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21 pages, 1370 KiB  
Article
Thermal, Molecular Dynamics, and Mechanical Properties of Poly(Ethylene Furanoate)/Poly(ε-Caprolactone) Block Copolymers
by Johan Stanley, Panagiotis A. Klonos, Aikaterini Teknetzi, Nikolaos Rekounas, Apostolos Kyritsis, Lidija Fras Zemljič, Dimitra A. Lambropoulou and Dimitrios N. Bikiaris
Molecules 2024, 29(24), 5943; https://doi.org/10.3390/molecules29245943 (registering DOI) - 16 Dec 2024
Abstract
This study presents the synthesis and characterization of a series of multiblock copolymers, poly(ethylene 2,5-furandicarboxylate)-poly(ε-caprolactone) (PEF-PCL), created through a combination of the two-step melt polycondensation method and ring opening polymerization, as sustainable alternatives to fossil-based plastics. The structural confirmation of these block copolymers [...] Read more.
This study presents the synthesis and characterization of a series of multiblock copolymers, poly(ethylene 2,5-furandicarboxylate)-poly(ε-caprolactone) (PEF-PCL), created through a combination of the two-step melt polycondensation method and ring opening polymerization, as sustainable alternatives to fossil-based plastics. The structural confirmation of these block copolymers was achieved through Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR), ensuring the successful integration of PEF and PCL segments. X-ray Photoelectron Spectroscopy (XPS) was employed for chemical bonding and quantitative analysis, providing insights into the distribution and compatibility of the copolymer components. Differential Scanning Calorimetry (DSC) analysis revealed a single glass transition temperature (Tg), indicating the effective plasticizing effect of PCL on PEF, which enhances the flexibility of the copolymers. X-ray Diffraction (XRD) studies highlight the complex relationship between PCL content and crystallization in PEF-PCL block copolymers, emphasizing the need to balance crystallinity and mechanical properties for optimal material performance. Broadband Dielectric Spectroscopy (BDS) confirmed excellent distribution of PEF-PCL without phase separation, which is vital for maintaining consistent material properties. Mechanical properties were evaluated using Nanoindentation testing, demonstrating the potential of these copolymers as flexible packaging materials due to their enhanced mechanical strength and flexibility. The study concludes that PEF-PCL block copolymers are promising candidates for sustainable packaging solutions, combining environmental benefits with desirable material properties. Full article
(This article belongs to the Special Issue Macromolecular Chemistry in Europe)
17 pages, 1668 KiB  
Article
Zein Nanoparticles-Loaded Flavonoids-Rich Fraction from Fridericia platyphylla: Potential Antileishmanial Applications
by Monica Araujo das Neves, Caroline Martins de Jesus, Jhones Luiz de Oliveira, Samuel dos Santos Soares Buna, Lucilene Amorim Silva, Leonardo Fernandes Fraceto and Cláudia Quintino da Rocha
Pharmaceutics 2024, 16(12), 1603; https://doi.org/10.3390/pharmaceutics16121603 - 16 Dec 2024
Abstract
Background/Objectives: Leishmaniasis, caused by protozoa of the genus Leishmania, is a major global health issue due to the limitations of current treatments, which include low efficacy, high costs, and severe side effects. This study aimed to develop a more effective and less [...] Read more.
Background/Objectives: Leishmaniasis, caused by protozoa of the genus Leishmania, is a major global health issue due to the limitations of current treatments, which include low efficacy, high costs, and severe side effects. This study aimed to develop a more effective and less toxic therapy by utilizing zein nanoparticles (ZNPs) in combination with a nonpolar fraction (DCMF) from Fridericia platyphylla (Syn. Arrabidaea brachypoda), a plant rich in dimeric flavonoids called brachydins. Methods: Zein nanoparticles were used as carriers to encapsulate DCMF. The system was characterized by measuring particle diameter, polydispersity index, zeta potential, and encapsulation efficiency. Analytical techniques such as FTIR, DSC, and AFM were employed to confirm the encapsulation and stability of DCMF. Antileishmanial activity was assessed against Leishmania amazonensis promastigotes and amastigotes, while cytotoxicity was tested on RAW264.7 macrophages. Results: The ZNP-DCMF system exhibited favorable properties, including a particle diameter of 141 nm, a polydispersity index below 0.2, and a zeta potential of 11.3 mV. DCMF was encapsulated with an efficiency of 94.6% and remained stable for 49 days. In antileishmanial assays, ZNP-DCMF inhibited the viability of promastigotes with an IC50 of 36.33 μg/mL and amastigotes with an IC50 of 0.72 μg/mL, demonstrating higher selectivity (SI = 694.44) compared to DCMF alone (SI = 43.11). ZNP-DCMF was non-cytotoxic to RAW264.7 macrophages, with a CC50 > 500 μg/mL. Conclusions: Combining F. platyphylla DCMF with zein nanoparticles as a carrier presents a promising approach for leishmaniasis treatment, offering improved efficacy, reduced toxicity, and protection of bioactive compounds from degradation. Full article
(This article belongs to the Special Issue Anti-parasitic Applications of Nanoparticles)
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<p>Chemical structure of brachydins present in the dichloromethane fraction (DCMF), (<b>1</b>) Brachydin 1 (BRA1), (<b>2</b>) Brachydin 2 (BRA2), and (<b>3</b>) Brachydin 3 (BRA3).</p>
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<p>Characterization of control zein nanoparticles (ZNPs) and zein nanoparticles containing DCMF (ZNP-DCMF). (<b>a</b>) Mean diameter (nm) by DLS, (<b>b</b>) polydispersity index, (<b>c</b>) zeta potential (mV), and (<b>d</b>) encapsulation efficiency (%). The analyses were carried out for 49 days and all in triplicate at 25 °C.</p>
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<p>Characterization by FTIR using the ATR mode. (<b>A</b>) DCMF, (<b>B</b>) Pluronic F-68, (<b>C</b>) zein, and (<b>D</b>) ZNP-DCMF.</p>
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<p>Characterization by differential scanning calorimetry (DSC). (<b>A</b>) DCMF, (<b>B</b>) Pluronic F-68, (<b>C</b>) zein and (<b>D</b>) ZNP-DCMF.</p>
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<p>Micrographs obtained for nanoparticle using an atomic force microscope: (<b>a</b>) zein nanoparticles loading DCMF (2D image); (<b>b</b>) zein nanoparticles loading DCMF (3D image); (<b>c</b>) size distribution for zein nanoparticles loading DCMF. The analyses were performed using Gwyddion software.</p>
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<p>Cytotoxic activity of ZNP-DCMF (<b>a</b>) and ZNP-WHITE (<b>b</b>) against RAW 264.7 macrophages strain treated for 48 h. NC = negative control; PC = positive control; * asterisks indicate statistically significant differences to the negative control at <span class="html-italic">p</span> &lt; 0.05.</p>
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14 pages, 1579 KiB  
Article
Drug–Phospholipid Co-Amorphous Formulations: The Role of Preparation Methods and Phospholipid Selection
by Keyoomars Khorami, Sam Darestani Farahani, Anette Müllertz and Thomas Rades
Pharmaceutics 2024, 16(12), 1602; https://doi.org/10.3390/pharmaceutics16121602 - 16 Dec 2024
Abstract
Background/Objectives: This study aims to broaden the knowledge on co-amorphous phospholipid systems (CAPSs) by exploring the formation of CAPSs with a broader range of poorly water-soluble drugs, celecoxib (CCX), furosemide (FUR), nilotinib (NIL), and ritonavir (RIT), combined with amphiphilic phospholipids (PLs), including [...] Read more.
