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Influence of railway wheel tread damage on wheel-rail impact loads and the durability of wheelsets

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Railway Engineering Science 2024年第1期32卷 20-35页

作者： Michele Maglio Tore Vernersson Jens C.O.Nielsen Anders Ekberg elena Kabo CHARMEC Department of Mechanical and Maritime SciencesChalmers University of TechnologySE‑41296 GothenburgSweden

Dynamic wheel-rail contact forces induced by a severe form of wheel tread damage have been measured by a wheel impact load detector during full-scale field tests at different vehicle *** on laser scanning,the measured three-dimensional damage geometry is employed in simulations of dynamic vehicle-track interaction to calibrate and verify a simulation *** relation between the magnitude of the impact load and various operational parameters,such as vehicle speed,lateral position of wheel-rail contact,track stiffness and position of impact within a sleeper bay,is *** calibrated model is later employed in simulations featuring other forms of tread damage;their effects on impact load and subsequent fatigue impact on bearings,wheel webs and subsurface initiated rolling contact fatigue of the wheel tread are *** results quantify the effects of wheel tread defects and are valuable in a shift towards condition-based maintenance of running gear,and for general assessment of the severity of different types of railway wheel tread damage.

关键词： Wheel tread damage Rolling contact fatigue cluster Field measurements Dynamic vehicle-track interaction Wheel-rail impact load Wheelset durability

Advancing immunosuppression in liver transplantation: A narrative review

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Hepatobiliary & Pancreatic Diseases International 2024年第5期23卷 441-448页

作者： Samuele Iesari Francesca Laura Nava Ilaria elena Zais Laurent Coubeau mariano Ferraresso Evaldo Favi Jan Lerut general Surgery and Kidney Transplantation Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico15 Via della Commenda20122 MilanItaly Institut de Recherche Expérimentale et Clinique Universitécatholique de Louvain10 Avenue Hippocrate1200 BrusselsBelgium Service de Chirurgie et Transplantation Abdominale Cliniques Universitaires Saint-Luc55 Avenue Hippocrate1200 BrusselsBelgium Department of Clinical Sciences and Community Health Universitàdegli Studi di Milano19 Via della Commenda20122 MilanItaly

Immunosuppression is essential to ensure recipient and graft survivals after liver transplantation(LT). However, our understanding and management of the immune system remain suboptimal. Current immunosuppressive therapy cannot selectively inhibit the graft-specific immune response and entails a significant risk of serious side effects, i.e., among others, de novo cancers, infections, cardiovascular events, renal failure, metabolic syndrome, and late graft fibrosis, with progressive loss of graft function. Pharmacological research, aimed to develop alternative immunosuppressive agents in LT, is behind other solidorgan transplantation subspecialties, and, therefore, the development of new compounds and strategies should get priority in LT. The research trajectories cover mechanisms to induce T-cell exhaustion, to inhibit co-stimulation, to mitigate non-antigen-specific inflammatory response, and, lastly, to minimize the development and action of donor-specific antibodies. Moreover, while cellular modulation techniques are complex, active research is underway to foster the action of T-regulatory cells, to induce tolerogenic dendritic cells, and to promote the function of B-regulatory cells. We herein discuss current lines of research in clinical immunosuppression, particularly focusing on possible applications in the LT setting.

关键词： Liver transplantation Immunosuppression Drug development Long-term results Clinical operational tolerance

A comprehensive review of genetic causes of obesity

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World Journal of Pediatrics 2024年第1期20卷 26-39页

作者： marcio Jose Concepcion-Zavaleta Juan Eduardo Quiroz-Aldave maria del Carmen Durand-Vasquez Elman Rolando gamarra-Osorio Juan del Carmen Valencia de la Cruz Claudia Mercedes Barrueto-Callirgos Susan Luciana Puelles-Leon elena de Jesus Alvarado-Leon Frans Leiva-Cabrera Francisca elena Zavaleta-gutierrez Luis Alberto Concepcion-Urteaga Jose Paz-Ibarra Universidad Cientifica del Sur Bolivar 2150 AvenuePueblo Libre15084LimaPeru Division of Medicine Hospital de Apoyo ChepénChepenPeru Division of Family Medicine Hospital de Apoyo ChepénChepenPeru Division of Endocrinology Hospital Victor Lazarte EchegarayTrujilloPeru Division of Pediatrics Hospital de Apoyo ChepenChepenPeru Division of Internal Medicine Hospital de Apoyo ChepenChepenPeru Division of genetics Universidad Nacional de TrujilloTrujilloPeru Division of Neonatology Hospital Belen de TrujilloTrujilloPeru Division of Internal Medicine Universidad Nacional de TrujilloTrujilloPeru Department of Medicine School of MedicineUniversidad Nacional Mayor de San MarcosLimaPeru

