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The multidrug resistance transporter P-glycoprotein confers resistance to ferroptosis inducers

Cancer Drug Resistance 2023年第3期6卷 468-480页

作者： William J.E.Frye Lyn m.Huff Josém.González Dalmasy Paula Salazar rachel m.carter Ryan T.Gensler Dominic Esposito Robert W.Robey Suresh V.Ambudkar michael m.Gottesman Laboratory of Cell Biology Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892USA Protein Expression Laboratory Frederick National Laboratory for Cancer ResearchLeidos Biomedical ResearchIncFrederickMD 21704USA

Aim:Ferroptosis is a non-apoptotic form of cell death caused by lethal lipid *** small molecule ferroptosis inducers(FINs)have been reported,yet little information is available regarding their interaction with the ATP-binding cassette(ABC)transporters P-glycoprotein(P-gp,ABCB1)and *** thus sought to characterize the interactions of FINs with P-gp and ABCG2,which may provide information regarding oral bioavailability and brain penetration and predict drug-drug ***:Cytotoxicity assays with ferroptosis-sensitive A673 cells transfected to express P-gp or ABCG2 were used to determine the ability of the transporters to confer resistance to FINs;confirmatory studies were performed in OVCAR8 and NCI/ADR-RES *** ability of FINs to inhibit P-gp or ABCG2 was determined using the fluorescent substrates rhodamine 123 or purpuin-18,***:P-gp overexpression conferred resistance to FIN56 and the erastin derivatives imidazole ketone erastin and piperazine erastin.P-gp-mediated resistance to imidazole ketone erastin and piperazine erastin was also reversed in UO-31 renal cancer cells by CRISPR-mediated knockout of *** FINs mL-162,GPX inhibitor 26a,and PACmA31 at 10µm were able to increase intracellular rhodamine 123 fluorescence over 10-fold in P-gp-expressing mDR-19 *** inhibitor 26a was able to increase intracellular purpurin-18 fluorescence over 4-fold in ABCG2-expressing R-5 ***:Expression of P-gp may reduce the efficacy of these FINs in cancers that express the transporter and may prevent access to sanctuary sites such as the *** ability of some FINs to inhibit P-gp and ABCG2 suggests potential drug-drug interactions.

关键词： Ferroptosis drug resistance P-glycoprotein ABCG2

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Disaster Awareness and Preparedness Among Older Adults in Canada Regarding Floods, Wildfires, and Earthquakes

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International Journal of Disaster Risk Science 2024年第2期15卷 198-212页

作者： Evalyna Bogdan rachel Krueger Julie Wright Kyle Woods Shaieree Cottar School of Administrative Studies Disaster and Emergency Management ProgramYork UniversityTorontoOntario M3J 1P3Canada Department of Geography and Environmental management University of WaterlooWaterlooOntario N2L 3G1Canada Partners for Action Faculty of EnvironmentUniversity of WaterlooWaterlooOntario N2L 3G1Canada

Older adults are significantly impacted by natural hazards and disasters that are exacerbated by climate change. Understanding their awareness and preparedness is essential for enhancing disaster resilience. This study investigated the attitudes, actions, and recommendations of older adults regarding natural hazards that pose risks in their geographic area—specifically floods, wildfires, and/or earthquakes in Canada. methods for this study included survey and focus groups with older adults(n = 161 and n = 10, respectively) and other high-risk groups from across Canada, that are vulnerable to these natural hazards. The main findings from this study are that current awareness and preparedness among older adults is low, though stronger perceptions of risks are associated with risks specific to geographic locations where respondents live. Several barriers, such as hazard vulnerability misperceptions, cost-related reasons, and lack of hazard awareness have resulted in low awareness and preparedness among these populations. The two main recommendations arising from this research are:(1) improve awareness and preparedness with tailor-made emergency preparedness materials for older adults;and(2) adopt community-based approaches to disaster preparedness through existing community groups to strengthen social connections with a focus on locally specific hazards. The findings from this research can be applied to other hazards, including heatwaves and pandemics.

