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Engineering hyaluronic acid-based nanoassemblies for monoclonal antibody delivery-design,characterization,and biological insights

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Nano Research 2024年第10期17卷 9111-9125页

作者： ana M.López-Estévez Y.Zhang María Medel Iker Arriaga Lucía Sanjurjo Cristian Huck-Iriart Nicola G.A.Abrescia María J.Vicent Defang Ouyang Dolores Torres María José Alonso Center for Research in Molecular Medicine and Chronic Diseases(CiMUS) University of Santiago de CompostelaSantiago de Compostela 15782Spain Department of Pharmacology Pharmacy and Pharmaceutical TechnologySchool of PharmacyUniversity of Santiago de CompostelaSantiago de Compostela 15782Spain Health Research Institute of Santiago de Compostela(IDIS) Santiago de Compostela 15782Spain State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences(ICMS)University of MacaoMacao 999078China Polymer Therapeutics Laboratory and CIBERONC Prince Felipe Research Centre Valencia E-46012Spain Structure and Cell Biology of Viruses Lab CIC bioGUNEBasque Research and Technology Alliance(BRTA)Derio 48160Spain ALBA Synchrotron Light Source Experiments DivisionCerdanyola del VallèsBarcelona 08290Spain IKERBASQUE Basque Foundation for ScienceBilbao 48009Spain

The current spotlight of cancer therapeutics is shifting towards personalized medicine with the widespread use of monoclonal antibodies(mAbs).Despite their increasing potential,mAbs have an intrinsic limitation related to their inability to cross cell membranes and reach intracellular *** offers promising solutions to overcome this limitation,however,formulation challenges *** challenges are the limited loading capacity(often insufficient to achieve clinical dosing),the complex formulation methods,and the insufficient characterization of mAb-loaded ***,we present a new nanocarrier consisting of hyaluronic acid-based nanoassemblies(Hanas)specifically designed to entrap mAbs with a high efficiency and an outstanding loading capacity(50%,w/w).Hanas composed by an mAb,modified HA and phosphatidylcholine(PC)resulted in sizes of~100 nm and neutral surface *** modeling identified the principal factors governing the high affinity of mAbs with the amphiphilic HA and *** composition and structural configuration were analyzed using the orthogonal techniques cryogenic transmission electron microscopy(cryo-TEM),asymmetrical flow field-flow fractionation(AF4),and small-angle X-ray scattering(SAXS).These techniques provided evidence of the formation of core-shell nanostructures comprising an aqueous core surrounded by a bilayer consisting of phospholipids and amphiphilic *** vitro experiments in cancer cell lines and macrophages confirmed Hanas’low toxicity and ability to transport mAbs to the intracellular *** reproducibility of this assembling process at industrial-scale batch sizes and the long-term stability was *** conclusion,these results underscore the suitability of Hanas technology to load and deliver biologicals,which holds promise for future clinical translation.

关键词： monoclonal antibody nanoparticles hyaluronic acid characterization particle size computational modeling

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Neuroprotective effects of G9a inhibition through modulation of peroxisome-proliferator activator receptor gamma-dependent pathways by miR-128

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Neural Regeneration Research 2024年第11期19卷 2532-2542页

作者： Aina Bellver-Sanchis Pedro AAvila-López Iva Tic David Valle-García Marta Ribalta-Vilella Luis Labrador Deb Ranjan Banerjee ana Guerrero Gemma Casadesus Coralie Poulard Mercè Pallàs Christian Grinán-Ferré Department of Pharmacology and Therapeutic Chemistry Institut de Neurociències-Universitat de BarcelonaBarcelonaSpain Department of Biochemistry and Molecular Genetics Feinberg School of MedicineNorthwestern UniversityChicagoILUSA Institute of Biotechnology National Autonomous University of MexicoCuernavacaMexico Department of Pharmacology and Therapeutics Health Science Center-University of FloridaGainesvilleFLUSA Department of Chemistry National Institute of Technology DurgapurM G AvenueDurgapurWest BengalIndia Cancer Research Cancer Lyon Universitéde LyonLyonFrance Inserm U1052 Centre de Recherche en Cancérologie de LyonLyonFrance CNRS UMR5286 Centre de Recherche en Cancérlogie de LyonLyonFrance Centro de Investigación en Red Enfermedades Neurodegenerativas(CIBERNED)Instituto de Salud Carlos IIIMadridSpain Neuroimmunology Department National Institute of Neurology and Neurosurgery“Manuel Velasco Suárez”Mexico CityMexico

