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61.
The interaction between the immune checkpoint PD-1 and PD−L1 promotes T-cell deactivation and cancer proliferation. Therefore, immune checkpoint inhibition therapy, which relies on prior assessment of the target, has been widely used for many cancers. As a non-invasive molecular imaging tool, radiotracers bring novel information on the in vivo expression of biomarkers (e. g., PD−L1), enabling a personalized treatment of patients. Our work aimed at the development of a PD−L1-specific, peptide-based PET radiotracer. We synthesized and evaluated a radiolabeled macrocyclic peptide adapted from a patent by Bristol Myers Squibb. Synthesis of [68Ga]Ga-NJMP1 yielded a product with a radiochemical purity>95 % that was evaluated in vitro. However, experiments on CHO−K1 hPD−L1 cells showed very low cell binding and internalization rates of [68Ga]Ga-NJMP1 in comparison to a control radiopeptide (WL12). Non-radioactive cellular assays using time-resolved fluorescence energy transfer confirmed the low affinity of the reported parent peptide and the DOTA-derivatives towards PD−L1. The results of our studies indicate that the macrocyclic peptide scaffold reported in the patent literature is not suitable for radiotracer development due to insufficient affinity towards PD−L1 and that C-terminal modifications of the macrocyclic peptide interfere with important ligand/receptor interactions. 相似文献
62.
MSc. Jessica A. I. Muller Dr. Nicole Lawrence Dr. Lai Yue Chan Dr. Peta J. Harvey Dr. Alysha G. Elliott Assoc. Prof. Mark A. T. Blaskovich Dr. Jacqueline C. Gonçalves Dr. Priscilla Galante Dr. Marcia R. Mortari Dr. Mônica C. Toffoli-Kadri Dr. Johannes Koehbach Prof. David J. Craik 《Chembiochem : a European journal of chemical biology》2021,22(8):1415-1423
Agelaia-MPI and protonectin are antimicrobial peptides isolated from the wasp Parachartergus fraternus that show antimicrobial and neuroactive activities. Previously, two analogues of these peptides, neuroVAL and protonectin-F, were designed to reduce nonspecific toxicity and improve potency. Here, the three-dimensional structures of neuroVAL, protonectin and protonectin-F were determined by using circular dichroism and NMR spectroscopy. Antibacterial, antifungal, cytotoxic and hemolytic activities were tested for the parent peptides and analogues. All peptides showed moderate antimicrobial activity against Gram-positive bacteria, with agelaia-MPI being the most active. Protonectin and protonectin-F were found to be toxic to cancerous and noncancerous cell lines. Internalization experiments revealed that these peptides accumulate inside both cell types. By contrast, neuroVAL was nontoxic to all tested cells and was able to enter cells without accumulating. In summary, neuroVAL has potential as a nontoxic cell-penetrating peptide, while protonectin-F needs further modification to realize its potential as an antitumor peptide. 相似文献
63.
Virginia Veronica Visconti Ida Cariati Simona Fittipaldi Riccardo Iundusi Elena Gasbarra Umberto Tarantino Annalisa Botta 《International journal of molecular sciences》2021,22(8)
DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions. 相似文献
64.
Joseph Cooney Isaac Hilton Melissa Marsh Annalisa Jones Silvana Martini 《Journal of the American Oil Chemists' Society》2023,100(3):225-236
The objective of this study was to evaluate the effect of cannabidiol (CBD) on the crystallization behavior and physical properties of various fats. Anhydrous milk fat (AMF), palm oil (PO), palm kernel oil (PKO), and cocoa butter (CB) were chosen for this study, for their unique crystallization behaviors. CBD was added at 1 and 2.5% wt/wt to these fats, and the crystallization behavior was evaluated at 26°C for AMF and PO and at 22°C for PKO and CB. Control samples with no CBD were prepared and evaluated as well. Results show that CBD delayed the crystallization of all fats with the least effect observed for the PO. Slight increases in crystal size were observed with the addition of CBD for all samples. CBD did not affect the melting profile of AMF or CB, but it increased the peak temperature of PO and decreased the enthalpy of PKO. Similarly, hardness was only affected by CBD in PO samples, with harder materials obtained for samples containing 2.5% CBD. The same trend was observed for elasticity. In addition, the elasticity of AMF increased with the addition of CBD but not its hardness. Overall, this study indicates that the effect of CBD on fat crystallization is highly dependent on the type of fat used. Producers of fat-based products that are willing to include CBD in their formulations must carefully control processing conditions to ensure product quality. 相似文献
65.