关键词： Canada Community-based disaster risk management Disaster awareness and preparedness Disaster resilience Natural hazards Older adults

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modelling the development of biological structures displaying longitudinal geometries in vitro:culturing pluripotent stem cells on plasma-treated,growth factor-coupled polycaprolactone fibres

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Engineered Regeneration 2024年第1期5卷 124-138页

作者： Badwi B.Boumelhem Stuart T.Fraser Syamak Farajikhah rachel A.Shparberg michael B.morris marcela m.m.Bilek Anyu Zhang Behnam Akhavan Simon Fleming maryanne Large School of Physics Faculty of ScienceUniversity of SydneyAustralia Sydney Nano Institute University of SydneyAustralia School of Chemical and Biomolecular Engineering University of SydneyAustralia School of medical Sciences Faculty of Medicine and HealthUniversity of SydneyAustralia School of Biomedical Engineering Faculty of EngineeringUniversity of SydneyAustralia School of Engineering University of NewcastleCallaghanNSW 2308Australia Hunter medical Research Institute(HmRI) Precision Medicine ProgramNew Lambton Heights NSW 2305Australia

many biological structures such as nerves,blood and lymphatic vessels,and muscle fibres exhibit longitudinal ge-ometries with distinct cell types extending along both the length and width of internal linear *** these three-dimensional structures in vitro is challenging:the best-defined stem-cell differentiation systems are mono-layer cultures or organoids using pluripotent stem *** stem cells can differentiate into functionally mature cells depending on the signals received,holding great promise for regenerative ***,the integration of in vitro differentiated cell types into diseased tissue remains a *** scaffolds can bridge this gap if the appropriate signalling systems are incorporated into the ***,we have taken a biomimicry approach to generate longitudinal structures in *** this approach,mouse embryonic stem cells are directed to differentiate to specific cell types on the surface of polycaprolactone(PCL)fibres treated by plasma-immersion ion implantation and to which with lineage-specifying molecules have been covalently *** demonstrate the simplicity and utility of our method for efficiently generating high yields of the following cell types from these pluripotent stem cells:neurons,vascular endothelial cells,osteoclasts,adipocytes,and cells of the erythroid,myeloid,and lymphoid *** arranged plasma-treated scaffolds with differentiated cell types could ultimately serve as a means for the repair or treatment of diseased or damaged tissue.

关键词： Pluripotent stem cells Lineage commitment Growth factors Biomaterial engineering Plasma-immersion ion implantation Covalent biomolecule attachment Polycaprolactone

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Decomposition of dynamic transcriptomic responses during effector-triggered immunity reveals conserved responses in two distinct plant cell populations

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Plant Communications 2024年第8期5卷 1-17页

作者： Xiaotong Liu Daisuke Igarashi rachel A.Hillmer Thomas Stoddard You Lu Kenichi Tsuda Chad L.myers Fumiaki Katagiri Department of Plant and microbial Biology University of Minnesota-Twin CitiesSt PaulMN 55108USA Department of Computer Science and Engineering University of Minnesota-Twin CitiesMinneapolisMN 55455USA Bioinformatics and Computational Biology Graduate Program University of Minnesota-Twin CitiesMinneapolisMN 55455USA Institute for Innovation Ajinomoto Co.Inc.KawasakiJapan State Key Laboratory of Agricultural microbiology Hubei Hongshan LaboratoryHubei Key Lab of Plant PathologyCollege of Plant Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Present address:225 S 6th St MinneapolisMN 55402USA Present address:Biotalys Inc.2520 Meridian Parkway Suite 480DurhamNC 27713USA Present address:Life Sciences Institute and Department of Cell and Developmental Biology University of Michigan Medical SchoolAnn ArborMI 48109USA

Rapid plant immune responses in the appropriate cells are needed for effective defense against *** transcriptome analysis is often used to describe overall immune responses,collection of transcriptome data with sufficient resolution in both space and time is *** reanalyzed public Arabidopsis time-course transcriptome data obtained after low-dose inoculation with a Pseudomonas syringae strain expressing the effector AvrRpt2,which induces effector-triggered immunity in ***-peak time-course patterns are prevalent among thousands of upregulated *** implemented a multicompartment modeling approach to decompose the double-peak pattern into two single-peak patterns for each *** decomposed peaks reveal an“echoing”pattern:the peak times of the first and second peaks correlate well across most upregulated *** demonstrated that the two peaks likely represent responses of two distinct cell populations that respond either cell autonomously or indirectly to ***,the peak decomposition has extracted spatial information from the time-course *** echoing pattern also indicates a conserved transcriptome response with different initiation times between the two cell populations despite different elicitor types.A gene set highly overlapping with the conserved gene set is also upregulated with similar kinetics during pattern-triggered *** of a WRKY network via different entry-point WRKYs can explain the similar but not identical transcriptome responses elicited by different elicitor *** discuss potential benefits of the properties of the WRKY activation network as an immune signaling network in light of pressure from rapidly evolving pathogens.