Dysregulation of G9a,a histone-lysine N-methyltransferase,has been observed in Alzheimer’s disease and has been correlated with increased levels of chronic inflammation and oxidative ***,microRNAs are involved in many biological processes and diseases playing a key role in pathogenesis,especially in multifactorial diseases such as Alzheimer’s ***,our aim has been to provide partial insights into the interconnection between G9a,microRNAs,oxidative stress,and *** better understand the biology of G9a,we compared the global microRNA expression between senescence-accelerated mouse-prone 8(SAMP8)control mice and SAMP8 treated with G9a inhibitor *** found a downregulation of miR-128 after a G9a inhibition treatment,which interestingly binds to the 3′untranslated region(3′-UTR)of peroxisome-proliferator activator receptor γ(PPARG)***,Pparg gene expression levels were higher in the SAMP8 group treated with G9a inhibitor than in the SAMP8 control *** also observed modulation of oxidative stress responses might be mainly driven Pparg after G9a *** confirm these antioxidant effects,we treated primary neuron cell cultures with hydrogen peroxide as an oxidative *** this setting,treatment with G9a inhibitor increases both cell survival and antioxidant ***,up-regulation of PPARγby G9a inhibitor could also increase the expression of genes involved in DNA damage responses and *** addition,we also described that the PPARγ/AMPK axis partially explains the regulation of autophagy markers ***,PPARγ/GADD45αpotentially contributes to enhancing synaptic plasticity and neurogenesis after G9a ***,we propose that pharmacological inhibition of G9a leads to a neuroprotective effect that could be due,at least in part,by the modulation of PPARγ-dependent pathways by miR-128.

关键词： aging cognitive decline epigenetics G9a inhibition microRNAs miR-128 peroxisome-proliferator activator receptorγ(PPARγ) PPARG SAMP8

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基于艺术治疗方法的护理干预在边缘型人格障碍患者中的应用

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International Journal of Nursing Sciences 2024年第2期11卷 205-213页

作者： ana Morales-Alonso Angela Iglesias-de-la-Iglesia Miriam Alonso-Maza Dr.Rodríguez Lafora Hospital(Hospital Dr.Rodríguez Lafora) MadridSpain Department of Nursing and Stomatology University Rey Juan CarlosAlcorconMadridSpain

目的ZentangleR艺术治疗方法被应用于心理健康相关领域,尚未在边缘型人格障碍患者得到验证。本研究分析边缘型人格障碍患者接受ZentangleR艺术治疗方法的练习体验。方法采用现象学解释方法,对患者进行半结构化访谈。患者均已在西班牙某... 详细信息

目的ZentangleR艺术治疗方法被应用于心理健康相关领域,尚未在边缘型人格障碍患者得到验证。本研究分析边缘型人格障碍患者接受ZentangleR艺术治疗方法的练习体验。方法采用现象学解释方法,对患者进行半结构化访谈。患者均已在西班牙某医院的人格障碍治疗室接受了每个月1次,共6次ZentangleR艺术治疗。本研究中共访谈了15例患者。Smith、Flowers和Larkin方法用于资料分析中的评估。结果根据研究结果,共提炼出3个类别的主题:有耕耘即有收获(参与者报告了注意力、放松、人际关系、与环境互动方面的改善,以及接受和改变的积极体验);众擎易举(患者认可在团体中感觉更好,并建立了相互联系;他们也描述了团体环境对个人行为的影响);画出自己的轨迹(通过绘画方式提供了自我表达和自我认识的媒介,通过情感表达提升了幸福感,提高了创造力,增强了自信心)。结论通过练习ZentangleR,患者可以作出灵活性和适应性等行为反应,通过焦虑管理、冲动控制改善情绪健康,学习应对问题,提高自尊或注意力。心理健康护理在边缘型人格的综合治疗及协同多样化补充性干预措施中发挥着积极作用。