Background Obesity is a multifactorial chronic disease with a high,increasing worldwide *** causes account for 7%of the cases in children with extreme *** sources This narrative review was conducted by searching for papers published in the PubMed/MEDLINE,Embase and SciELO databases and included 161 *** search used the following search terms:"obesity","obesity and genetics","leptin","Prader-Willi syndrome",and"melanocortins".The types of studies included were systematic reviews,clinical trials,prospective cohort studies,cross-sectional and prospective studies,narrative reviews,and case *** The leptin-melanocortin pathway is primarily responsible for the regulation of appetite and body ***,several important aspects of the pathophysiology of obesity remain *** causes of obesity can be grouped into syndromic,monogenic,and polygenic causes and should be assessed in children with extreme obesity before the age of 5 years,hyperphagia,or a family history of extreme obesity.A microarray study,an analysis of the melanocortin type 4 receptor gene mutations and leptin levels should be performed for this *** are three therapeutic levels:lifestyle modifications,pharmacological treatment,and bariatric *** genetic study technologies are in constant development;however,we are still far from having a personalized approach to genetic causes of obesity.A significant proportion of the affected individuals are associated with genetic causes;however,there are still barriers to its approach,as it continues to be underdiagnosed.

关键词： Leptin Melanocortin Obesity Prader-Willi syndrome Precision medicine

The role of singlet oxygen and hydroxyl radical in the photobleaching of meso-substituted cationic pyridyl porphyrins in the presence of folic acid

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Journal of Innovative Optical Health Sciences 2024年第5期17卷 67-80页

作者： Lusine Mkrtchyan Torgom Seferyan marina Parkhats Sergei Lepeshkevich Boris Dzhagarov gagik Shmavonyan elena Tuchina Valery Tuchin grigor gyulkhandanyan Laboratory of Bioengineering Institute of Biochemistry After H.Buniatyan of the NAS of Armenia 5/1 Paruyr Sevak StreetYerevan 0014Armenia Laboratory of Biomedical Research Institute of Biochemistry after H.Buniatyan of the NAS of Armenia 5/1 Paruyr Sevak StreetYerevan 0014Armenia B.I.Stepanov Institute of Physics NAS of Belarus 68-2 Nezavisimosti Avenue Minsk 220072Belarus National Polytechnic University of Armenia 105 Teryan Street Yerevan 0009Armenia Science Medical Centre Saratov State University 83 Astrakhanskaya StreetSaratov 410012Russia

Using a photosensitizer(PS),light,and oxygen,photodynamic therapy creates cytotoxic reactive oxygen species,such as singlet oxygen(1O2),that kill cancer *** cancer cell lines have up to 300 times more folic acid receptors than healthy ***,folic acid is often used to improve selectivity of *** poses a disadvantage for *** this paper,we have studied the photoinduced changes of meso-substituted cationic pyridyl porphyrins in the presence of folic acid using uorescence and absorption *** this work,it was demonstrated that L-histidine,which is a 1O2 quencher,and D-mannitol,which is a hydroxyl radical quencher,can reduce photobleaching of cationic porphyrins and their interaction products with *** implies both singlet oxygen and hydroxyl radicals are involved in ***,our study revealed certain important features of the photobleaching of cationic porphyrins in the presence of folic acid.

关键词： Photodynamic therapy cancer quenchers histidine mannitol

Liver-brain axis with alcohol:Role of fibroblast growth factor 21(FgF21)

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genes & Diseases 2024年第2期11卷 509-511页

作者： Ke Zhang elena Blokhina Evgeny Krupitsky marina Vetrova Ti-Fei Yuan Hua Wang Shanghai Key Laboratory of Psychotic Disorders Brain Health InstituteNational Center for Mental DisordersShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghai 200030China Pavlov University Valdman Institute of PharmacologySt.Petersburg 197022Russia Bekhterev National Medical Research Center for Psychiatry and Neurology St.Petersburg 192019Russia Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu 226007China Department of Oncology The First Affiliated Hospital of Anhui Medical UniversityHefeiAnhui 230032China

Fibroblast growth factor21(FgF21)is a hormone that can balance nutrient fluctuations,control metabolic processes,and maintain energy *** FgF21 is produced by a variety of cell types,including hepatocytes,adipocytes,bone cells,myocardial cells,and pancreas cells,and act on various effector tissues such as brain,adipose tissue,liver,heart,and skeletal muscle.1 The target that FgF21 interacts with is the cell-surface receptor composed of FgF receptors in complex with the single-pass transmembrane proteinβ-*** receptors are abundantly expressed,both in peripheral tissues and some regions of the CNS,such as the hypothalamus and amygdala and the locus coeruleus(LC).2 Physiologically,FgF21 can be induced by various metabolic stresses,including hunger,protein deficiency,monosaccharides,and alcohol,by acting onβ-Klotho receptor in corresponding tissues,ultimately exerting regulatory effects(Fig.1)

