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Development of a Ready-to-Use PsMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio stephano João Ezequiel Oliveira carlos.roberto jorge s.ares.ana cláudia camargo miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda Garcia Luiz Felipe s. Teixeira Maria Helena Marumo Bellini Natanael Gomes da silva Luiza Mascarenhas Balieiro Joel Mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil Departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PsMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PsMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PsMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DsC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PsMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PsMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PsMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PsMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PsMA-11 Prostate-specific Membrane Antigen (PsMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging

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High-resolution multi-scale air pollution system:Evaluation of modelling performance and emission control strategies

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Journal of Environmental sciences 2024年第3期137卷 65-81页

作者： Diogo Lopes Joana Ferreira sandra Rafael Ka In Hoi Xin Li Yuan Liu Ka-Veng Yuen Kai Meng Mok ana Isabel miranda Department of Environment and Planning&CEsAM University of AveiroAveiroPortugal Department of Civil&Environmental Engineering Faculty of Science and TechnologyUniversity of MacaoMacao SARChina

A high percentage of the world's population lives in areas where air pollutant concentrations exceed the World Health Organization *** work aims to develop and test,a high-resolution multi-scale air pollution modelling system by integrating a set of adequate *** system is able to provide detailed air pollutant concentrations in urban areas and support air quality management strategies through a better identification of different atmospheric *** also allows furthering the design and assessment of air pollution control measures for a specific *** evaluate its performance and suitability,the system was applied to the Macao special Administrative Region(sAR),China,one of the most densely populated areas on earth,during a winter period when this area is affected by high levels of Particulate Matter(PM).Although the developed system tends to underestimate the PM concentrations,it revealed a good performance in reproducing the temporal and spatial air pollution *** exceedances of the Chinese air quality standards were calculated and high population exposure to PM pollution was *** tested urban atmospheric emission reduction scenarios have shown air quality improvements,indicating that emission reduction measures at urban level should focus on the domestic ***,it is crucial to implement joint pollution prevention strategies with neighbouring regions to improve the air quality in Macao *** approach developed in this work can support policymakers in defining new strategies to reduce atmospheric pollution in urban areas.

关键词： Urban areas High-resolution emission inventory Particulate matter Population exposure

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Testicular prostheses-impact on quality of life and sexual function

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Asian Journal of Andrology 2024年第2期26卷 160-164页

作者： ana sofia Araujo sara anacleto Ricardo Rodrigues Catarina Tinoco Andreia Cardoso carlos Oliveira Ricardo Leao Department of Urology Braga's HospitalBraga 4710Portugal Faculty of Medicine Coimbra UniversityCoimbra 3000Portugal

Orchiectomy is the recommended treatment for many testicular ***,testicular prosthesis placement is not always performed for different *** this study,we aimed to evaluate patients'opinions and the impact on sexual function and quality of *** retrospective observational single-center study included patients who underwent orchiectomy between January 2014 and December 2020 at the Department of Urology,Braga's Hospital(Braga,Portugal),where testicular implants were always available and the decision to undergo the procedure was made fully independent of *** completed four questionnaires that assessed demographic data,satisfaction,self-esteem,and sexual *** the 96 patients who underwent orchidectomy,59 replied to the questionnaires,and of these patients,86.4%decided to undergo silicone-based testicular prostheses *** remaining 13.6%refused the implant based on concerns about complications(37.5%),because they felt that it was unnecessary(37.5%),or because it was not offered by the doctor(25.0%).Overall,96.1%of these patients were satisfied with the implant;however,25.5%classified it as"too firm".No statistically significant differences were found in sexual function(all P>0.05).However,it can be observed that there are more patients with prostheses presenting normal sexual activity compared to patients without prostheses(74.0%vs 50.0%),and none of them reported severe erectile dysfunction(0 vs 16.7%).Regarding self-esteem,both patients with and without prostheses present very similar average scores with no statistically significant *** present study highlights the highest level of satisfaction among patients who received testicular *** prostheses implantation is a safe procedure that does not hamper sexual function after orchiectomy.

