The 2023 MDPI Annual Report has
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18 pages, 5040 KiB  
Article
A High-Voltage Pulse Modulator Composed of SiC MOSFETs/IGBTs in a Hybrid Connecting State
by Zhuang Kang, Xiaofeng Xie, Yang Liu, Daibing Chen, Haitao Yuan, Liu Zhao, Hai Zhao, Chengliang Yang and Guiqiang Zheng
Electronics 2024, 13(11), 2108; https://doi.org/10.3390/electronics13112108 (registering DOI) - 29 May 2024
Abstract
In order to solve problems such as a slow switching speed, a high switching power, a loss of pure IGBT modulators, and the weak withstanding load short-circuit ability of pure SiC MOSFET modulators used for vacuum loads, this paper proposes a new scheme [...] Read more.
In order to solve problems such as a slow switching speed, a high switching power, a loss of pure IGBT modulators, and the weak withstanding load short-circuit ability of pure SiC MOSFET modulators used for vacuum loads, this paper proposes a new scheme for high-voltage pulse modulators based on SiC MOSFET/IGBT hybrid connecting circuits. It has a low power loss like the pure SiC MOSFET modulator and a strong withstanding load short-circuit ability like the pure IGBT modulator. Firstly, the principle circuit of the hybrid connecting modulator are discussed and chosen. And the basic working processes of the hybrid parallel-series modulator is described in detail. Secondly, three key points in this new scheme are analyzed and designed as follows: the static and dynamic voltage sharing; the actualizing of the ZVS process for IGBTs; the improvement of short-circuit protection for SiC MOSFETs. A modulator consisting of 16-stage 1200 V-SiC MOSFETs and 1200 V-IGBTs in hybrid parallel-series states is tested. Based on the sample circuit, the working data, such as high-voltage pulse waveforms of 10 kV/2 KHz/10 μs, static and dynamic voltage sharing, the driving control sequence, the U/I sequence of the IGBT, the short-circuit protection waveform, and the calculation, are obtained and discussed. Full article
(This article belongs to the Special Issue Advances in Pulsed-Power and High-Power Electronics)
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23 pages, 3534 KiB  
Article
Emergency and Elective Colorectal Cancer—Relationship between Clinical Factors, Tumor Topography and Surgical Strategies: A Cohort Study
by Ionuţ Simion Coman, Raluca Cristina Vital, Violeta Elena Coman, Cosmin Burleanu, Mircea Liţescu, Costin George Florea, Daniel Alin Cristian, Gabriel-Petre Gorecki, Petru Adrian Radu, Iancu Emil Pleşea, Anwar Erchid and Valentin Titus Grigorean
Medicina 2024, 60(6), 898; https://doi.org/10.3390/medicina60060898 (registering DOI) - 29 May 2024
Abstract
Background and Objectives: The purpose of the study was to analyze the relationships among several clinical factors and also the tumor topography and surgical strategies used in patients with colorectal cancer. Materials and Methods: We designed an analytical, observational, retrospective study that [...] Read more.
Background and Objectives: The purpose of the study was to analyze the relationships among several clinical factors and also the tumor topography and surgical strategies used in patients with colorectal cancer. Materials and Methods: We designed an analytical, observational, retrospective study that included patients admitted to our emergency surgical department and diagnosed with colorectal cancer. The study group inclusion criteria were: patients admitted during 2020–2022; patients diagnosed with colorectal cancer (including the ileocecal valve); patients who benefited from a surgical procedure, either emergency or elective. Results: In our study group, consisting of 153 patients, we accounted for 56.9% male patients and 43.1% female patients. The most common clinical manifestations were pain (73.2% of the study group), followed by abdominal distension (69.3% of the study group) and absence of intestinal transit (38.6% of the study group). A total of 69 patients had emergency surgery (45.1%), while 84 patients (54.9%) benefited from elective surgery. The most frequent topography of the tumor was the sigmoid colon, with 19.60% of the patients, followed by the colorectal junction, with 15.68% of the patients, and superior rectum and inferior rectum, with 11.11% of the patients in each subcategory. The most frequent type of procedure was right hemicolectomy (21.6% of the study group), followed by rectosigmoid resection (20.9% of the study group). The surgical procedure was finished by performing an anastomosis in 49% of the patients, and an ostomy in 43.1% of the patients, while for 7.8% of the patients, a tumoral biopsy was performed. Conclusions: Colorectal cancer remains one of the most frequent cancers in the world, with a heavy burden that involves high mortality, alterations in the quality of life of patients and their families, and also the financial costs of the medical systems. Full article
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22 pages, 684 KiB  
Review
Clinical Applications of Adipose-Derived Stem Cell (ADSC) Exosomes in Tissue Regeneration
by Konstantinos S. Papadopoulos, Christina Piperi and Penelope Korkolopoulou
Int. J. Mol. Sci. 2024, 25(11), 5916; https://doi.org/10.3390/ijms25115916 (registering DOI) - 29 May 2024
Abstract
Adipose-derived stem cells (ADSCs) are mesenchymal stem cells with a great potential for self-renewal and differentiation. Exosomes derived from ADSCs (ADSC-exos) can imitate their functions, carrying cargoes of bioactive molecules that may affect specific cellular targets and signaling processes. Recent evidence has shown [...] Read more.
