The 2023 MDPI Annual Report has
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17 pages, 464 KiB  
Article
Combined Cubature Kalman and Smooth Variable Structure Filtering Based on Multi-Kernel Maximum Correntropy Criterion for the Fully Submerged Hydrofoil Craft
by Hongmin Niu and Sheng Liu
Appl. Sci. 2024, 14(9), 3952; https://doi.org/10.3390/app14093952 (registering DOI) - 06 May 2024
Abstract
This paper introduces a novel filter algorithm termed as an MKMC-CSVSF which combined square-root cubature Kalman (SR-CKF) and smooth variable structure filtering (SVSF) under multi-kernel maximum correntropy criterion (MKMC) for accurately estimating the state of the fully submerged hydrofoil craft (FSHC) under the [...] Read more.
This paper introduces a novel filter algorithm termed as an MKMC-CSVSF which combined square-root cubature Kalman (SR-CKF) and smooth variable structure filtering (SVSF) under multi-kernel maximum correntropy criterion (MKMC) for accurately estimating the state of the fully submerged hydrofoil craft (FSHC) under the influence of uncertainties and multivariate heavy-tailed non-Gaussian noises. By leveraging the precision of the SR-CKF and the robustness of the SVSF against system uncertainties, the MKMC-CSVSF integrates these two methods by introducing a time-varying smooth boundary layer along with multiple fading factors. Furthermore, the MKMC is introduced for the adjustment of kernel bandwidths across different channels to align with the specific noise characteristics of each channel. A fuzzy rule is devised to identify the appropriate kernel bandwidths to ensure filter accuracy without undue complexity. The precision and robustness of state estimation in the face of heavy-tailed non-Gaussian noises are improved by modifying the SR-CKF and the SVSF using a fixed-point approach based on the MKMC. The experimental results validate the efficacy of this algorithm. Full article
(This article belongs to the Section Marine Science and Engineering)
20 pages, 559 KiB  
Review
Ketoacidosis and SGLT2 Inhibitors: A Narrative Review
by Carmela Morace, Giuseppe Lorello, Federica Bellone, Cristina Quartarone, Domenica Ruggeri, Annalisa Giandalia, Giuseppe Mandraffino, Letteria Minutoli, Giovanni Squadrito, Giuseppina T. Russo and Herbert Ryan Marini
Metabolites 2024, 14(5), 264; https://doi.org/10.3390/metabo14050264 (registering DOI) - 06 May 2024
Abstract
An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as [...] Read more.
An acute metabolic complication of diabetes mellitus, especially type 1, is diabetic ketoacidosis (DKA), which is due to an increase in blood ketone concentrations. Sodium/glucose co-transporter-2 inhibitor (SGLT2-i) drugs have been associated with the occurrence of a particular type of DKA defined as euglycemic (euDKA), characterized by glycemic levels below 300 mg/dL. A fair number of euDKA cases in SGLT2-i-treated patients have been described, especially in the last few years when there has been a significant increased use of these drugs. This form of euDKA is particularly insidious because of its latent onset, associated with unspecific symptomatology, until it evolves (progressing) to severe systemic forms. In addition, its atypical presentation can delay diagnosis and treatment. However, the risk of euDKA associated with SGLT2-i drugs remains relatively low, but it is essential to promptly diagnose and manage it to prevent its serious life-threatening complications. In this narrative review, we intended to gather current research evidence on SGLT2i-associated euDKA from randomized controlled trials and real-world evidence studies, its diagnostic criteria and precipitating factors. Full article
(This article belongs to the Special Issue Lipid Metabolism in Obesity and Diabetes, 2nd Edition)
21 pages, 3013 KiB  
Article
Retinoic Acid-Mediated Control of Energy Metabolism is Essential for Lung Branching Morphogenesis
by Hugo Fernandes-Silva, Marco G. Alves, Marcia R. Garcez, Jorge Correia-Pinto, Pedro F. Oliveira, Catarina C. F. Homem and Rute S. Moura
Int. J. Mol. Sci. 2024, 25(9), 5054; https://doi.org/10.3390/ijms25095054 (registering DOI) - 06 May 2024
Abstract
Lung branching morphogenesis relies on intricate epithelial–mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic acid (RA) signaling influences lung proximal­–distal patterning and branching morphogenesis, but its role as a metabolic [...] Read more.
