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Therapeutic targeting of cellular prion protein: toward the development of dual mechanism anti-prion compounds

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Neural Regeneration Research 2025年第4期20卷 1009-1014页

作者： antonio Masone Chiara Zucchelli Enrico Caruso Giovanna Musco Roberto Chiesa Laboratory of Prion Neurobiology Department of NeuroscienceIstituto di Ricerche Farmacologiche Mario Negri IRCCSMilanItaly Biomolecular NMR Unit Division of Genetics and Cell BiologyIRCCS Ospedale San RaffaeleMilanItaly Department of Biotechnology and Life Sciences University of InsubriaVareseItaly

PrPSc,a misfolded,aggregation-prone isoform of the cellular prion protein(PrPC),is the infectious prion agent responsible for fatal neurodegenerative diseases of humans and other *** adopt different pathogenic conformations(prion strains),which can be resistant to potential drugs,or acquire drug resistance,posing challenges for the development of effective *** PrPCis the obligate precursor of any prion strain and serves as the mediator of prion neurotoxicity,it represents an attractive therapeutic target fo r prion *** this minireview,we briefly outline the approaches to target PrPCand discuss our recent identification of Zn(Ⅱ)-Bn PyP,a PrPC-targeting porphyrin with an unprecedented bimodal mechanism of *** argue that in-depth understanding of the molecular mechanism by which Zn(Ⅱ)-Bn PyP targets PrPCmay lead toward the development of a new class of dual mechanism anti-prion compounds.

关键词： anti-prion drug anti-PrPC antibody antisense oligonucleotide neurodegeneration pharmacological chaperone porphyrin prion disease PrPC degrader PrPC shedding zinc finger repressor

A numerical assessment of two geometries for reducing elbow erosion

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Particuology 2020年第2期18卷 117-133页

作者： Carlos antonio ribeiro Duarte Francisco Joséde Souza Diego Nei Venturi Martin Sommerfeld Department of Engineering Federal University of Goiás-Regional Catal(a)oAv.Dr.Lamartine Pinto de Avelar1120Catal(a)oGoiásBrazil School of Mechanical Engineering Federal University of Uberl(a)ndiaAv.Joāo Naves de(A)vila2121 Bloco 5PUberl(a)ndiaMinas GeraisBrazil Multiphase Flow Systems(MPS) Otto-von-Guericke-University MagdeburgZeppelinstraβe 1D-06130 Halle(Saale)Germany

Elbows in pneumatic conveying systems are normally prone to the erosive effects of conveyed *** are a number of solutions available to reduce such damage.A widely used geometric alternative for replacing the 90°elbow and reducing erosive wear is the plugged *** option,although less commonly used,is the vortex-chamber *** both cases,the effective reduction in erosion brought about is unclear,as it strongly depends on the operating *** present study assesses relative erosion among the plugged tee,vortex-chamber elbow,and standard elbow for a dilute gas-solid multiphase flow.A numerical model is employed to predict the penetration ratio and validated using experimental data for the plugged *** are run for the standard and vortex-chamber elbows and plugged tee under the same conditions to compare the mechanics involved and the relative erosion *** analysis uses variables relating to particle-wall interactions(impact angle,impact velocity,impact frequency)to illustrate the nature of the erosive process in each pipe *** general,the geometric configurations of both the plugged tee and vortex-chamber elbow promote changes in particle dynamics that reduce the rate of *** the basis of the relative erosion of the standard elbow,the plugged tee proves to be an interesting option in cases of a low mass loading,while the vortex-chamber elbow demonstrates its erosion reduction potential for higher mass loading ***,the advantages and disadvantages of each fitting are highlighted.