Adipose-derived stem cells (ADSCs) are mesenchymal stem cells with a great potential for self-renewal and differentiation. Exosomes derived from ADSCs (ADSC-exos) can imitate their functions, carrying cargoes of bioactive molecules that may affect specific cellular targets and signaling processes. Recent evidence has shown that ADSC-exos can mediate tissue regeneration through the regulation of the inflammatory response, enhancement of cell proliferation, and induction of angiogenesis. At the same time, they may promote wound healing as well as the remodeling of the extracellular matrix. In combination with scaffolds, they present the future of cell-free therapies and promising adjuncts to reconstructive surgery with diverse tissue-specific functions and minimal adverse effects. In this review, we address the main characteristics and functional properties of ADSC-exos in tissue regeneration and explore their most recent clinical application in wound healing, musculoskeletal regeneration, dermatology, and plastic surgery as well as in tissue engineering. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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13 pages, 838 KiB  
Review
RNA Binding by the m6A Methyltransferases METTL16 and METTL3
by Kyle D. Mansfield
Biology 2024, 13(6), 391; https://doi.org/10.3390/biology13060391 (registering DOI) - 29 May 2024
Abstract
Methyltransferases are a wide-ranging, yet well-conserved, class of molecules that have been found to modify a wide variety of substrates. Interest in RNA methylation has surged in recent years with the identification of the major eukaryotic mRNA m6A methyltransferase METTL3. METTL16 has also [...] Read more.
Methyltransferases are a wide-ranging, yet well-conserved, class of molecules that have been found to modify a wide variety of substrates. Interest in RNA methylation has surged in recent years with the identification of the major eukaryotic mRNA m6A methyltransferase METTL3. METTL16 has also been identified as an RNA m6A methyltransferase; however, much less is known about its targets and actions. Interestingly, in addition to their catalytic activities, both METTL3 and METTL16 also have “methylation-independent” functions, including translational regulation, which have been discovered. However, evidence suggests that METTL16’s role as an RNA-binding protein may be more significant than is currently recognized. In this review, we will introduce RNA methylation, specifically m6A, and the enzymes responsible for its deposition. We will discuss the varying roles that these enzymes perform and delve deeper into their RNA targets and possible roles as methylation-independent RNA binding proteins. Finally, we will touch upon the many open questions still remaining. Full article
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13 pages, 2953 KiB  
Article
A Single-Atom Au Catalyst Boosts High-Efficiency Electrochemical Seawater Oxidation
by Qihao Sha, Jian Shen, Guotao Yang, Tianshui Li, Wei Liu, Yun Kuang and Xiaoming Sun
Catalysts 2024, 14(6), 348; https://doi.org/10.3390/catal14060348 (registering DOI) - 29 May 2024
Abstract
Alkaline seawater electrolysis has garnered significant attention as an efficient, green, and sustainable method for producing green hydrogen in recent years. However, the lack of highly active anodes in seawater electrolysis to prevent chloride oxidation reactions has limited its commercial application. In this [...] Read more.
Alkaline seawater electrolysis has garnered significant attention as an efficient, green, and sustainable method for producing green hydrogen in recent years. However, the lack of highly active anodes in seawater electrolysis to prevent chloride oxidation reactions has limited its commercial application. In this study, Au single atoms were deposited on NiCoFeS through the electrochemical deposition method. The optimized catalyst exhibited significantly enhanced activity in seawater electrolyte; the Au@NiCoFeS catalyst achieved a current density of 10 mA/cm2 with only 183 mV and maintained its performance without degradation for 250 h at a current density of 200 mA/cm2, with no corrosion observed on either the catalyst or the substrate. Full article
(This article belongs to the Special Issue Study on Electrocatalytic Activity of Metal Oxides)
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21 pages, 2407 KiB  
Article
Fatty Acid Synthase as Interacting Anticancer Target of the Terpenoid Myrianthic Acid Disclosed by MS-Based Proteomics Approaches
by Alessandra Capuano, Gilda D’Urso, Erica Gazzillo, Gianluigi Lauro, Maria Giovanna Chini, Maria Valeria D’Auria, Maria Grazia Ferraro, Federica Iazzetti, Carlo Irace, Giuseppe Bifulco and Agostino Casapullo
Int. J. Mol. Sci. 2024, 25(11), 5918; https://doi.org/10.3390/ijms25115918 (registering DOI) - 29 May 2024
Abstract
This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of drug affinity responsive [...] Read more.
This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of drug affinity responsive target stability (DARTS) and targeted-limited proteolysis coupled to mass spectrometry (t-LiP-MS) led to the identification of the enzyme fatty acid synthase (FAS) as an interesting macromolecular counterpart of myrianthic acid. This result, confirmed by comparison with the natural ursolic acid, was thoroughly investigated and validated in silico by molecular docking, which gave a precise picture of the interactions in the MA/FAS complex. Moreover, biological assays showcased the inhibitory activity of myrianthic acid against the FAS enzyme, most likely related to its antiproliferative activity towards tumor cells. Given the significance of FAS in specific pathologies, especially cancer, the myrianthic acid structural moieties could serve as a promising reference point to start the potential development of innovative approaches in therapy. Full article
(This article belongs to the Section Molecular Pharmacology)
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12 pages, 878 KiB  
Article
Sex-Specific Sarcopenia Prevalence and Risk Factors in the Korean Population: A Cross-Sectional Epidemiological Study
by Do-Youn Lee
Medicina 2024, 60(6), 899; https://doi.org/10.3390/medicina60060899 (registering DOI) - 29 May 2024
Abstract
Background and Objective: This study aimed to identify the incidence of sarcopenia and disease risk factors in Korean adults and to provide data for sarcopenia prevention. Materials and Methods: Based on the Korea National Health and Nutrition Survey, 2008–2011, we selected 14,185 adults [...] Read more.