关键词：艺术治疗边缘型人格障碍心理健康护理 Zentangle®

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The biosynthetic pathway of the hallucinogen mescaline and its heterologous reconstruction

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Molecular Plant 2024年第7期17卷 1129-1150页

作者： Paula Berman Luis Alejandro de Haro ana-Rita Cavaco Sayantan Panda Younghui Dong Nikolay Kuzmich Gabriel Lichtenstein Yoav Peleg Hila Harat Adam Jozwiaki Jianghua Cai Uwe Heinig Sagit Meir Ilana Rogachev Asaph Aharoni Department of Plant and Environmental Sciences Weizmann Institute of ScienceRehovot 7610001Israel Life Sciences Core Facilities Weizmann Institute of ScienceRehovot 7610001Israel The Maurice and Vivienne Wohl Institute for Drug Discovery Weizmann Institute of ScienceRehovot 7610001Israel Present address:Department of Cell and Metabolic Biology Leibniz Institute of Plant BiochemistryWeinberg 306120 Halle(Saale)Germany Department of Molecular&Cellular Pharmacology University of Miami Miler School of MedicineMiamiFL 33136USA Department of Botany and Plant Sciences University of California RiversideRiversideCA 92521USA Laboratory of Plant Hormones and Development Regulation of Chongqing School of Life SciencesChongqing UniversityChongqing 401331China

Mescaline,among the earliest identified natural hallucinogens,holds great potential in psychotherapy ***,despite the existence of a postulated biosynthetic pathway for more than half a century,the specific enzymes involved in this process are yet to be *** this study,we investigated the cactus Lophophora williamsii(Peyote),the largest known natural producer of the phenethylamine *** employed a multi-faceted approach,combining de novo whole-genome and transcriptome sequencing with comprehensive chemical profiling,enzymatic assays,molecular modeling,and pathway engineering for pathway *** identified four groups of enzymes responsible for the six catalytic steps in the mescaline biosynthetic pathway,and an N-methyltransferase enzyme that N-methylates all phenethylamine intermediates,likely modulating mescaline levels in ***,we reconstructed the mescaline biosynthetic pathway in both Nicotiana benthamiana plants and yeast cells,providing novel insights into several challenges hindering complete heterologous mescaline *** together,our study opens up avenues for exploration of sustainable production approaches and responsible utilization of mescaline,safeguarding this valuable natural resource for future generations.

关键词： mescaline Lophophora williamsi Peyote biosynthetic pathway de novo genome sequencing mo-lecular modeling

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Platelet-rich plasma treatment for chronic wounds:A case report and literature review

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World Journal of Clinical Cases 2024年第33期12卷 6635-6643页

作者： ana Dimova Martin Boroš Stefan Dimov Janja Konjevod Maja Svetec Department of Surgery Zabok General Hospital and the Croatian Veterans HospitalZabok 49210Croatia Department of Surgery St Catherine Specialty HospitalZagreb 10000Croatia Department of Emergency Medicine Zabok General Hospital and the Croatian Veterans HospitalZabok 49210Croatia

BACKGROUND Wound healing is a complicated process that can be heavily influenced by patient comorbidities,in some cases leading to a chronic non-healing *** presented in the medical literature supporting the clinical use of autologous platelet-rich plasma(PRP)in treatment of such wounds is becoming increasingly *** involved include complex interactions between the patient’s thrombocytes,cytokines,and growth *** SUMMARY We present a case of a 72-year-old male patient with a long-standing chronic wound and multiple *** the course of more than 7 months,the patient was unsuccessfully treated with all routinely used measures,including different dressing *** antibiotic regimens were administered for wound infection,with repeated evaluation of microbiological swab ***,after three PRP applications,the wound showed clinical improvement with complete restitution of the epithelial layer of the *** PRP treatment may be beneficial to reduce healing time in chronic wounds.