Background/Objectives: This study aims to broaden the knowledge on co-amorphous phospholipid systems (CAPSs) by exploring the formation of CAPSs with a broader range of poorly water-soluble drugs, celecoxib (CCX), furosemide (FUR), nilotinib (NIL), and ritonavir (RIT), combined with amphiphilic phospholipids (PLs), including soybean phosphatidylcholine (SPC), hydrogenated phosphatidylcholine (HPC), and mono-acyl phosphatidylcholine (MAPC). Methods: The CAPSs were initially prepared at equimolar drug-to-phospholipid (PL) ratios by mechano-chemical activation-based, melt-based, and solvent-based preparation methods, i.e., ball milling (BM), quench cooling (QC), and solvent evaporation (SE), respectively. The solid state of the product was characterized by X-ray powder diffraction (XRPD), polarized light microscopy (PLM), and differential scanning calorimetry (DSC). The long-term physical stability of the CAPSs was investigated at room temperature under dry conditions (0% RH) and at 75% RH. The dissolution behavior of the CCX CAPS and RIT CAPS was studied. Results: Our findings indicate that SE consistently prepared CAPSs for CCX-PLs, FUR-PLs, and RIT-PLs, whereas the QC method could only form CAPSs for RIT-PLs, CCX-SPC, and CCX-MAPC. In contrast, the BM method failed to produce CAPSs, but all drugs alone could be fully amorphized. While the stability of each drug varied depending on the PLs used, the SE CAPS consistently demonstrated the highest stability by a significant margin. Initially, a 1:1 molar ratio was used for screening all systems, though the optimal molar ratio for drug stability remained uncertain. To address this, various molar ratios were investigated to determine the ratio yielding the highest amorphous drug stability. Our results indicate that all systems remained physically stable at a 1.5:1 ratio and with excess of PL. Furthermore, the CAPS formed by the SE significantly improves the dissolution behavior of CCX and RIT, whereas the PLs provide a slight precipitation inhibition for supersaturated CCX and RIT. Conclusions: These findings support the use of a 1:1 molar ratio in screening processes and suggest that CAPSs can be effectively prepared with relatively high drug loads compared to traditional drug–polymer systems. Furthermore, the study highlights the critical role of drug selection, the preparation method, and the PL type in developing stable and effective CAPSs. Full article
19 pages, 7699 KiB  
Article
Development of New Chitosan-Based Complex with Bioactive Molecules for Regenerative Medicine
by Natasha Maurmann, Gabriela Moraes Machado, Rafaela Hartmann Kasper, Marcos do Couto, Luan Paz, Luiza Oliveira, Juliana Girón Bastidas, Paola Arosi Bottezini, Lucas Machado Notargiacomo, Carlos Arthur Ferreira, Luciano Pighinelli, Caren Serra Bavaresco, Patricia Pranke and Myrian Brew
Future Pharmacol. 2024, 4(4), 873-891; https://doi.org/10.3390/futurepharmacol4040046 (registering DOI) - 16 Dec 2024
Abstract
Background/Objectives: The development of new materials incorporating bioactive molecules for tissue regeneration is a growing area of interest. The objective of this study was to develop a new complex specifically designed for bone and skin tissue engineering, combining chitosan, ascorbic acid-2-magnesium phosphate (ASAP), [...] Read more.
Background/Objectives: The development of new materials incorporating bioactive molecules for tissue regeneration is a growing area of interest. The objective of this study was to develop a new complex specifically designed for bone and skin tissue engineering, combining chitosan, ascorbic acid-2-magnesium phosphate (ASAP), and β-tricalcium phosphate (β-TCP). Methods: Chitosan and the complexes chitosan/ASAP and chitosan/ASAP/β-TCP were prepared in membrane form, macerated to a particulate format, and then subjected to characterization through Fourier transform infrared (FTIR) spectroscopy, optical and scanning electron microscopy (SEM), zeta potential, thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Cell viability was evaluated through a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and with fluorescein diacetate (FDA) and propidium iodide (PI) staining in stem cells obtained from deciduous teeth. Statistical analyses were performed using analysis of variance (ANOVA), followed by Tukey’s test. Results: The FTIR results indicated the characteristic bands in the chitosan group and the complexation between chitosan, ASAP, and β-TCP. Microscopic characterization revealed a polydisperse distribution of micrometric particles. Zeta potential measurements demonstrated a reduction in surface charge upon the addition of ASAP and β-TCP to the chitosan matrix. TGA and DSC analyses further indicated complexation between the three components and the successful formation of a cross-linked structure in the chitosan matrix. Stem cells cultured with the particulate biomaterials demonstrated their biocompatibility. Statistical analysis revealed a significant increase in cell viability for the chitosan/ASAP and chitosan/ASAP/β-TCP groups compared to the chitosan control. Conclusions: Therefore, the chitosan/ASAP complex demonstrated potential for skin regeneration, while the chitosan/ASAP/β-TCP formulation showed promise as a biomaterial for bone regeneration due to the presence of β-tricalcium phosphate. Full article
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<p>Summary of experiments: (<b>a</b>) schematic presentation of the chemical structure and dissolution of chitosan in an aqueous solution of hydrochloric acid; (<b>b</b>) chemical structure and dissolution of L-ascorbic acid 2-phosphate sesquimagnesium salt hydrate (ASAP) in an aqueous solution of hydrochloric acid; (<b>c</b>) chemical structure and dissolution of beta-tricalcium phosphate (β-TCP) in the aqueous solution of hydrochloric acid; (<b>d</b>) filtration; (<b>e</b>) pasty material; (<b>f</b>) dried membrane; (<b>g</b>) particulate biomaterial obtained after maceration; (<b>h</b>) ultraviolet radiation in a laminar hood to reduce the risk of contamination.</p>
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<p>FTIR spectrum of the chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP).</p>
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<p>Micrographs of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP): (<b>a</b>) optical microscopy reveals the general morphology of the particles; (<b>b</b>) scanning electron microscopy offers a high-resolution view, highlighting surface details of the particles. The scale bar represents 100 μm, except for in 2000× magnification, which is 10 μm.</p>
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<p>Micrographs of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP): (<b>a</b>) optical microscopy reveals the general morphology of the particles; (<b>b</b>) scanning electron microscopy offers a high-resolution view, highlighting surface details of the particles. The scale bar represents 100 μm, except for in 2000× magnification, which is 10 μm.</p>
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<p>Zeta potential measurement of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP) in 1 mM NaCl: (<b>a</b>) graphical representation with data expressed as mean ± standard deviation. Different letters indicate significant differences (<span class="html-italic">p</span> ≤ 0.05) by ANOVA, followed by Tukey’s test. (<b>b</b>) Distribution.</p>
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<p>Thermogravimetric analysis (TGA) of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP).</p>
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<p>Differential scanning calorimetry (DSC) of chitosan particles (Chit), chitosan/ascorbic acid-2-magnesium phosphate complex (Chit/ASAP), and the complex with β-tricalcium phosphate (Chit/ASAP/β-TCP).</p>
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<p>Biological test with mesenchymal stem cells (MSCs). (<b>a</b>) Fibroblastoid morphology of cells adhered to in vitro culture plastics, and osteogenic, adipogenic, and chondrogenic differentiation of MSCs, stained with alizarin red S, oil red O, and alcian blue, respectively. The scale bar represents 50 μm. Viability of MSCs 3 days after treatment with particles: (<b>b</b>) MTT assay; (<b>c</b>) staining of live/dead cells with fluorescein diacetate and propidium iodide. The scale bar represents 100 μm. The control corresponds to cells grown directly in the wells of the tissue culture plate; Chit, to 10 mg/mL of chitosan; Chit/ASAP, to 10.3 mg/mL of the complex chitosan with ascorbic acid-2-magnesium phosphate; and Chit/ASAP/TCP, to 20.3 mg/mL of the complex Chit/ASAP with β-tricalcium phosphate. Data expressed as mean ± standard error of the mean. * indicates a statistically significant difference (<span class="html-italic">p</span> &lt; 0.05) in relation to the control by ANOVA followed by Tukey’s test.</p>
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<p>Biological test with mesenchymal stem cells (MSCs). (<b>a</b>) Fibroblastoid morphology of cells adhered to in vitro culture plastics, and osteogenic, adipogenic, and chondrogenic differentiation of MSCs, stained with alizarin red S, oil red O, and alcian blue, respectively. The scale bar represents 50 μm. Viability of MSCs 3 days after treatment with particles: (<b>b</b>) MTT assay; (<b>c</b>) staining of live/dead cells with fluorescein diacetate and propidium iodide. The scale bar represents 100 μm. The control corresponds to cells grown directly in the wells of the tissue culture plate; Chit, to 10 mg/mL of chitosan; Chit/ASAP, to 10.3 mg/mL of the complex chitosan with ascorbic acid-2-magnesium phosphate; and Chit/ASAP/TCP, to 20.3 mg/mL of the complex Chit/ASAP with β-tricalcium phosphate. Data expressed as mean ± standard error of the mean. * indicates a statistically significant difference (<span class="html-italic">p</span> &lt; 0.05) in relation to the control by ANOVA followed by Tukey’s test.</p>
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14 pages, 6781 KiB  
Article
Identification of Vertebrae in CT Scans for Improved Clinical Outcomes Using Advanced Image Segmentation
by Sushmitha, M. Kanthi, Vishnumurthy Kedlaya K, Tejasvi Parupudi, Shyamasunder N. Bhat and Subramanya G. Nayak
Signals 2024, 5(4), 869-882; https://doi.org/10.3390/signals5040047 (registering DOI) - 16 Dec 2024
Viewed by 83
Abstract
This study proposes a comprehensive framework for the segmentation and identification of vertebrae in CT scans using a combination of deep learning and traditional machine learning techniques. The Res U-Net architecture is employed to achieve a high model accuracy of 93.62% on the [...] Read more.