关键词： Arabidopsis Pseudomonas syringae plant immune response multi-compartment model WRKY transcription factors resilient immune signaling network

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The Combined Effect of Lumenato and Ceramide in the Protection of Collagen Damage Induced by Neutrophils in Normal Human Dermal Fibroblasts

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Advances in Bioscience and Biotechnology 2024年第2期15卷 140-159页

作者： Yulia Solomonov rachel Levy Immunology and Infectious Diseases Laboratory Department of Clinical Biochemistry and Pharmacology Faculty of Health Sciences Ben-Gurion University of The Negev Beer-Sheva Israel

Introduction: Collagen is the primary structural protein fibroblasts produce in the skin’s extracellular matrix. Infiltration of neutrophils into the epidermis and dermis by exposure to UV causes collagen damage and contributes to photoaging. methods: To study the combined effect of Lumenato and ceramide in preventing collagen-1 damage induced by phagocytes, we used co-cultures of normal human dermal fibroblasts (fibroblasts) and activated human neutrophils. The present study aimed to determine the protective effect of the combination of Lumenato and ceramide on fibroblast collagen-1 damage induced by neutrophils. Results: Lumenato (in the range of 6.5 - 208 μg/ml) or ceramide (in the range of 0.1 - 50 μm) inhibited the production of superoxides and mPO by TNFα-stimulated neutrophils, as well as the production of NO by LPS-stimulated macrophages in a dose-dependent manner. The combinations of Lumenato and ceramide, in low concentrations, caused synergistic prevention of fibroblasts’ collagen-1 damage induced by TNFα-activated neutrophils, detected by fluorescence immunostaining and WB analysis. mPO activity in the supernatants of the co-cultures was also synergistically inhibited. Adding Lumenato or ceramide singly or in combinations in these low concentrations to the fibroblast cultures did not affect the expression of collagen-1. The combinations of Lumenato or ceramide in these concentrations also caused a synergistic inhibition of NO production by activated macrophages. Conclusions: The results suggest that combining low concentrations of Lumenato and ceramide results in synergistic protection against fibroblasts’ collagen-1 damage induced by neutrophils, thus indicating their possible potential for enhanced skin health.

关键词： Dermal Fibroblasts Neutrophils Collagen-1 Lumenato Ceramide

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Survey of international experts on research priorities to improve care for healthy ageing

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Family medicine and Community Health 2024年第3期12卷 36-39页

作者： matteo Cesari Yuka Sumi Hyobum Jang Jotheeswaran Amuthavalli Thiyagarajan Yejin Lee rachel Albone marco Canevelli monica R Perracini Andrew m Briggs Anshu Banerjee Department of maternal NewbornChild and Adolescent Health and AgeingWorld Health OrganizationGenevaSwitzerland Department of Clinical Sciences and Community Health University of MilanMilanItaly Department of Human Neuroscience Universitàdegli Studi di Roma La SapienzaRomeItaly Department of Neurobiology Care Sciences and SocietyStockholm UniversityStockholmSweden National Center for Disease Prevention and Health Promotion Italian National Institute of HealthRomeItaly master's and Doctoral Program in Physical Therapy Universidade Cidade de São PauloSão PauloBrazil Curtin School of Allied Health Curtin enAble InstituteCurtin UniversityPerthWAAustralia

INTRODUCTION The United Nations(UN)Decade of Healthy Ageing(2021–2030),coordinated by the World Health Organization(WHO),1 is a global collaborative initiative aimed at improving the lives of older people,their families and the communities.23 The Action Areas 3(ie,‘deliver person-centred,integrated care and primary health services responsive to older people’)and 4(ie,‘provide access to long-term care(LTC)for older people who need it’)of the Decade’s work programme focus on reorienting health and care systems to promote‘ageing in place’and the delivery of personalised interventions in a seamless continuum of care.