Lung branching morphogenesis relies on intricate epithelial–mesenchymal interactions and signaling networks. Still, the interplay between signaling and energy metabolism in shaping embryonic lung development remains unexplored. Retinoic acid (RA) signaling influences lung proximal­–distal patterning and branching morphogenesis, but its role as a metabolic modulator is unknown. Hence, this study investigates how RA signaling affects the metabolic profile of lung branching. We performed ex vivo lung explant culture of embryonic chicken lungs treated with DMSO, 1 µM RA, or 10 µM BMS493. Extracellular metabolite consumption/production was evaluated by using 1H-NMR spectroscopy. Mitochondrial respiration and biogenesis were also analyzed. Proliferation was assessed using an EdU-based assay. The expression of crucial metabolic/signaling components was examined through Western blot, qPCR, and in situ hybridization. RA signaling stimulation redirects glucose towards pyruvate and succinate production rather than to alanine or lactate. Inhibition of RA signaling reduces lung branching, resulting in a cystic-like phenotype while promoting mitochondrial function. Here, RA signaling emerges as a regulator of tissue proliferation and lactate dehydrogenase expression. Furthermore, RA governs fatty acid metabolism through an AMPK-dependent mechanism. These findings underscore RA’s pivotal role in shaping lung metabolism during branching morphogenesis, contributing to our understanding of lung development and cystic-related lung disorders. Full article
19 pages, 26111 KiB  
Article
Optimization Design of Variable Reluctance Resolver Based on Three-phase Symmetrical Winding
by Xinmin Li, Jiannan Chen and Zhen Zhang
World Electr. Veh. J. 2024, 15(5), 201; https://doi.org/10.3390/wevj15050201 (registering DOI) - 06 May 2024
Abstract
In order to ease the structure and manufacturing process of the variable reluctance (VR) resolver, the three-phase symmetrical single-layer winding commonly used in the stator winding of permanent magnet synchronous motors (PMSM) is applied to the VR resolver in this paper. The proposed [...] Read more.
In order to ease the structure and manufacturing process of the variable reluctance (VR) resolver, the three-phase symmetrical single-layer winding commonly used in the stator winding of permanent magnet synchronous motors (PMSM) is applied to the VR resolver in this paper. The proposed resolver has the same winding direction and number of turns on all teeth. And the non-overlapping distribution of the three-phase windings of the resolver is ensured. For this novel resolver, the resolver-to-digital conversion (RDC) method references the ultra-high-frequency (UHF) signal injection method used when a PMSM is powered off and restarted. Instead of the need for the orthogonal envelope RDC required by conventional resolvers, the absolute position of the rotor can be obtained. In this paper, the prototype of the proposed resolver and the peripheral circuits are fabricated and compared with the position detected by the optical encoder, and the validity of the proposed resolver and the accuracy of the RDC are verified by the results of the comparison experiments. Full article
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12 pages, 5987 KiB  
Article
Detection of In Vivo-Like Cells by a Biosensor Chip Based on Metamaterials in Terahertz Regime
by Lulu Han, Yuchen Wang, Kanglong Chen, Hengyu Gao, Kexin Xia, Qinggang Ge, Jun Yang, Wei Shi and Cunjun Ruan
Biosensors 2024, 14(5), 230; https://doi.org/10.3390/bios14050230 (registering DOI) - 06 May 2024
Abstract
Early diagnosis of diseases, especially cancer, is critical for effective treatment. The unique properties of terahertz technology have attracted attention in this field. However, current terahertz bio-detection methods face challenges due to differences between the test environment and the actual in vivo conditions. [...] Read more.
