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Erythrocyte sphingolipid species as biomarkers of Alzheimer's disease

Journal of Pharmaceutical Analysis 2022年第1期12卷 178-185页

作者： jericha mill Vihar Patel Ozioma Okonkwo Lingjun Li Thomas Raife Department of Chemistry University of Wisconsin-MadisonMadisonWI53706USA Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public HealthMadisonWI53705USA Clinical Science Center Wisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin School of Medicine and Public HealthMadisonWI53792USA School of Pharmacy University of Wisconsin-MadisonMadisonWI53705USA

Diagnosing Alzheimer’s disease(AD)in the early stage is challenging.Informative biomarkers can be of great value for population-based screening.Metabolomics studies have been used to find potential biomarkers,but commonly used tissue sources can be difficult to obtain.The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD.Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue,erythrocytes are plentiful and easily accessed.Moreover,erythrocytes are metabolically active,a feature that distinguishes this sample source from other bodily fluids like plasma and urine.In this preliminary pilot study,the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD(control(CTRL))were compared.Whole blood was collected post-mortem and erythrocytes were analyzed using ultraperformance liquid chromatography tandem mass spectrometry.Over 750 metabolites were identified in AD and CTRL erythrocytes.Seven were increased in AD while 24 were decreased(P<0.05).The majority of the metabolites increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism.Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients.Sphingolipids have been previously implicated in AD and other neurological conditions.Furthermore,previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal,healthy adults.Together,these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.

关键词： Alzheimer’s disease Neurodegenerative disease Mass spectrometry Erythrocytes Biomarkers Metabolomics

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Recent Advances in Understanding of Alzheimer’s Disease Progression Through Mass Spectrometry-Based Metabolomics

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Phenomics 2022年第1期2卷 1-17页

作者： jericha mill Lingjun Li Department of Chemistry University of Wisconsin-MadisonMadisonWI 53706USA School of Pharmacy University of Wisconsin-MadisonMadisonWI 53705USA

Alzheimer’s disease(AD)is the leading cause of dementia in the aging population,but despite extensive research,there is no consensus on the biological cause of AD.While AD research is dominated by protein/peptide-centric research based on the amyloid hypothesis,a theory that designates dysfunction in beta-amyloid production,accumulation,or disposal as the primary cause of AD,many studies focus on metabolomics as a means of understanding the biological processes behind AD progression.In this review,we discuss mass spectrometry(MS)-based AD metabolomics studies,including sample type and preparation,mass spectrometry data acquisition strategies,and data analysis,as well as biological insights gleaned from these studies,with the hope of informing future AD metabolomic studies.

关键词： Alzheimer’s disease Mass spectrometry Metabolomics

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Revisiting the analytical solutions for ultimate bearing capacity of pile embedded in rocks

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Journal of Rock Mechanics and Geotechnical Engineering 2023年第6期15卷 1506-1519页

作者： A.Picardo M.A.millán R.Galindo A.Alencar Escuela Técnica Superior de Arquitectura Universidad Politécnica de MadridMadrid28040Spain Escuela Técnica Superior de Ingenieros de Caminos Canales y Puertos de MadridUniversidad Politécnica de MadridMadrid28040Spain

This paper investigates the validity and shortcomings of the existing analytical solution for the ultimate bearing capacity of a pile embedded in a rock mass using the modified HoekeBrown failure criterion.Although this criterion is considered a reference value for empirical and numerical calculations,some limitations of its basic simplifications have not been clarified yet.This research compares the analytical results obtained from the novel discontinuity layout optimization(DLO)method and the numerical solutions from the finite difference method(FDM).The limitations of the analytical solution are considered by comparing different DLO failure modes,thus allowing for the first time a critical evaluation of its scope and conditioning for implementation.Errors of up to 40%in the bearing capacity and unrealistic failure modes are the main issues in the analytical solution.The main aspects of the DLO method are also analyzed with an emphasis on the linearization of the rock failure criterion and the accuracy resulting from the discretization size.The analysis demonstrates DLO as a very efficient and accurate tool to address the pile tip bearing capacity,presenting considerable advantages over other methods.

关键词： Discontinuity layout optimization(DLO) Analytical solution Bearing capacity Deep foundations HoekeBrown failure criterion Finite difference method(FDM)

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Are we ready for telemonitoring inflammatory bowel disease?A review of advances,enablers,and barriers

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World Journal of Gastroenterology 2023年第7期29卷 1139-1156页

作者： Javier Del Hoyo Mónica millán Alejandro Garrido-Marín Mariam Aguas Department of Gastroenterology La Fe University and Polytechnic HospitalValencia 46026Spain Department of Surgery La Fe University and Polytechnic HospitalValencia 46026Spain Health Research Institute La Fe La Fe University and Polytechnic HospitalValencia 46026Spain