关键词： Relative erosion Plugged tee Erosion reduction Pipe fitting Computational fluid dynamics

Endoscopic techniques for the diagnosis of pancreatic cystic lesions

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World Journal of Gastroenterology 2025年第1期31卷 1-7页

作者： Sahib Singh Saurabh Chandan Rakesh Vinayek Jahnvi Dhar Jayanta Samanta Gabriele Capurso Ivo Boskoski Cristiano Spada Jorge D Machicado Stefano Francesco Crinò antonio Facciorusso Department of Internal Medicine Sinai HospitalBaltimoreMD 21215United States Division of Gastroenterology and Hepatology Creighton University School of MedicineOmahaNE 68131United States Department of Gastroenterology Sinai Hospital of BaltimoreBaltimoreMD 21215United States Department of Gastroenterology Postgraduate Institute of Medical Education and ResearchChandigarh 160012India Division of Pancreato-Biliary Endoscopy and Endosonography Pancreas Translational and Clinical Research CenterIRCCS San Raffaele Scientific InstituteVita-Salute San Raffaele UniversityMilano 20132Italy Digestive Endoscopy Unit Fondazione Policlinico Universitario Agostino Gemelli IRCSSUniversitàCattolica del Sacro Cuore di RomaCenter for Endoscopic Research Therapeutics and TrainingRoma 00168Italy Department of Gastroenterology and Endoscopy Catholic UniversityRoma 00168Italy Department of Gastroenterology University of Michigan HealthAnn ArborMI 48107United States Department of Endoscopy University of VeronaVerona 37121VenetoItaly Gastroenterology Unit Department of Medical and Surgical SciencesUniversity of FoggiaFoggia 71122Italy

Pancreatic cysts are mostly incidental findings on computed tomography or magnetic resonance imaging scans,with few patients presenting with abdominal pain or other *** accurate diagnosis of cysts is important as management depends on the type(neoplastic or non-neoplastic).Cross-sectional imaging is fast being replaced with endoscopic ultrasound(EUS)and various techniques based on that such as EUS-guided fine needle aspiration,EUS-guided needle confocal laser endomicroscopy,EUS-through-the-needle biopsy,and contrast-enhanced *** studies have reported varying diagnostic and adverse event rates with these *** addition,American,European,and Kyoto guidelines for the diagnosis and management of pancreatic cysts have provided different *** this editorial,we elaborate on the clinical guidelines,recent studies,and comparison of different endoscopic methods for the diagnosis of pancreatic cysts.

关键词： Endoscopic ultrasound Fine needle aspiration Needle confocal laser endomicroscopy Through-the-needle biopsy Contrast-enhanced endoscopic ultrasound

Plasma betatrophin levels in patients with liver cirrhosis

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World Journal of Gastroenterology 2015年第37期21卷 10662-10668页

作者： Maria Teresa Arias-Loste Maria Teresa García-Unzueta Susana Llerena Paula Iruzubieta Angela Puente Joaquín Cabezas Carmen Alonso antonio Cuadrado José antonio amado Javier Crespo Emilio Fábrega Gastroenterology and Hepatology Unit Marqués de Valdecilla University HospitalInstituto de Investigación Sanitaria ValdecillaAvenida Valdecilla s/n 39008 Santander Cantabria Spain Endocrinology Unit Marqués de Valdecilla University HospitalInstituto de Investigación Sanitaria Valdecilla Avenida Valdecilla s/n 39008 Santander Cantabria Spain

AIM: To investigate the plasma levels of betatrophin in patients with ***: Forty patients diagnosed at the clinic with liver cirrhosis according to biological, ultrasonographic,or histological criteria were *** severity of cirrhosis was classified according to Pugh's modification of Child's classification and MELD score. Insulin resistance(IR) was assessed by the Homeostasis Model Assessment. A total of 20 patients showed a MELD score higher than 14. The control group consisted in 15 sex-and aged-matched *** blood samples were obtained for subsequent analysis. Serum insulin was determined by Liaison automated immune chemiluminiscence assay(DiaSorin S.p.A.) using a sandwich assay. The sensitivity of the assay was 0.2 μU/mL. The intra and interassay variation coefficients were < 4% and < 10%,respectively. The normal values were between 2 and17 μU/mL. Human active betatrophin was analyzed by specific quantitative sandwich ELISA(Aviscera Bioscience). The sensitivity of the assay was 0.4 ng/mL, and the intra and interassay reproducibility were< 6% and < 10%, ***: Plasma betatrophin levels were significantly increased in patients with cirrhosis compared with those in healthy subjects(P = 0.0001). Betatrophin levels were also associated with disease severity, being higher in Child-Pugh C patients compared to Child-Pugh B(P< 0.0005) and in patients who displayed a MELD score higher than 14 points compared to patients with lower punctuation(P = 0.01). In addition, we found a positive correlation between plasma betatrophin levels and the severity of cirrhosis according to Child-Pugh classification(r = 0.53; P < 0.01) or MELD score(r = 0.45; P <0.01). In the overall cohort, a moderate correlation between serum betatrophin and plasmatic bilirrubin(r= 0.39; P < 0.01) has been observed, as well as an inverse correlation between betatrophin and albumin(r =-0.41; P < 0.01) or prothrombin time(r =-0.44;P <0.01). Moreover, insulin

