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13 pages, 941 KiB  
Article
Tumorspheres as In Vitro Model for Identifying Predictive Chemoresistance and Tumor Aggressiveness Biomarkers in Breast and Colorectal Cancer
by Toni Martinez-Bernabe, Pere Miquel Morla-Barcelo, Lucas Melguizo-Salom, Margalida Munar-Gelabert, Alba Maroto-Blasco, Margalida Torrens-Mas, Jordi Oliver, Pilar Roca, Mercedes Nadal-Serrano, Daniel Gabriel Pons and Jorge Sastre-Serra
Biology 2024, 13(9), 724; https://doi.org/10.3390/biology13090724 (registering DOI) - 15 Sep 2024
Abstract
Chemoresistance remains a major challenge in the treatment of breast and colorectal cancer. For this reason, finding reliable predictive biomarkers of response to chemotherapy has become a significant research focus in recent years. However, validating in vitro results may be problematic due to [...] Read more.
Chemoresistance remains a major challenge in the treatment of breast and colorectal cancer. For this reason, finding reliable predictive biomarkers of response to chemotherapy has become a significant research focus in recent years. However, validating in vitro results may be problematic due to the outcome heterogeneity. In this study, we evaluate the use of tumorspheres as an in vitro model for validating biomarkers of chemoresistance in breast and colorectal cancer. Our investigation highlights the crucial role of inflammation-related pathways in modulating the response to chemotherapy. Using in silico approaches, we identified specific markers elevated in responders versus non-responders patients. These markers were consistently higher in three-dimensional (3D) tumorsphere models compared to traditional adherent cell culture models. Furthermore, the number of tumorspheres from breast and colorectal cancer cells increased in response to cisplatin and oxaliplatin treatment, respectively, whereas cell viability decreased in adherent cell culture. This differential response underscores the importance of the 3D tumorsphere model in mimicking the tumor microenvironment more accurately than adherent cell culture. The enhanced chemoresistance observed in the 3D tumorspheres model and their correlation of data with the in silico study suggest that 3D culture models are a better option to approach the in vivo model and also to validate in silico data. Our findings indicate that tumorspheres are an ideal model for validating chemoresistance biomarkers and exploring the interplay between inflammation and chemoresistance in breast and colon cancer. Full article
(This article belongs to the Special Issue Cancer and Signalling: Targeting Cellular Pathways)
5 pages, 785 KiB  
Editorial
Immune Mechanisms and Biomarkers in Systemic Lupus Erythematosus
by Ioannis Parodis and Christopher Sjöwall
Int. J. Mol. Sci. 2024, 25(18), 9965; https://doi.org/10.3390/ijms25189965 (registering DOI) - 15 Sep 2024
Abstract
The immense heterogeneity of the chronic, inflammatory, autoimmune disease systemic lupus erythematosus (SLE), both with regard to immunological aberrancies and clinical manifestations, poses diagnostic difficulties and challenges in the management of patients [...] Full article
(This article belongs to the Special Issue Immune Mechanisms and Biomarkers in Systemic Lupus Erythematosus)
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<p>Visual representation of the content of the Special Issue. AGEs: advanced glycation end-products; anti-oxLDL: anti-oxidised low-density lipoprotein; HSP: heat shock protein; IL: interleukin; sTfR: soluble transferrin.</p>
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23 pages, 6574 KiB  
Review
Polymer Capacitor Films with Nanoscale Coatings for Dielectric Energy Storage: A Review
by Liang Cao, Rui Xi, Chen Zhou, Gaohui He, Feng Yang, Lingna Xu and He Li
Coatings 2024, 14(9), 1193; https://doi.org/10.3390/coatings14091193 (registering DOI) - 15 Sep 2024
Abstract
Enhancing the energy storage properties of dielectric polymer capacitor films through composite materials has gained widespread recognition. Among the various strategies for improving dielectric materials, nanoscale coatings that create structurally controlled multiphase polymeric films have shown great promise. This approach has garnered considerable [...] Read more.
Enhancing the energy storage properties of dielectric polymer capacitor films through composite materials has gained widespread recognition. Among the various strategies for improving dielectric materials, nanoscale coatings that create structurally controlled multiphase polymeric films have shown great promise. This approach has garnered considerable attention in recent years due to its effectiveness. This review examines surface-coated polymer composites used for dielectric energy storage, discussing their dielectric properties, behaviors, and the underlying physical mechanisms involved in energy storage. The review thoroughly examines the fabrication methods for nanoscale coatings and the selection of coating materials. It also explores the latest advancements in the rational design and control of interfaces in organic–inorganic, organic–organic, and heterogeneous multiphase structures. Additionally, the review delves into the structure–property relationships between different interfacial phases and various interface structures, analyzing how nanoscale coatings the impact dielectric constant, breakdown strength, conduction and charge transport mechanisms, energy density and efficiency, thermal stability, and electrothermal durability of polymeric capacitor films. Moreover, the review summarizes relevant simulation methods and offers computational insights. The potential practical applications and characteristics of such nanoscale coating techniques are discussed, along with the existing challenges and practical limitations. Finally, the review concludes with a summary and outlook, highlighting potential research directions in this rapidly evolving field. Full article
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<p>(<b>a</b>) Applications of dielectric energy storage capacitors in areas of wind and solar power, electric vehicles, electrified aircrafts, and space shuttles. (<b>b</b>) Comparison of power density and energy density among energy storage devices including film capacitors, batteries, electrochemical capacitors, and fuel cells. (<b>c</b>) Scheme of charging (blue line) and discharging (red line) processes in dielectric energy storage capacitors, in which the gray area represents energy loss <span class="html-italic">U</span><sub>l</sub> and the orange area represents <span class="html-italic">U</span><sub>d</sub>.</p>
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<p>Schematic of (<b>a</b>) electronic breakdown, (<b>b</b>) electromechanical breakdown, (<b>c</b>) thermal breakdown, (<b>d</b>) charge injection (representative of the Schottky injection), and (<b>e</b>) charge migration (representative of the hopping conduction) processes.</p>
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<p>Schematic of chemical methods including (<b>a</b>) CVD (reused with permission, [<a href="#B73-coatings-14-01193" class="html-bibr">73</a>] © 2018, WILEY-VCH Verlag GmbH &amp; Co. KGaA), (<b>b</b>) ALD (reused with permission, [<a href="#B74-coatings-14-01193" class="html-bibr">74</a>] © 2024, Springer Nature), and (<b>c</b>) in situ (reused with permission, [<a href="#B75-coatings-14-01193" class="html-bibr">75</a>] © 2022, Springer Nature) growing methods for deposition.</p>
