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Critical size limit of biodegradable nanopartides for enhanced lymph node traffick.ng and paracortex penetration

Nano Research 2019年第4期12卷 837-844页

作者： Gregory P. Howard Garima Verma Xiyu k. Winter M. Thayer Timothy Hamerly victoria k. baxter John E. Lee Rhoel R. Dinglasan Hai-Quan Mao Department of Biomedical Engineering Johns Hopkins School of Medicine Baltimore MD 21218 USA Institute for NanoBioTechnology Johns Hopkins University Baltimore MD 2121 & USA W. Harry Feinstone Department of Molecular Microbiology & Immunology and the Malaria Research Institute Johns Hopkins Bloomberg School of Public Health Baltimore MD 21205 USA Emerging Pathogens Institute Department of Infectious Diseases & Immunology College of Veterinary Medicine University of Florida Gainesville FL 32611 USA Department of Materials Science and Engineering Whiting School of Engineering Johns Hopkins University Baltimore MD 21218 USA Johns Hopk.ns School of Nursing Baltimore MD 21205 USA Department of Molecular and Comparative Pathobiology Johns Hopkins School of Medicine Baltimore MD 21205 USA Department of Biomedical Engineering Yale University New Haven CT 06520 USA Translational Tissue Engineering Center Johns Hopkins University School of Medicine Baltimore MD 21231 USA

Lymph node (LN) targeti ng through interstitial drain age of nan oparticles (NPs) is an attractive strategy to stimulate a pote nt immune respo nse, as LNs are the primary site for lymphocyte priming by antigen presenting cells (APCs) and triggering of an adaptive immune response. NP size has been shown to influence the efficiency of LN-targeting and retention after subcutaneous injection. For clinical translation, biodegradable NPs are preferred as carrier for vaccine delivery. However, the selective "size gateM for effective LN-drainage, particularly the k.netics of LN traffick.ng, is less well defined. This is partly due to the challenge in generating size-controlled NPs from biodegradable polymers in the sub-100-nm range. Here, we report the preparation of three sets of poly(lactic-co-glycolic)-b-poly(ethylene-glycol)(PLGA-b-PEG) NPs with number average diameters of 20-, 40-, and 100-nm and narrow size distributions using flash nanoprecipitation. Using NPs labeled with a near-infrared dye, we showed that 20-nm NPs drain rapidly across proximal and distal LNs following subcutaneous inoculation in mice and are retai ned in LNs more effectively than NPs with a nu mber average diameter of 40-nm. The drain age of 100-nm NPs was n egligible. Furthermore, the 20-nm NPs showed the highest degree of penetration around the paracortex region and had enhanced access to dendritic cells in the LNs. Together, these data confirmed that small, size-controlled PLGA-b-PEG NPs at the lower threshold of about 30-nm are most effective for LN traffick.ng, retention, and APC uptak. after s.c. administration. This report could inform the design of LN-targeted NP carrier for the delivery of therapeutic or prophylactic vaccines.

关键词： biodegradable nano particle lymph node traffick.ng vaccine delivery nanoparticle size an tigen presenting cells in vivo imaging

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Proton pump inhibitors and all-cause mortality risk.among cancer patients

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World Journal of Clinical Oncology 2025年第1期16卷 34-42页

作者： Arunk.mar k.ishnan Carolin victoria Schneider Declan Walsh Department of Supportive Oncology Atrium Health Levine CancerCharlotteNC 28204United States Department of Medicine Section of Hematology and OncologyWake Forest University School of MedicineWinston-SalemNC 27101United States Department of Medicine Ⅲ GastroenterologyMetabolic Diseasesand Intensive CareUniversity Hospital RWTH AachenAachen 52074Germany

BACk.ROUND Proton pump inhibitors(PPIs)are widely used,including among cancer patients,to manage gastroesophageal reflux and other gastric acid-related *** evidence suggests associations between long-term PPI use and higher risk. for various adverse health outcomes,including greater *** To investigate the association between PPI use and all-cause mortality among cancer patients by a comprehensive analysis after adjustment for various confounders and a robust methodological approach to minimize *** This retrospective cohort study used data from the TriNetX research network.with electronic health records from multiple healthcare *** study employed a new-user,active comparator design,which compared newly treated PPI users with non-users and newly treated histamine2 receptor antagonists(H2RA)users among adult cancer *** prescribed PPIs(esomeprazole,lansoprazole,omeprazole,pantoprazole,or rabeprazole)users were compared to non-users or newly prescribed H2RAs(cimetidine,famotidine,nizatidine,or ranitidine)*** primary outcome was all-cause *** patient in the main group was matched to a patient in the control group using 1:1 propensity score matching to reduce confounding *** Cox regression models were used to estimate hazard ratios(HRs)and 95% confidence interval(CI).RESULTS During the follow-up period(median 5.4±1.8 years for PPI users and 6.5±1.0 years for non-users),PPI users demonstrated a higher all-cause mortality rate than non-users after 1 year,2 years,and at the end of follow up(HRs:2.34-2.72).Compared with H2RA users,PPI users demonstrated a higher rate of all-cause mortality HR:1.51(95%CI:1.41-1.69).Similar results were observed across sensitivity analyses by excluding deaths from the first 9 months and 1-year post-exposure,confirming the robustness of these *** a sensitivity analysis,we analyzed all-cause mortality outcomes between former PPI users and individual