关键词： services ageing centre

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Systematic Radio Telescope Alignment Using Portable Fringe Projection Profilometry

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Nanomanufacturing and metrology 2024年第1期7卷 75-85页

作者： Joel Berkson Justin Hyatt Nathan Julicher Byeongjoon Jeong Isaac Pimienta rachel Ball Wyatt Ellis Jason Voris Diego Torres‑Barajas Daewook Kim James C.Wyant College of Optical Sciences University of Arizona1630 E.University Blvd.TucsonAZ 85721USA Department of Astronomy at Steward Observatory University of Arizona933 N Cherry Ave.TucsonAZ 85721USA

In 2019,the Event Horizon Telescope(EHT)released the first-ever image of a black hole event *** are now aiming for higher angular resolutions of distant targets,like black holes,to understand more about the fundamental laws of gravity that govern our *** achieve this higher resolution and increased sensitivity,larger radio telescopes are needed to operate at higher frequencies and in larger *** like the next-generation Very Large Array(ngVLA)and the Square-Kilometer Array(SKA)require building hundreds of telescopes with diameters greater than 10 ms over the next *** has a twofold *** telescope surfaces need to be more accurate to operate at higher frequencies,and the logistics involved in maintaining a radio telescope need to be simplified to support them properly in large *** of these problems can be solved with improved methods for surface metrology that are faster and more accurate with a higher *** leads to faster and more accurate panel alignment and,therefore,a more productive *** this paper,we present the use of binocular fringe projection profilometry as a solution to this problem and demonstrate it by aligning two panels on a 3-m radio telescope *** measurement takes only 10 min and directly delivers feedback on the tip,tilt,and piston of each panel to create the ideal reflector shape.

关键词： metrology Fringe projection profilometry Off-axis alignment Radio astronomy Radio antenna

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modeling and Characterization of Fine Particulate matter Dynamics in Bujumbura Using Low-Cost Sensors

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Journal of Applied mathematics and Physics 2024年第1期12卷 256-267页

作者： Egide Ndamuzi rachel Akimana Paterne Gahungu Elie Bimenyimana Doctorate School of the University of Burundi Bujumbura Burundi Department of Physics University of Burundi Bujumbura Burundi Department of mathematics Imperial College London London UK Climate and Atmosphere Research Centre (CARE-C) The Cyprus Institute Nicosia Cyprus

Air pollution is a result of multiple sources including both natural and anthropogenic activities. The rapid urbanization of the cities such as Bujumbura, economic capital of Burundi, is one of these factors. The very first characterization of the spatio-temporal variability of Pm2.5 in Bujumbura and the forecasting of Pm2.5 concentration have been conducted in this paper using data collected during a year, from August 2022 to August 2023, by low-cost sensors installed in Bujumbura city. For each commune, an hourly, daily and seasonal analysis was carried out and the results showed that the mass concentrations of Pm2.5 in the three municipalities differ from one commune to another. The average hourly and annual Pm2.5 concentrations exceed the World Health Organization standards. The range is between 28.3 and 35.0 μg/m3. In order to make a prediction of Pm2.5 concentration, an investigation of Recurrent Neural Networks with Long Short-Term memory has been undertaken.

关键词： Particulate matter Recurrent Neural Networks Calibration

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SImAP500: A novel risk score to identify recipients at higher risk of hepatocellular carcinoma recurrence following liver transplantation

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World Journal of Transplantation 2024年第3期14卷 132-143页

作者： Amr Alnagar Nekisa Zakeri Konstantinos Koilias Rosemary E Faulkes rachel Brown Owen Cain m Thamara P R Perera Keith J Roberts Rebeca Sanabria-mateos David C Bartlett Yuk Ting ma Shivan Sivakumar Shishir Shetty Tahir Shah Bobby V m Dasari Department of HBP and Liver Transplantation Surgery Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152GWUnited Kingdom Centre for Liver Research Institute of Biomedical ResearchBirmingham B152TTUnited Kingdom Department of Hepatology Queen Elizabeth HospitalUniversity Hospitals BirminghamBirmingham B152GWUnited Kingdom Department of Pathology University Hospitals Birmingham NHS Foundation TrustBirmingham B152GWUnited Kingdom Department of Oncology Queen Elizabeth HospitalUniversity Hospitals of BirminghamBirmingham B152GWUnited Kingdom