Background and Objective: This study aimed to identify the incidence of sarcopenia and disease risk factors in Korean adults and to provide data for sarcopenia prevention. Materials and Methods: Based on the Korea National Health and Nutrition Survey, 2008–2011, we selected 14,185 adults over the age of 20 who participated in sarcopenia diagnostic tests and health surveys. We analyzed sarcopenia risk factors using complex sample multi-logistic regression analysis. Results: The prevalence of sarcopenia in Korea was 31.3%, with 20.2% in men and 40.4% in women. In men, there was a higher risk of sarcopenia in those of older age, without a spouse, with a low body mass index (BMI), who never engage in resistance exercise, or who do mid-level intensity resistance exercises. In women, sarcopenia risk was higher in those in their 20s compared to those in their 60s, and risk factors included a low BMI, high-density lipoprotein cholesterol and waist circumference measurements, alcohol consumption, aerobic exercise, and resistance exercise. Conclusions: Interventions and lifestyle improvements will help prevent the onset of sarcopenia in elderly men and young women with risk factors such as a low BMI. Full article
(This article belongs to the Section Epidemiology & Public Health)
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11 pages, 286 KiB  
Article
Applying Trust Patterns to Model Complex Trustworthiness in the Internet of Things
by Fabrizio Messina, Domenico Rosaci and Giuseppe M. L. Sarnè
Electronics 2024, 13(11), 2107; https://doi.org/10.3390/electronics13112107 (registering DOI) - 29 May 2024
Abstract
Key aspects of communities of the Internet of Things (IoT) smart objects presenting social aspects are represented by trust and reputation relationships between the objects. Several trustworthiness models have been presented in the literature in the context of multi-smart object community that could [...] Read more.
Key aspects of communities of the Internet of Things (IoT) smart objects presenting social aspects are represented by trust and reputation relationships between the objects. Several trustworthiness models have been presented in the literature in the context of multi-smart object community that could be adopted in the IoT scenario; however, most of these approaches represent the different dimensions of trust using scalar measures, then integrating these measures in a global trustworthiness value. In this paper, we discuss the limitation of this approach in the IoT context, highlighting the necessity of modeling complex trust relationships that cannot be captured by a vector-based model, and we propose a new trust model in which the trust perceived by an object with respect to another object is modeled by a directed, weighted graph whose vertices are trust dimensions and whose arcs represent relationships between trust dimensions. By using this new model, we provide the IoT community with the possibility of representing also situations in which an object does not know a trust dimension, e.g., reliability, but it is able to derive it from another one, e.g., honesty. The introduced model can represent any trust structure of the type illustrated above, in which several trust dimensions are mutually dependent. Full article
(This article belongs to the Special Issue Security and Trust in Internet of Things and Edge Computing)
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22 pages, 1580 KiB  
Article
A Soft Sensor for Flow Estimation and Uncertainty Analysis Based on Artificial Intelligence: A Case Study of Water Supply Systems
by Gabryel M. Raposo de Alencar, Fernanda M. Lima Fernandes, Rafael Moura Duarte, Petrônio Ferreira de Melo, Altamar Alencar Cardoso, Heber Pimentel Gomes and Juan M. Mauricio Villanueva
Automation 2024, 5(2), 106-127; https://doi.org/10.3390/automation5020008 (registering DOI) - 29 May 2024
Abstract
The fourth industrial revolution has transformed the industry, with information technology playing a crucial role in this shift. The increasing digitization of industrial systems demands efficient sensing and control methods, giving rise to soft sensors that have the potential to replace traditional physical [...] Read more.
The fourth industrial revolution has transformed the industry, with information technology playing a crucial role in this shift. The increasing digitization of industrial systems demands efficient sensing and control methods, giving rise to soft sensors that have the potential to replace traditional physical sensors in order to reduce costs and enhance efficiency. This study explores the implementation of an artificial neural network (ANN) based soft sensor model in a water supply system to predict flow rates within the system. The soft sensor is centered on a Long Short-Term Memory (LSTM) artificial neural network model using Monte Carlo dropout to reduce uncertainty and improve estimation performance. Based on the results of this work, it is concluded that the proposed soft sensor (with Monte Carlo dropout) can predict flow rates more precisely, contributing to the reduction in water losses, as well as cost savings. This approach offers a valuable solution for minimizing water losses and ensuring the efficient use of this vital resource. Regarding the use of soft sensors based on LSTM neural networks with a careful choice of Monte Carlo dropout parameters, when compared to the multilayer perceptron model, the LSTM model with Monte Carlo dropout showed better mean absolute error, root mean square error, and coefficient of determination: 0.2450, 0.3121, and 0.996437 versus 0.2556, 0.3522, and 0.9954. Furthermore, this choice of Monte Carlo dropout parameters allowed us to achieve an LSTM network model capable of reducing uncertainty to 1.8290, keeping the error metrics also at low levels. Full article
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23 pages, 8810 KiB  
Article
The Development of a Bacterial Nanocellulose/Cationic Starch Hydrogel for the Production of Sustainable 3D-Printed Packaging Foils
by Špela Dermol, Bojan Borin, Diana Gregor-Svetec, Lidija Slemenik Perše and Gregor Lavrič
Polymers 2024, 16(11), 1527; https://doi.org/10.3390/polym16111527 (registering DOI) - 29 May 2024
Abstract
Polymers have become an important part of everyday life, but most of the polymers currently used are petroleum-based. This poses an environmental problem, especially with respect to products that are quickly discarded. For this reason, current packaging development focuses on sustainable materials as [...] Read more.