This study proposes a comprehensive framework for the segmentation and identification of vertebrae in CT scans using a combination of deep learning and traditional machine learning techniques. The Res U-Net architecture is employed to achieve a high model accuracy of 93.62% on the VerSe’20 dataset demonstrating effective performance in segmenting lumbar and thoracic vertebrae. Feature extraction is enhanced through the application of Otsu’s method which effectively distinguishes the vertebrae from the surrounding tissue. The proposed method achieves a Dice Similarity Coefficient (DSC) of 87.10% ± 3.72%, showcasing its competitive performance against other segmentation techniques. By accurately extracting vertebral features this framework assists medical professionals in precise preoperative planning, allowing for the identification and marking of critical anatomical features required during spinal fusion procedures. This integrated approach not only addresses the challenges of vertebrae segmentation but also offers a scalable and efficient solution for analyzing large-scale medical imaging datasets with the potential to significantly improve clinical workflows and patient outcomes. Full article
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<p>Segmentation of the vertebrae using Res U-Net.</p>
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<p>Architecture of the Res U-Net model for vertebrae segmentation. The model includes Convolutional Blocks (CA Blocks), Max-Pooling Layers for down-sampling, Up-Convolution Layers for up-sampling, and a Hierarchical Dense Aggregation (HDAC) Layer for efficient multi-scale feature aggregation. Input CT scans with a resolution of 512 × 512 pixels are processed through this network to generate segmented images.</p>
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<p>Training accuracy of the Res U-Net model over iterations for three datasets.</p>
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<p>Validation loss over epochs for three different datasets.</p>
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<p>Otsu’s feature extraction algorithm.</p>
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<p>Vertebra segmentation using Res U-Net (<b>a</b>) CT scan image (<b>b</b>) Ground truth (<b>c</b>) Segmented vertebrae.</p>
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<p>Vertebra feature extraction using Otsu’s method. (<b>a</b>) CT scan image (<b>b</b>). Segmented binary mask. (<b>c</b>) CT image with segmented contour.</p>
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<p>Final segmented 3D image of the vertebrae.</p>
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17 pages, 2503 KiB  
Article
Preparation and Characterization of Poly(vinyl-alcohol)/Chitosan Polymer Blend Films Chemically Crosslinked with Glutaraldehyde: Mechanical and Thermal Investigations
by Daniel Pugar, Tatjana Haramina, Mirela Leskovac and Lidija Ćurković
Molecules 2024, 29(24), 5914; https://doi.org/10.3390/molecules29245914 (registering DOI) - 14 Dec 2024
Viewed by 344
Abstract
In this study, poly(vinyl-alcohol) (PVA)/chitosan (CS) polymer blend films with different amounts of CS (0, 5, 20 and 35 wt. %) crosslinked by glutaraldehyde (GA) were prepared. The structure and properties of the prepared polymer films were studied by means of dynamic mechanical [...] Read more.
In this study, poly(vinyl-alcohol) (PVA)/chitosan (CS) polymer blend films with different amounts of CS (0, 5, 20 and 35 wt. %) crosslinked by glutaraldehyde (GA) were prepared. The structure and properties of the prepared polymer films were studied by means of dynamic mechanical analysis (DMA), differential scanning calorimetry (DSC), and the time-lag permeation technique. The DMA analysis showed that CS reduces the crystallinity degree of PVA, leading to a higher amount of the amorphous phase contributing to the α relaxation that corresponds to the glass-to-rubber transition. However, the mobility of the amorphous phase can be restricted with crosslinking with 1 wt. % GA. Interaction between the PVA and the CS was confirmed by DCS analysis. Additionally, the influence of the CS and crosslinking on the permeation of nitrogen molecules was investigated. The permeation was examined by the time-lag method. It was found that the addition of CS and GA to PVA improves barrier properties. Full article
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Figure 1
<p>Temperature dependence of tan <span class="html-italic">δ</span> for PVA films with 0 wt. % (PVA), wt. % (CS1), 20 wt. % (CS2), and 35 wt. % (CS3) of CS.</p>
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<p>Storage modulus <span class="html-italic">E</span>′ vs. temperature for PVA films with 0 wt. % (PVA), wt. % (CS1), 20 wt. % (CS2), and 35 wt. % (CS3) of CS.</p>
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<p>Damping factor tan <span class="html-italic">δ</span> as a function of temperature for crosslinked and non-crosslinked PVA films with the following mass fractions of CS: (<b>a</b>) 0 wt. %, (<b>b</b>) 5 wt. %, (<b>c</b>) 20 wt. %, (<b>d</b>) 35 wt. %.</p>
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<p>Storage modulus <span class="html-italic">E</span>′ as a function of temperature of crosslinked and non-crosslinked PVA films with different amounts of CS: (<b>a</b>) 0 wt. %, (<b>b</b>) 5 wt. %, (<b>c</b>) 20 wt. %, (<b>d</b>) 35 wt. %.</p>
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<p>DMA spectra of pure PVA, PVA with 20 wt. % of CS (CS2) and crosslinked PVA with 20 wt. % of CS (CS2/GA); (<b>a</b>) damping factor tan <span class="html-italic">δ</span> and (<b>b</b>) storage modulus <span class="html-italic">E</span>′ depending on temperature.</p>
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<p>DSC thermograms of PVA/CS blends crosslinked with glutaraldehyde and with different amounts of CS: 0 wt. % (PVA), 5 wt. % (CS1), 20 wt. % (CS2), and 35 wt. % (CS3).</p>
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<p>Melting enthalpy of PVA/CS blends.</p>
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<p>Results of permeability measurements for PVA films with different amounts of CS: 0 wt. % (PVA), 5 wt. % (CS1), 20 wt. % (CS2), and 35 wt. % (CS3).</p>
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<p>Influence of CS on the permeability of PVA films; data are representative of the results of repeated experiments (n = 3) and expressed as the mean value.</p>
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<p>Influence of crosslinking on the permeability of PVA films with 0, 5, 20, and 35 wt. % amount of CS; data are representative of the results of repeated experiments (n = 3) and expressed as the mean value.</p>
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12 pages, 1239 KiB  
Article
Exploring the Interaction of 3-Hydroxy-4-pyridinone Chelators with Liposome Membrane Models: Insights from DSC and EPR Analysis
by Luísa M. P. F. Amaral, Tânia Moniz and Maria Rangel
Molecules 2024, 29(24), 5905; https://doi.org/10.3390/molecules29245905 (registering DOI) - 14 Dec 2024
Viewed by 404
Abstract
In this study, we synthesized a series of 3-hydroxy-4-pyridinone (3,4-HPO) chelators with varying lipophilicity by modifying the length of their alkyl chains. To investigate their interaction with lipid membranes, we employed differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy using dimyristoylphosphatidylcholine [...] Read more.