关键词： Liver cirrhosis Betatrophin Insulin resistance Bet

Quasi-freestanding graphene on Ni（110）： A graphene/ metal contact with suppressed interface states

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Nano Research 2016年第6期9卷 1795-1800页

作者： antonio Politano Department of Physics University of Calabria via Ponte Bucci 3 I/C 1-87036 Rende (CS) Italy

Graphene/Ni（110） has been studied by time-resolved X-ray photoelectron spectroscopy and near-edge X-ray absorption fine structure. The C ls core level shows a splitting typical of periodically rippled interfaces. The analysis of the C K-edge reveals that the interface states previously observed for graphene/Ni（111） are suppressed in graphene/Ni（110）. This suppression is due to the reduced hybridization of the Dirac-cone electrons in graphene with the d-bands of the （110）-oriented nickel contacts. Our results show that, contrary to commensurate growth of graphene on Ni（111）, epitaxially grown graphene on Ni（110） behaves as a quasi-freestanding sheet, as the lattice mismatch gives rise to a moir6 reconstruction.

关键词： graphene electronic properties synchrotron radiation X-ray photoelectronspectroscopy near-edge X-rayphotoelectron spectroscopy

Few-mode fibre-optic microwave photonic links

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Light(Science & Applications) 2017年第1期6卷 684-691页

作者： He Wen Hongjun Zheng Qi Mo amado Manuel Velázquez-Benítez Cen Xia Bin Huang Huiyuan Liu Huang Yu Pierre Sillard Jose Enrique antonio Lopez Rodrigo Amezcua Correa Guifang Li CREOL The College of Optics and PhotonicsUniversity of Central FloridaOrlandoFL 32816USA The College of Precision Instruments and Opto-Electronics Engineering Tianjin UniversityTianjin 300072China School of Physics Science and Information Technology Shandong Provincial Key Lab of Optical Communication Science and TechnologyLiaocheng UniversityShandong 252059China State Key Laboratory of Optical Communication Technologies and Networks FiberHome Telecommunication Technologies Co.LtdWuhan Research Institute of Posts and TelecommunicationsNo.88 Youkeyuan RoadHongshan DistrictWuhan 430074China Prysmian Group Parc des Industries Artois FlandresHaisnes 62092France

The fibre-optic microwave photonic link has become one of the basic building blocks for microwave *** the optical power at the receiver is the best way to improve all link performance metrics including gain,noise figure and dynamic *** though lasers can produce and photodetectors can receive optical powers on the order of a Watt or more,the power-handling capability of optical fibres is orders-of-magnitude *** this paper,we propose and demonstrate the use of few-mode fibres to bridge this power-handling gap,exploiting their unique features of small acousto-optic effective area,large effective areas of optical modes,as well as orthogonality and walk-off among spatial *** specially designed few-mode fibres,we demonstrate order-of-magnitude improvements in link performances for single-channel and multiplexed *** work represents the first step in few-mode microwave *** spatial degrees of freedom can also offer other functionalities such as large,tunable delays based on modal dispersion and wavelength-independent lossless signal combining,which are indispensable in microwave photonics.