关键词： orchiectomy patient satisfaction quality of life sexual dysfunction sexual health testicular prostheses

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A review on the scale-up of high-shear wet granulation processes and the impact of process parameters

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Particuology 2024年第9期92卷 180-195页

作者： ana Rita Alves Marta Filipe simões sérgio simões João Gomes University of Coimbra CERESDepartment of Chemical EngineeringFaculty of Sciences and TechnologyRua Sílvio Lima3030-790CoimbraPortugal Bluepharma-Indústria Farmacêutica São Martinho do BispoCoimbra3045-016Portugal Faculty of Pharmacy University of CoimbraAzinhaga de Santa Comba3000-548CoimbraPortugal

Wet granulation is one of the most important agglomeration processes,and high-shear granulation(HsG)one of the most employed technologies in the pharmaceutical *** most critical process parameters of HsG are discussed in this *** main concern in scaling up the wet granulation process is the differences between scales,which prevent the particles from having the same experience across all *** scale-up of wet granulation processes is commonly divided into two categories:engineering and attribute-based *** engineering-based scale-up approach is a strategy based on dimensional analysis and an attribute-based supported on the principles of“equifinality”,where process variables are adjusted to obtain equivalent granule *** work presents the effect of different HsG process parameters on the scale-up,as well as the use of process analytical tools(PAT)and modelling *** aim is to review applied scale-up approaches in HsG and discuss benefits and *** is proven why the scale-up for oral solid pharmaceutical products is still considered a hot topic and a very challenging task for development and engineering teams.

关键词： High-shear wetgranulation Parametric-based Attribute-based Physics-based modelling Impeller design scale-up

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The dorsal root ganglion as a target for neurorestoration in neuropathic pain

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Neural Regeneration Research 2024年第2期19卷 296-301页

作者： Guillermo Estivill-Torrús ana Belen Martínez-Padilla Lourdes sánchez-salido Anne Baron-Van Evercooren Beatriz García-Díaz Instituto de Investigación Biomédica de Málaga y Plataforma en Nanomedicina(IBIMA Plataforma BIONAND) MálagaSpain Unidad clínica de Neurociencias Hospital Regional Universitario de MálagaMálagaSpain Departamento de Biología Molecular y Bioquímica Universidad de MálagaSpain sorbonne Université Institut du Cerveau-Paris Brain Institute-ICMINSERMCNRSAP-HPHôpital Pitié-SalpêtrièreParisFrance

Neuropathic pain is a severe and chronic condition widely found in the general *** reason for this is the extensive variety of damage or diseases that can spark this unpleasant constant feeling in *** the processing of pain,the dorsal root ganglia constitute an important region where dorsal root ganglion neurons play a crucial role in the transmission and propagation of sensory electrical ***,the dorsal root ganglia have recently exhibited a regenerative capacity that should not be neglected in the understanding of the development and resolution of neuropathic pain and in the elucidation of innovative ***,we will review the complex interplay between cells(satellite glial cells and inflammatory cells)and factors(cytokines,neurotrophic factors and genetic factors)that takes place within the dorsal root ganglia and accounts for the generation of the aberrant excitation of primary sensory neurons occurring in neuropathic *** importantly,we will summarize an updated view of the current pharmacologic and nonpharmacologic therapies targeting the dorsal root ganglia for the treatment of neuropathic pain.