关键词： Klotho homeostasis alcohol

Plant cell wall-mediated disease resistance:Current understanding and future perspectives

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Molecular Plant 2024年第5期17卷 699-724页

作者： Antonio Molina Lucıa Jorda Miguel Angel Torres marina martın-Dacal Diego Jose Berlanga Patricia Fernandez-Calvo elena gomez-Rubio Sonsoles martın-Santamarıa Centro de Biotecnología y genómica de Plantas Universidad Politécnica de Madrid(UPM)-Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria(INIA/CSIC)Campus de Montegancedo UPMPozuelo de Alarcon(Madrid)Spain Departamento de Biotecnologıa-Biología Vegetal Escuela Técnica Superior de Ingenierıa AgronomicaAlimentarıa y de BiosistemasUPMMadridSpain Centro de Investigaciones Biologicas margarita Salas Consejo Superior de Investigaciones Científicas(CSIC)Ramiro de Maeztu 928040 MadridSpain Misión Biológica de galicia Consejo Superior de Investigaciones Científicas(CSIC)Campus de Montegancedo UPMPozuelo de Alarcón(Madrid)Spain

Beyond their function as structural barriers,plant cell walls are essential elements for the adaptation of plants to environmental *** walls are dynamic structures whose composition and integrity can be altered in response to environmental challenges and developmental *** wall changes are perceived by plant sensors/receptors to trigger adaptative responses during development and upon stress *** cell wall damage caused by pathogen infection,wounding,or other stresses leads to the release of wall molecules,such as carbohydrates(glycans),that function as damage-associated molecular patterns(DAMPs).DAMPs are perceived by the extracellular ectodomains(ECDs)of pattern recognition receptors(PRRs)to activate pattern-triggered immunity(PTI)and disease ***,glycans released from the walls and extracellular layers of microorganisms interacting with plants are recognized as microbe-associated molecular patterns(MAMPs)by specific ECD-PRRs triggering PTI *** number of oligosaccharides DAMPs/MAMPs identified that are perceived by plants has increased in recent ***,the structural mechanisms underlying glycan recognition by plant PRRs remain ***,this knowledge is mainly focused on receptors of the LysM-PRR family,which are involved in the perception of various molecules,such as chitooligosaccharides from fungi and lipo-chitooligosaccharides(i.e.,Nod/MYC factors from bacteria and mycorrhiza,respectively)that trigger differential physiological ***,additional families of plant PRRs have recently been implicated in oligosaccharide/polysaccharide *** include receptor kinases(RKs)with leucine-rich repeat and Malectin domains in their ECDs(LRR-MAL RKs),Catharanthus roseus RECEPTOR-LIKE KINASE 1-LIKE group(CrRLK1L)with Malectin-like domains in their ECDs,as well as wall-associated kinases,lectin-RKs,and *** characterization of structural basis of glycans recogniti

关键词： Arabidopsis thaliana cell wall damage-associated molecular patterns DAMPs disease resistance glycans oligosaccharides pattern-triggered immunity PTl pattern recognition receptor PRRs

Evaluation of Clinical Characteristics and Plasma Cortisol Concentrations in Individuals with COVID-19 and Post-COVID Syndrome

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Case Reports in Clinical Medicine 2024年第1期13卷 12-24页

作者： David Alejandro garcía López Stephania Ramos Hernández Yamile López-Hernández maría Argelia López Luna elena Donaji Ramírez Alvarado Rosa maría Ramírez Santoyo Sergio Hugo Sánchez Rodríguez Laboratorio de Biología Celular y Neurobiología Universidad Autónoma de Zacatecas México Zacatecas Unidad Académica de Ciencias Químicas Universidad Autónoma de Zacatecas México Zacatecas Laboratorio de Metabolómica y Proteómica Universidad Autónoma de Zacatecas México Zacatecas Laboratorio de Bacterias y Hongos filamentosos Universidad Autónoma de Zacatecas México Zacatecas

