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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

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

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

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

Thermo-and pH-sensitive Polymer with Pendant Spacer-linked Imidazole Cycles

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Chinese Journal of Polymer Science 2024年第4期42卷 437-445页

作者： Natalya V.Zakharova Stanislav N.Zelinskiy Mariya S.Strelova elena N.Danilovtseva Vadim V.Annenkov Institute of Macromolecular Compounds of the Russian Academy of Sciences Saint Petersburg199004Russia Limnological Institute of Siberian Branch of the Russian Academy of Sciences Irkutsk664033Russia

By the reaction of poly(acryloyl chloride) with N-(3-aminopropyl)imidazole, poly(N-(3-(1H-imidazol-1-yl)propyl)acrylamide) was synthesized. The new polymer contains an imidazole ring removed from the main chain by a spacer of five bonds. The structure and purity, molecular weight, hydrodynamic and thermosensitive properties of the obtained sample were studied by1H-and13C-NMR, FTIR spectroscopy, acid-base titration, light scattering, turbidimetry and viscometry. The observed ability of the imidazole-containing polymer to form and destroy associates in water-salt solutions at pH 6.6-7.4 and temperatures of 29-48℃ indicates that these are promising candidates for designing complex biomedical systems. The new polymer is able to form complexes with oligo-DNA more actively than poly(1-vinylimidazole), which is of interest for gene delivery applications. The polymer cross-linked with epichlorohydrin gives micro-relief coatings on the plastic surface, and the modified surface is able to attach negatively charged objects. This thermo-and pH-sensitive polymer modification can be applied to create finely controlled surfaces for cell culturing.

关键词： Imidazole-containing polymer Thermolability pH-sensitivity The modified surface DNA immobilization

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

Calcium-sensitive protein MLC1 as a possible modulator of the astrocyte functional state

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Neural Regeneration Research 2025年第7期20卷 2008-2010页

作者： elena Ambrosini Angela Lanciotti Maria Stefania Brignone Department of Neuroscience Istituto Superiore di SanitàRomeItaly

Astrocytes,the main population of glial cells in the central nervous system(CNS),exert essential tasks for the control of brain tissue homeostasis,supporting neuron and other glial cell activity from the developmental stage to adult *** maintain the optimal functionality of the brain,astroglial cells are particularly committed to reacting to every change in tissue homeostatic conditions,from mild modifications of the physiological environment,a process called astrocyte activation,to the more severe alterations occurring in pathological situations causing astrocyte reactivity or reactive astrogliosis(Escartin et al.,2021).During these reactive states,astrocytes mount an active,progressive response encompassing morphological,molecular,and interactional remodeling,leading to the acquisition of new functions and the loss of others,whose intensity,duration,and reversibility are dependent on the nature of the stimulus and regulated in a context-specific manner.

关键词： alterations modulator maintain

The challenge of molecular selection in liver-limited metastatic colorectal cancer for surgical resection: a systematic review and meta-analysis in the context of current and future approaches

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Oncology Research 2024年第9期32卷 1407-1422页

作者： ROSSANA RONCATO JERRY POLESEL FEDERICA TOSI elena PERUZZI ERIKA BRUGUGNOLI CLAUDIA LAURIA PANTANO MARIA FURFARO FILIPPO DI GIROLAMO ALESSANDRO NANI ARIANNA PANI NOEMI MILAN elena DE MATTIA ANDREA SARTORE-BIANCHI ERIKA CECCHIN Experimental and Clinical Pharmacology Unit Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Medicine(DMED) University of UdineUdine33100Italy Unit of Cancer Epidemiology Centro di Riferimento Oncologico di Aviano(CRO)IRCCSAviano33081Italy Department of Oncology and Hemato-Oncology Universitàdegli Studi di MilanoMilan20122Italy Department of Hematology Oncologyand Molecular MedicineGrande Ospedale Metropolitano NiguardaMilan20122Italy Oncology Pharmacy Unit IRCCS Istituto Romagnolo per lo Studio dei Tumori Dino AmadoriMeldola47014Italy Pharmacy Unit Fondazione IRCCS Istituto Tumori di MilanoMilan20122Italy Department of Pharmacy Ca’Foncello Treviso Regional HospitalPiazzale Ospedale 1Treviso31100Italy Department of Medical Surgical and Health Sciences University of TriesteTrieste34127Italy Hospital Pharmacy Cattinara HospitalAzienda Sanitaria Universitaria Giuliano IsontinaTrieste34148Italy Department of Oncology and Onco-Hematology Postgraduate School of Clinical Pharmacology and ToxicologyUniversity of MilanMilan20122Italy

Objectives:Treatment of metastatic colorectal cancer(mCRC)includes resection of liver metastases(LM),however,no validated biomarker identifies patients most likely to benefit from this *** meta-analysis aimed to assess the impact of the most relevant molecular alterations in cancer-related genes of CRC(i.e.,RAS,BRAF,SMAD4,PIK3CA)as prognostic markers of survival and disease recurrence in patients with mCRC surgically treated by LM ***:A systematic literature review was performed to identify studies reporting data regarding survival and/or recurrence in patients that underwent complete liver resection for CRC LM,stratified according to RAS,BRAF,PIK3CA,and SMAD4 mutational *** ratios(HRs)from multivariate analyses were pooled in the meta-analysis and various adjustment strategies for confounding factors were *** search was conducted in numerous databases,including MEDLINE(PubMed),Embase,Cumulative Index to Nursing and Allied Health Literature(CINAHL)(EBSCO host),and WHO Global Index Medicus,through March 18th,***-analyses,editorials,letters to the editor,case reports,studies on other primary cancers,studies with primary metastatic sites other than the liver,studies lacking specific oncological outcome variables or genetic data,non-English language studies,and studies omitting residual disease data from liver metastasectomy were *** remaining 47 studies were summarized in a descriptive table which outlines the key characteristics of each study and final results were graphically ***:RAS mutation status was negatively associated with overall survival(OS)(HR,1.68;95%CI,1.54–1.84)and recurrence free survival(RFS)(HR,1.46;95%CI,1.33–1.61).A negative association was also found for BRAF regarding OS(HR,2.64;95%CI,2.15–3.24)and RFS(HR,1.89;95%CI,1.32–2.73)and SMAD4 regarding OS(HR,1.93;95%CI,1.56–2.38)and RFS(HR,1.95;95%CI,1.31–2.91).For PIK3CA only three studies were eligible and no significant associati

关键词： Metastasectomy Liver metastases RAS BRAF SMAD4 PIK3CA Colorectal