Early diagnosis of diseases, especially cancer, is critical for effective treatment. The unique properties of terahertz technology have attracted attention in this field. However, current terahertz bio-detection methods face challenges due to differences between the test environment and the actual in vivo conditions. In this study, a novel method is proposed for detecting in vivo-like cells using a biosensor chip composed of metamaterials and a cavity. The cavity has a thickness of ~50 μm. The structure can protect cells from damage and provides a liquid environment like an in vivo state. Through simulation analysis, the metamaterials sensor exhibits a theoretical sensitivity of 0.287 THz/RIU (Refractive Index Unit) with a 50 μm thick analyte. The detection method is experimentally validated using the apoptosis of glioma cells and various cell types. The biosensor investigates the apoptosis of glioma cells under the impact of temozolomide, and the trend of the results was consistent with the Cell Counting Kit-8 method. Furthermore, at a concentration of ~5200 cells/cm2, the experimental results demonstrate that the sensor can distinguish between neurons and glioma cells with a resonance frequency difference of approximately 30 GHz. This research has significant potential for detecting glioma cells and offers an alternative approach to in vivo-like cell detection. Full article
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54 pages, 1162 KiB  
Review
Long COVID in Children, Adults, and Vulnerable Populations: A Comprehensive Overview for an Integrated Approach
by Valeria Calcaterra, Sara Zanelli, Andrea Foppiani, Elvira Verduci, Beatrice Benatti, Roberto Bollina, Francesco Bombaci, Antonio Brucato, Selene Cammarata, Elisa Calabrò, Giovanna Cirnigliaro, Silvia Della Torre, Bernardo Dell’osso, Chiara Moltrasio, Angelo Valerio Marzano, Chiara Nostro, Maurizio Romagnuolo, Lucia Trotta, Valeria Savasi, Valeria Smiroldo and Gianvincenzo Zuccottiadd Show full author list remove Hide full author list
Diseases 2024, 12(5), 95; https://doi.org/10.3390/diseases12050095 (registering DOI) - 06 May 2024
Abstract
Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing [...] Read more.
Long COVID affects both children and adults, including subjects who experienced severe, mild, or even asymptomatic SARS-CoV-2 infection. We have provided a comprehensive overview of the incidence, clinical characteristics, risk factors, and outcomes of persistent COVID-19 symptoms in both children and adults, encompassing vulnerable populations, such as pregnant women and oncological patients. Our objective is to emphasize the critical significance of adopting an integrated approach for the early detection and appropriate management of long COVID. The incidence and severity of long COVID symptoms can have a significant impact on the quality of life of patients and the course of disease in the case of pre-existing pathologies. Particularly, in fragile and vulnerable patients, the presence of PASC is related to significantly worse survival, independent from pre-existing vulnerabilities and treatment. It is important try to achieve an early recognition and management. Various mechanisms are implicated, resulting in a wide range of clinical presentations. Understanding the specific mechanisms and risk factors involved in long COVID is crucial for tailoring effective interventions and support strategies. Management approaches involve comprehensive biopsychosocial assessments and treatment of symptoms and comorbidities, such as autonomic dysfunction, as well as multidisciplinary rehabilitation. The overall course of long COVID is one of gradual improvement, with recovery observed in the majority, though not all, of patients. As the research on long-COVID continues to evolve, ongoing studies are likely to shed more light on the intricate relationship between chronic diseases, such as oncological status, cardiovascular diseases, psychiatric disorders, and the persistent effects of SARS-CoV-2 infection. This information could guide healthcare providers, researchers, and policymakers in developing targeted interventions. Full article
(This article belongs to the Special Issue COVID-19 and Global Chronic Disease 2024: The Post-pandemic Era)
15 pages, 2132 KiB  
Article
Effect of Acrylic Resin on the Protection Performance of Epoxy Coating for Magnesium Alloy
by Xinyu Liu, Yingjun Zhang, Yong Jiang, Mengyang Li, Jianjun Bai and Xiaorong Zhou
Coatings 2024, 14(5), 577; https://doi.org/10.3390/coatings14050577 (registering DOI) - 06 May 2024
Abstract
The low toughness of epoxy resin can influence its shielding performance against a corrosive medium and strength of adhesion to metal surfaces. Extensive efforts have been made to modify epoxy resin. In this research, acrylic resin was synthesized by the solution method, and [...] Read more.
The low toughness of epoxy resin can influence its shielding performance against a corrosive medium and strength of adhesion to metal surfaces. Extensive efforts have been made to modify epoxy resin. In this research, acrylic resin was synthesized by the solution method, and 1 wt.%, 2.5 wt.%, and 5 wt.% were added to epoxy resin (E44 brand) to prepare coatings on the surface of AZ31B magnesium alloy. The effects of acrylic resin on the mechanical and protective properties of epoxy coatings were investigated via experiments measuring impact resistance, flexibility, and adhesion as well as the electrochemical impedance technique. Compared with the pure epoxy coating, the adhesion between the coating and the substrate increases by 1.37 MPa after the addition of 2.5 wt.% acrylic resin. Meanwhile, the pencil hardness has a slight change from 5B to 6B, and the flexibility significantly improves. Therefore, the epoxy coating exhibits enhanced anticorrosive properties after the addition of 2.5 wt.% acrylic resin. Full article
(This article belongs to the Special Issue Advances in Corrosion-Resistant Coatings, 2nd Edition)
25 pages, 1041 KiB  
Article
Is There a Link between Remittances, Capital Formation, Structural Transformation and Economic Growth? A Dynamic Panel Analysis for Latin America under the PVAR Approach
by Eduardo Germán Zurita Moreano, María Gabriela González Bautista, Juan Pablo Vallejo Mata and Víctor Dante Ayaviri-Nina
Economies 2024, 12(5), 109; https://doi.org/10.3390/economies12050109 (registering DOI) - 06 May 2024
Abstract
The literature has mainly focused on analyzing the relationship of remittances with economic growth and social welfare, neglecting more complex aspects where remittances can have relevant implications. To contribute to the literature, the objective of this research is to examine the dynamic relationship [...] Read more.