BACKGROUND Recurrence of hepatocellular carcinoma(HCC)following liver transplantation(LT)has a devastating influence on recipients’survival;however,the risk of recur-rence is not routinely *** stratification is vital with a long LT waiting time,as that could influence the recurrence despite strict listing *** This study aims to identify predictors of recurrence and develop a novel risk pre-diction score to forecast HCC recurrence following *** A retrospective review of LT for HCC recipients at University Hospitals Bir-mingham between July 2011 and February *** and multivariate analyses were performed to identify recurrence predictors,based on which the novel SImAP500(satellite nodules,increase in size,microvascular invasion,AFP>500,poor differentiation)risk score was *** 234 LTs for HCC were performed with a median follow-up of 5.3 *** developed in 25 patients(10.7%).On univariate analyses,RETREAT score>3,α-fetoprotein(AFP)at listing 100-500 and>500,bridging,increased tumour size between imaging at the listing time and explant histology,increase in the size of viable tumour between listing and explant,presence of satellite nodules,micro-and macrovascular invasion on explant and poor differentiation of tumours were significantly associated with recurrence,based on which,the SImAP500 risk score is *** SImAP500 demonstrated an excellent predictive ability(c-index=0.803)and outper-formed the RETREAT score(c-index=0.73).SImAP500 is indicative of the time to disease *** SImAP500 risk score identifies the LT recipients at risk of HCC *** stratification allows patient-centric post-transplant surveillance *** validation of the score is recommended.

关键词： Liver transplantation Hepatocellular carcinoma Recurrence Survival

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Evaluation of the Antibacterial and Antifungal Capacity of Nanoemulsions Loaded with Synthetic Chalcone Derivatives Di-Benzyl Cinnamaldehyde and Benzyl 4-Aminochalcone

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Journal of Renewable materials 2024年第2期12卷 285-304页

作者： Flavia Oliveira monteiro da Silva Abreu Taysse Holanda Joice Farias do Nascimento Henety Nascimento Pinheiro rachel menezes Castelo Hélcio Silva dos Santos Thais Benincá Patrícia da Silva malheiros Júlio César Sousa Prado Raquel de Oliveira Fontenelle maria madalena de Camargo Forte Natural Polymers Laboratory PPGCNState University of CearáFortaleza60.714.903Brazil Polymeric materials Laboratory PPGE3MFederal University of Rio Grande do SulPorto Alegre91501-970Brazil Natural Product Chemistry Laboratory PPGCNState University of CearáFortaleza60.714.903Brazil Food Hygiene and microbiology Laboratory PPGCTAFederal University of Rio Grande do SulPorto Alegre91501-970Brazil microbiology Laboratory Medicine SchoolFederal University of CearáSobral62010-560Brazil

With the increase in antimicrobial resistance,it has become necessary to explore alternative approaches for combating and preventing ***-cinnamaldehyde(CNm)and Benzyl4-amino(B4Am)are bioactive compounds derived from chalcones but with restricted solubility in aqueous *** can enhance the solubility of compounds and can be a promising alternative in the development of novel antimicrobials,with reduced side effects and prolonged *** objective of this study was to evaluate the stability of oil-in-water nanoemulsions loaded with two distinct types of chalcones at two different dosages,to propose a stable formulation with antimicrobial *** showed that nanoemulsions presented high encapsulation efficiency,low polydispersity index(PDI)and particle size below 200 nm,indicating that emulsification was a suitable method for nanoemulsion *** with higher dosages exhibited significant antimicrobial effects when compared to free chalcones and positive ***,B4Am nanoemulsions at higher dosages showed expressive activity against Salmonella minnesota,with a 420%greater inhibitory response compared to the free form and showing equivalence to the positive *** nanoemulsions showed excellent inhibitory activity at the highest dosage,equivalent to the positive control against *** and Staphylococcus *** greater number of conjugated bonds in CNm increased the antimicrobial activity in comparison with B4Am,and the formation of nanometric domains enhanced the bioavailability,being a promising alternative for antimicrobial applications.

关键词： Polysaccharide nanoemulsions S.aureus S.minnesota chalcones alginate

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