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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

Study and ICH validation of a reverse-phase liquid chromatographic method for the quantification of the intact monoclonal antibody cetuximab

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Journal of Pharmaceutical Analysis 2016年第2期6卷 117-124页

作者： antonio Martinez-Ortega Agustin Herrera antonio Salmeron-Garcia Jose Cabeza Luis Cuadros-Rodriguez Natalia navas Department of Analytical Chemistry University of Granada Faculty of Science Campus Fuentenueva s/n E-18071 Granada Spain UGC intercentro Interniveles Farmacia Granada San Cecilio Hospital Biomedical Research Institute ibs. GRANADA. Hospitales Universitarios de Granada University of Granada E-18012 Granada Spain Department of Analytical Chemistry Science Faculty Biomedical Research Institute ibis. GRANADA University of Granada Campus Fuentenuevo s/n E-18071 Granada Spain

Cetuximab （CTX） is a potent chimeric mouse/human monoclonal antibody （mAb） approved worldwide for treatment of metastatic colorectal cancer. Among the various biological and physical analyses per- formed for full study on this biopharmaceutic, the determination of the concentration preparations throughout manufacturing and subsequent handling in hospital is particularly relevant. In the present work, the study and validation of a method for quantifying intact CTX by reverse-phase high-perfor- mance liquid chromatography with diode array detection （（RP）HPLC/DAD） is presented. With that end, we checked the performance of a chromatographic method for quantifying CTX and conducted a study to validate the method as stability-indicating in accordance with the International Conference on Harmo- nization guidelines （ICH） for biotechnological drugs; therefore, we evaluated linearity, accuracy, preci- sion, detection and quantification limits, robustness and system suitability. The specificity of the method and the robustness of the mAb formulation against external stress factors were estimated by compre- hensive chromatographic analysis by subjecting CTX to several informative stress conditions. As de- monstrated, the method is rapid, accurate, and reproducible for CTX quantification. It was also suc- cessfully used to quantify CTX in a long-term stability study performed under hospital conditions.

关键词： Reverse-phase high performance liquidchromatography Diode detector Stress study Biopharmaceuticals Cetuximab

Use of subcutaneous tocilizumab to prepare intravenous solutions for COVID-19 emergency shortage:Comparative analytical study of physicochemical quality attributes

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Journal of Pharmaceutical Analysis 2020年第6期10卷 532-545页

作者： Natalia navas Jesús Hermosilla Anabel Torrente-Lopez Jose Hernandez-Jimenez Jose Cabeza Raquel Perez-Roblesa antonio Salmeron-García Department of Analytical Chemistry Science Faculty/Biomedical Research Institute ibs.GranadaUniversity of GranadaGranadaE-18071Spain UGC Farmacia Hospitalaria Biomedical Research Institute ibs.Granada.Hospital Universitario San Cecilio de GranadaGranadaE-18012Spain

COVID-19,a disease caused by the novel coronavirus SARS-Co V-2,has produced a serious emergency for global public health,placing enormous stress on national health systems in many *** studies suggest that cytokine storms(interleukins)may play an important role in severe cases of *** key inflammatory factors in cytokine release syndrome(CRS)could therefore be of great value in reducing the mortality ***(TCZ)in its intravenous(IV)form of administration-Ro Actemra?20 mg/m L(Roche)-is indicated for treatment of severe CRS *** investigations have concluded that inhibition of IL-6 with TCZ appears to be efficacious and safe,with several ongoing clinical *** has led to a huge increase in demand for IV TCZ for treating severe COVID-19 patients in hospitals,which has resulted in drug ***,we present a comparability study assessing the main critical physicochemical attributes of TCZ solutions used for infusion,at 6 mg/m L and 4 mg/m L,prepared from Ro Actemra?20 mg/m L(IV form)and from Ro Actemra?162 mg(0.9 m L solution pre-filled syringe,subcutaneous(SC)form),to evaluate the use of the latter for preparing clinical solutions required for IV administration,so that in a situation of shortage of the IV medicine,the SC form could be used to prepare the solutions for IV delivery of *** is important to remember that during the current pandemic all the medicines are used off-label,since none of them has yet been approved for the treatment of COVID-19.

关键词： COVID-19 Tocilizumab Critical quality attributes IV and SC medicines

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

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

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

Impact of radiative cooling on the energy performance of courtyards in Mediterranean climate

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Building Simulation 2024年第9期17卷 1491-1513页

作者： Carlos-antonio Domínguez-Torres antonio Domínguez-Delgado Escuela Técnica Superior de Arquitectura Universidad de SevillaAv.de Reina Mercedes241012 SevillaSpain Department of Applied Mathematics 1 Escuela Técnica Superior de ArquitecturaUniversidad de SevillaAv.de Reina Mercedes241012 SevillaSpain

Radiative cooling has proven to be a useful tool to address the problems of lack of comfort and excessive energy consumption in situations of high temperatures,overheating and heat ***,incorporating courtyards in warm climate zones has been found to be highly beneficial in addressing similar ***,there is interest in analyzing the combined effects of both:radiative cooling and *** paper presents an analysis of the impact of the application of radiative cooling on a courtyard using a comprehensive simulation approach that includes a CFD model for the thermodynamic airflow in the adjacent roofs and inside the courtyard,equations for the transient heat conduction through roofs,walls and courtyard slabs,and a hybrid raytracing-radiosity model for the evaluation of the solar radiation reaching the building surfaces and its reflections,both of specular and diffuse origin,and for the calculation of the thermal radiation exchange,especially with the *** results show that in the hot season,the courtyard with radiative cooling always provides lower temperatures than the initial courtyard does,with a temperature range of 18.33℃to 33.78℃,compared to a range of 19.32℃to 38.00℃in the initial courtyard,and producing a greater difference with outdoor temperatures that can reach 12℃versus 8℃for the reference *** addition,it was found that the courtyard with radiative cooling is able to significantly reduce the observed nighttime overheating by providing lower temperatures than the outdoor temperatures in the 50%of the nights *** was also found that the thermal loads to achieve indoor thermal comfort in the spaces adjacent to the courtyard were reduced by 63.46%to 69.85%.

关键词： radiative cooling passive cooling CFD three-dimensional modeling energy saving thermal comfort

Tannin-Based Biofoams-A Review

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Journal of Renewable Materials 2019年第5期7卷 477-492页

作者： antonio Pizzi LERMAB-ENSTIB University of Lorraine27 rue Philippe Seguin88000 EpinalFrance

This review details the development of tannin-based biofoams for fire resistance and acoustic insulation and details the different varieties of these foams that have been developed,from tannin-furanic self-blowing foa... 详细信息

关键词： Biofoams tannins tannin-furanic tannin-carbohydrates,nonisocyanate polyurethanes(NIPU)

Molecular conformation-induced interfacial stress at the origin of the instability of organic transistors

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Science China Chemistry 2021年第9期64卷 1437-1438页

作者： antonio Facchetti Department of Chemistry and Materials Research Center Northwestern University2145 Sheridan RoadEvanstonIL60208USA Flexterra Corporation 8025 Lamon AvenueSkokieIL60077USA

As one of the most important organic electronic building block,organic field-effect transistors(OFETs)have broad application prospects in the fields of flexible displays,electronic skins,and wearable *** more than 30 years of development,the performance(e.g.,the carrier mobility)and processing technology of OFETs have made considerable progress^([1,2]).

关键词： transistors interfacial origin