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<p>(<b>a</b>) Cross-sectional SEM image displaying the coating layers on a polymer film. (<b>b</b>) Electric field distortion in both uncoated PP and SiO<sub>2</sub>-coated PP films, as measured by the pulsed electroacoustic (PEA) method at 120 °C and 100 MV·m<sup>−1</sup>. (<b>c</b>) <span class="html-italic">η</span> and <span class="html-italic">U</span><sub>d</sub> of BOPP and BOPP-SiO<sub>2</sub> films with 180 nm coatings on both sides, evaluated at 120 °C. (<b>d</b>) <span class="html-italic">η</span> of different dielectric films before and after coating, tested at 150 °C (reused with permission, [<a href="#B73-coatings-14-01193" class="html-bibr">73</a>] © 2018, WILEY-VCH Verlag GmbH &amp; Co. KGaA). (<b>e</b>) Energy band diagrams showing the interfaces between metal electrodes and various deposited layers. (<b>f</b>) Diagram illustrating the sandwich structure and corresponding equivalent circuit. (<b>g</b>) Schematic of Schottky emission, where <span class="html-italic">ϕ</span><sub>B</sub> represents the electron potential barrier and LUMO denotes the lowest unoccupied molecular orbital. (<b>h</b>) Energy diagram illustrating the reduction in potential barrier due to image forces and applied electric fields (reused with permission, [<a href="#B76-coatings-14-01193" class="html-bibr">76</a>] © 2021, Elsevier). (<b>i</b>) Cross-sectional SEM images of nanolaminates with varying layer counts and 10 nm PEI interlayers. Pink areas represent Al<sub>2</sub>O<sub>3</sub>, and blue areas represent PEI. The scale bar is 50 nm in all images. (<b>j</b>) Optical photograph (left) of a 7-layer nanolaminate on a flexible substrate, with cross-sectional SEM images showing the nanolaminate under bending (middle) and a magnified view (right). The scale bar is 1 cm for the left image, 400 μm for the middle, and 200 nm for the right. (<b>k</b>) Schematic of a metal wire-based nanolaminate capacitor, with an optical photograph comparing it to commercial metalized PP and PET capacitors (reused with permission, [<a href="#B74-coatings-14-01193" class="html-bibr">74</a>] © 2021, Elsevier).</p>
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<p>Schematic of physical methods including (<b>a</b>) PVD (reused with permission, [<a href="#B80-coatings-14-01193" class="html-bibr">80</a>] © 2022 John Wiley &amp; Sons Australia, Ltd.; [<a href="#B81-coatings-14-01193" class="html-bibr">81</a>] © 2019, Elsevier) and (<b>b</b>) spraying and hot pressing (reused with permission, [<a href="#B82-coatings-14-01193" class="html-bibr">82</a>] © 2020, Elsevier) methods for deposition.</p>
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<p>(<b>a</b>) Flow chart of preparation of sandwich structure film; working principal diagram of surface h-BN functional layer. (<b>b</b>) A schematic representation of a real capacitor with a height of H = 40 mm and a diameter of D = 40 mm made by winding BN/PC/BN nanocomposite films. Internal temperature distribution when the ambient temperature is 80 °C, operating at an applied electric field of 100 MV/m in different capacitors made by composite films of PC/BN composites (reused with permission, [<a href="#B82-coatings-14-01193" class="html-bibr">82</a>] © 2020, Elsevier). (<b>c</b>) Schematic illustration of the fabrication process of sandwich-structured nanocomposite films. (<b>d</b>) Comparison of <span class="html-italic">U</span><sub>d</sub> and <span class="html-italic">η</span> (reused with permission, [<a href="#B93-coatings-14-01193" class="html-bibr">93</a>] © 2023, Elsevier).</p>
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<p>Schematic of molecular-level surface modification methods for deposition, represented by irradiation (reused with permission, [<a href="#B66-coatings-14-01193" class="html-bibr">66</a>] © 2024, John Wiley &amp; Sons).</p>
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<p>(<b>a</b>) Energy levels, LUMO, and HOMO for pristine PP and PP with carbonyl. (<b>b</b>) <span class="html-italic">U</span><sub>d</sub> and (<b>c</b>) <span class="html-italic">η</span> versus electric field for pristine BOPP and <span class="html-italic">γ</span>-irradiated BOPP films (reused with permission, [<a href="#B96-coatings-14-01193" class="html-bibr">96</a>] © 2024, John Wiley &amp; Sons). (<b>d</b>) The schematic drawing of the preparation of the irradiated dielectric film. The filter is used to select ultraviolet (UV) rays with different frequencies, leading to the formation of free radicals in the shallow surface of polymer films after UV irradiation. The free radicals trap injected charges, accordingly, suppressing the electric field at the electrode–dielectric interface and inhibiting further charge injection. (<b>e</b>) Molecular structure and highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) energy levels of the repeating unit of PEI and repeating unit of PEI with free radicals; the right axis represents the relative energy level in a vacuum. (<b>f</b>) Comparison of the <span class="html-italic">U</span><sub>d</sub> at <span class="html-italic">η</span> ≈ 90% between the pristine polymer dielectrics and irradiated polymer dielectrics at 150 and 200 °C (reused with permission, [<a href="#B99-coatings-14-01193" class="html-bibr">99</a>] © 2024, John Wiley &amp; Sons).</p>
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<p>Schematic of (<b>a</b>) polymeric coating in polymer composites, in which coated layer embedded with nanoparticles (green colored circles) could effectively impede dielectric breakdown pathway. [<a href="#B62-coatings-14-01193" class="html-bibr">62</a>] © 2024 John Wiley &amp; Sons. Schematic of polymeric coating methods including (<b>b</b>) successive drop-casting (reused with permission, [<a href="#B112-coatings-14-01193" class="html-bibr">112</a>] © 2020, American Chemical Society), (<b>c</b>) hot pressing (reused with permission, [<a href="#B116-coatings-14-01193" class="html-bibr">116</a>] © 2022, Elsevier), (<b>d</b>) electrospinning (reused with permission, [<a href="#B117-coatings-14-01193" class="html-bibr">117</a>] © 2024, John Wiley &amp; Sons), and (<b>e</b>) dip coating (reused with permission, [<a href="#B118-coatings-14-01193" class="html-bibr">118</a>] © 2023, Elsevier) methods for deposition.</p>
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<p>(<b>a</b>) Schematic diagram of AFM-IR technology. (<b>b</b>) Optical image of the cross-section of the sandwiched film and the area selected for characterization (reused with permission, [<a href="#B120-coatings-14-01193" class="html-bibr">120</a>] © 2022, Elsevier). (<b>c</b>) Schematic of the fabrication of PS-<span class="html-italic">b</span>-P4VP(PDP)/ZrO<sub>2</sub> NP supramolecular nanocomposites. (<b>d</b>) Simulated leakage current distributions of the ordered and disordered PS-<span class="html-italic">b</span>-P4VP(PDP) nanocomposites with 9 vol% ZrO<sub>2</sub> NPs under an applied electric field of 200 MV m<sup>−1</sup> (reused with permission, [<a href="#B62-coatings-14-01193" class="html-bibr">62</a>] © 2024, John Wiley &amp; Sons). (<b>e</b>) The incomplete breakdown in sandwich BaTiO<sub>3</sub>/PVDF nanocomposites at the applied voltage of 9 kV simulated using the finite element method (reused with permission, [<a href="#B121-coatings-14-01193" class="html-bibr">121</a>] © 2024, John Wiley &amp; Sons).</p>
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24 pages, 5133 KiB  
Review
Advancements in Microfluidic Platforms for Glioblastoma Research
by Rachana Raman, Vijendra Prabhu, Praveen Kumar and Naresh Kumar Mani
Chemistry 2024, 6(5), 1039-1062; https://doi.org/10.3390/chemistry6050060 (registering DOI) - 15 Sep 2024
Abstract
Glioblastoma (GBM) is a malignant cancer affecting the brain. As per the WHO classifications, it is a grade IV glioma and is characterized by heterogenous histopathology, high recurrence rates, and a high median age of diagnosis. Most individuals diagnosed with GBM are aged [...] Read more.