Gustavo Gonzalez María Arévalo Annalisa Chiappone Enrique Martínez Campos Candido Fabrizio Pirri Ignazio Roppolo Paula Bosch 《大分子材料与工程》2023,308(11):2300118
Light- induced polymeric 3D printing is becoming a well-established fabrication method, showing manifold advantages such as control of the local chemistry of the manufactured devices. It can be considered a green technology, since the parts are produced when needed and with minimum amount of materials. In this work 3D printing is combined with another green technology, microwave-assisted reaction, to fabricate objects of complex geometry with controllable surface properties, exploiting the presence of remaining functional groups on the surface of 3D printed specimens. In this context, surface functionalization with different amines is studied, optimizing formulations, reaction times, and avoiding surface deterioration. Then, two different applications are investigated. MW-functionalized filter-type structures have been tested against Staphylococcus aureus bacteria, showing high bactericidal activity on the surface along all areas of the complex-shaped structure. Second, a fluidic chip composed of three separated channels is 3D printed, filled with different amine-reactive dyes (dansyl and eosine derivatives), and made to react simultaneously. Complete and independent functionalization of the surface of the three channels is achieved only after 2 min of irradiation. This study demonstrates that light induced 3D printing and microwave-induced chemistry can be used together effectively, and used to produce functional devices. 相似文献
66.
L. Fewtrell BSc MSc PhD D. Kay BSc PhD A. Godfree BSc 《Water and Environment Journal》1998,12(1):45-47
This paper provides a detailed assessment of the microbiological quality of a selection of private water supplies. Samples were taken from 91 supplies and analyzed for total coliforms, faecal coliforms and faecal streptococci. The microbiological quality of the samples was generally poor, with almost 50% of the supplies failing to meet the required standards on at least one occasion. Given the high level of sanitary microbiological failures, there is the possibility that harmful microorganisms could be present and a significant risk to health cannot be discounted. 相似文献
67.
L. Fewtrell BSc MSc PhD D. Kay BSc PhD A. Godfree BSc 《Water and Environment Journal》1998,12(2):98-100
This paper provides a detailed assessment of the microbiological quality of a selection of private water supplies. Samples were taken from 91 supplies and analyzed for total coliforms, faecal coliforms and faecal streptococci. The microbiological quality of the samples was generally poor, with almost 50% of the supplies failing to meet the required standards on at least one occasion. Given the high level of sanitary microbiological failures, there is the possibility that harmful microorganisms could be present and a significant risk to health cannot be discounted. 相似文献
68.
C. Soulsby BSc PhD C. N. Gibbons BSc PhD T. Robins BSc MSc 《Water and Environment Journal》1999,13(3):213-223
During the dry years between 1989 and 1994, inter-basin water transfers from the Kielder system augmented flows in the River Derwent, and these flows substituted compensation releases from Derwent reservoir to retain storage for supply and recreational purposes.
The paper discusses the use of the Kielder transfers together with their impact upon (a) flow regime, (b) water quality, and (c) instream ecology of the River Derwent. Also, implications of the increasing use of water transfers in the UK are critically evaluated from the perspective of sustainability. 相似文献
The paper discusses the use of the Kielder transfers together with their impact upon (a) flow regime, (b) water quality, and (c) instream ecology of the River Derwent. Also, implications of the increasing use of water transfers in the UK are critically evaluated from the perspective of sustainability. 相似文献
69.
The North London Artificial Recharge scheme, which comprises thirty-seven wells and boreholes, is designed to boost resources during a drought. All sources discharge groundwater either to the Lee Valley reservoirs or the New River during the abstraction, which avoids the need for expensive on-site water treatment and significantly enhances the cost effectiveness of the scheme. Fully treated drinking water provides the source of gravity-fed artificial-recharge water, via the normal distribution system.
This paper describes the strategy which was introduced in 1997, in response to a deteriorating water-resources situation. Abstraction occurred over a period of four months prior to the onset of autumnal winter rainfall. Daily abstraction rates peaked at 150 Ml/d, and a total of about 10 700 Ml were withdrawn. 相似文献
This paper describes the strategy which was introduced in 1997, in response to a deteriorating water-resources situation. Abstraction occurred over a period of four months prior to the onset of autumnal winter rainfall. Daily abstraction rates peaked at 150 Ml/d, and a total of about 10 700 Ml were withdrawn. 相似文献
70.
The paper describes the design and operation of a submerged biotower, i.e. flooded upflow reactor which utilises a random-packed polypropylene medium for supporting the biomass. The process can be used for carbonaceous removal or nitrification. In the application which is described, the process has been used for tertiary nitrification of a poultry abattoir wastewater as an extension to the existing effluent-treatment plant. Details of process commissioning at low temperatures are given and results from twelve months'operation are discussed. Operating costs are compared with other processes. 相似文献