In this study, we synthesized a series of 3-hydroxy-4-pyridinone (3,4-HPO) chelators with varying lipophilicity by modifying the length of their alkyl chains. To investigate their interaction with lipid membranes, we employed differential scanning calorimetry (DSC) and electron paramagnetic resonance (EPR) spectroscopy using dimyristoylphosphatidylcholine (DMPC) and palmitoyloleoylphosphatidylcholine (POPC) liposomes as membrane model systems. DSC experiments on DMPC liposomes revealed that hexyl-substituted chelators significantly altered the thermotropic phase behavior of the lipid bilayer, indicating their potential as membrane property modulators. EPR studies on DMPC and POPC liposomes provided detailed insights into the depth-dependent effects of chelators on membrane fluidity. Our findings highlight the crucial role of alkyl chain length in determining the interaction of 3,4-HPO chelators with lipid membranes and offer valuable insights for the design of lipid-interacting therapeutic agents based on this scaffold. Full article
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<p>Formulae and abbreviations of the 3-hydroxy-4-pyridinone chelators studied in this work.</p>
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<p>The DSC heating thermograms for the main phase transition of DMPC unilamellar vesicles (LUVs), in the presence and absence of different concentrations of chelators: (<b>a</b>) butmpp; (<b>b</b>) hexylmpp; (<b>c</b>) butetpp; and (<b>d</b>) hexyletpp.</p>
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<p>Hyperfine splitting (2A<sub>max</sub>) (<b>a</b>,<b>c</b>) rotational correlation time (τ) (<b>b</b>,<b>d</b>) obtained for POPC (<b>a</b>,<b>b</b>) and DMPC (<b>c</b>,<b>d</b>) liposomes in the absence (control) or in the presence of the chelators. The 5-DSA (<b>a</b>,<b>c</b>) and 16-DSA (<b>b</b>,<b>d</b>) spin probes have been used to study interaction of the compounds in the hydrophilic and hydrophobic region of the lipossomes, respectively. The data represent the mean ± standard error (SE) from three replicates. Statistical analysis was performed using one-way ANOVA. ** <span class="html-italic">p</span> ≤ 0.01; *** <span class="html-italic">p</span> ≤ 0.001; **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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19 pages, 5654 KiB  
Article
Fullerenol C60(OH)36: Antioxidant, Cytoprotective, Anti-Influenza Virus Activity, and Self-Assembly in Aqueous Solutions and Cell Culture Media
by Alina A. Borisenkova, Mikhail Y. Eropkin, Nadezhda I. Konovalova, Anna V. Titova, Maria A. Markova, Zhanna B. Lyutova, Anton S. Mazur, Victor P. Sedov, Vera A. Orlova, Anna N. Lykholay, Diana N. Orlova and Alexandr V. Arutyunyan
Antioxidants 2024, 13(12), 1525; https://doi.org/10.3390/antiox13121525 - 13 Dec 2024
Viewed by 461
Abstract
Viral infections and many other dangerous diseases are accompanied by the development of oxidative stress, which is a consequence of an increase in the level of the reactive oxygen species (ROS). In this regard, the search for effective antioxidants remains highly relevant. We [...] Read more.
Viral infections and many other dangerous diseases are accompanied by the development of oxidative stress, which is a consequence of an increase in the level of the reactive oxygen species (ROS). In this regard, the search for effective antioxidants remains highly relevant. We tested fullerenol C60(OH)36 in the context of the connection between its self-assembly in aqueous solutions and cell culture media, antiradical activity, UV cytoprotective action, and antiviral activity against international reference strains of influenza virus A(H1N1)pdm09, A(H3N2), and B subtypes in vitro on the MDCK cell line. Various characterization techniques, including Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, NMR and ESR spectrometry, MALDI-TOF mass spectrometry, thermal analysis (TGA and DSC), dynamic light-scattering (DLS), and ζ-potential measurements, were used to confirm the production of fullerenol and study its self-assembly in aqueous solutions and cell culture media. Fullerenol C60(OH)36 demonstrated the ability to scavenge DPPH, OH, O2•− radicals and 1O2 and was non-toxic in the range of the studied concentrations (up to 200 μg/mL) when incubated with MDCK cells for 24 h. In addition, fullerenol exhibited a cytoprotective effect under UV irradiation (EC50 = 29.7 ± 1.0 μM) and showed moderate activity against human influenza viruses of subtypes A(H1N1)pdm09 (SI = 9.9 ± 4.6) and A(H3N2) (SI = 12.5 ± 1.3) when determined by the hemagglutination assay (HA-test) and the MTT assay. At the same time, C60(OH)36 was ineffective in vitro against the actual strain of influenza B virus (Victoria lineage). The high bioavailability of fullerenol in combination with its cytoprotective effect, as well as its antiradical and antiviral activity combined with a relatively low toxicity, allows to consider it a promising compound for biomedical applications. Full article
(This article belongs to the Special Issue Recent Trends in Nanoantioxidants)
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<p>A schematic representation of fullerenol synthesis.</p>
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<p>(<b>A</b>) Solid-state <sup>13</sup>C-NMR spectra of fullerene C<sub>60</sub> (a), Sample A (b), and Sample B (c). (<b>B</b>) <sup>1</sup>H Solid-state <sup>1</sup>H-NMR spectra of Sample A (a) and Sample B (b).</p>
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<p>(<b>A</b>) FTIR spectra of fullerene C<sub>60</sub> and Samples A and B. (<b>B</b>) Raman spectra of pristine C<sub>60</sub> and Sample A. (<b>C</b>) Absorbance spectra of Sample B in aqueous solutions. (<b>D</b>) ESR spectrum for solid-state Sample B at 298 K. (<b>E</b>) TGA curves of fullerene C<sub>60</sub> and Sample A and B obtained at 10 °C/min heating rate under Ar atm. (<b>F</b>) MALDI-MS profile of Sample B and matrix effect of the CHCA.</p>
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<p>Radical scavenging activity of fullerenol. (<b>A</b>) DPPH radicals scavenging activity. (<b>B</b>) Superoxide radicals scavenging activity. (<b>C</b>) Hydroxyl radical scavenging activity. (<b>D</b>) Singlet oxygen scavenging activity. The data are presented as mean values ± SD (<span class="html-italic">n</span> = 6 independent experiments). In (<b>A</b>–<b>D</b>), the difference between the control and the experiments is reliable (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>The viability of MDCK cells incubated with C<sub>60</sub>(OH)<sub>36</sub> for 24 h (<b>A</b>) and 72 h (<b>B</b>) obtained by MTT assay. The results are mean values ± SD (<span class="html-italic">n</span> ≥ 6 independent experiments). In (<b>A</b>), the difference between the control and the experiments is unreliable (<span class="html-italic">p</span> ≥ 0.05). In (<b>B</b>) nonlinear approximation, 4-parameter model (GraphPad Prism Software Vers. 8.0). **** <span class="html-italic">p</span> &lt; 0.0001.</p>
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<p>Protective effects of fullerenol against UV irradiation. (<b>A</b>) Morphology of MDCK cells without fullerenol in dark control. (<b>B</b>) Morphology of MDCK cells after UV irradiation for 2.5 min. (<b>C</b>) Morphology of MDCK cells under UV irradiation for 2.5 min in the presence of 100 μg/mL fullerenol. (<b>D</b>) Protective effect of fullerenol on cells in culture against UV phototoxicity. Fullerenol concentration is 50 µg/mL, and irradiation time is 2.5 ÷ 10 min. After irradiation, the cells were incubated for 18–20 h in the dark. * <span class="html-italic">p</span> &lt; 0.05; ** <span class="html-italic">p</span> &lt; 0.001 (<b>E</b>) Effect of fullerenol concentration on UV-mediated toxicity in vitro. Irradiation time: 7 min. **** <span class="html-italic">p</span> &lt; 0.0001. Values are expressed as the mean ± S.D. (<span class="html-italic">n</span> ≥ 6).</p>
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<p>Activity of C<sub>60</sub>(OH)<sub>36</sub>·10H<sub>2</sub>O against the A/California/07/2009 (H1N1)pdm09 reference strain, measured by the MTT test. The results are mean values ± SD (<span class="html-italic">n</span> ≥ 6 independent experiments).</p>
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23 pages, 11747 KiB  
Article
The Effect of Textile Structure Reinforcement on Polymer Composite Material Mechanical Behavior
by Svetlana Risteska, Vineta Srebrenkoska, Silvana Zhezhova, Sara Srebrenkoska, Sanja Risteski, Sonja Jordeva and Saska Golomeova Longurova
Polymers 2024, 16(24), 3478; https://doi.org/10.3390/polym16243478 - 13 Dec 2024
Viewed by 360
Abstract
Investigating the impact of textile structure reinforcement on the mechanical characteristics of polymer composites produced by the compression molding technique was the goal of this work. An epoxy resin system served as the matrix, and various woven (plain, twill, basket), nonwoven (mat), and [...] Read more.