Glioblastoma (GBM) is a malignant cancer affecting the brain. As per the WHO classifications, it is a grade IV glioma and is characterized by heterogenous histopathology, high recurrence rates, and a high median age of diagnosis. Most individuals diagnosed with GBM are aged between 50 and 64 years, and the prognosis is often poor. Untreated GBM patients have a median survival of 3 months, while treatments with Temozolomide (TMZ) and radiotherapy can improve the survival to 10–14 months. Tumor recurrence is common, owing to the inefficiency of surgical resection in removing microscopic tumor formations in the brain. A crucial component of GBM-related research is understanding the tumor microenvironment (TME) and its characteristics. The various cellular interactions in the TME contribute to the higher occurrence of malignancy, resistance to treatments, and difficulty in tumor resection and preventative care. Incomplete pictures of the TME have been obtained in 2D cultures, which fail to incorporate the ECM and other crucial components. Identifying the hallmarks of the TME and developing ex vivo and in vitro models can help study patient-specific symptoms, assess challenges, and develop courses of treatment in a timely manner which is more efficient than the current methods. Microfluidic models, which incorporate 3D cultures and co-culture models with various channel patterns, are capable of stimulating tumor conditions accurately and provide better responses to therapeutics as would be seen in the patient. This facilitates a more refined understanding of the potential treatment delivery systems, resistance mechanisms, and metastatic pathways. This review collates information on the application of such microfluidics-based systems to analyze the GBM TME and highlights the use of such systems in improving patient care and treatment options. Full article
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<p>Overview of the potential materials for chips, major fabrication techniques, components of microfluidic chips for disease-related applications, and applications in biology.</p>
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<p>Integration of microfluidics in GBM research has several important applications (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Symptoms associated with GBM, with corresponding tumor locations and diagnosis methods. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Cells found in the TME, along with the main components needed for niche formation and the resulting features that define GBM. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>(<b>A</b>): Biomarkers in GBM that are associated with different processes related to tumor maintenance and proliferation. They are used to quantify effects such as metastasis, proliferation and tumor recurrence [<a href="#B49-chemistry-06-00060" class="html-bibr">49</a>]. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>). (<b>B</b>): Biomarkers in GBM that are associated with different processes related to tumor maintenance and proliferation. They are used to quantify effects such as metastasis, proliferation, chemoresistance, and tumor recurrence [<a href="#B49-chemistry-06-00060" class="html-bibr">49</a>]. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>(<b>A</b>): Biomarkers in GBM that are associated with different processes related to tumor maintenance and proliferation. They are used to quantify effects such as metastasis, proliferation and tumor recurrence [<a href="#B49-chemistry-06-00060" class="html-bibr">49</a>]. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>). (<b>B</b>): Biomarkers in GBM that are associated with different processes related to tumor maintenance and proliferation. They are used to quantify effects such as metastasis, proliferation, chemoresistance, and tumor recurrence [<a href="#B49-chemistry-06-00060" class="html-bibr">49</a>]. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Current treatment and pre-clinical models being used contrasted to the emerging techniques for GBM. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>(<b>A</b>) Sorting technique that utilizes forces generated in spiral microfluidic technology to isolate CTCS from blood samples [<a href="#B27-chemistry-06-00060" class="html-bibr">27</a>]. (<b>B</b>) Parsortix system used to separate and collect chosen samples, which are CTCs in this case, for analysis and testing [<a href="#B32-chemistry-06-00060" class="html-bibr">32</a>]. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Bioprinting techniques are an emerging method of creating microfluidic chips with co-culture systems for drug testing and development [<a href="#B19-chemistry-06-00060" class="html-bibr">19</a>]. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>(<b>A</b>) Construction of microfluidic platform for nanoparticle-loaded macrophage delivery to tumors, serving the dual function of tumor clearance/killing, as well as personalized and targeted treatment delivery [<a href="#B33-chemistry-06-00060" class="html-bibr">33</a>]. (<b>B</b>) Construction of TME and Tumor model for the study of GBM using ECM components [<a href="#B26-chemistry-06-00060" class="html-bibr">26</a>]. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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<p>Applications of various microfluidic devices used in GBM-related studies. (Created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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18 pages, 2857 KiB  
Article
AnyFace++: Deep Multi-Task, Multi-Domain Learning for Efficient Face AI
by Tomiris Rakhimzhanova, Askat Kuzdeuov and Huseyin Atakan Varol
Sensors 2024, 24(18), 5993; https://doi.org/10.3390/s24185993 (registering DOI) - 15 Sep 2024
Abstract
Accurate face detection and subsequent localization of facial landmarks are mandatory steps in many computer vision applications, such as emotion recognition, age estimation, and gender identification. Thanks to advancements in deep learning, numerous facial applications have been developed for human faces. However, most [...] Read more.
Accurate face detection and subsequent localization of facial landmarks are mandatory steps in many computer vision applications, such as emotion recognition, age estimation, and gender identification. Thanks to advancements in deep learning, numerous facial applications have been developed for human faces. However, most have to employ multiple models to accomplish several tasks simultaneously. As a result, they require more memory usage and increased inference time. Also, less attention is paid to other domains, such as animals and cartoon characters. To address these challenges, we propose an input-agnostic face model, AnyFace++, to perform multiple face-related tasks concurrently. The tasks are face detection and prediction of facial landmarks for human, animal, and cartoon faces, including age estimation, gender classification, and emotion recognition for human faces. We trained the model using deep multi-task, multi-domain learning with a heterogeneous cost function. The experimental results demonstrate that AnyFace++ generates outcomes comparable to cutting-edge models designed for specific domains. Full article
(This article belongs to the Section Biomedical Sensors)
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<p>The AnyFace++ network architecture is built on the YOLOv8 backbone network, includes its two existing output layers (object classification and bounding box regression) and also introduces new output layers (facial landmark regression, age regression, gender classification, and emotion classification).</p>
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<p>Examples of unlabeled faces in the validation set of Wider Face, detected by AnyFace++. The red bounding boxes are ground truth. The green bounding boxes with confidence scores are predictions: (<b>a</b>) dark faces, (<b>b</b>) blurry faces, and (<b>c</b>) a toy face.</p>
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<p>Examples of predictions by the multi-domain, multi-task face AI model, AnyFace++.</p>
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<p>Examples of predictions by AnyFace++: (<b>a</b>) underwater animals, (<b>b</b>) dolls, and (<b>c</b>) facelike objects.</p>
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12 pages, 3140 KiB  
Article
Study of Intergranular Corrosion Behaviors of Mn-Increased 5083 Al Alloy with Controlled Precipitation States of Al6Mn Formed during Homogenization Annealing
by Peng Zhang, Yue Wang, Pizhi Zhao, Zhengyi Jiang, Yinbao Tian, Yang Yang and Jian Han
Metals 2024, 14(9), 1053; https://doi.org/10.3390/met14091053 (registering DOI) - 15 Sep 2024
Abstract
In this study, as a vital part of the production of Mn-increased 5083 Al alloy, i.e., homogenization annealing before hot rolling, the target states of key Al6Mn precipitation, including the dispersed, initial coarsening and intensive coarsening states, were designed, and the [...] Read more.