关键词： cytokines dorsal root ganglia genetic factors neuropathic pain neurotrophic factors pharmacologic and nonpharmacologic therapies satellite glial cells sensory neurons

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Towards efficient strain engineering of 2D materials:A four-points bending approach for compressive strain

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Nano Research 2024年第6期17卷 5317-5325页

作者： Hao Li Félix Carrascoso ana Borrás Gloria P.Moreno Francisco J.Aparicio Ángel Barranco Andrés Castellanos Gómez Campus de Cantoblanco Instituto de Ciencia de Materiales de MadridC.Sor Juana Inés de la Cruz328049 MadridSpain Nanotechnology on surfaces and Plasma Lab Instituto de Ciencia de Materiales de Sevilla(CSIC-Universidad de Sevilla).C/Americo Vespucio 49E-41092 SevilleSpain Departamento de Física Aplicada I Escuela Politécnica SuperiorUniversidad de Sevillac/Virgen deÁfrica 7E-41011 SevilleSpain

strain engineering,as a powerful strategy to tune the optical and electrical properties of two-dimensional(2D)materials by deforming their crystal lattice,has attracted significant interest in recent years.2D materials can sustain ultra-high strains,even up to 10%,due to the lack of dangling bonds on their surface,making them ideal brittle *** remarkable mechanical resilience,together with a strong strain-tunable band structure,endows 2D materials with a broad optical and electrical response upon ***,strain engineering based on 2D materials is restricted by their nanoscale and strain quantification *** this study,we have modified a homebuilt three-points bending apparatus to transform it into a four-points bending apparatus that allows for the application of both compressive and tensile strains on 2D *** approach allows for the efficient and reproducible construction of a strain system and minimizes the buckling effect caused by the van der Waals interaction by adamantane encapsulation *** results demonstrate the feasibility of introducing compressive strain on 2D materials and the potential for tuning their optical and physical properties through this approach.

关键词： uniaxial compressive strain polymer encapsulation differential reflectance spectroscopy exciton tunability

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Laminated solid Timber slab with Transverse Prestressing Using the strategy of Interleaved Vertical Displacement of Lamellae

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Journal of Civil Engineering and Architecture 2024年第4期18卷 186-198页

作者： Bianca Bispo dos Reis jorge Daniel de Melo Moura Marcos Vinício de camargo Everaldo Pletz Graduate Program in Architecture and Urbanism Londrina State UniversityJardim Portal de Versalhes 1Londrina 86057-970PRBrazil Department of Civil Engineering Federal Technological University of Paraná(UTFPR)Apucarana 86812-460PRBrazil Retired professor Department of structural Engineering Londrina State UniversityLondrina 86057-970PRBrazil

This article presents a study on the structural behavior of transversely prestressed laminated timber slabs,focusing on an innovative approach:vertically misaligned *** misalignment,achieved by sliding vertically the wooden lamellae rather than aligning them,enhances the slab’s cross-section moment of inertia,thereby improving load-bearing capacity and *** involved two groups of structural size specimens:one with vertically aligned lamellae(control group)and the other with misaligned lamellae(study group).Results showed the study group exhibited 42%superior stiffness and 10%less load capacity compared to the *** typically occurred individually in the lamellae,particularly in those with defects or lower modulus of elasticity,concentrated in the middle third of the slabs’free span where tensile stresses *** a higher number of failed lamellae,the study group demonstrated promising *** of prestressing bar indicated no damage at all in the thread,suggesting potential for reducing bar *** findings offer crucial insights into applying these slabs in timber construction as well as to any kind of construction.

关键词： Transversal prestressed slabs wooden construction plantation wood flexural testing design methodology

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Colorectal cancer screening:A review of current knowledge and progress in research

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1119-1133页

作者： sara Ramos Lopes claudio Martins Inês Costa santos Madalena Teixeira Élia Gamito ana Luisa Alves Department of Gastroenterology Centro Hospitalar de SetúbalSetúbal 2910-446Portugal

Colorectal cancer(CRC)is one of the most prevalent malignancies worldwide,being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths *** the progress in screening,early diagnosis,and treatment,approximately 20%-25%of CRC patients still present with metastatic disease at the time of their initial ***,the burden of disease is still expected to increase,especially in individuals younger than 50 years old,among whom early-onset CRC incidence has been *** and early detection are pivotal to improve CRC-related *** is well established that CRC screening not only reduces incidence,but also decreases deaths from *** screening strategies have proven effective in decreasing both CRC incidence and mortality,though variations in efficacy have been reported across the ***,uncertainties persist regarding the optimal screening method,age intervals and ***,adherence to CRC screening remains globally *** recent years,emerging technologies,notably artificial intelligence,and non-invasive biomarkers,have been developed to overcome these ***,controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily *** this review,we aim to cover the current evidence surrounding CRC *** will further critically assess novel approaches under investigation,in an effort to differentiate promising inno-vations from mere novelties.