This review summarizes the evidence about telemonitoring in patients with inflammatory bowel disease(IBD). To give an overview of the advances performed, as well as the enablers and barriers which favoured/hindered telemonitoring implementation. We performed a literature search in Pub Med, EMBASE, MEDLINE, Cochrane Database, Web of Science and Conference Proceedings. Titles and abstracts published up to September 2022 were screened for a set of inclusion criteria: telemonitoring intervention, IBD as the main disease, and a primary study performed. Ninety-seven reports were selected for full review. Finally, 20 were included for data extraction and critical appraisal. Most studies used telemonitoring combined with tele-education, and programs evolved from home telemanagement systems towards web portals through m Health applications. Web systems demonstrated patients’ acceptance, improvement in quality of life, disease activity and knowledge, with a good cost-effectiveness profile in the short-term. Initially, telemonitoring was almost restricted to ulcerative colitis, but new patient reported outcome measures, home-based tests and mobile devices favoured its expansion to different patients’ categories. However, technological and knowledge advances led to legal, ethical, economical and logistic issues. Standardization of remote healthcare is necessary, to improve the interoperability of systems as well as to address liability concerns and users’ preferences. Telemonitoring IBD is well accepted and improves clinical outcomes at a lower cost in the short-term. Funders, policymakers, providers, and patients need to align their interests to overcome the emerging barriers for its full implementation.

关键词： Inflammatory bowel disease Telemedicine Telemonitoring Information and communication technology Crohn´s disease Ulcerative colitis

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Restabilization Process in Matching Markets with Workers Proposing

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Open Journal of Discrete Mathematics 2022年第4期12卷 101-112页

作者： millán Beatriz Instituto de Matemática Aplicada San Luis IMASL Universidad Nacional de San Luis and CONICET San Luis Argentina Departamento de Matemática Universidad Nacional de San Juan San Juan Argentina

This paper is focused on the analysis, in the framework of lattice theory, of the matchings obtained from restabilization (after disruption) of stable matchings. When the disruption is due to entry workers or closure of firms the unemployed workers make offers to firms. The stable matching obtained is the firms-worst stable matching of the set of stable matchings that the firms weakly prefer to the initial stable matching (i.e., before being disrupted by changes in the population). More precisely, their position within the lattice of stable matchings is shown.

关键词： Stable Matchings Restabilization Lattice

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Nylon 6-cellulose composite hosted in a hypodermic needle: Biofluid extraction and analysis by ambient mass spectrometry in a single device

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Journal of Pharmaceutical Analysis 2023年第11期13卷 1346-1352页

作者： Jaime millan-Santiago Rafael Lucena Soledad Cardenas Affordable and Sustainable Sample Preparation(AS2P)Research Group Analytical Chemistry DepartmentChemical Institute for Energy and Environment(IQUEMA)University of CordobaE-14071CordobaSpain

This study proposes a hypodermic needle(HN)as a sorbent holder and an electrospray(ESI)emitter,thus combining extraction and analysis in a single device.A novel nylon 6-cellulose(N6-Cel)composite sorbent is proposed to extract methadone from oral fluid samples.The cellulosic substrate provides the composite with high porosity,permitting the flow-through of the sample,while the polyamide contributes to the extraction of the analyte.The low price of the devices(considering the holder and the sorbent)contributes to the affordability of the method,and their small size allows easy transportation,opening the door to on-site extractions.Under the optimum conditions,the analyte can be determined by high-resolution ambient ionization mass spectrometry at a limit of detection(LOD)as low as 0.3 mg/L and precision(expressed as relative standard deviation,RSD)better than 9.3%.The trueness,expressed as relative recovery(RR),ranged from 90%to 109%.As high-resolution mass spectrometers are not available in many laboratories,the method was also adapted to low-resolution spectrometers.In this sense,the direct infusion of the eluates in a triple quadrupole-mass spectrometry provided an LOD of 2.2 mg/L.The RSD was better than 5.3%,and the RR ranged from 96%to 121%.

关键词： ESI emitter Mass spectrometry Hypodermic needle Composite Methadone

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Efficiency of white lupin in the removal of mercury from contaminated soils: Soil and hydroponic experiments

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Journal of Environmental Sciences 2010年第3期22卷 421-427页

作者： Pilar Zornoza Rocío milln M. Jos Sierra Almudena Seco Elvira Esteban Department of Agricultural Science Autonomous University of Madrid Francisco Tomsy Valiente 7. E-28049 Madrid Spain Research Center for Energy Environment and Technology Environmental Department. Soil Degradation Research Unit. Av. Complutense 22. E-28040 Madrid Spain