In this study, as a vital part of the production of Mn-increased 5083 Al alloy, i.e., homogenization annealing before hot rolling, the target states of key Al6Mn precipitation, including the dispersed, initial coarsening and intensive coarsening states, were designed, and the corresponding precipitates formed via the control of the temperature and holding time in the annealing process. By means of metallographic corrosion and nitric acid mass loss tests (NAMLT) for assessing the intergranular corrosion (IGC) resistance, temperatures ranging from 175 °C to 225 °C were determined to induce a transition from sensitization to stabilization for this innovative 5083. At a temperature of 175 °C for a duration of up to 24 h (2 h, 4 h, 8 h, 16 h, 24 h), the results show that when the soak time is 24 h, the sample with initially coarsened Al6Mn phases has a lower degree of sensitization (DOS) compared to the samples with Al6Mn phases in both the dispersed and intensive coarsening states, and its NAMLT is reduced by 11% and 15%, respectively. Subsequently, transmission electron microscopy (TEM) analysis has investigated that for the sample with the best IGC resistance, i.e., that with initially coarsened Al6Mn phases, plate-like Al6Mn particles (200~500 nm) can act as heterogenous nucleation sites for β phases, driving their preferential precipitation on Al6Mn particles and resisting their precipitation along grain boundaries, ultimately improving the IGC resistance of 5083 Al alloy after homogenization annealing. Full article
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<p>(<b>a</b>) DSC curve and (<b>b</b>) Al<sub>6</sub>Mn state variations with homogenization process.</p>
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<p>TEM bright-field micrographs of (<b>a</b>,<b>d</b>) initially coarsened, (<b>b</b>,<b>e</b>) intensively coarsened and (<b>c</b>) dispersed Al<sub>6</sub>Mn.</p>
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<p>Corrosion results for samples held at (<b>a</b>–<b>d</b>) 175 °C, (<b>e</b>–<b>h</b>) 200 °C, and (<b>i</b>–<b>l</b>) 225 °C for 4, 8, 16 and 24 h.</p>
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<p>The NAMLT results after being heat-treated at different sensitization temperatures.</p>
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<p>Observation of β phase: (<b>a</b>) no precipitation, (<b>b</b>,<b>c</b>) continuous precipitation and EDS of Mg, and (<b>d</b>–<b>f</b>) triple junction precipitation and EDS of Mg.</p>
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<p>The NAMLT results of different Al<sub>6</sub>Mn states in 175 °C.</p>
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<p>TEM bright-field micrographs and EDS of (<b>a</b>–<b>c</b>) plate-like Al<sub>6</sub>Mn and (<b>d</b>) rod-like Al<sub>6</sub>Mn.</p>
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<p>TEM bright-field micrographs and EDS of rhombic Al<sub>6</sub>Mn precipitated during homogenization stage (<b>a</b>) initial coarsening and (<b>b</b>) intensive coarsening.</p>
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19 pages, 7905 KiB  
Article
Synergistic Effects of Radical Distributions of Soluble and Insoluble Polymers within Electrospun Nanofibers for an Extending Release of Ferulic Acid
by Ran Dong, Wenjian Gong, Qiuyun Guo, Hui Liu and Deng-Guang Yu
Polymers 2024, 16(18), 2614; https://doi.org/10.3390/polym16182614 (registering DOI) - 15 Sep 2024
Abstract
Polymeric composites for manipulating the sustained release of an encapsulated active ingredient are highly sought after for many practical applications; particularly, water-insoluble polymers and core–shell structures are frequently explored to manipulate the release behaviors of drug molecules over an extended time period. In [...] Read more.
Polymeric composites for manipulating the sustained release of an encapsulated active ingredient are highly sought after for many practical applications; particularly, water-insoluble polymers and core–shell structures are frequently explored to manipulate the release behaviors of drug molecules over an extended time period. In this study, electrospun core–shell nanostructures were utilized to develop a brand-new strategy to tailor the spatial distributions of both an insoluble polymer (ethylcellulose, EC) and soluble polymer (polyvinylpyrrolidone, PVP) within the nanofibers, thereby manipulating the extended-release behaviors of the loaded active ingredient, ferulic acid (FA). Scanning electron microscopy and transmission electron microscopy assessments revealed that all the prepared nanofibers had a linear morphology without beads or spindles, and those from the coaxial processes had an obvious core–shell structure. X-ray diffraction and attenuated total reflectance Fourier transform infrared spectroscopic tests confirmed that FA had fine compatibility with EC and PVP, and presented in all the nanofibers in an amorphous state. In vitro dissolution tests indicated that the radical distributions of EC (decreasing from shell to core) and PVP (increasing from shell to core) were able to play their important role in manipulating the release behaviors of FA elaborately. On one hand, the core–shell nanofibers F3 had the advantages of homogeneous composite nanofibers F1 with a higher content of EC prepared from the shell solutions to inhibit the initial burst release and provide a longer time period of sustained release. On the other hand, F3 had the advantages of nanofibers F2 with a higher content of PVP prepared from the core solutions to inhibit the negative tailing-off release. The key element was the water permeation rates, controlled by the ratios of soluble and insoluble polymers. The new strategy based on core–shell structure paves a way for developing a wide variety of polymeric composites with heterogeneous distributions for realizing the desired functional performances. Full article
(This article belongs to the Special Issue Advanced Electrospinning Fibers II)
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<p>A diagram of the coaxial electrospinning apparatus, the electrospun core–shell nanofibers, and the brand-new strategy of tailoring the radical distributions of soluble and insoluble polymers for achieving a high-quality sustained-release profile.</p>
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<p>A concentric spinneret for coaxial electrospinning: (<b>a</b>) A diagram showing the parameters for fabricating the homemade concentric spinneret, the fixing and connection of the different parts, and the inserting of inner stainless steel capillaries. (<b>b1</b>,<b>b2</b>) Digital images of the whole concentric spinneret, and the co-outlet of the spinneret’s nozzle, respectively. (<b>c</b>) Two concentric spinnerets commercially available.</p>
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<p>Implementations of the three electrospinning processes for creating the three kinds of nanofibers: (<b>a</b>) An aerial view of the whole coaxial electrospinning apparatus with two pumps and a power supply. (<b>b</b>) The convergent point of two working fluids and electrostatic energy transferring. (<b>c</b>) A typical working process for preparing the homogeneous nanofibers F1 from the shell fluid with methylene blue as a color marker; the bottom inset is an image of the blue Taylor cone. (<b>d</b>) A typical working process for preparing the homogeneous nanofibers F2 from the core fluid; the bottom inset is an image of the transparent Taylor cone. (<b>e</b>) A typical working process for preparing the core–shell nanofibers F3; the bottom inset is a typical image of the compound core–shell Taylor cone.</p>
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<p>The morphologies of the prepared nanofibers and their diameter distributions: (<b>a1</b>,<b>a2</b>) Monolithic nanofibers F1. (<b>b1</b>,<b>b2</b>) Monolithic nanofibers F2. (<b>c1</b>,<b>c2</b>) Core–shell nanofibers F3; the <b>upper-right</b> insets are the enlarged SEM images of the corresponding nanofibers.</p>
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<p>TEM images of the prepared nanofibers: (<b>a</b>) monolithic nanofibers F1; (<b>b</b>) monolithic nanofibers F2; and (<b>c</b>) core–shell nanofibers F3.</p>
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<p>Physical state characterizations: (<b>a</b>) XRD patterns of the starting materials (PVP, EC, and FA) and their nanofibers F1 and F2 and their core–shell nanofibers F3; the plants for extracting FA, its right powders, and their polarized microscopic image. (<b>b</b>) DSC curves of FA, PVP, EC, and their composite nanofibers F1 to F3.</p>
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<p>ATR-FTIR spectra of the starting materials (PVP, EC, and FA) and their nanofibers F1 and F2 and their core–shell nanofibers F3, and their molecular formula.</p>
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<p>The in vitro dissolution profiles of the homogeneous nanofibers F1 and F2, and the core–shell nanofibers F3.</p>
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<p>The drug release mechanisms of nanofibers (<b>a</b>) F1, (<b>b</b>) F2, and (<b>c</b>) F3, regressed according to the Peppas equation.</p>
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<p>A diagram about drug molecule release behaviors from the homogeneous nanofibers F1 and F2, and the core–shell nanofibers F3.</p>
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33 pages, 3210 KiB  
Review
Diet and Nutrients in Rare Neurological Disorders: Biological, Biochemical, and Pathophysiological Evidence
by Marilena Briglia, Fabio Allia, Rosanna Avola, Cinzia Signorini, Venera Cardile, Giovanni Luca Romano, Giovanni Giurdanella, Roberta Malaguarnera, Maria Bellomo and Adriana Carol Eleonora Graziano
Nutrients 2024, 16(18), 3114; https://doi.org/10.3390/nu16183114 (registering DOI) - 15 Sep 2024
Abstract
Background/Objectives: Rare diseases are a wide and heterogeneous group of multisystem life-threatening or chronically debilitating clinical conditions with reduced life expectancy and a relevant mortality rate in childhood. Some of these disorders have typical neurological symptoms, presenting from birth to adulthood. Dietary [...] Read more.