Polymers have become an important part of everyday life, but most of the polymers currently used are petroleum-based. This poses an environmental problem, especially with respect to products that are quickly discarded. For this reason, current packaging development focuses on sustainable materials as an alternative to synthetic ones. Nanocellulose, a relatively new material derived from cellulose, has unique properties such as high strength, low density, high surface area, and good barrier properties, making it popular in various applications. Additionally, 3D printing technologies have become an important part of industrial and commercial processes, enabling the realization of innovative ideas and functionalities. The main aim of this research was to develop a hydrogel of bacterial nanocellulose with suitable rheological properties for the 3D printing of polymer foils. Three variations of bacterial nanocellulose hydrogel differing in ratios of bacterial nanocellulose to cationic starch were produced. The rheological studies confirmed the suitability of the hydrogels for 3D printing. Foils were successfully 3D-printed using a modified 3D printer. The physical-mechanical, surface, and optical properties of the foils were determined. All foils were homogeneous with adequate mechanical properties. The 3D-printed foils with the highest amount of cationic starch were the most homogeneous and transparent and, despite their rigidity, very strong. All foils were semi-transparent, had a non-glossy surface, and retained poor water wettability. Full article
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15 pages, 13143 KiB  
Article
The Effect of Iron Oxide Insertion on the In Vitro Bioactivity, and Antibacterial Properties of the 45S5 Bioactive Glass
by Imen Hammami, Suresh Kumar Jakka, Isabel Sá-Nogueira, João Paulo Borges and Manuel Pedro Fernandes Graça
Biomimetics 2024, 9(6), 325; https://doi.org/10.3390/biomimetics9060325 (registering DOI) - 29 May 2024
Abstract
The aging population and increasing incidence of trauma among younger age groups have heightened the increasing demand for reliable implant materials. Effective implant materials must demonstrate rapid osseointegration and strong antibacterial properties to ensure optimal patient outcomes and decrease the chance of implant [...] Read more.
The aging population and increasing incidence of trauma among younger age groups have heightened the increasing demand for reliable implant materials. Effective implant materials must demonstrate rapid osseointegration and strong antibacterial properties to ensure optimal patient outcomes and decrease the chance of implant rejection. This study aims to enhance the bone–implant interface by utilizing 45S5 bioglass modified with various concentrations of Fe3O4 as a coating material. The effect of the insertion of Fe3O4 into the bioglass structure was studied using Raman spectroscopy which shows that with the increase in Fe3O4 concentration, new vibration bands associated with Fe-related structural units appeared within the sample. The bioactivity of the prepared glasses was evaluated using immersion tests in simulated body fluid, revealing the formation of a calcium phosphate-rich layer within 24 h on the samples, indicating their potential for enhanced tissue integration. However, the sample modified with 8 mol% of Fe3O4 showed low reactivity, developing a calcium phosphate-rich layer within 96 h. All the bioglasses showed antibacterial activity against the Gram-positive and Gram-negative bacteria. The modified bioglass did not present significant antibacterial properties compared to the bioglass base. Full article
(This article belongs to the Special Issue Advances in Bioceramics for Bone Regeneration)
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25 pages, 5207 KiB  
Article
Spatial-Temporal Variations and Driving Factors of the Coupling and Coordination Level of the Digital Economy and Sustainable Rural Development: A Case Study of China
by Wanxiang Nong, Jun Wen and Jingyue He
Agriculture 2024, 14(6), 849; https://doi.org/10.3390/agriculture14060849 (registering DOI) - 29 May 2024
Abstract
Sustainable rural development forms a robust foundation for economic and social sustainability. Moreover, the digital economy acts as a catalyst for advancing rural sustainable development by altering the distribution of production factors. Thus, this study concentrates on 30 provinces in China, constructing an [...] Read more.
Sustainable rural development forms a robust foundation for economic and social sustainability. Moreover, the digital economy acts as a catalyst for advancing rural sustainable development by altering the distribution of production factors. Thus, this study concentrates on 30 provinces in China, constructing an evaluation index system for both the digital economy and rural sustainable development. The study employs various methods and models to analyze the spatiotemporal changes and driving factors affecting the coupling and coordination between these two aspects. The research findings are as follows: the coupling and coordination levels among provinces in China have been on the rise year by year. By 2022, the coupling and coordination levels of most provinces range between 0.5 and 0.6. Regional disparities are the primary determinant of the poor overall coupling and coordination level in China. In 2022, the coupling and coordination level in the eastern region is 0.6663, compared to 0.5420 in the central region and 0.5087 in the western region. Factors such as urbanization, industrial structure transformation, technological innovation, higher education, economic development, and government support significantly influence the coupling and coordination level. Nevertheless, their effects vary across regions, with a more pronounced impact in the eastern region than in the central and western regions. Therefore, this paper proposes policy recommendations, including infrastructure optimization, rural digitization promotion, regional resource allocation enhancement, cross-regional development mechanism exploration, and differentiated development strategy implementation. Full article
(This article belongs to the Section Agricultural Economics, Policies and Rural Management)
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18 pages, 1474 KiB  
Article
Hybrid Genetic Algorithm and CMA-ES Optimization for RNN-Based Chemical Compound Classification
by Zhenkai Guo, Dianlong Hou and Qiang He
Mathematics 2024, 12(11), 1684; https://doi.org/10.3390/math12111684 (registering DOI) - 29 May 2024
Abstract
The compound classification strategies addressed in this study encounter challenges related to either low efficiency or accuracy. Precise classification of chemical compounds from SMILES symbols holds significant importance in domains such as drug discovery, materials science, and environmental toxicology. In this paper, we [...] Read more.