This study examined the ability of the white lupin to remove mercury （Hg） from a hydroponic system （Hg concentrations 0, 1.25, 2.5, 5 and 10 μmol/L） and from soil in pots and lysimeters （total Hg concentration （19.2 ± 1.9） mg/kg availability 0.07%, and （28.9 ± 0.4） mg/kg availability 0.09%, respectively）, and investigated the accumulation and distribution of Hg in different parts of the plant. White lupin roots efficiently took up Hg, but its translocation to the harvestable parts of the plant was low. The Hg concentration in the seeds posed no risk to human health according to the recommendations of the World Health Organization, but the shoots should not be used as fodder for livestock, at least when unmixed with other fodder crops. The accumulation of Hg in the hydroponically-grown plants was linear over the concentration range tested. The amount of Hg retained in the roots, relative to the shoots, was almost constant irrespective of Hg dose （90%）. In the soil experiments, Hg accumulation increased with exposure time and was the greater in the lysimeter than in the pot experiments. Although Hg removal was the greater in the hydroponic system, revealing the potential of the white lupin to extract Hg, bioaccumulation was the greatest in the lysimeter-grown plants; the latter system more likely reflects the true behaviour of white lupin in the field when Hg availability is a factor that limits Hg removal. The present results suggest that the white lupin could be used in long-term soil reclamation strategies that include the goal of profitable land use in Hg-polluted areas.

关键词： edible plant parts hydroponic-soil-lysimeter experiments Lupinus albus L. mercury

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Quaternary Climate and Environment in the Lop Nur,Xinjiang

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Acta Geologica Sinica(English Edition) 2000年第2期74卷 273-278页

作者： WANG mill PU Qingyu LIU Chenglin CHEN Yongzhi Geological Society of China 26 Baiwanzhuang Rd.Beijing 100037 Institute of Mineral Deposits Chinese Academy of Geological Sciences26 Baiwanzhuang Rd.Beijing 100037

Since the middle Early Pleistocene (1.20 Ma B.P.), the desert steppe climate and environment have predominated in the Lop Nur area, Xinjiang, characterized by warm humid epochs interrupted by dry cold intervals. The grain-size and magnetic susceptibility curves record 30 climatic oscillations, each with a ca. 40 ka cycle, in the area since 1.2 Ma B.P., which reflects the controlling effects exerted by the astronomic factor on the environment. The Quaternary sedimentary environment in the Lop Nur gradually changed from a fresh lake through a brackish lake to a saline lake, showing a spiral evolution, and finally it evolved into a playa.

关键词： Lop Nur Quaternary palaeoclimate sedimentary environment sporopollen

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Crystal-field levels of Nd3+ in a new langasite compound Nd3CrGe3Be2O14

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Journal of Rare Earths 2019年第11期37卷 1250-1254页

作者： Sergei A.Klimin Boris V.mill Marina N.Popova Institute of Spectroscopy Russian Academy of SciencesTroitskMoscow 108840Russia Faculty of Physics M.V.Lomonosov Moscow State UniversityMoscow 119991Russia

We report on the crystal-field(CF)levels of Nd^3+in Nd3CrGe3Be2O14,a representative of recently synthesized Be-containing langasites.They are the first in the family to contain two magnetic subsystems,1 D chromium and Kagome-like rare-earth ones.High-resolution broad-band temperature-dependent spectra allow us to find all five CF Kramers doublets of the ground 4I9/2 CF multiplet and 38 levels of the excited 4I11/2,13/2,15/2,4F3/2,4F5/2+2H9/2,4F7/2+4S3/2 and 4F9/2 CF multiplets.These data form a basis for a future exploration of this interesting two-sublattice magnet with frustrated interactions.Optical transitions between Kramers doublets of Nd^3+indicate magnetic activity of 1D-chromium chains at T<20 K.

关键词： Langasite Two magnetic subsystems High-resolution spectroscopy Crystal-field levels Magnetic correlations Rare earths

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Cellular targets in diabetic retinopathy therapy

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World Journal of Diabetes 2021年第9期12卷 1442-1462页

作者： María Lucía Rodríguez Iván millán Ángel Luis Ortega Department of Physiology Faculty of PharmacyUniversity of ValenciaBurjassot 46100ValenciaSpain Neonatal Research Group Health Research Institute La FeValencia 46026ValenciaSpain

Despite the existence of treatment for diabetes,inadequate metabolic control triggers the appearance of chronic complications such as diabetic retinopathy.Diabetic retinopathy is considered a multifactorial disease of complex etiology in which oxidative stress and low chronic inflammation play essential roles.Chronic exposure to hyperglycemia triggers a loss of redox balance that is critical for the appearance of neuronal and vascular damage during the development and progression of the disease.Current therapies for the treatment of diabetic retinopathy are used in advanced stages of the disease and are unable to reverse the retinal damage induced by hyperglycemia.The lack of effective therapies without side effects means there is an urgent need to identify an early action capable of preventing the development of the disease and its pathophysiological consequences in order to avoid loss of vision associated with diabetic retinopathy.Therefore,in this review we propose different therapeutic targets related to the modulation of the redox and inflammatory status that,potentially,can prevent the development and progression of the disease.

关键词： Diabetic retinopathy Oxidative stress Inflammation Cellular target Diabetic macular edema

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