关键词： All-cause mortality Cancer Histamine-2 receptor antagonists Mortality Malignancy Proton pump inhibitors Carcinoma Outcome

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The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-lik. ethanol treatment in adolescence

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Neural Regeneration Research 2025年第4期20卷 1153-1163页

作者： Susana Mellado María JoséMorillo-Bargues Carla Perpiñá-Clérigues Francisco García-García victoria Moreno-Manzano Consuelo Guerri María Pascual Department of Physiology School of Medicine and DentistryUniversity of ValenciaValenciaSpain Bioinformatics and Biostatistics Unit Príncipe Felipe Research CenterValenciaSpain Neuronal and Tissue Regeneration Laboratory Príncipe Felipe Research CenterValenciaSpain

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain *** stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-lik. ethanol treatment in adolescent *** the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge *** demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleuk.n-1β,interleuk.n-18,inducible nitric oxide synthase,nuclear factor-k.ppa B,monocyte chemoattractant protein-1,and C–X3–C motif chemok.ne ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-lik. ethanol treatment in adolescent *** analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-lik. receptor signaling *** together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drink.ng in adolescence.

关键词： adolescence binge-lik. ethanol treatment extracellular vesicles hippocampus mesenchymal stem cells neuroinflammation NOD-,LRR-and pyrin domain-containing protein 3(NLRP3)

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Targeting harmful effects of non-excitatory amino acids as an alternative therapeutic strategy to reduce ischemic damage

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Neural Regeneration Research 2025年第9期20卷 2454-2463页

作者： victoria Jiménez Carretero IrisÁlvarez-Merz Jorge Hernández-Campano Sergei A.k.rov Jesús M.Hernández-Guijo Department of Pharmacology and Therapeutic School of MedicineUniv.Autónoma de MadridMadridSpain Ramón y Cajal Institute for Health Research(IRYCIS) Neurobiology-Research ServiceHospital Ramón y CajalMadridSpain Institute of Neurobiology Faculty of Mathematics and Natural SciencesHeinrich Heine University DüsseldorfDüsseldorfGermany Department of Neuroscience and Regenerative Medicine&Department of Neurosurgery Medical College of Georgia at Augusta UniversityAugustaGAUSA

The involvement of the excitatory amino acids glutamate and aspartate in ce rebral ischemia and excitotoxicity is ***,the role of non-excitatory amino acids in brain damage following a strok. or brain trauma remains largely *** release of amino acids by necrotic cells in the ischemic core may contribute to the expansion of the *** findings indicated that the reversible loss of field excitato ry postsynaptic potentials caused by transient hypoxia became irreversible when exposed to a mixture of just four non-excitatory amino acids(L-alanine,glycine,L-glutamine,and L-serine)at their plasma *** amino acids induce swelling in the somas of neurons and astrocytes during hypoxia,along with permanent dendritic damage mediated by N-methyl-D-aspartate *** N-methyl-D-aspartate receptors prevented neuronal damage in the presence of these amino acids during *** is lik.ly that astroglial swelling caused by the accumulation of these amino acids via the alanine-serine-cysteine transporter 2 exchanger and system N transporters activates volume-regulated anion channels,leading to the release of excitotoxins and subsequent neuronal damage through N-methyl-D-aspartate receptor ***,previously unrecognized mechanisms involving non-excitatory amino acids may contribute to the progression and expansion of brain injury in neurological emergencies such as strok. and traumatic brain *** these pathways co uld highlight new therapeutic targets to mitigate brain injury.