The compound classification strategies addressed in this study encounter challenges related to either low efficiency or accuracy. Precise classification of chemical compounds from SMILES symbols holds significant importance in domains such as drug discovery, materials science, and environmental toxicology. In this paper, we introduce a novel hybrid optimization framework named GA-CMA-ES which integrates Genetic Algorithms (GA) and the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) to train Recurrent Neural Networks (RNNs) for compound classification. Leveraging the global exploration capabilities og GAs and local exploration abilities of the CMA-ES, the proposed method achieves notable performance, attaining an 83% classification accuracy on a benchmark dataset, surpassing the baseline method. Furthermore, the hybrid approach exhibits enhanced convergence speed, computational efficiency, and robustness across diverse datasets and levels of complexity. Full article
(This article belongs to the Section Mathematical Biology)
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11 pages, 2106 KiB  
Article
Fucoidan from Lessonia trabeculata Induces Apoptosis through Caspase Dependent and Caspase-Independent Activation in 4T1 Breast Adenocarcinoma In Vitro
by Raisa Teresa Cruz Riquelme, Erasmo Honorio Colona-Vallejos, Libertad Alzamora-Gonzales and Rosa María Condori Macuri
Mar. Drugs 2024, 22(6), 251; https://doi.org/10.3390/md22060251 (registering DOI) - 29 May 2024
Abstract
Experiments conducted on triple-negative breast cancer have shown that fucoidan from Lessonia trabeculata (FLt) exhibits cytotoxic and antitumor properties. However, further research is necessary to gain a complete understanding of its bioactivity and level of cytotoxicity. The cytotoxic effect of FLt was determined [...] Read more.
Experiments conducted on triple-negative breast cancer have shown that fucoidan from Lessonia trabeculata (FLt) exhibits cytotoxic and antitumor properties. However, further research is necessary to gain a complete understanding of its bioactivity and level of cytotoxicity. The cytotoxic effect of FLt was determined by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was analyzed using annexin V and caspase 3/7 staining kit and DNA fragmentation. In addition, transcriptional expression of antiapoptotic (Bcl-2 and XIAP) and proapoptotic (caspase 8, caspase 9, and AIF) genes were analyzed in TNBC 4T1 cells. After 72 h of culture, the IC50 for FLt was 561 μg/mL, while doxorubicin (Dox) had an IC50 of 0.04 μg/mL. In addition, assays for FLt + Dox were performed. Annexin V and caspase 3/7 revealed that FLt induces early and late-stage apoptosis. DNA fragmentation results support necrotic death of 4T1 cells. Similarly, transcripts that prevent cell death were decreased, while transcripts that promote cell death were increased. This study showed that FLt induces apoptosis by both caspase-dependent and caspase-independent mechanisms. These findings suggest that FLt may have potential applications in breast cancer treatment. Further research will provide more information to elucidate the mechanism of action of FLt. Full article
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23 pages, 3219 KiB  
Review
Extracellular Interactors of the IGF System: Impact on Cancer Hallmarks and Therapeutic Approaches
by Caterina Mancarella, Andrea Morrione and Katia Scotlandi
Int. J. Mol. Sci. 2024, 25(11), 5915; https://doi.org/10.3390/ijms25115915 (registering DOI) - 29 May 2024
Abstract
Dysregulation of the insulin-like growth factor (IGF) system determines the onset of various pathological conditions, including cancer. Accordingly, therapeutic strategies have been developed to block this system in tumor cells, but the results of clinical trials have been disappointing. After decades of research [...] Read more.
Dysregulation of the insulin-like growth factor (IGF) system determines the onset of various pathological conditions, including cancer. Accordingly, therapeutic strategies have been developed to block this system in tumor cells, but the results of clinical trials have been disappointing. After decades of research in the field, it is safe to say that one of the major reasons underlying the poor efficacy of anti-IGF-targeting agents is derived from an underestimation of the molecular complexity of this axis. Genetic, transcriptional, post-transcriptional and functional interactors interfere with the activity of canonical components of this axis, supporting the need for combinatorial approaches to effectively block this system. In addition, cancer cells interface with a multiplicity of factors from the extracellular compartment, which strongly affect cell destiny. In this review, we will cover novel extracellular mechanisms contributing to IGF system dysregulation and the implications of such dangerous liaisons for cancer hallmarks and responses to known and new anti-IGF drugs. A deeper understanding of both the intracellular and extracellular microenvironments might provide new impetus to better decipher the complexity of the IGF axis in cancer and provide new clues for designing novel therapeutic approaches. Full article
(This article belongs to the Special Issue The Role of the IGF Axis in Disease 3.0)
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19 pages, 8534 KiB  
Article
Prediction of Suitable Habitat of Alien Invasive Plant Ambrosia trifida in Northeast China under Various Climatic Scenarios
by Shengjie Chen, Xuejiao Bai, Ji Ye, Weiwei Chen and Guanghao Xu
Diversity 2024, 16(6), 322; https://doi.org/10.3390/d16060322 (registering DOI) - 29 May 2024
Abstract
Ambrosia trifida is an invasive alien plant species, which has very high reproductive and environmental adaptability. Through strong resource acquisition ability and allelopathy, it could inhibit the growth and reproduction of surrounding plants and destroy the stability of an invasive ecosystem. It is [...] Read more.