关键词： Wound healing Platelet-rich plasma Growth factors Antibiotics Wound Infection Case report

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Giant Cystic and Mediastinal Parathyroid Adenoma with Non-Uptake in Scintigraphy

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Journal of Cancer Therapy 2018年第11期9卷 850-856页

作者： Raquel alfonso-Ballester ana Izquierdo Moreno Rosa Martí fernández Nicolás Tarigo Norberto Cassinello fernández Joaquin Ortega Serrano Department of Surgery Clinic University Hospital of Valencia Valencia Spain General Surgery Department Clinic Hospital Faculty of Medicine Republic University Montevideo Uruguay

Introduction: In 85% of patients, the cause of Primary Hyperparathyroidism (PHPT) is an adenoma. Parathyroid adenoma localization is usually simple. 96% of localizations prior to surgery are achieved with ultrasound and scintigraphy combination. Difficulties can appear. If the gland is not located in a cervical position and has no uptake in scintigraphy but there is high suspition of an adenoma causing the PHPT, some extra tests should be considered. Case Report: We present a case of giant cystic mediastinal adenoma, a quite rare condition, which was diagnosed as a thyroid colloid cyst by ultrasound, and was not localized by scintigraphy. We report the CT scan and the magnetic resonance imaging (MRI) images that show the tumour. It was surgically resected by a cervical approach. After the excision, the patient recovered normal levels of Calcium and Parathormone (PTH). Conclusion: We review literature about cystic and mediastinal adenomas and diagnostic methods when the standard ones do not give an accurate localization diagnosis.

关键词： Primary Hyperparathyroidism Cystic Parathyroid Adenoma Mediastinal Parathyroid Adenoma

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Systemic epigallocatechin gallate protects against retinal degeneration and hepatic oxidative stress in the P23H-1 rat

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Neural Regeneration Research 2022年第3期17卷 625-631页

作者： Lorena Perdices Lorena Fuentes-Broto Francisco Segura ana Cavero Elvira Orduna-Hospital Gema Insa-Sánchez ana Isabel Sánchez-Cano Laura fernández-Sánchez Nicolás Cuenca Isabel Pinilla Aragón Institute for Health Research(IIS Aragón) ZaragozaSpain Pharmacology Physiology&Legal and Forensic MedicineUniversity of ZaragozaZaragozaSpain Department of Applied Physics University of ZaragozaZaragozaSpain Health Sciences Faculty San Jorge UniversityVillanueva de GállegoSpain Department of Ophthalmology Miguel Servet University HospitalZaragozaSpain Department of Physiology Genetics and MicrobiologyUniversity of AlicanteAlicanteSpain Department of Surgery Gynecology and ObstetricsUniversity of ZaragozaZaragozaSpain/Department of OphthalmologyLozano Blesa University HospitalZaragozaSpain