Background/Objectives: Rare diseases are a wide and heterogeneous group of multisystem life-threatening or chronically debilitating clinical conditions with reduced life expectancy and a relevant mortality rate in childhood. Some of these disorders have typical neurological symptoms, presenting from birth to adulthood. Dietary patterns and nutritional compounds play key roles in the onset and progression of neurological disorders, and the impact of alimentary needs must be enlightened especially in rare neurological diseases. This work aims to collect the in vitro, in vivo, and clinical evidence on the effects of diet and of nutrient intake on some rare neurological disorders, including some genetic diseases, and rare brain tumors. Herein, those aspects are critically linked to the genetic, biological, biochemical, and pathophysiological hallmarks typical of each disorder. Methods: By searching the major web-based databases (PubMed, Web of Science Core Collection, DynaMed, and Clinicaltrials.gov), we try to sum up and improve our understanding of the emerging role of nutrition as both first-line therapy and risk factors in rare neurological diseases. Results: In line with the increasing number of consensus opinions suggesting that nutrients should receive the same attention as pharmacological treatments, the results of this work pointed out that a standard dietary recommendation in a specific rare disease is often limited by the heterogeneity of occurrent genetic mutations and by the variability of pathophysiological manifestation. Conclusions: In conclusion, we hope that the knowledge gaps identified here may inspire further research for a better evaluation of molecular mechanisms and long-term effects. Full article
(This article belongs to the Special Issue The Effect of Nutrients on Neurological Disorders)
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<p>Main characteristics of rare neurological diseases and possible investigations for symptomatic treatments (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>, accessed on 3 September 2024).</p>
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<p>Factors that influence alimentary wellness by modulator effects on the main homeostatic functions (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>, accessed on 27 June 2024).</p>
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<p><span class="html-italic">In vitro</span> models as tools in rare neurological disease research and therapeutic development (partially created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>, accessed on 7 August 2024).</p>
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<p>Animal models for rare neurological diseases (created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>, accessed on 3 September 2024).</p>
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<p>MeCP2 gene structure and its activity on target genes. The meCP2 gene has N-terminal (NTD); methyl binding (MBD); intervening (ID); transcription repression (TRD); and C-terminal (CTD) domains. MeCP2 recruits a transcriptional corepressor complex containing Sin3A and histone deacetylase (HDAC) to methylated CpG islands and induces transcription inhibition in the target gene (TRD, transcriptional repression domain; MBD, methyl-CpG-binding domain). MeCP2 can activate gene transcription by recruiting CREB and other transcriptional factors to non-methylated CG DNA regions (partially created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>, accessed on 10 August 2024).</p>
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24 pages, 918 KiB  
Article
Quality of Service-Aware Multi-Objective Enhanced Differential Evolution Optimization for Time Slotted Channel Hopping Scheduling in Heterogeneous Internet of Things Sensor Networks
by Aida Vatankhah and Ramiro Liscano
Sensors 2024, 24(18), 5987; https://doi.org/10.3390/s24185987 (registering DOI) - 15 Sep 2024
Abstract
The emergence of the Internet of Things (IoT) has attracted significant attention in industrial environments. These applications necessitate meeting stringent latency and reliability standards. To address this, the IEEE 802.15.4e standard introduces a novel Medium Access Control (MAC) protocol called Time Slotted Channel [...] Read more.
The emergence of the Internet of Things (IoT) has attracted significant attention in industrial environments. These applications necessitate meeting stringent latency and reliability standards. To address this, the IEEE 802.15.4e standard introduces a novel Medium Access Control (MAC) protocol called Time Slotted Channel Hopping (TSCH). Designing a centralized scheduling system that simultaneously achieves the required Quality of Service (QoS) is challenging due to the multi-objective optimization nature of the problem. This paper introduces a novel optimization algorithm, QoS-aware Multi-objective enhanced Differential Evolution optimization (QMDE), designed to handle the QoS metrics, such as delay and packet loss, across multiple services in heterogeneous networks while also achieving the anticipated service throughput. Through co-simulation between TSCH-SIM and Matlab, R2023a we conducted multiple simulations across diverse sensor network topologies and industrial QoS scenarios. The evaluation results illustrate that an optimal schedule generated by QMDE can effectively fulfill the QoS requirements of closed-loop supervisory control and condition monitoring industrial services in sensor networks from 16 to 100 nodes. Through extensive simulations and comparative evaluations against the Traffic-Aware Scheduling Algorithm (TASA), this study reveals the superior performance of QMDE, achieving significant enhancements in both Packet Delivery Ratio (PDR) and delay metrics. Full article
(This article belongs to the Special Issue Advanced Applications of WSNs and the IoT)
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<p>Sample tree topology showing sink, transmitting nodes, and flows.</p>
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<p>Simple wireless network topology with an example TSCH schedule.</p>
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<p>QoS-oriented Multi-objective Differential Evolution Optimization flowchart.</p>
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<p>Sample of six pool statuses corresponding to six time slots.</p>
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<p>Process of mapping the generated matrix values to sensors for TSCH schedule creation: (<b>a</b>) random matrix generation, (<b>b</b>) normalization, (<b>c</b>) mapping the sensor’s position in the pool, and (<b>d</b>) assign nodes and matching pairs.</p>
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<p>Co-simulation: sequence diagram of QMDE using Matlab and TSCH-SIM.</p>
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<p>Optimization progress in scenario 5 with 64 nodes.</p>
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<p>Slotframe size of QMDE algorithm in various scenarios.</p>
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<p>Evaluation of delay between applications in (<b>a</b>) Scn 1, (<b>b</b>) Scn 2, (<b>c</b>) Scn 3, (<b>d</b>) Scn 4, and (<b>e</b>) Scn 5.</p>
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<p>Evaluation of PDR for two applications in (<b>a</b>) Scn 1, (<b>b</b>) Scn 2, (<b>c</b>) Scn 3, (<b>d</b>) Scn 4, and (<b>e</b>) Scn 5.</p>
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<p>Time complexity of QMDE algorithm in various scenarios.</p>
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<p>Delay comparison between QMDE and TASA in (<b>a</b>) Scn 1, (<b>b</b>) Scn 2, (<b>c</b>) Scn 3, (<b>d</b>) Scn 4, and (<b>e</b>) Scn 5.</p>
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<p>PDR comparison between QMDE and TASA in (<b>a</b>) Scn 1, (<b>b</b>) Scn 2, (<b>c</b>) Scn 3, (<b>d</b>) Scn 4, and (<b>e</b>) Scn 5.</p>
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14 pages, 8768 KiB  
Article
Surface Evolution and Optimizing Strategy for Polishing Natural Heterogeneous Marble Using Sol-Gel Diamond Pad
by Shengui Huang, Jing Lu, Xipeng Xu and Changcai Cui
Appl. Sci. 2024, 14(18), 8314; https://doi.org/10.3390/app14188314 (registering DOI) - 15 Sep 2024
Abstract
Inefficiency and poor quality are the main problems in polishing natural heterogeneous marbles using sol-gel (SG) diamond pads. A strategy was proposed to address these issues by establishing a natural heterogeneous marble polishing model based on the optimal polishing time. The surface evolution [...] Read more.