Ambrosia trifida is an invasive alien plant species, which has very high reproductive and environmental adaptability. Through strong resource acquisition ability and allelopathy, it could inhibit the growth and reproduction of surrounding plants and destroy the stability of an invasive ecosystem. It is very important to predict the change of suitable distribution area of A. trifida with climate change before implementing scientific control measures. Based on 106 A. trifida distribution data and 14 points of environmental data, the optimal parameter combination (RM = 0.1, FC = LQ) was obtained using the MaxEnt (version 3.4.1) model optimized by Kuenm package, and thus the potential suitable areas of A. trifida in Northeast China under three different climate scenarios (RCP2.6, RCP4.5, RCP8.5) with different emission intensities in the future (2050, 2070) were predicted. The changes of A. trifida suitable area in Northeast China under three climate scenarios were compared, and the relationship between the change of suitable area and emission intensity was analyzed. In general, the suitable area of A. trifida in Northeast China will expand gradually in the future, and the area of its highly suitable area will also increase with the increasing emission intensity, which is unfavorable to the control of A. trifida. Full article
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12 pages, 242 KiB  
Review
Targeted Therapies for EGFR Exon 20 Insertion Mutation in Non-Small-Cell Lung Cancer
by Donghyun Seo and Jun Hyeok Lim
Int. J. Mol. Sci. 2024, 25(11), 5917; https://doi.org/10.3390/ijms25115917 (registering DOI) - 29 May 2024
Abstract
Non-small-cell lung cancer (NSCLC) frequently harbors mutations in the epidermal growth factor receptor (EGFR), with exon 20 insertions comprising 1–10% of these mutations. EGFR exon 20 insertions are less responsive to conventional tyrosine kinase inhibitors (TKIs), leading to the development of targeted agents. [...] Read more.
Non-small-cell lung cancer (NSCLC) frequently harbors mutations in the epidermal growth factor receptor (EGFR), with exon 20 insertions comprising 1–10% of these mutations. EGFR exon 20 insertions are less responsive to conventional tyrosine kinase inhibitors (TKIs), leading to the development of targeted agents. This review explores key therapeutic agents, such as Amivantamab, Mobocertinib, Poziotinib, Zipalertinib, and Sunvozertinib, which have shown promise in treating NSCLC with EGFR exon 20 insertions. Amivantamab, a bispecific antibody-targeting EGFR and c-MET, demonstrates significant efficacy, particularly when combined with chemotherapy. Mobocertinib, a TKI, selectively targets EGFR exon 20 mutations but faces limitations in efficacy. Poziotinib, another oral TKI, shows mixed results due to mutation-specific responses. Zipalertinib and Sunvozertinib have emerged as potent TKIs with promising clinical data. Despite these advances, challenges in overcoming resistance mutations and improving central nervous system penetration remain. Future research should focus on optimizing first-line combination therapies and enhancing diagnostic strategies for comprehensive mutation profiling. Full article
(This article belongs to the Special Issue Editorial Board Members’ Collection Series: Cancer Metastasis)
12 pages, 1614 KiB  
Article
O-Phthalaldehyde Derivatization for the Paper-Based Fluorometric Determination of Glutathione in Nutritional Supplements
by Maria Tarara, Paraskevas D. Tzanavaras and George Z. Tsogas
Molecules 2024, 29(11), 2550; https://doi.org/10.3390/molecules29112550 (registering DOI) - 29 May 2024
Abstract
Herein, a new, direct paper-based fluorimetric method is described for the quantitative determination of glutathione (GSH) molecules in nutritional supplements. Briefly, the proposed analytical method is based on the fluorescence emission resulting from the direct and selective chemical reaction of GSH molecules with [...] Read more.
Herein, a new, direct paper-based fluorimetric method is described for the quantitative determination of glutathione (GSH) molecules in nutritional supplements. Briefly, the proposed analytical method is based on the fluorescence emission resulting from the direct and selective chemical reaction of GSH molecules with the derivatization reagent that is o-phthalaldehyde (OPA) in acidic conditions at room temperature. The intensity of the emitted fluorescence on the surface of the analytical paper devices after irradiation with a lamp at 365 nm is proportional to the concentration of GSH and is measured using a smartphone as the detector. This methodology, which is suitable for measurements in laboratories with limited resources, does not require specialized instrumentation or trained personnel. The protocol governing the proposed method is simple and easily applicable. Essentially, the chemical analyst should adjust the value of pH on the surface of the paper by adding a minimal amount of buffer solution; then, after adding a few microliters of the derivatization reagent, wait for the surface of the paper to dry and, finally, add the analyte. Subsequently, the irradiation of the sensor and the measurement of the emitted fluorescence can be recorded with a mobile phone. In the present study, several parameters affecting the chemical reaction and the emitted fluorescence were optimized, the effect of interfering compounds that may be present in dietary supplements was examined, and the stability of these paper sensors under different storage conditions was evaluated. Additionally, the chemical stability of these paper devices in various maintenance conditions was studied, with satisfactory results. The detection limit calculated as 3.3 S/N was 20.5 μmol L−1, while the precision of the method was satisfactory, ranging from 3.1% (intra-day) to 7.3% (inter-day). Finally, the method was successfully applied to three different samples of dietary supplements. Full article
(This article belongs to the Special Issue Qualitative and Quantitative Analyses of Food and Drugs)
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14 pages, 2026 KiB  
Article
Machine Learning Metabolomics Profiling of Dietary Interventions from a Six-Week Randomised Trial
by Afroditi Kouraki, Ana Nogal, Weronika Nocun, Panayiotis Louca, Amrita Vijay, Kari Wong, Gregory A. Michelotti, Cristina Menni and Ana M. Valdes
Metabolites 2024, 14(6), 311; https://doi.org/10.3390/metabo14060311 (registering DOI) - 29 May 2024
Abstract
Metabolomics can uncover physiological responses to prebiotic fibre and omega-3 fatty acid supplements with known health benefits and identify response-specific metabolites. We profiled 534 stool and 799 serum metabolites in 64 healthy adults following a 6-week randomised trial comparing daily omega-3 versus inulin [...] Read more.