Retinitis pigmentosa(RP) is a group of inherited retinal disorders that lead to photoreceptor *** has been reported to be related to oxidative stress,autophagy,and inflammation.(-)-Epigallocatechin gallate(EGCG),the most abundant catechin-based flavonoid in green tea leaves,has significant antioxidant,anti-carcinogenic,antimicrobial,and neuroprotective ***,given its low molecular weight and hydrophilic properties,can cross the blood-retinal barrier and is able to reach different ocular tissues such as the lens,cornea,and *** has been shown to provide retinal protection against ischemia;sodium nitroprusside-,N-methyl-D-aspartate-,lipopolysaccharide-,light-,sodium iodate-,or H2 O2-induced damage and diabetic *** suggests that systemic EGCG administration has the potential to protect against retinal degenerative or neurodegenerative diseases such as *** aim of this work was to investigate whether EGCG can protect against RP progression in the animal P23 H line 1,the model of *** P23 H rats were crossed with pigmented Long Evans rats to produce offspring exhibiting the clinical features of *** P23 H rats were treated via intraperitoneal injection with saline or EGCG at a dose of 25 mg/kg every week from P100 to P160 and then compared to wild-type Long Evans *** treated with EGCG showed better visual and retinal electrical function with increased contrast sensitivity and b-wave values compared with those observed in P23 H rats treated with *** reduced lipid peroxidation and increased total antioxidant capacity and catalase and superoxide dismutase *** differences were observed in visual acuity,nitrate levels,nitrite levels or glutathione S-transferase *** conclusion,EGCG not only reduced the loss of visual function in P23 H rats but also improved the levels of antioxidant enzymes and reduced oxidative *** study was approved by the Institutional Animal Care and Use Committee(CE

关键词： antioxidants contrast sensitivity electroretinogram green tea neurodegeneration oxidative stress retinal degeneration retinitis pigmentosa systemic visual acuity

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Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

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World Journal of Cardiology 2024年第8期16卷 448-457页

作者： Petra Grubić Rotkvić Luka Rotkvić ana Đuzel Čokljat Maja Cigrovski Berković Department of Cardiology University Hospital Centre ZagrebZagreb 10000Croatia Department of Cardiology Magdalena Clinic for Cardiovascular DiseaseKrapinske Toplice 49217Croatia Department of Internal Medicine General Hospital DubrovnikDubrovnik 20000Croatia Department for Sport and Exercise Medicine University of Zagreb Faculty of KinesiologyZagreb 10000Croatia

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of *** previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic *** groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic *** To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body *** The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood *** evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was *** There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of *** independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy *** SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic *** control contributes to the i

关键词： Sodium-dependent glucose transporter 2 inhibitors Dipeptidyl peptidase-4 inhibitors Type 2 diabetes mellitus Heart failure Diabetic cardiomyopathy Cardiovascular disease

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A Novel and Functional Artificial Bruch’s Membrane Made of Poly (ε-Caprolactone)/Gelatin for Retinal Pigment Epithelium Restoration

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Advances in Bioscience and Biotechnology 2024年第8期15卷 443-461页

作者： López Edith Silva-Bermudez Phaedra Gonzalez-Salinas Roberto Velasquillo Cristina Torres-Romero Abigail López-Colomé ana María Pérez Armando Gina Prado-Prone Edgar Ramos-Martínez Iván Ramos-Martínez Quiroz-Mercado Hugo Hernández-Zimbrón Luis fernando Instituto de Fisiologa Celular Universidad Nacional Autnoma de Mxico Ciudad de Mxico City Mxico Unidad de Ingeniería de Tejidos Terapia Celular y Medicina Regenerativa Instituto Nacional de Rehabilitación Luis Guiller-mo Ibarra Ibarra Ciudad de México México Departamento de Investigacin Asociacin Para Evitar la Ceguera Ciudad de Mxico Mxico Subdireccin de Investigacin Tecnolgica Instituto Nacional de Rehabilitacin Luis Guillermo Ibarra Ibarra Ciudad de Mxico Mxico Departamento de Biologa Celular y Tisular Facultad de Medicina Universidad Nacional Autnoma de Mxico Ciudad de Mxico Mxico Escuela de Ciencias Universidad Autnoma Benito Jurez de Oaxaca Oaxaca Mxico Departamento de Medicina y Zootecnia de Cerdos Facultad de Medicina Veterinaria y Zootecnia Universidad Nacional utnoma de Mxico Mxico Laboratorio de Investigacion Interdisciplinaria rea de Optometria Escuela Nacional de Estudios Superiores Unidad Len Universidad Nacional Autnoma de Mxico Len Guanajuato Mxico Laboratorio Nacional de ptica de la Visin-Centro de Investigaciones en ptica Len Guanajuato Mxico