COVID-19 generates systematic alterations in humans both in active stages of infection and over time, called post-COVID syndrome. Cortisol is a hormone that is overexpressed in inflammation and cellular stress processes. Its main function is to return to physiological homeostasis, so its evaluation together with other clinical parameters can allow us to determine the degree of systemic affectation by COVID-19. Objective: To evaluate changes in clinical parameters and plasma cortisol concentrations in patients with active COVID-19 and post-COVID syndrome. Material and Methods: Healthy patients, in stages of mild infection, critical and with post-COVID syndrome, were recruited, obtaining, through clinical diagnoses and interviews, their main clinical characteristics, in addition to plasma, in which cortisol concentrations were determined using competitive ELISA. Results: The critical stage group had higher frequencies of comorbidities, clinical symptoms, as well as more altered laboratory parameters compared to the other subgroups. In the post-COVID syndrome group after the initial infection, most laboratory parameters recovered, however, several clinical symptoms remained latent over time. The determination of cortisol showed an increase in its concentration, being higher in patients in critical stage and with post-COVID syndrome. Conclusion: COVID-19 disease generates clinical alterations that trigger an increase in plasma cortisol. These alterations increase as the stages of infection become more severe and some of them remain altered in patients with post-COVID syndrome.

关键词： COVID-19 Cortisol Post-COVID Syndrome

Beyond wrecking a wall:revisiting the concept of blood–brain barrier breakdown in ischemic stroke

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Neural Regeneration Research 2025年第7期20卷 1944-1956页

作者： Julia Castillo-gonzález elena gonzález-Rey Institute of Parasitology and Biomedicine Lopez-Neyra(IPBLN) CSICPT SaludGranadaSpain

The blood–brain barrier constitutes a dynamic and interactive boundary separating the central nervous system and the peripheral *** tightly modulates the ion transport and nutrient influx,while restricting the entry of harmful factors,and selectively limiting the migration of immune cells,thereby maintaining brain *** the well-established association between blood–brain barrier disruption and most neurodegenerative/neuroinflammatory diseases,much remains unknown about the factors influencing its physiology and the mechanisms underlying its ***,the role of blood–brain barrier breakdown in the translational failure underlying therapies for brain disorders is just starting to be *** review aims to revisit this concept of“blood–brain barrier breakdown,”delving into the most controversial aspects,prevalent challenges,and knowledge gaps concerning the lack of blood–brain barrier *** moving beyond the oversimplistic dichotomy of an“open”/“bad”or a“closed”/“good”barrier,our objective is to provide a more comprehensive insight into blood–brain barrier dynamics,to identify novel targets and/or therapeutic approaches aimed at mitigating blood–brain barrier ***,in this review,we advocate for considering the diverse time-and location-dependent alterations in the blood–brain barrier,which go beyond tight-junction disruption or brain endothelial cell breakdown,illustrated through the dynamics of ischemic stroke as a case *** this exploration,we seek to underscore the complexity of blood–brain barrier dysfunction and its implications for the pathogenesis and therapy of brain diseases.

关键词： blood–brain barrier disruption drug delivery ischemic stroke neuroinflammation tight-junctions

Long-term normothermic machine perfusion of fatty livers:towards transplanting untransplantable livers?

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Hepatobiliary Surgery and Nutrition 2024年第4期13卷 681-685页

作者： Damiano Patrono Nicola De Stefano elena Vissio Alessandro gambella Renato Romagnoli general Surgery 2U–Liver Transplant Unit Azienda Ospedaliero Universitaria Cittàdella Salute e della Scienza di TorinoTurinItaly Pathology Unit Azienda Ospedaliero Universitaria Cittàdella Salute e della Scienza di TorinoTurinItaly Department of Medical Sciences University of TurinTurinItaly

Since the very early days of clinical liver transplantation(LT),transplant surgeons and professionals have been confronted with the increased risk of failure associated with the use of fatty liver grafts(1).Notwithstanding the wide variability in steatosis assessment across different centers and pathologists(2),utilization of livers with moderate(≥30%)or severe(≥60%)macrovesicular steatosis has been consistently associated with an increased risk of primary non-function,early allograft dysfunction,acute kidney injury,as well as inferior graft and patient survival(3).The mechanisms behind the increased susceptibility of steatotic livers to ischemia-reperfusion injury(IRI)are multiple,including disturbances to microcirculation due to sinusoidal narrowing,increased oxidative stress upon reperfusion and enhanced lipid peroxidation,leading to an increased release of inflammatory mediators like IL6,IL1βand so-called damage associated molecular patterns(DAMP),like cell-free DNA and mitochondrial ***,this is reflected by hepatocyte death by necrosis rather than apoptosis,pseudopeliotic steatosis(i.e.,the expulsion of lipid droplets into the extracellular space)and lately,by tissue remodelling and fibrosis(4,5).

关键词： Liver transplantation(LT) steatosis macrovesicular steatosis large droplet fat normothermic machine perfusion