关键词： cell swelling N-methyl-D-aspartate receptor non-excitatory amino acids strok. synaptic transmission

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Developmental exposure to heavy metals alters visually-guided behaviors in zebrafish

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Current Zoology 2017年第2期63卷 221-227页

作者： Matthew k. LEFAUVE victoria P. CONNAUGHTON who is now at Department of Biological Sciences George Washington University Washington DC 20052 USA

This laboratory-based study determined the consequences of heavy metal exposure using zebra- fish Danio rerio. Embryos were transiently exposed to environmentally-relevant concentrations of cadmium or nick.l until 72 h postfertilization （hpf）, then they were returned to system water and allowed to grow until 7, 9, and 11 days postfertilization （dpf）, when they were examined morpho- logically and behaviorally. Morphological measures of notochord length, eye diameter, and inter- eye distance were not different across treatments; however, significant differences in optomotor responses were observed in treated larvae at all ages tested. These results suggest that initial de- velopmental exposure to cadmium and nick.l significantly impacts visually-guided larval behavior. The absence of significant differences in gross morphology suggests that the effects of these metals are subtle and may occur at the cellular level. By using this ecologically relevant model and pollutant type, this study has broad application and implications with regard to safe levels of con- taminant in drink.ng water and freshwater ecosystems.

关键词： cadmium nick.l optomotor response zebrafish.

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Methods to Identify Individual Eddy Structures in Turbulent Flow

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Tsinghua Science and Technology 2013年第2期18卷 125-136页

作者： Shengwen Wang Jack.Goldfeather Ellen k. Longmire victoria Interrante the Department of Computer Science and Engineering University of Minnesota Minneapolis MN 55455 USA the Mathematics and Computer Science Department Carleton College Northfield MinnesotaMN 55057 USA the Department of Aerospace Engineering and Mechanics University of MinnesotaMinneapolis MN 55455 USA

Turbulent flows are intrinsic to many processes in science and engineering, and efforts to elucidate the physics of turbulence are of critical importance to many fields. However, ongoing efforts to achieve a fundamental understanding of the mechanisms of turbulent flow are hindered by the difficulty of quantifying the complex, nonlinear interactions between individual eddies in these flows. The difficulty of this task.is compounded by the lack.of robust methods for accurately identifying individual eddy structures and characterizing their dynamic evolution and organization across multiple scales. In this paper we address this problem by proposing several novel approaches for more accurately segmenting individual eddy structures in turbulent flows.

关键词： flow visualization segmentation vortices turbulent flow

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Generation of nanomaterials by reactive laser-synthesis in liquid

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Science China(Physics,Mechanics & Astronomy) 2022年第7期65卷 3-47页

作者： Laysa M.Frias Batista Ashish Nag victoria k.Meader k.tharine Moore Tibbetts Department of Chemistry Virginia Commonwealth UniversityRichmond VA 23284USA

Nanomaterials with tailored structures and surface chemistry are in high demand, as these materials play increasingly important roles in biology, catalysis, energy storage, and manufacturing. Their heightened demand has attracted attention towards the development of synthesis routes, particularly, laser-synthesis techniques. These efforts drove the refinement of laser ablation in liquid(LAL) and related methods over the past two decades and have led to the emergence of reactive laser-synthesis techniques that exploit these methods’ characteristic, non-equilibrium conditions. Reactive laser-synthesis approaches foster unique chemical reactions that enable the formation of composite products lik. multimetallic nanoparticles, supported nanostructures, and complex minerals. This review will examine emerging reactive laser-synthesis methods in the context of established methods lik. *** focus will be on the chemical reactions initiated within the laser plasma, with the goal of understanding how these reactions lead to the formation of unique nanomaterials. We will provide the first systematic review of laser reaction in liquid(LRL) in the literature, and bring a focus to the chemical reaction mechanisms in LAL and reactive-LAL techniques that have not yet been emphasized in reviews. Discussion of the current challenges and future investigative opportunities into reactive laser-synthesis will impart guidance for researchers interested in designing reactive laser-synthesis approaches to novel nanomaterial production.

关键词： laser ablation in liquids laser reduction in liquids nanoparticles

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Modelling the nesting-habitat of threatened vulture species in the caucasus:An ecosystem approach to formalising environmental factors in species distribution models

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Avian Research 2023年第4期14卷 572-585页

作者： Rustam Pshegusov victoria Chadaeva Tembotov Institute of Ecology of Mountain Territories of Russian Academy of Science I.Armand Str.37а360051NalchikRussia