Inefficiency and poor quality are the main problems in polishing natural heterogeneous marbles using sol-gel (SG) diamond pads. A strategy was proposed to address these issues by establishing a natural heterogeneous marble polishing model based on the optimal polishing time. The surface evolution and optimal time for polishing natural heterogeneous marble were systematically investigated. Six different types of marbles were polished by the sol-gel diamond pads. The surface glossiness, roughness, peak–valley value, and surface morphology of the marbles were measured and analyzed after different polishing times. The optimal polishing time for each marble was revealed using sol-gel diamond pads. The experimental results show that the standard deviation of the hardness distribution of marble tile significantly affects the material removal inconsistency and evolution of the surface during polishing, resulting in different optimal polishing times for different kinds of marble. The larger the standard deviation of the hardness of the marble is, the more difficult it is to obtain better surface quality, and the orange peel effect is more likely to occur. Furthermore, the optimal polishing time has a good logarithmic relationship with the standard deviation of the hardness distribution. Finally, a curve model of the optimal polishing time for each marble was established. The determination of the optimal polishing time can effectively optimize the polishing process, simplify the processing flow, improve production efficiency, and reduce production costs. The proposed method and obtained results in this paper can provide a theoretical basis and reference for polishing other types of heterogeneous stone materials. Full article
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<p>Natural marble tiles used in this study: (<b>a</b>) Volakos (VO), (<b>b</b>) Sofitel King (SK), (<b>c</b>) Castle Gray (CG), (<b>d</b>) Yinding Gray (YG), (<b>e</b>) Focus Cream (FC), and (<b>f</b>) Crema Marfil (CM). The optical images were taken by a camera.</p>
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<p>Schematic of the fabrication process of the SG polishing pads.</p>
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<p>(<b>a</b>) SG polishing pad with a grain size of 20 μm and (<b>b</b>) its microstructure. Images (<b>a</b>) and (<b>b</b>) were taken by a camera and a Hirox KH8700 3D digital microscope, respectively.</p>
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<p>(<b>a</b>) Illustration of the marble tile polishing process, (<b>b</b>) pre-grinding with traditional grinding pad, and (<b>c</b>) polishing with SG polishing pad.</p>
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<p>(<b>a</b>) Vickers hardness and (<b>b</b>) SDD value of the hardness of the marble tiles.</p>
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<p>(<b>a</b>) The surface glossiness–time curves of marble tiles during the polishing process using the SG pad with a grain size of 20 μm, (<b>b</b>) is the enlarged view of the red elliptical circle in (<b>a</b>).</p>
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<p>Surface roughness, surface glossiness, and surface peak–valley value of VO marble tile after polishing for different times with SG polishing pad with a grain size of 20 μm.</p>
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<p>Three-dimensional surface topography of the VO marble tile after polishing for different times with 20 μm diamond abrasive: (<b>a</b>) 4 min polishing, (<b>b</b>) 8 min polishing, (<b>c</b>) 12 min polishing, and (<b>d</b>) 16 min polishing.</p>
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<p>Surface profile at different polishing times: (<b>a</b>) 4 min polishing, (<b>b</b>) 8 min polishing, (<b>c</b>) 12 min polishing, and (<b>d</b>) 16 min polishing.</p>
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<p>Vickers hardnesses of different zones of the marble tile surface after the orange peel effect appeared during polishing: (<b>a</b>) Vickers hardness of the rough zone, (<b>b</b>) surface with the orange peel effect, and (<b>c</b>) Vickers hardness of the smooth zone. The green arrow pointed in (<b>b</b>) is the zone with orange peel effect, and the green rectangle represents the location where hardness was tested.</p>
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<p>Illustration of the deteriorating mechanism of the polishing surface of VO marble: (<b>a</b>) before polishing, (<b>b</b>) during polishing, (<b>c</b>) after 8 min of polishing, and (<b>d</b>) after 16 min of polishing.</p>
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<p>Surface roughness, glossiness, and surface peak–valley of VO marble tile after polishing with different diamond abrasive sizes.</p>
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<p>Three-dimensional surface topography of the VO marble tile after polishing with an abrasive size of (<b>a</b>) 20 μm, (<b>b</b>) 10 μm, and (<b>c</b>) 5 μm.</p>
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<p>Surface profile after polishing with different abrasive sizes: (<b>a</b>) 20 μm, (<b>b</b>) 10 μm, and (<b>c</b>) 5 μm.</p>
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<p>The relationship between the optimal polishing time and the SDD of the hardness of different types of marble.</p>
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10 pages, 12226 KiB  
Article
Exploring Tumor Heterogeneity: Radiogenomic Assessment of ADFP in Low WHO/ISUP Grade Clear Cell Renal Cell Carcinoma
by Federico Greco, Andrea Panunzio, Valerio D’Andrea, Mariavittoria Vescovo, Alessandro Tafuri, Simone Carotti, Bruno Beomonte Zobel and Carlo Augusto Mallio
Cancers 2024, 16(18), 3164; https://doi.org/10.3390/cancers16183164 (registering DOI) - 15 Sep 2024
Viewed by 80
Abstract
This study aimed to investigate the association between metabolic lipid computed tomography (CT) features and adipose differentiation-related protein (ADFP) expression in clear cell renal cell carcinoma (ccRCC), providing insights into non-invasive methods for assessing ADFP expression and tumor characteristics. This study utilized data [...] Read more.