Metabolomics can uncover physiological responses to prebiotic fibre and omega-3 fatty acid supplements with known health benefits and identify response-specific metabolites. We profiled 534 stool and 799 serum metabolites in 64 healthy adults following a 6-week randomised trial comparing daily omega-3 versus inulin supplementation. Elastic net regressions were used to separately identify the serum and stool metabolites whose change in concentration discriminated between the two types of supplementations. Random forest was used to explore the gut microbiome’s contribution to the levels of the identified metabolites from matching stool samples. Changes in serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate and indoleproprionate levels accurately discriminated between fibre and omega-3 (area under the curve (AUC) = 0.87 [95% confidence interval (CI): 0.63–0.99]), while stool eicosapentaenoate indicated omega-3 supplementation (AUC = 0.86 [95% CI: 0.64–0.98]). Univariate analysis also showed significant increases in indoleproprionate with fibre, 3-carboxy-4-methyl-5-propyl-2-furanpropanoate, and eicosapentaenoate with omega-3. Out of these, only the change in indoleproprionate was partly explained by changes in the gut microbiome composition (AUC = 0.61 [95% CI: 0.58–0.64] and Rho = 0.21 [95% CI: 0.08–0.34]) and positively correlated with the increase in the abundance of the genus Coprococcus (p = 0.005). Changes in three metabolites discriminated between fibre and omega-3 supplementation. The increase in indoleproprionate with fibre was partly explained by shifts in the gut microbiome, particularly Coprococcus, previously linked to better health. Full article
(This article belongs to the Collection Advances in Metabolomics)
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24 pages, 14048 KiB  
Article
Polyploidization Impact on Plant Architecture of Watermelon (Citrullus lanatus)
by Eftekhar Mahmud, Hongju Zhu, Mohamed Omar Kaseb, Muhammad Zeeshan Sajjad, Nan He, Xuqiang Lu and Wenge Liu
Horticulturae 2024, 10(6), 569; https://doi.org/10.3390/horticulturae10060569 (registering DOI) - 29 May 2024
Abstract
Plant architecture includes traits such as plant height, stem diameter, and branching pattern, which have significant impacts on yield and fruit quality. Polyploidization can bring changes in plant architectural traits in different crops along with other agronomic and biochemical attributes; however, the specific [...] Read more.
Plant architecture includes traits such as plant height, stem diameter, and branching pattern, which have significant impacts on yield and fruit quality. Polyploidization can bring changes in plant architectural traits in different crops along with other agronomic and biochemical attributes; however, the specific physiological and biochemical mechanisms are still unclear. In this study, we utilized five watermelon lines: ‘91E7’, ‘Zhengzhou No. 3’, ‘Fanzu No. 1’, ‘Shenlong’, and ‘Houlv’, along with their corresponding autopolyploid derivatives (diploid, autotriploid, and autotetraploid) to compare plant architecture differences in different polyploidy watermelon plants. The results showed that the growth habits of diploid, triploid, and tetraploid watermelon plants were noticeably different. Triploid and tetraploid watermelon plants had greater stem diameters and larger leaf sizes. The leaf angle was also larger in polyploid watermelons than in their diploid ancestor lines. Although vine length was significantly higher in diploid watermelon, there was no significant difference in node number, indicating that the short vine length was due to the short internodal length. The major differences between diploid and polyploid watermelon plants were found in the branching pattern, as diploid watermelon lines have more branching compared to their polyploid sister lines. Furthermore, we examined the phytohormone content of diploid, triploid, and tetraploid ‘Fanzu No. 1’. The reasons for the selection of this material are its robust growth and profuse branching habit, which cause visible differences among the ploidy levels. Hormone analysis showed distinct variations in abscisic acid in the nodal and stem regions, gibberellin in the auxiliary bud regions, and brassinosteroids in the apical meristematic regions. The correlation coefficient also strongly correlated these hormones with architecture-related traits. Our findings indicated that gibberellin, ABA, and brassinosteroids might be associated with variations in plant architectural traits like branching, vine length, internodal length, stem thickness, and leaf angle among different ploidy levels of watermelon. The exogenous application of GA3 showed a positive effect on branching, whereas ABA showed a negative effect on branching. The application of brassinosteroid at the apical meristem demonstrated its effect on leaf angle, leaf size, and internodal length. The results of this study can provide a theoretical reference and valuable insights into the link between plant architecture and ploidy levels. Full article
(This article belongs to the Special Issue The Role of Plant Growth Regulators in Horticulture)
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23 pages, 3616 KiB  
Systematic Review
Transformers for Remote Sensing: A Systematic Review and Analysis
by Ruikun Wang, Lei Ma, Guangjun He, Brian Alan Johnson, Ziyun Yan, Ming Chang and Ying Liang
Sensors 2024, 24(11), 3495; https://doi.org/10.3390/s24113495 (registering DOI) - 29 May 2024
Abstract
Research on transformers in remote sensing (RS), which started to increase after 2021, is facing the problem of a relative lack of review. To understand the trends of transformers in RS, we undertook a quantitative analysis of the major research on transformers over [...] Read more.