Purpose: The primary aim of this paper is to design, create, and improve functional and artificial Bruch’s membranes (BM) using bioengineering techniques, which can be applied in the treatment of maculopathies by supporting the growth and maintenance of retinal pigment epithelium (RPE) cells, thereby potentially enabling subretinal implantation in patients. Methods: We fabricated by electrospinning ultrathin 3D nanofibrous membranes from Polycaprolactone (PCL), and different concentrations of gelatin (5%, 15% and 30%). ARPE-19 cells were seeded onto these artificial membranes. MTT assays were performed in order to evaluate ARPE-19 cell viability and cytotoxicity. IF assays were realized to observe the ARPE-19 cells onto each membrane. Ultrastructure of the modified Bruch’s membrane and ARPE-19 morphology after 25 days of culture were studied with transmission and scanning electron microscopy. To evaluate expression changes in markers of ARPE-19 (RPE65 and ZO-1) qRT-PCR assays were realized. Data from three independent experiments were pooled and expressed as the mean SD. A confidence level of P 0.05 was considered to be statistically significant. Results ARPE-19 cells grew on PCL/Gelatin membranes mainly in PCL/30% gelatin combination, which had not cytotoxic effect. RPE65/cytokeratin-18/ and actin-positive ARPE-19 cells formed a correctly orientated monolayer of polygonal cells with morphological polarity. The apical cell surfaces exhibited abundant protruding microfolds. Moreover, zones of polygonal border look as if ARPE-19 cells fused among, suggesting the presence of tight junctions. The expression of RPE65 and ZO-1 was unchanged. Conclusions: PCL/30% Gelatine membranes may imitate the natural BM to such extent that they support RPE-cells and exhibited RPE-like morphology. The engineering of a human RPE monolayer with these artificial BM, emulating the in vivo retina, arouse their potential subretinal implantation in patients with wet age-related macular degene

关键词： Artificial Bruch’s Membrane Electrospinning ARPE-19 Cells Age-Related Macular Degeneration

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Historical fluxes of metal and metalloids in an aquatic ecosystem affected by land-use change and mining activities in northwestern Mexico

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International Journal of Sediment Research 2023年第5期38卷 724-738页

作者： Ochoa-Contreras Roberto Jara-Marini Martín Enrique Ruiz-fernández ana Carolina Sanchez-Cabeza Joan Albert Meza-Figueroa Diana Pérez-Bernal Libia Hascibe Posgrado en Ciencias Centro de Investigación en Alimentación y Desarrollo Unidad Hermosillo 2. Centro de Investigación en Alimentación y Desarrollo Unidad Hermosillo Unidad Acad emica Mazatlán Instituto de Ciencias del Mar y Limnología Universidad Nacional Autónoma de M exico Departamento de Geología División de Ciencias Exactas y Naturales Universidad de Sonora Rosales y Encinas

Freshwater reservoirs are essential owing because of their ecological, economic, and social *** are particularly vulnerable to contamination, as of metal and metalloids, derived from anthropogenic activities like mining. The temporal variations in trace element concentrations(arsenic(As),mercury(Hg), chromium(Cr), copper(Cu), nickel(Ni), lead(Pb), and zinc(Zn)), enrichment, fluxes, and possible sources were evaluated by studying two sediment cores from the La Angostura(ANG) Reservoir(northwest Mexico), using210Pb geochronology. The enrichment factors showed from null to minor enrichment for most elements, but moderate to severe enrichment of mercury(Hg). Most trace element concentrations had a detrital origin, and notable Hg concentration increases since the past decade were associated with severe drought periods, likely resulting from wildfires. The observed sediment concentrations of As and Hg can cause adverse effects on biota in the ecosystem since they are above the probable effect level(PEL). Development of strategies for metal attenuation in this reservoir is recommended and metals should be controlled until specific ecotoxicological studies are performed.

关键词： Aquatic ecosystems ~(210)Pb geochronology Mining activities Metals Metalloids Enrichment factors

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