This study aimed to investigate the association between metabolic lipid computed tomography (CT) features and adipose differentiation-related protein (ADFP) expression in clear cell renal cell carcinoma (ccRCC), providing insights into non-invasive methods for assessing ADFP expression and tumor characteristics. This study utilized data from The Cancer Genome Atlas and the Cancer Imaging Archive to analyze genetic alterations and imaging characteristics in ccRCC patients. Tumoral Hounsfield units (HU) analysis and quantification of abdominal adipose tissue compartments were performed using CT images. Statistical analyses were conducted to compare tumoral HU values according to ADFP gene expression and World Health Organization/International Society of Urological Pathology (WHO/ISUP) tumor grade, as well as to explore correlations between tumoral HU values and adipose tissue quantification. Among the 174 identified patients, those with ADFP gene expression showed significantly lower minimum tumoral HU values in low-grade cancers compared to high-grade cancers. Similarly, patients with low-grade cancers expressing ADFP exhibited lower minimum tumoral HU values compared to those without ADFP expression. Negative correlations were observed between minimum tumoral HU values and visceral adipose tissue, subcutaneous adipose tissue, and total adipose tissue in both ccRCC patients with and without ADFP expression. This study reveals a significant association between metabolic lipid CT features and ADFP expression in ccRCC patients. Lower minimum tumoral HU values, suggestive of higher intracellular lipid accumulation, were observed in tumors with low WHO/ISUP grade and ADFP expression. Full article
(This article belongs to the Collection Molecular Signaling Pathways and Networks in Cancer)
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<p>Scatterplots illustrating the relationship between minimum tumoral HU and quantification of adipose tissue compartments according to ADFP expression [(<b>A</b>): yes vs. (<b>B</b>): no].</p>
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<p>Unenhanced axial CT images of patients with low WHO/ISUP grade ccRCC with ADFP expression (<b>A</b>) and low WHO/ISUP grade ccRCC without ADFP expression (<b>B</b>) show yellow ROIs with different minimum tumor HU values (HU −35 and −7, respectively).</p>
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<p>The histological images illustrate two samples of ccRCC (same patients of <a href="#cancers-16-03164-f002" class="html-fig">Figure 2</a>) stained with hematoxylin and eosin (original magnification 20×). Image (<b>A</b>): ccRCC with ADFP expression characterized by cells with nested architecture, small nuclei, inconspicuous nucleoli, and abundant clear cytoplasm. Image (<b>B</b>): ccRCC without ADFP expression characterized by cells with granular eosinophilic cytoplasm.</p>
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16 pages, 6073 KiB  
Article
Thermo-Responsive Hydrogel Based on Lung Decellularized Extracellular Matrix for 3D Culture Model to Enhance Cancer Stem Cell Characteristics
by Lei Chen, Fanglu Li, Ruobing Li, Ke Zheng, Xinyi Zhang, Huijing Ma, Kaiming Li and Lei Nie
Molecules 2024, 29(18), 4385; https://doi.org/10.3390/molecules29184385 (registering DOI) - 15 Sep 2024
Viewed by 102
Abstract
Cancer stem cells (CSCs) are most likely the main cause of lung cancer formation, metastasis, drug resistance, and genetic heterogeneity. Three-dimensional (3D) ex vivo cell culture models can facilitate stemness improvement and CSC enrichment. Considering the critical role of extracellular matrix (ECM) on [...] Read more.
Cancer stem cells (CSCs) are most likely the main cause of lung cancer formation, metastasis, drug resistance, and genetic heterogeneity. Three-dimensional (3D) ex vivo cell culture models can facilitate stemness improvement and CSC enrichment. Considering the critical role of extracellular matrix (ECM) on CSC properties, the present study developed a thermo-responsive hydrogel using the porcine decellularized lung for 3D cell culture, and the cell-laden hydrogel culturing model was used to explore the CSC characteristics and potential utilization in CSC-specific drug evaluation. Results showed that the lung dECM hydrogel (LEH) was composed of the main ECM components and displayed excellent cellular compatibility. In addition, lung cancer cells 3D cultured in LEH displayed the overexpression of metastasis-related genes and enhanced migration properties, as compared with those in two-dimensional (2D) conditions. Notably, the CSC features, including the expression level of stemness-associated genes, colony formation capability, drug resistance, and the proportion of cancer stem-like cells (CD133+), were also enhanced in 3D cells. Furthermore, the attenuation effect of epigallocatechin gallate (EGCG) on CSC properties in the 3D model was observed, confirming the potential practicability of the 3D culture on CSC-targeted drug screening. Overall, our results suggest that the fabricated LEH is an effective and facile platform for 3D cell culture and CSC-specific drug evaluation. Full article
(This article belongs to the Section Macromolecular Chemistry)
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<p>(<b>A</b>) Lung dECM hydrogel (LEH) could be fabricated using lung decellularized matrix via increasing temperature over 25 °C. (<b>B</b>) Storage modulus (G′) and loss modulus (G″) of LEH over temperature, indicating the sol–gel transition process. (<b>C</b>) SEM images of dried LEH using different magnifications show the porous microstructure. (<b>D</b>) Pore size distribution analysis of LEH based on SEM images using ImageJ software (Version 1.54).</p>
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<p>(<b>A</b>) Gross appearance and H&amp;E staining of fresh lung tissue and LEH. Scale bar: gross appearance, 5 mm; H&amp;E staining, 100 μm. (<b>B</b>) Quantification of DNA content in fresh lung tissue and LEH. (<b>C</b>) Histological and IHC staining of ECM components. MT, AB, and EVG staining were utilized to visualize collagen, elastin, and GAGs, respectively. IHC staining showed the retention and distribution of collagen I, collagen III, collagen IV, laminin, and fibronectin in LEH. Scale bar: 100 μm. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Cancer cell 3D cultured in LEH. (<b>A</b>) LSCM images of cancer cells in LEH at day 1 and 5. The morphology of cells embedded in the hydrogel was shown by FDA (green) staining. The live/dead assay was displayed by Hoechst 33342/PI (blue/red) staining. Scale bar: 100 μm. (<b>B</b>) H&amp;E staining of 3D structure sections at time points of 1 and 11 days. Scale bar: 100 μm. (<b>C</b>) The proliferation of cancer cells in LEH was detected by MTT assay.</p>
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<p>Upregulation of metastatic properties in 3D cancer cells. (<b>A</b>) Representative images of cancer cell morphological alternation. Scale bar: 50 μm. (<b>B</b>) Representative images and quantitative results of Trans-well migration assay. Scale bar: 100 μm. (<b>C</b>) Representative images of scratch wound healing assay. Scale bar: 200 μm. (<b>D</b>) The relative transcription level of metastasis-related genes as measured by qRT-PCR. GAPDH mRNA was utilized to normalize gene expression data, and the results were relative to 2D cells. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Analysis of self-renewal improvement in 3D cells. (<b>A</b>) Representative images and statistical results of soft agar colony formation assay. (<b>B</b>) Single-cell colony formation assay of cancer cells. (<b>C</b>) Flow cytometric analysis of CD133<sup>+</sup> cells. (<b>D</b>) The relative transcription level of CSC-associated genes as measured by qRT-PCR. GAPDH mRNA was utilized to normalize gene expression data, and the results were relative to 2D cells. Scale bar: 100 μm. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>The drug resistance of cancer cells cultured in 2D and 3D. Anti-cancer drugs, including epirubicin HCl (<b>A</b>), cisplatin (<b>B</b>), 5-FU (<b>C</b>), and mitomycin (<b>D</b>), were utilized to treat cancer cells both in 2D and 3D conditions. Cell viability was determined by MTT assay. Results were shown as mean ± S.D. IC50 values for 2D and 3D cell cultures were given. * <span class="html-italic">p</span> &lt; 0.01 and ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Inhibition effects of EGCG on CSC migration and invasion properties. (<b>A</b>) Trans-well assay. (<b>B</b>) Hydrogel invasion assay of 3D structure. The number of cells invading into hydrogel was calculated. Scale bar: 100 μm. (<b>C</b>) qRT-PCR assay of metastasis-related genes. GAPDH mRNA was utilized to normalize gene expression data, and the results were relative to 3D control. ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Attenuation effects of EGCG on CSC self-renewal properties in 3D condition. (<b>A</b>) Soft agar colony formation assay. (<b>B</b>) Single-cell colony formation assay. (<b>C</b>) Flow cytometry analysis of CD133<sup>+</sup> proportion. (<b>D</b>) qRT-PCR assay of CSC-associated genes. GAPDH mRNA was utilized to normalize gene expression data, and the results were relative to 3D control. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>The schematic illustration of fabricating lung dECM hydrogel (LEH) using porcine lung via the decellularization process for CSCs 3D cell culture.</p>
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24 pages, 2304 KiB  
Systematic Review
Targeting NETosis in Acute Brain Injury: A Systematic Review of Preclinical and Clinical Evidence
by Marzia Savi, Fuhong Su, Elda Diletta Sterchele, Elisa Gouvêa Bogossian, Zoé Demailly, Marta Baggiani, Giuseppe Stefano Casu and Fabio Silvio Taccone
Cells 2024, 13(18), 1553; https://doi.org/10.3390/cells13181553 (registering DOI) - 14 Sep 2024
Viewed by 360
Abstract
Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments [...] Read more.