Investigating the impact of textile structure reinforcement on the mechanical characteristics of polymer composites produced by the compression molding technique was the goal of this work. An epoxy resin system served as the matrix, and various woven (plain, twill, basket), nonwoven (mat), and unidirectional (UD) textile structures made from E-glass fibers were employed as reinforcement elements. Compression molding of pre-impregnated textile materials (prepregs) was used to create the composites. The well-impregnated textile structures with resin into prepreg and the good interface between layers of the composites were verified during the manufacture of the polymer–textile composites using DSC thermal analysis and an SEM microscope. For the mechanical behavior, flexural properties were determined. The composite samples with unidirectional prepreg reinforcement have the highest longitudinal flexural strengths at roughly 900 MPa. The woven prepreg-based composite laminates show balanced flexural properties in both directions. Composites based on plane and basket prepregs have a flexural strength of about 450 MPa. Their flexural strength is over 20% lower than that of the samples made using twill prepreg. In both directions, nonwoven prepreg-reinforced composite samples show the least amount of resistance to bending stresses (flexural strength of roughly 150 MPa). Full article
(This article belongs to the Collection Feature Papers in Polymer Processing and Engineering)
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<p>Tensile strength test using the universal test machine by Schenck.</p>
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<p>(<b>a</b>) Machine impregnation. (<b>b</b>) Hand impregnation.</p>
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<p>Press machine.</p>
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<p>Flexural strength test using a three-point flexural method and the universal testing machine (UTM).</p>
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<p>Scanning electron microscope VEGA3 LMU from the company Tescan.</p>
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<p>Microphotographs from (<b>a</b>) Sample I, (<b>b</b>) Sample II, and (<b>c</b>) Sample III.</p>
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<p>Tensile strength and tensile deformation of applied woven fabric according to (<b>a</b>) warp and (<b>b</b>) weft.</p>
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<p>Diagrams from the DSC instrument from which Tg is read for all plates. (<b>a</b>) L−I; (<b>b</b>) L−II: (<b>c</b>) L−III; (<b>d</b>) L−IV; and (<b>e</b>) L−V.</p>
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<p>Force and displacement graphs for L−V MD and L−V CD test samples with three replications presented with different colors of the curves</p>
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<p>Flexural strength of composite plates.</p>
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<p>Flexural modulus of composite plates.</p>
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<p>Optical and scanning electron images of prepregs and composite plates. (<b>a</b>) SEM image of glass woven prepregs: good fiber–matrix interface in the prepreg (in the impregnation process). (<b>b</b>) Illustrations of the deformation and fiber breakage after the breakage test of Sample L-I-MD and an optical microscope image. (<b>c</b>) SEM image of the glass UD prepreg (<b>left</b>) and SEM image of a cross-section of the broken L-V composite plate (<b>right</b>) after testing.</p>
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<p>Optical and scanning electron images of prepregs and composite plates. (<b>a</b>) SEM image of glass woven prepregs: good fiber–matrix interface in the prepreg (in the impregnation process). (<b>b</b>) Illustrations of the deformation and fiber breakage after the breakage test of Sample L-I-MD and an optical microscope image. (<b>c</b>) SEM image of the glass UD prepreg (<b>left</b>) and SEM image of a cross-section of the broken L-V composite plate (<b>right</b>) after testing.</p>
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25 pages, 5617 KiB  
Article
Effect of Co-Solvents, Modified Starch and Physical Parameters on the Solubility and Release Rate of Cryptotanshinone from Alcohologels
by Justyna Kobryń, Patryk Demski, Bartosz Raszewski, Tomasz Zięba and Witold Musiał
Molecules 2024, 29(24), 5877; https://doi.org/10.3390/molecules29245877 - 12 Dec 2024
Viewed by 339
Abstract
(1) Background: The aim of the work was to investigate the influence of selected physico-chemical factors on the solubility and release rate of CT (cryptotanshinone) in alcohologels. (2) Methods: The alcohologels of methylcellulose (MC), hydroksyethylcellulose (HEC), polyacrylic acid (PA) and polyacrylic acid crosspolymer [...] Read more.
(1) Background: The aim of the work was to investigate the influence of selected physico-chemical factors on the solubility and release rate of CT (cryptotanshinone) in alcohologels. (2) Methods: The alcohologels of methylcellulose (MC), hydroksyethylcellulose (HEC), polyacrylic acid (PA) and polyacrylic acid crosspolymer (PACP) with CT were prepared and/or doped with native potato starch (SN) and modified citrate starches (SM2.5 and SM10). The analytical methods included evaluation of CT release profiles, Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and electrospray ionization mass spectrometry (ESI-MS), and scanning electron microscope (SEM) images were performed. (3) Results: The release and decomposition kinetics of CT in relation to the phosphate buffer solution (PBS) and methanol were observed. The amount of cryptotanshinone (CT) released into PBS was significantly lower (2.5%) compared to its release into methanol, where 22.5% of the CT was released into the model medium. The addition of SM2.5 to the alcohologel significantly increased the CT content to 70% in the alcohologel preparation containing NaOH (40%), and this enhanced stability was maintained for up to two months. The ATR-FTIR exhibited interactions between PA and 2-amino-2-methyl-1,3-propanediol (AMPD) as well as between PA and NaOH in case of the alcohologels. Moreover, it indicated the interaction between CT and NaOH. PXRD diffractograms confirmed the FTIR study. (4) Conclusions: The study observed the influence of a number of factors on the solubility and release rate of CT, as: alkalizers and their concentration, SM2.5 addition. The transition of CT in the presence of NaOH to the tanshinone V sodium (T-V sodium) form was suspected. Full article
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<p>Release percentage of CT: (<b>a</b>) into PBS from alcohologels A-PA(i) (the bars with vertical lines) and N-PA(i) (the bars with horizontal lines) over 94 h, 37 ± 0.5 °C, (<b>b</b>) into methanol from alcohologels A-PA (the bars with vertical lines) and N-PA (the bars with horizontal lines) over 6 h, 22 ± 0.5 °C, <span class="html-italic">n</span> = 3. (i) refers to the alcohologels containing 20% ethanol.</p>
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<p>Mean content of CT in alcohologels stored in cool conditions for 60 days depending on preparation parameters: ultrasound and 60 °C (the bars with red lines), adding SN (the bars with yellow lines), SM2.5 (the bars with green lines) and SM10 (the bars with blue lines) with AMPD (A) and NaOH (N) as compared to referent alcohologels (A-PA and N-PA) (the bars with black lines), <span class="html-italic">n</span> = 5. The asterisk (*) indicates alcohologels preparation method with higher concentrations of alkalizers and ultrasonication at 60 °C.</p>
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<p>ATR-FTIR spectrogram of the raw substances, suspensions (s), cryo-alcohologels and physical mixtures (mix); c index indicates cryo-alcohologels. The asterisk (*) indicates alcohologels preparation method with higher concentrations of alkalizers and ultrasonication at 60 °C.</p>
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<p>PXRD diffractograms of the raw substances, suspensions (s), cryo-alcohologels and physical mixtures (mix); c index indicates cryo-alcohologels. The asterisk (*) indicates alcohologels preparation method with higher concentrations of alkalizers and ultrasonication at 60 °C.</p>
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<p>DSC thermograms of the raw substances, suspensions (s) alcohologels and physical mixtures (mix); c index indicates cryo-alcohologels at the first (<b>a</b>) and second (<b>b</b>) cycle of heating. The asterisk (*) indicates alcohologels preparation method with higher concentrations of alkalizers and ultrasonication at 60 °C.</p>
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<p>ESI-MS spectra of suspensions containing CT in negative mode prepared with 1% AMPD solution after the first day (<b>a</b>) and 0.36% NaOH solution after the first day (<b>b</b>).</p>
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<p>ESI-MS spectra of suspensions with CT prepared with: methanol (<b>a</b>), ethanol (<b>b</b>), 1% AMPD solution after the first day (<b>c</b>) and after 30 days (<b>d</b>), 0.36% NaOH solution after the first day (<b>e</b>) and after 30 days (<b>f</b>).</p>
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<p>SEM micrographs of CT (<b>A</b>), the suspensions: A-CT(s) (<b>B</b>), N-CT(s) (<b>C</b>) and the cryo-alcohologels: A-PA(0)<sup>c</sup> (<b>D</b>), A-PA<sup>c</sup> (<b>E</b>), A-PA(*)<sup>c</sup> (<b>F</b>), N-PA(0)<sup>c</sup> (<b>G</b>), N-PA<sup>c</sup> (<b>H</b>) and N-PA(*)<sup>c</sup> (<b>I</b>), from 100 to 16,000 magnification.</p>
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<p>The FTIR spectra exhibited interactions between CT and. The asterisk (*) indicates alcohologels preparation method with higher concentrations of alkalizers and ultrasonication at 60 °C.</p>
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<p>Comparison of the initial (<b>a</b>) and after 30 days (<b>b</b>) ESI-MS signals derived from CT at <span class="html-italic">m</span>/<span class="html-italic">z</span> 297.1485 ([M + H]<sup>+</sup>) dissolved in test solvents with a reference-calculated CT signal.</p>
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<p>Comparison of the initial (<b>a</b>) and after 30 days (<b>b</b>) ESI-MS signals derived from CT at <span class="html-italic">m</span>/<span class="html-italic">z</span> 319.1305 ([M + Na]<sup>+</sup>) dissolved in test solvents with a reference-calculated CT signal.</p>
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<p>The structure of tanshinone V (T-V) after CT hydrolysis and its isomeric forms (I, II) [<a href="#B72-molecules-29-05877" class="html-bibr">72</a>].</p>
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18 pages, 10957 KiB  
Article
The Formulation, Preparation, and Evaluation of Celecoxib Nanosuspensions: Nanosizing via High-Pressure Homogenization and Conversion of the Nanosuspensions into Dry Powders by Spray Drying and Freeze Drying
by Rukesh Machamasi, Sung-Joo Hwang and Linh Dinh
J. Pharm. BioTech Ind. 2024, 1(1), 20-37; https://doi.org/10.3390/jpbi1010004 - 12 Dec 2024
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Abstract
Celecoxib (CEL), a nonsteroidal anti-inflammation drug (NSAID), is categorized as a Class II drug (low solubility, high permeability) in the Biopharmaceutics Classification System (BCS). The aim of this study is to develop a novel formulation of CEL nanosuspensions in the form of dried [...] Read more.