Abiotic factors play an important role in species localisation,but biotic and anthropogenic predictors must also be considered in distribution modelling for models to be biologically *** this study,we formalised the biotic predictors of nesting sites for four threatened Caucasian vultures by including species distribution models(wild ungulates,nesting tree species)as biotic layers in the vulture Maxent *** was applied in the R dismo pack.ge and the best set of the model parameters were defined in the R ENMeval *** metrics were continuous Boyce index,Ak.ik.'s information criterion,the area under receiver operating curve and true sk.ll *** also calculated and evaluated the null *** density estimation method was applied to assess the overlap of vulture ecological niches in the environmental *** accessibility of anthropogenic food resources was estimated using the Path Distance measure that considers elevation *** availability of pine forests(Scots Pine)and wild ungulates(Alpine Chamois and Caucasian Goat)contributed the most(29.6%and 34.3%)to Cinereous Vulture(Aegypius monachus)nesting site *** ungulate distribution also contributed significantly(about 46%)to the Bearded Vulture(Gypaetus barbatus)*** scavenger nests in the highlands of the Caucasus at a minimum distance of 5–10 k. from anthropogenic *** contrast,livestock.as a food source was most important in colony distribution of Griffon Vulture(Gyps fulvus).The contribution of distances to settlements and agricultural facilities to the model was 45%.The optimal distance from Egyptian Vulture(Neophron percnopterus)nesting sites to settlements was only 3–10 k.,to livestock.facilities no more than 15 k. with the factor contribution of about 57%.Excluding the wild ungulate availability,the ecological niches of studied vultures overlapped *** similar foraging and nesting requirements,Caucasian vultures are no

关键词： Caucasian vultures Ecological niche differentiation Maxent Nesting sites Species distribution models

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Unmet supportive care needs in families of children with chronic health conditions: an Australian cross‑sectional study

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World Journal of Pediatrics 2023年第12期19卷 1181-1191页

作者： Sangeetha Thomas Linda k.Byrne Nicholas P.Ryan Christel Hendrieck. victoria White School of Psychology Faculty of HealthDeakin UniversityMelbourneVIC 3125Australia Department of Paediatrics University of MelbourneMelbourneVICAustralia Australian Centre for Behavioural Research in Diabetes MelbourneVICAustralia Institute of Health Transformation Deakin UniversityMelbourneVICAustralia Cancer Council victoria MelbourneVICAustralia

Back.round The aim of this study was to identify similarities and diferences in the unmet supportive care needs(USCN)of families of children with major chronic health conditions(CHCs)using a universal need assessment *** A cross-sectional online survey involving parents of children with congenital heart disease(CHD),type 1 diabetes mellitus(T1D),cancer,and asthma diagnosed within the last 5 years recruited via social media and support ***-four items assessing the USCN across six domains(care needs,physical and social needs,informational needs,support needs,fnancial needs,child-related emotional needs)were responded to on a 4-point Lik.rt scale[no need(1)to high need(4)].Descriptive statistics identifed the level of need,and linear regressions identifed factors associated with higher need domain *** to small numbers,the asthma group was excluded from comparisons across *** One hundred and ninety-four parents completed the survey(CHD:n=97,T1D:n=50,cancer:n=39,and asthma:n=8).Parents of children with cancer were most lik.ly to report at least one USCN(92%),followed by parents of children with T1D(62%).The fve most commonly reported USCN across CHCs were drawn from four domains:child-related emotional,support,care,and *** need items were included in the top fve needs for all conditions.A higher USCN was associated with a greater frequency of hospital visits and the absence of parental *** Using a universal need assessment tool,this is one of the frst studies to characterize USCN in families of children diagnosed with common *** proportions endorsing diferent needs varied across conditions,the most endorsed needs were similar across the illness *** suggests that support programs or services could be shared across diferent CHCs.

关键词： Children Chronic illness Need assessment Unmet supportive care needs

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Shop&Go:TSP heuristics for an optimal shopping with smartphones

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Science China(Information Sciences) 2013年第11期56卷 45-56页

作者： Inmaculada PARDINES victoria LOPEZ Department of Computer Architecture Faculty of Computer Science Universidad ComplutenseMadrid 28040 Spain

Mobile technology has been under constant growth in last *** emergence of smartphones has encouraged the development of a wide variety of mobile *** of them are related to daily *** this regard,we propose the Shop&Go mobile application which allows a supermark.t customer to do the shopping covering the shortest distance1).An analysis of the routing problem applied to an efcient way of doing the shopping is made.A map with items distribution and distances between products is provided by the *** on these information two heuristics have been proposed to do the shopping following the optimum *** heuristics have been compared,proving that neither of them can be defned as the best one in all *** products in the shopping list determine which is the best solution for each ***,both algorithms have been included in our application,letting the user decide which route he/she wants to ***&Go has also other functionalities which are extensively described in the *** over an HTC Desire mobile are shown to demonstrate the proper tool ***,a study of consumer acceptance has been made to k.ow its possibilities of success in the mobile technology mark.t.

关键词： mobile applications routing problems Android operating system shopping list optimum path

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