related inflammatory diseases.

关键词： sPM Nanoprobe Nanobiology sECM ROs stiffness

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Continuity of care by a primary midwife(caseload midwifery):a cost analysis using results from the COsMOs randomised controlled trial

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Gynecology and Obstetrics Clinical Medicine 2024年第2期4卷 94-101页

作者： emily J Callander Hannah Jackson Helen L McLachlan Mary-Ann Davey Della A Forster University of Technology sydney SydneyNew South WalesAustralia The Royal Women's Hospital MelbourneVictoriaAustralia Faculty of Health University of Technology SydneyBroadwayNew South WalesAustralia Judith Lumley Centre La Trobe UniversityMelbourneVictoriaAustralia school of Nursing and Midwifery a Trobe UniversityMelbourneVictoriaAustralia Department of Obstetrics and Gynaecology Monash UniversityClaytonVictoriaAustralia

Introduction Caseload midwifery(continuity of midwifery carer)offers benefits including lower caesarean section rates,lower risks of preterm birth and stilbirth,and improved maternal satisfaction of *** these advantages,concerns about additional costs hinder widespread *** study examinesthecost of caseload midwifery compared with standard maternity care from the perspective of both public hospitals and public *** A cost analysis was conducted using data from a randomised controlled trial of 2314 low-risk pregnant women in Melbourne,*** randomised to caseload care received antenatal,intrapartum and postpartum care from a primary midwife,with some care provided by a‘back-up'*** in standard care received midwifery-led care with varying levels of continuity,junior obstetric care or community-based medical *** cost analysis compared differences in mean costs of health resources to public hospitals and to public ***,a budget impact analysis estimated total costs to the health system between 2023 and *** For public hospitals,there was no significant difference in overall costs between women receiving caseload midwifery(n=1146)versus standard care(n=1151)($sA12363(sD:$A4967)vs$A12323(sD:$A7404);p=0.85).Conversely,public funders incurred lower expenditures for women receiving caseload midwifery($A20330(sD:$A8312))versus standard care($A21637(sD:$A11818);psis estimated savings of sA625million to the health system over the next 5 years with expanded access to caseloadmidwifery *** Caseloadmidwifery in low-risk women is cost-neutral to public hospitals and cost-saving to public *** abstract Continuity of midwifery for low-risk women reduces costs to public funders,with no additional costs to hospitals.

关键词： random continuity Continuity

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Dietary(poly)phenol intake is associated with cardiometabolic health parameters in adolescents

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Food science and Human Wellness 2024年

作者： emily P.Laveriano-santos sara Castro-Barquero Camila Arancibia-Riveros Ana María Ruiz-León Rosa Casas Ramón Estruch Patricia Bodega Mercedes de Miguel Amaya de Cos-Gandoy Jesús Martínez-Gómez Gloria santos-Beneit Juan M.Fernández-Alvira Rodrigo Fernández-Jiménez Rosa M.Lamuela-Raventós Anna Tresserra-Rimbau The Zena and Michael A.Wiener Cardiovascular Institute， Icahn school of Medicine at Mount sinai Department de Nutrició， Ciències de l'Alimentació I Gastronomia， XIA， Facultat de Farmàcia i Ciències de l'alimentació， Institut de Recerca en Nutrició i seguretat Alimentària (INsA-UB)， Universitat de Barcelona Department of Internal Medicine， Hospital Clínic， Institutd'Investigacions Biomèdiques August Pi I sunyer (IDIBAPs)， University of Barcelona Consorcio CIBER， M.P.Fisiopatología de la Obesidad y Nutrición (CIBERObn)， Instituto de salud Carlos III (IsCIII) Mediterranean Diet Foundation 5. Foundation for science， Health and Education (sHE) 6. Centro Nacional de Investigaciones Cardiovasculares (CNIC) CIBER de Enfermedades Cardiovasculares (CIBERCV) 9. Hospital Universitario Clínico san Carlos

Background: The protective role of (poly)phenols against metabolic disorders has been extensively studied in adults but not in ***: To assess associations of dietary (poly)phenols and their subclasses with cardiometabolic health parameters in adolescents. Methods: A cross-sectional study was conducted in 944 individuals aged 11 to 14 years enrolled in the sI! Program for secondary schools trial (NCT03504059). (Poly)phenol intake was assessed using semi-quantitative food frequency questionnaires and the Phenol-Explorer database. The measured cardiometabolic parameters were waist circumference (WC) age-sex z-score， blood pressure (BP) age-sex z-score， blood glucose (BG)， triglycerides (TG)， and high-density lipoprotein cholesterol (HDL-c). Multilevel mixed-effect linear regression models were applied to examine the association between (poly)phenol quintiles and cardiometabolic health ***: Compared to the lowest quintile， adolescents in the highest quintile of total (poly)phenol intake had lower WC z-scores (β=-0.09， 95%CI=-0.09;-0.08， P-for trend=0.002)， mean arterial pressure z-scores (β =-0.11， 95%CI=-0.12;-0.09， P-for trend=0.206)， and HDL-c (β=-1.52， 95%CI=-2.90;-0.14， P-for trend=0.108)， after multivariable adjustment. The WC z-scores (β=-0.11， 95%CI=-0.19;-0.03， P-for trend=0.013) and HDL-c (β=-2.16， 95%CI=-3.78;-0.53， P-for trend=0.046) were lower in the highest quintile of flavonoid intake compared to the lowest quintile. The highest quintile of phenolic acid intake was associated with a lower WC z-score (β=-0.14， 95%CI=-0.26;-0.02， P-for trend=0.011) and TG levels (β=-8.83， 95%CI=-12.37;-5.30， P-for trend st quintile of stilbene intake with lower BG (β=-1.83， 95%CI= -3.103;-0.64， P-for trend st quintile. Conclusion: A higher intake of (poly)phenols， espe

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相爱相杀的文坛两生花 A.s.拜厄特：《占有》与它扭转的一切

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世界博览 2024年第1期 63-65+62页

作者：赵小斌 emily

2023年11月16日，英国著名作家、学者A.s.拜厄特在亲人陪伴下于家中安详离世，享年87岁。拜厄特曾被《泰晤士报》评为“1945年以来英国50位伟大作家”之一，这位出身于文学世家有着浓郁的剑桥背景和学术底色的才女，一直以来备受全球读...

2023年11月16日，英国著名作家、学者A.s.拜厄特在亲人陪伴下于家中安详离世，享年87岁。拜厄特曾被《泰晤士报》评为“1945年以来英国50位伟大作家”之一，这位出身于文学世家有着浓郁的剑桥背景和学术底色的才女，一直以来备受全球读者的喜爱。拜厄特几乎所有重要作品都有汉译本，她也多次来中国进行出版和学术交流，在北京、上海、南京等地给诸多后辈作家和普通读者留下了深刻印象。

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