Celecoxib (CEL), a nonsteroidal anti-inflammation drug (NSAID), is categorized as a Class II drug (low solubility, high permeability) in the Biopharmaceutics Classification System (BCS). The aim of this study is to develop a novel formulation of CEL nanosuspensions in the form of dried powder for tableting or capsuling. In this study, CEL was formulated into nanosuspensions to improve its solubility. CEL nanosuspensions were prepared using the precipitation method followed by high-pressure homogenization. Drying of the nanosuspensions was performed by spray drying and freeze drying. We examined the impact of various formulation and processing parameters on the nanoparticles. The CEL nanoparticles were characterized by particle size analysis, differential scanning calorimetry (DSC), powder X-Ray diffraction (PXRD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), and dissolution tests. The choice of solvent, stabilizer, and surfactant appeared to have significant impacts on the crystallization and particle size and, consequently, the solubility of the CEL nanoparticles. CEL chemical stability was maintained throughout both drying processes. Both spray-dried and freeze-dried CEL nanosuspensions showed rapid dissolution profiles compared to raw CEL due to the nanosized particle dispersion with the presence of a lag phase. The freeze-dried nanosuspension showed a slight delay in the first 20 min compared to the spray-dried nanosuspension, after which dissolution progressed with a lag phase that represents aggregation. Full article
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<p>Differential Scanning Calorimetry (DSC) thermograms of (<b>a</b>) raw Celecoxib (CEL) and spray-dried formulations 1–5; (<b>b</b>) raw CEL and freeze-dried formulation 1–5.</p>
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<p>ATR FTIR results of (<b>a</b>) raw CEL and spray-dried formulations 1–5; (<b>b</b>) raw CEL and freeze-dried formulation 1–5.</p>
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<p>PXRD results of (<b>a</b>) raw CEL and spray-dried formulations 1–5; (<b>b</b>) raw CEL and freeze-dried formulation 1–5.</p>
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<p>SEM picture of raw CEL powder.</p>
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<p>SEM picture of (<b>a</b>) freeze-dried formulation 1; (<b>b</b>) freeze-dried formulation 2; (<b>c</b>) freeze-dried formulation 3; (<b>d</b>) freeze-dried formulation 4; (<b>e</b>) freeze-dried formulation 5.</p>
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<p>SEM picture of (<b>a</b>) spray-dried formulation 1; (<b>b</b>) spray-dried formulation 4; (<b>c</b>) spray-dried formulation 5.</p>
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<p>Dissolution profiles of (<b>a</b>) raw CEL and spray-dried formulations 1–5 in 0.1 M HCl with 0.2% SLS dissolution media; (<b>b</b>) raw CEL and freeze-dried formulations 1–5 in 0.1 M HCl with 0.2% SLS dissolution media; (<b>c</b>) raw CEL and freeze-dried formulations 1–5 in SLS-free dissolution media; (<b>d</b>) raw CEL and spray-dried formulations 1–5 in SLS-free dissolution media.</p>
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15 pages, 3365 KiB  
Article
Robust Automated Mouse Micro-CT Segmentation Using Swin UNEt TRansformers
by Lu Jiang, Di Xu, Qifan Xu, Arion Chatziioannou, Keisuke S. Iwamoto, Susanta Hui and Ke Sheng
Bioengineering 2024, 11(12), 1255; https://doi.org/10.3390/bioengineering11121255 - 11 Dec 2024
Viewed by 473
Abstract
Image-guided mouse irradiation is essential to understand interventions involving radiation prior to human studies. Our objective is to employ Swin UNEt TRansformers (Swin UNETR) to segment native micro-CT and contrast-enhanced micro-CT scans and benchmark the results against 3D no-new-Net (nnU-Net). Swin UNETR reformulates [...] Read more.
Image-guided mouse irradiation is essential to understand interventions involving radiation prior to human studies. Our objective is to employ Swin UNEt TRansformers (Swin UNETR) to segment native micro-CT and contrast-enhanced micro-CT scans and benchmark the results against 3D no-new-Net (nnU-Net). Swin UNETR reformulates mouse organ segmentation as a sequence-to-sequence prediction task using a hierarchical Swin Transformer encoder to extract features at five resolution levels, and it connects to a Fully Convolutional Neural Network (FCNN)-based decoder via skip connections. The models were trained and evaluated on open datasets, with data separation based on individual mice. Further evaluation on an external mouse dataset acquired on a different micro-CT with lower kVp and higher imaging noise was also employed to assess model robustness and generalizability. The results indicate that Swin UNETR consistently outperforms nnU-Net and AIMOS in terms of the average dice similarity coefficient (DSC) and the Hausdorff distance (HD95p), except in two mice for intestine contouring. This superior performance is especially evident in the external dataset, confirming the model’s robustness to variations in imaging conditions, including noise and quality, and thereby positioning Swin UNETR as a highly generalizable and efficient tool for automated contouring in pre-clinical workflows. Full article
(This article belongs to the Special Issue AI and Data Science in Bioengineering: Innovations and Applications)
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<p>Swin UNETR architecture and 3D nnU-Net architecture used in this study.</p>
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<p>Example of the median-scored case in mouse multi-organ segmentation in coronal view from the NACT test set. Yellow arrows highlight key differences in segmentation outcomes between the two 3D models, Swin UNETR and nnU-Net.</p>
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<p>Example of the median-scored case in mouse multi-organ segmentation in coronal view from the CECT test set. Yellow arrows highlight key differences in segmentation outcomes between the two 3D models, Swin UNETR and nnU-Net.</p>
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<p>Example of the median-scored case in mouse multi-organ segmentation in coronal view from the IHCT test set. Yellow arrows highlight key differences in segmentation outcomes between the three models, 3D Swin UNETR, 3D nnU-Net, and 2D AIMOS.</p>
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<p>Box plots of DSC (%) and HD95p (mm) per organ for predictions by Swin UNETR (green) vs. nnU-Net (orange). Each box extends from the lower to the upper quartile values of the data, with a black line at the median; the whiskers extend to the outermost data point within 1.5 times the interquartile range.</p>
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<p>DSC (%) performance comparisons for each individual mouse in the IHCT test set.</p>
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18 pages, 30123 KiB  
Article
Magnetic Resonance Imaging Liver Segmentation Protocol Enables More Consistent and Robust Annotations, Paving the Way for Advanced Computer-Assisted Analysis
by Patrick Jeltsch, Killian Monnin, Mario Jreige, Lucia Fernandes-Mendes, Raphaël Girardet, Clarisse Dromain, Jonas Richiardi and Naik Vietti-Violi
Diagnostics 2024, 14(24), 2785; https://doi.org/10.3390/diagnostics14242785 - 11 Dec 2024
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Abstract
Background/Objectives: Recent advancements in artificial intelligence (AI) have spurred interest in developing computer-assisted analysis for imaging examinations. However, the lack of high-quality datasets remains a significant bottleneck. Labeling instructions are critical for improving dataset quality but are often lacking. This study aimed to [...] Read more.