Acute brain injury (ABI) remains one of the leading causes of death and disability world-wide. Its treatment is challenging due to the heterogeneity of the mechanisms involved and the variability among individuals. This systematic review aims at evaluating the impact of anti-histone treatments on outcomes in ABI patients and experimental animals and defining the trend of nucleosome levels in biological samples post injury. We performed a search in Pubmed/Medline and Embase databases for randomized controlled trials and cohort studies involving humans or experimental settings with various causes of ABI. We formulated the search using the PICO method, considering ABI patients or animal models as population (P), comparing pharmacological and non-pharmacological therapy targeting the nucleosome as Intervention (I) to standard of care or no treatment as Control (C). The outcome (O) was mortality or functional outcome in experimental animals and patients affected by ABI undergoing anti-NET treatments. We identified 28 studies from 1246 articles, of which 7 were experimental studies and 21 were human clinical studies. Among these studies, only four assessed the effect of anti-NET therapy on circulating markers. Three of them were preclinical and reported better outcome in the interventional arm compared to the control arm. All the studies observed a significant reduction in circulating NET-derived products. NETosis could be a target for new treatments. Monitoring NET markers in blood and cerebrospinal fluid might predict mortality and long-term outcomes. However, longitudinal studies and randomized controlled trials are warranted to fully evaluate their potential, as current evidence is limited. Full article
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<p>PRISMA flowchart of the review.</p>
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<p>Summary of preclinical and clinical findings and future directions for the clinical application of research on NETosis (illustration created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>). Acronyms: NET: neutrophil extracellular trap; ABI: acute brain injury; TBI: traumatic brain injury; SAH: subarachnoid aneurysmal haemorrhage; MPO-DNA: myeloperoxidase-deoxy-ribonuclease acid; CSF: cerebral spinal fluid.</p>
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<p>The main pathways of NET formation involved in neuroinflammation (illustration created with <a href="http://BioRender.com" target="_blank">BioRender.com</a>).</p>
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16 pages, 2518 KiB  
Systematic Review
An Exploration of the Viral Coverage of Mosquito Viromes Using Meta-Viromic Sequencing: A Systematic Review and Meta-Analysis
by Shenglin Chen, Yuan Fang, Ryosuke Fujita, Emad I. M. Khater, Yuanyuan Li, Wenya Wang, Peijun Qian, Lulu Huang, Zhaoyu Guo, Yi Zhang and Shizhu Li
Microorganisms 2024, 12(9), 1899; https://doi.org/10.3390/microorganisms12091899 (registering DOI) - 14 Sep 2024
Viewed by 216
Abstract
The aim of this review was to delve into the extent of mosquito virome coverage (proportion of viral reads) via meta-viromic sequencing and uncover potential factors of heterogeneity that could impact this coverage. Data sources were PubMed, Web of Science, Embase, Scopus, Science-Direct, [...] Read more.
The aim of this review was to delve into the extent of mosquito virome coverage (proportion of viral reads) via meta-viromic sequencing and uncover potential factors of heterogeneity that could impact this coverage. Data sources were PubMed, Web of Science, Embase, Scopus, Science-Direct, Google Scholar, and the China National Knowledge Infrastructure. Pooled coverage was estimated using random-effects modeling, and subgroup analyses further reveal potential heterogeneous factors. Within the three mosquito genera studied, Culex exhibited the highest pooled viral coverage of mosquito viromes at 7.09% (95% CI: 3.44–11.91%), followed by Anopheles at 5.28% (95% CI: 0.45–14.93%), and Aedes at 2.11% (95% CI: 0.58–7.66%). Subgroup analyses showed that multiple processing methods significantly affected the viral coverage of mosquito viromes, especially pre-treatment of mosquito samples with saline buffer/medium and antibiotics prior to DNase/RNase treatment and removal of the host genome prior to RNA library construction. In conclusion, the results of this study demonstrate that the viral coverage of mosquito viromes varies between mosquito genera and that pre-treatment of mosquito samples with saline buffer/medium and antibiotics before DNase/RNase treatment and removing host genomes prior to RNA library construction are critical for the detection of RNA viruses in mosquito vectors using meta-viromic sequencing. Full article
(This article belongs to the Section Virology)
18 pages, 616 KiB  
Review
Fluids, Vasopressors, and Inotropes to Restore Heart–Vessel Coupling in Sepsis: Treatment Options and Perspectives
by Francesca Innocenti, Vittorio Palmieri and Riccardo Pini
Anesth. Res. 2024, 1(2), 128-145; https://doi.org/10.3390/anesthres1020013 (registering DOI) - 14 Sep 2024
Viewed by 188
Abstract
Sepsis is a complex syndrome with heterogeneous clinical presentation and outcome, characterized by an abnormal inflammatory response, potentially leading to multiorgan damage and hemodynamic instability. Early resuscitation with fluids and timely control of the source of sepsis are key treatment targets in septic [...] Read more.
Sepsis is a complex syndrome with heterogeneous clinical presentation and outcome, characterized by an abnormal inflammatory response, potentially leading to multiorgan damage and hemodynamic instability. Early resuscitation with fluids and timely control of the source of sepsis are key treatment targets in septic patients. Recommendations on when to add vasopressors and inotropes are mostly empirical and anecdotal, therefore remaining a topic of debate. This narrative review was developed to present and discuss current options in the early management of hemodynamic derangement induced by sepsis. We discuss the strengths and drawbacks of the recommended treatment with fluids and how to optimize volume resuscitation in order to avoid fluid overload or under-resuscitation. The choice and timing of vasopressor use represent hot topics in the early management of septic patients. We describe the advantages and limitations of the early introduction of vasopressors and new catecholamine-sparing strategies. We conclude with a description of the inotropes, considering that the heart plays a key role in the pathophysiology of septic shock. Full article
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Figure 1

Figure 1
<p>Main mechanisms of organ damage during sepsis.</p>
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