Research on transformers in remote sensing (RS), which started to increase after 2021, is facing the problem of a relative lack of review. To understand the trends of transformers in RS, we undertook a quantitative analysis of the major research on transformers over the past two years by dividing the application of transformers into eight domains: land use/land cover (LULC) classification, segmentation, fusion, change detection, object detection, object recognition, registration, and others. Quantitative results show that transformers achieve a higher accuracy in LULC classification and fusion, with more stable performance in segmentation and object detection. Combining the analysis results on LULC classification and segmentation, we have found that transformers need more parameters than convolutional neural networks (CNNs). Additionally, further research is also needed regarding inference speed to improve transformers’ performance. It was determined that the most common application scenes for transformers in our database are urban, farmland, and water bodies. We also found that transformers are employed in the natural sciences such as agriculture and environmental protection rather than the humanities or economics. Finally, this work summarizes the analysis results of transformers in remote sensing obtained during the research process and provides a perspective on future directions of development. Full article
(This article belongs to the Special Issue Application of Satellite Remote Sensing in Geospatial Monitoring)
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14 pages, 5299 KiB  
Article
Vertebral Bone Density Variations in Scoliotic vs. Non-Scoliotic Juveniles, and Its Implications for Schmorl’s Node Development: A CT-Based Analysis Using the New Mexico Decedent Image Database
by Ellen Shakeshaft, Matteo Borrini and Constantine Eliopoulos
Anatomia 2024, 3(2), 110-123; https://doi.org/10.3390/anatomia3020009 (registering DOI) - 29 May 2024
Abstract
Scoliosis, characterized by an abnormal lateral curvature of the spine, is predominantly idiopathic, underscoring the need to delve into its underlying causes for effective treatment and preventive strategies. This study investigates a potential correlation between scoliosis and Schmorl’s nodes (intervertebral disc herniations) influenced [...] Read more.
Scoliosis, characterized by an abnormal lateral curvature of the spine, is predominantly idiopathic, underscoring the need to delve into its underlying causes for effective treatment and preventive strategies. This study investigates a potential correlation between scoliosis and Schmorl’s nodes (intervertebral disc herniations) influenced by Wolff’s law, which posits that bones adapt to external pressures. We analyzed CT scans from 108 juvenile decedents, including 56 with scoliosis and 52 without. After running multiple statistical tests, there was no significance between the mean bone density when compared to having scoliosis. An independent t-test provided a t-value of 0.041, which, when compared to the original significance level of 0.05, is statistically significant, although weak. When compared to the Bonferroni correction level of 0.008, it throws out the significance to give a result of not being statistically significant. It was the same in the cases of L3 (t = 0.103), L2 (t = 0.084), and L1 (t = 0.053). If compared to the regular significance level of 0.05, T12 (t = 0.012) and T11 (t = 0.042) had weak significance, but that was then excluded when the Bonferroni correction was applied. When looking at any significance of densities in different vertebral regions, the results from a one-way ANOVA (p-value = 0.213) suggest that it is likely that the results are due to random variability or chance, and that there is no statistical significance. With a value of 0.273 from a Chi-squared (χ2)/Fisher’s exact test, it suggests that there is no statistically significant correlation or difference between the variables of scoliosis and Schmorl’s nodes. The general pattern seems to follow that as the spine ascends, the density increases, and this is true in both scoliotic and non-scoliotic individuals. As a whole, it is evident that those with scoliosis have a lower vertebral density than those without, in all of the vertebral regions. There is, however, a weak negative linear relationship between bone density and age in both scoliotic and non-scoliotic individuals. A p-value of −0.229 obtained from a Pearson correlation coefficient analysis in non-scoliotic individuals, as well as a p-value of −0.069 in scoliotic individuals, was obtained. Overall, the findings of this study are comparable to some existing studies on similar topics, but there are few results that hold statistical significance and so this would be interesting to research further, potentially using a different dataset or a larger sample size that is more representative. Full article
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15 pages, 4848 KiB  
Article
Detection Method for Gene Doping in a Mouse Model Expressing Human Erythropoietin from Adeno-Associated Virus Vector-9
by Takehito Sugasawa, Atsushi Hirokawa, Norihiro Otani, Yasuharu Kanki, Kieu DM Nguyen, Tohru Takemasa, Koichi Watanabe, Yoshinori Takeuchi, Naoya Yahagi and Yoichiro Takahashi
Genes 2024, 15(6), 709; https://doi.org/10.3390/genes15060709 (registering DOI) - 29 May 2024
Abstract
With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletics has become a concern. However, there is still room for improvement in gene-doping testing methods, and a robust animal model needs to [...] Read more.
With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletics has become a concern. However, there is still room for improvement in gene-doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9, including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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