Background/Objectives: Recent advancements in artificial intelligence (AI) have spurred interest in developing computer-assisted analysis for imaging examinations. However, the lack of high-quality datasets remains a significant bottleneck. Labeling instructions are critical for improving dataset quality but are often lacking. This study aimed to establish a liver MRI segmentation protocol and assess its impact on annotation quality and inter-reader agreement. Methods: This retrospective study included 20 patients with chronic liver disease. Manual liver segmentations were performed by a radiologist in training and a radiology technician on T2-weighted imaging (wi) and T1wi at the portal venous phase. Based on the inter-reader discrepancies identified after the first segmentation round, a segmentation protocol was established, guiding the second round of segmentation, resulting in a total of 160 segmentations. The Dice Similarity Coefficient (DSC) assessed inter-reader agreement pre- and post-protocol, with a Wilcoxon signed-rank test for per-volume analysis and an Aligned-Rank Transform (ART) for repeated measures analyses of variance (ANOVA) for per-slice analysis. Slice selection at extreme cranial or caudal liver positions was evaluated using the McNemar test. Results: The per-volume DSC significantly increased after protocol implementation for both T2wi (p < 0.001) and T1wi (p = 0.03). Per-slice DSC also improved significantly for both T2wi and T1wi (p < 0.001). The protocol reduced the number of liver segmentations with a non-annotated slice on T1wi (p = 0.04), but the change was not significant on T2wi (p = 0.16). Conclusions: Establishing a liver MRI segmentation protocol improves annotation robustness and reproducibility, paving the way for advanced computer-assisted analysis. Moreover, segmentation protocols could be extended to other organs and lesions and incorporated into guidelines, thereby expanding the potential applications of AI in daily clinical practice. Full article
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<p>Liver segmentations process. Abbreviations: <span class="html-italic">n</span>—number of patients; wi—weighted imaging; FS—Fat Saturated; s—number of segmentations; PVP—portal venous phase.</p>
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<p>Examples of liver segmentations on T2wi (<b>a</b>–<b>d</b>) illustrated in blue (first annotator) and green (second annotator) before (<b>b</b>) and after (<b>c</b>) protocol implementation; (<b>d</b>) illustrates the expert segmentation, which was considered as the reference. This figure illustrates the importance of excluding the hepatic hilum and the variation in margin taken by the annotators at the border of the liver. Before protocol implementation (<b>b</b>), each annotator segmented the liver with their own style; one included the hilum (green segmentation), while the other did not (blue segmentation). Additionally, one annotator (blue segmentation) took a larger margin than the other at the border of the liver. After protocol implementation (<b>c</b>), these differences were lessened, improving the precision of the liver delineation and the inter-reader agreement.</p>
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<p>Examples of liver segmentations on T1wi (<b>a</b>–<b>d</b>) before (<b>b</b>) and after (<b>c</b>) protocol implementation; (<b>d</b>) illustrates the expert segmentation, which was considered as the reference. The portal vein was not always excluded from the liver contour before the use of the protocol (<b>b</b>). One annotator included it (blue segmentation), leading to potential overestimation of the liver volume, while the other did not (green segmentation). The implementation of the protocol ensured its exclusion in the annotations (<b>c</b>).</p>
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<p>Examples of liver segmentations on T1wi (<b>a</b>–<b>d</b>) before (<b>b</b>) and after (<b>c</b>) protocol implementation; (<b>d</b>) illustrates the expert segmentation, which was considered as the reference. Sometimes, the use of the protocol did not improve the inter-reader agreement, since one annotator (blue segmentation) still included the portal vein while the other did not.</p>
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<p>Examples of annotations on T2wi (<b>a</b>) with a missing extreme cranial slice from one annotator (green segmentation not visible) before the use of the protocol (<b>b</b>), while it was segmented by both annotators (blue and green segmentations) after protocol implementation (<b>c</b>).</p>
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<p>Example of an over-saturated window (red line illustrating the segmentation process).</p>
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<p>Example of appropriate windowing and magnification settings (red line illustrating the segmentation process).</p>
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<p>Example of a segmentation with inclusion of the hepatic hilum (red line illustrating the segmentation process).</p>
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<p>Example of a segmentation with exclusion of the hepatic hilum creating a “niche” (red line illustrating the segmentation process).</p>
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<p>Example illustrating small vessels segmentation (red line marking the segmentation process).</p>
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<p>Example illustrating the segmentation of hepatic hilum vessels (red line marking the segmentation process).</p>
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<p>Example illustrating the segmentation of the ligamentum venosum (red arrow).</p>
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<p>Example illustrating the segmentation of the falciform ligament (red arrow).</p>
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<p>Example illustrating multipart liver segmentation (red line marking the segmentation process).</p>
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<p>Example illustrating multipart liver segmentation (red line marking the segmentation process).</p>
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<p>Example illustrating respiratory artifacts (red line marking the segmentation process).</p>
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<p>Example illustrating respiratory artifacts (red line marking the segmentation process).</p>
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<p>Example illustrating severe respiratory artifacts without segmentation being feasible.</p>
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<p>Example illustrating severe respiratory artifacts without segmentation being feasible.</p>
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<p>Example of liver segmentation on T2wi with ascites obscuring the anterior contour of the liver (red arrow).</p>
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<p>Example of the same slice as <a href="#diagnostics-14-02785-f0A15" class="html-fig">Figure A15</a> on T1wi providing clearer differentiation of hepatic contours.</p>
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21 pages, 6543 KiB  
Article
Synthesis of Cyclic Oligomers of Polyether Ketone Ketone (PEKK) for Ring-Opening Polymerisation (ROP) Applications
by David Szmalko, Richard A. Evans, Jessirie Dilag and Stuart Bateman
Polymers 2024, 16(24), 3465; https://doi.org/10.3390/polym16243465 - 11 Dec 2024
Viewed by 514
Abstract
Entropy-Driven Ring-Opening Polymerisation represents an attractive mechanism to produce high-performance polymeric materials as it can be performed using neat, low-viscosity precursors and without the production of by-products or release of volatiles. Macrocyclic oligomers (MCOs) of polyether ketone ketone (PEKK) were synthesised and investigated [...] Read more.