关键词： analogue optic-fibre link few-mode fibre fibre nonlinearity microwave photonics space-division multiplexing

Interplay between the glass and the gel transition

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Science China(Physics,Mechanics & Astronomy) 2019年第10期62卷 45-50页

作者： Annalisa Fierro antonio de Candia antonio Coniglio CNR-SPIN c/o Complesso di Monte S.AngeloNapoli 80126Italy Dipartimento di Fisica"Pancini" Universita di Napoli"FedericoⅡ"Complesso di Monte S.AngeloNapoli 80126Italy

By changing the control parameters, many physical systems reach a slow dynamics regime followed by an arrested or a quasiarrested state. Examples, among others, are gels and glasses. In this paper, we discuss some experimental and theoretical results in polymer and colloidal systems, where gel and glass transitions interfere, and use models from Mode Coupling Theory（MCT）to illustrate the rich phenomenology observed. The continuous and the discontinuous transition lines, found in the MCT models,are considered suitable to describe respectively the gel and the glass transitions, so we suggest that the interplay between gel and glass may be interpreted in terms of the F13 MCT model, clarifying also the origin of logarithmic decays often observed in such systems. In particular, the theoretical predictions of the MCT in the F13 model are compared with Molecular Dynamics simulations in model systems for chemical gels and charged colloids.

关键词： glass gel and sol colloid

Mindfulness training in medical education as a means to improve resilience,empathy,and mental health in the medical profession

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World Journal of Psychiatry 2024年第4期14卷 489-493页

作者： Edison Iglesias de Oliveira Vidal Luiz Fernando Alvarenga ribeiro Marco antonio de Carvalho-Filho Fernanda Bono Fukushima Internal Medicine Department Botucatu Medical SchoolSao Paulo State University(UNESP)Botucatu 18618-687SPBrazil Wenckebach Institute for Education and Training LEARN-Lifelong LearningEducation and Assessment Research NetworkUniversity Medical Center GroningenGroningen 9713AVGroningenNetherlands Assertiva Mindfulness Botucatu 18603-970SPBrazil Surgical Specialties and Anesthesiology Department Botucatu Medical SchoolSão Paulo State University(UNESP)Botucatu 18618-687SPBrazil

The high rates of depression,burnout,and increased risk of suicide among medical students,residents,and physicians in comparison with other careers signal a mental health crisis within our *** contend that this crisis coupled with the inadequate acquisition of interpersonal skills during medical education results from the interaction between a challenging environment and the mental capital of ***,we posit that mindfulness-based practices are instrumental for the development of major components of mental capital,such as resilience,flexibility of mind,and learning skills,while also serving as a pathway to enhance empathy,compassion,self-awareness,conflict resolution,and relational ***,the evidence base supporting the effectiveness of mindfulness-based interventions has been increasing over the years,and a growing number of medical schools have already integrated mindfulness into their *** we acknowledge that mindfulness is not a panacea for all educational and mental health problems in this field,we argue that there is currently an unprecedented opportunity to gather momentum,spread and study mindfulness-based programs in medical schools around the world as a way to address some longstanding shortcomings of the medical profession and the health and educational systems upon which it is rooted.

关键词： Mindfulness Medical education Mental capital Mental health Medical students Resilience

Cost-effective synthesis of giant molecule acceptors(GMAs)for stable polymer solar cells

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Science China Chemistry 2024年第4期67卷 1041-1043页

作者： antonio Facchetti Department of Chemistry and the Materials Research Center Northwestern University2145 Sheridan Road60208 EvanstonIllinoisUSA School of Materials Science and Engineering Georgia Institute of Technology771 Ferst Drive30332 AtlantaGeorgiaUSA

Polymer solar cells(PSCs)have emerged as a disruptive energy technology due to simple device architecture,earthabundant elemental composition,lightweight nature,and inherent mechanical flexibility[1,2].Via a strategic acceptordonor-acceptor(A-D-A)design of small-molecule acceptors(SMAs),device power conversion efficiency(PCE)has now increased>19%.

关键词： acceptor synthesis donor