关键词： Colorectal cancer screening Review Oncology Artificial intelligence

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Hydroxytyrosol and Parkinson's disease:protective actions against alpha-synuclein toxicity

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Neural Regeneration Research 2024年第7期19卷 1427-1428页

作者： Ruth Hornedo-Ortega ana M.Espinosa-Oliva Departamento de Nutrición y Bromatología Toxicología y Medicina LegalFacultad de FarmaciaUniversidad de SevillaSevilleSpain Instituto de Biomedicina de sevilla IBiS/Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Departamento de Bioquímica y Biología Molecular Facultad de FarmaciaUniversidad de SevillaSevillaSpain

Parkinson’s disease:Parkinson’s disease(PD) is the second most prevalent neurodegenerative disease,after Alzheimer’s disease,affecting 1%of the general population over the age of *** to data from the World Health Organization(WHO),its prevalence has doubled in the past 25 *** 2019,global estimates indicated over 8.5 million individuals with PD and it is suggested that PD caused 329000 deaths,an increase of over 100% since 2000(WHO,2022).

关键词： protective Alzheimer prevalence

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A comprehensive look at the psychoneuroimmunoendocrinology of spinal cord injury and its progression: mechanisms and clinical opportunities

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Military Medical Research 2024年第2期11卷 228-267页

作者： Miguel A.Ortega Oscar Fraile-Martinez Cielo García-Montero sergio Haro Miguel Ángel Álvarez-Mon Diego De Leon-Oliva ana M.Gomez-Lahoz jorge Monserrat Mar Atienza-Pérez David Díaz Elisa Lopez-Dolado Melchor Álvarez-Mon Department of Medicine and Medical specialities University of Alcala28801 Alcala de HenaresSpain Ramón y Cajal Institute of sanitary Research(IRYCIs) 28034 MadridSpain Department of Psychiatry and Mental Health Hospital Universitario Infanta Leonor28031 MadridSpain service of Rehabilitation National Hospital for Paraplegic PatientsCarr.de la PeraledaS/N45004 ToledoSpain Immune system Diseases‑Rheumatology service and Internal Medicine University Hospital Príncipe de Asturias(CIBEREHD)28806 Alcala de HenaresSpain

spinal cord injury(sCI)is a devastating and disabling medical condition generally caused by a traumatic event(primary injury).This initial trauma is accompanied by a set of biological mechanisms directed to ameliorate neural damage but also exacerbate initial damage(secondary injury).The alterations that occur in the spinal cord have not only local but also systemic consequences and virtually all organs and tissues of the body incur important changes after sCI,explaining the progression and detrimental consequences related to this ***(PNIE)is a growing area of research aiming to integrate and explore the interactions among the different systems that compose the human organism,considering the mind and the body as a *** initial traumatic event and the consequent neurological disruption trigger immune,endocrine,and multisystem dysfunction,which in turn affect the patient's psyche and *** the present review,we will explore the most important local and systemic consequences of sCI from a PNIE perspective,defining the changes occurring in each system and how all these mechanisms are ***,potential clinical approaches derived from this knowledge will also be collectively presented with the aim to develop integrative therapies to maximize the clinical management of these patients.

关键词： spinal cord injury(sCI) Psychoneuroimmunoendocrinology(PNIE) secondary injury Immunoinflammatory dysfunction Gut microbiota Translational opportunities

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