Entropy-Driven Ring-Opening Polymerisation represents an attractive mechanism to produce high-performance polymeric materials as it can be performed using neat, low-viscosity precursors and without the production of by-products or release of volatiles. Macrocyclic oligomers (MCOs) of polyether ketone ketone (PEKK) were synthesised and investigated as an in situ method of forming this high-performance thermoplastic. Cyclic oligomers were successfully synthesised by pseudo-high dilution methods, and the reaction conditions were optimised through careful addition of starting materials and carbonate base selection. These novel compounds were characterised, X-ray crystal structures were obtained, and the synthesis method was extended from the homopolymers to MCOs with the structural isomers predominantly used in industry. PEKK formed from MCOs were characterised by DSC, TGA and GPC and found to have similar glass transitions and molecular weight averages to those of a commercial PEKK polymer. Full article
(This article belongs to the Section Polymer Chemistry)
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Figure 1

Figure 1
<p>MALDI-ToF spectrum of <span class="html-italic">m-</span>PEKK MCOs (<b>3</b>) with LiBr cationising agent. [M(cyclic monomer unit)] calculated for C<sub>20</sub>H<sub>12</sub>O<sub>3</sub> = 300.08 <span class="html-italic">m</span>/<span class="html-italic">z</span>. [M(tetramer)+Li]<sup>+</sup> calculated for C<sub>80</sub>H<sub>48</sub>O<sub>12</sub>Li = 1207.33 <span class="html-italic">m</span>/<span class="html-italic">z</span> and found as 1207.38 <span class="html-italic">m</span>/<span class="html-italic">z</span>.</p>
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<p>Mechanism of back-biting reaction responsible for presence of odd-numbered oligomers.</p>
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<p>Single-crystal X-ray structure of <span class="html-italic">m-</span>PEKK MCO dimer (<b>3</b>) with adjacent methanol where the dark (dark red) components represent the oxygen molecules present.</p>
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<p>Successive molecules of dimer (<b>3</b>) crystalise by stacking in columns parallel to the a-axis (in square outline to show a-b axis) where the dark (dark red) components represent the oxygen molecules present.</p>
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<p>Single-crystal X-ray structure of <span class="html-italic">p-</span>PEKK MCO dimer (<b>6</b>) with adjacent chloroform.</p>
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<p>Orthogonally spaced groups of parallel-stacked <span class="html-italic">p-</span>PEKK dimers (<b>6</b>). The square represents the a-b axis with respect to 0.</p>
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<p><sup>1</sup>H NMR (300 MHz) of 60/40 T/I PEKK MCOs (<b>7</b>) with 10% TFA-d (10.8 ppm) in DCM-d<sub>2</sub> (5.34 ppm) as solvent. Peaks were annotated with respect to the structure shown.</p>
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<p><sup>1</sup>H NMR (300 MHz) of Arkema 6002 PEKK, with 20% TFA-d (11.3 ppm) in DCM-d2 (5.34 ppm) as solvent. Peaks were annotated with respect to the structure shown.</p>
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<p>DSC comparison of Arkema 6002 (red) with MCO-derived 60/40 T/I PEKK (blue) for first (<b>A</b>) and second (<b>B</b>) consecutive heating cycles to 350 °C at a rate of 5 °C/min, demonstrating a similarity in glass transitions.</p>
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<p>DSC comparison of Arkema 6002 (red) with MCO-derived 60/40 T/I PEKK (blue) for first (<b>A</b>) and second (<b>B</b>) consecutive heating cycles to 350 °C at a rate of 5 °C/min, demonstrating a similarity in glass transitions.</p>
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<p>DSC results of heating a sample of 60/40 T/I PEKK MCO (<b>7</b>) with a CsF initiator to 250 °C and then cooling and subsequently heating to 300 °C and cooling again, showing (<b>A</b>) Tg on the initial heat ramp, with the appearance of a glass transition when heated above 250 °C on the cooling response in and (<b>B</b>) in both the heat and cooling response.</p>
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<p>GPC chromatograms of MCO ED-ROP experiments conducted within a DSC pan with a 2 mol% CsF initiator, demonstrating that heating to 320 °C (<b>B</b>) could form a higher-molecular-weight polymer shoulder. Heating to &gt;400 °C (<b>C</b>) or &lt;300 °C (<b>A</b>) yielded chromatograms with molecular weights similar to the starting MCOs, though in the samples heated at higher temperatures, there was a lower detector response and much more insoluble material had been filtered off.</p>
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<p>DSC of <span class="html-italic">m-</span>PEKK formed under high-vacuum conditions, displaying a glass transition on heating (lower line) and cooling (upper line) similar to both previous DSC experiments and the commercial comparison.</p>
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<p>GPC chromatogram of (<b>A</b>) <span class="html-italic">m-</span>PEKK MCO sample and (<b>B</b>) derivatised <span class="html-italic">m-</span>PEKK polymerised from MCOs under high-vacuum conditions (runcorrected for derivatisation).</p>
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<p>Outline of Friedel–Crafts acylation of diphenyl ether by terepthaloyl and isopthaloyl chloride, producing a PEKK polymer with a mixed amount of <span class="html-italic">para</span> and <span class="html-italic">meta</span> ketone linkages (i.e., the T/I ratio).</p>
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<p>Proposed route for synthesis of PEKK MCOs (such as the example tetramer) and their polymerisation by ED-ROP.</p>
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<p>Synthesis of <span class="html-italic">m-</span>PEKK precursors by Friedel–Crafts acylation and subsequent hydrolysis.</p>
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<p>Synthesis of <span class="html-italic">m-</span>PEKK MCOs under pseudo high-dilution conditions.</p>
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<p>Synthesis of <span class="html-italic">p-</span>PEKK precursors by Friedel–Crafts acylation and subsequent hydrolysis.</p>
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<p>Synthesis of <span class="html-italic">p-</span>PEKK MCOs under pseudo high-dilution conditions.</p>
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<p>ED-ROP of <span class="html-italic">m-</span>PEKK MCO.</p>
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<p>Thioketal derivatisation of <span class="html-italic">m-</span>PEKK.</p>
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14 pages, 5446 KiB  
Article
Effect of Acrylate Emulsion on the Mechanical and Microscopic Properties of Straw Fiber-Reinforced Cement-Magnesium Slag Stabilized Soil
by Chunqiu Xia, Xuanhao Cao, Jiuran Wen, Jun Li, Li Dai and Bowen Guan
Polymers 2024, 16(24), 3462; https://doi.org/10.3390/polym16243462 - 11 Dec 2024
Viewed by 266
Abstract
In order to investigate the mechanism of mechanical performance enhancement and the curing mechanisms of acrylate emulsion (AE) in cement and magnesium slag (MS) composite-stabilized soil (AE-C-M), this study has conducted a comprehensive analysis of the compressive strength and microstructural characteristics of AE-C-M [...] Read more.
In order to investigate the mechanism of mechanical performance enhancement and the curing mechanisms of acrylate emulsion (AE) in cement and magnesium slag (MS) composite-stabilized soil (AE-C-M), this study has conducted a comprehensive analysis of the compressive strength and microstructural characteristics of AE-C-M stabilized soil. The results show that the addition of AE significantly improves the compressive strength of the stabilized soil. When the AE content is 0.4%, the cement content is 3%, and the magnesium slag content is 3% (AE4-C3M3), the strength of the formula reaches 4.21 MPa, which meets the requirements of heavy traffic load conditions in the construction of high-speed or main road base layers. Some reactive groups on the polymer side chains (-COOH) engage in bridging with Ca2+ and RCOO to form a chemically bonded interpenetrating network structure, thereby enabling the acrylate emulsion to enhance the water damage resistance of the specimens. The notable improvement in strength is attributed to the film-forming and solidifying actions of AE, the binding and filling effects of C-S-H gel, and the reinforcing effect of straw fibers. FT-IR and TG-DSC analysis reveals the presence of polar electrostatic interactions between AE and the soil matrix. AE enhances the bonding among soil particles and facilitates the attachment of C-S-H gel onto the surfaces of the straw fibers, thereby increasing the strength and toughness of the material. The application of MS in conjunction with straw fibers within polymer-modified stabilized soil serves to promote the recycling of waste materials, thereby providing an environmentally friendly solution for the engineering application of solid waste. Full article
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<p>Appearance images of raw materials: (<b>a</b>) OPC; (<b>b</b>) MS; (<b>c</b>) SEM image of MS; (<b>d</b>) soil; (<b>e</b>) straw fiber; (<b>f</b>) acrylate emulsion.</p>
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<p>(<b>a</b>) Particle size distribution curve of MS. (<b>b</b>) The phase composition of OPC and MS.</p>
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<p>Sample preparation and performance testing process.</p>
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<p>7d Compressive strength of AE-C-M stabilized soil.</p>
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<p>(<b>a</b>) Effect of dry–wet cycles on the 7d compressive strength of AE-C-M. (<b>b</b>) Strength loss rate of AE-C-M under dry–wet cycles.</p>
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<p>XRD spectrum of AE-C-M stabilized soil.</p>
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<p>FTIR spectra of AE-C-M stabilized soil.</p>
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<p>TG and DSC curves of AE-C-M stabilized soil: (<b>a</b>) TG curve; (<b>b</b>) DSC curve.</p>
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<p>SEM images of AE-C-M stabilized soil: (<b>a</b>) AE0-C6M0; (<b>b</b>) AE4-C6M0; (<b>c</b>) AE4-C0M6.</p>
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