The literature has mainly focused on analyzing the relationship of remittances with economic growth and social welfare, neglecting more complex aspects where remittances can have relevant implications. To contribute to the literature, the objective of this research is to examine the dynamic relationship between remittances, capital formation, structural transformation and economic growth in 15 Latin American countries during the period 1996–2019. To meet the objective, a panel vector autoregressive regression (PVAR) model was estimated, focusing on the analysis of the impulse-response function and variance decomposition. The results show a positive effect of remittances on economic growth and capital formation and a negative effect of remittances on structural transformation for initial periods and positive for later periods, framing a non-linear relationship. In addition, it was determined that structural transformation does not have a significant impact on economic growth. Finally, it was found that capital formation has a partial positive effect on economic growth. It is concluded that public policies should generate support mechanisms for the efficient channeling of these resources so that they become engines of growth. Full article
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10 pages, 716 KiB  
Article
Understanding Patterns of Adherence to Antifibrotic Treatment in Idiopathic Pulmonary Fibrosis: Insights from an Italian Prospective Cohort Study
by Marica Iommi, Francesca Gonnelli, Martina Bonifazi, Andrea Faragalli, Federico Mei, Marco Pompili, Flavia Carle and Rosaria Gesuita
J. Clin. Med. 2024, 13(9), 2727; https://doi.org/10.3390/jcm13092727 (registering DOI) - 06 May 2024
Abstract
Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014–2021 in newly [...] Read more.
Pirfenidone and Nintedanib have significantly improved the prognosis of patients with idiopathic pulmonary fibrosis (IPF), reducing mortality risk and exacerbations. This study aimed to analyze antifibrotic treatment utilization and its association with clinical outcomes (i.e., acute exacerbation or death) during 2014–2021 in newly diagnosed IPF patients, using Healthcare Utilization Databases of the Marche Region, Italy. Methods: The first 12-month adherence to antifibrotic was estimated using the Proportion of Days Covered (PDC), defining adherence as PDC ≥ 75%. State Sequence Analysis over the initial 52 weeks of treatment was used to identify adherence patterns. The role of adherence patterns on acute exacerbations/death, adjusted by demographic, clinical features, and monthly adherence after the 52-week period (time-dependent variable), was assessed with Cox regression. Results: Among 667 new IPF cases, 296 received antifibrotic prescriptions, with 62.8% being adherent in the first year. Three antifibrotic utilization patterns emerged—high adherence (37.2%), medium adherence (42.5%), and low adherence (20.3%)—with median PDCs of 95.3%, 79.5%, and 18.6%, respectively. These patterns did not directly influence three-year mortality/exacerbation probability, but sustained adherence reduced risk over time. Conclusions: Good adherence was observed in in this population-based study, emphasizing the importance of continuous antifibrotics therapy over time to mitigate adverse outcomes. Full article
(This article belongs to the Special Issue Pulmonary Fibrosis: Therapeutic and Management Strategies)
19 pages, 4842 KiB  
Article
A 4D-Printable Photocurable Resin Derived from Waste Cooking Oil with Enhanced Tensile Strength
by Yan Liu, Meng-Yu Liu, Xin-Gang Fan, Peng-Yu Wang and Shuo-Ping Chen
Molecules 2024, 29(9), 2162; https://doi.org/10.3390/molecules29092162 (registering DOI) - 06 May 2024
Abstract
In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series [...] Read more.
In pursuit of enhancing the mechanical properties, especially the tensile strength, of 4D-printable consumables derived from waste cooking oil (WCO), we initiated the production of acrylate-modified WCO, which encompasses epoxy waste oil methacrylate (EWOMA) and epoxy waste oil acrylate (EWOA). Subsequently, a series of WCO-based 4D-printable photocurable resins were obtained by introducing a suitable diacrylate molecule as the second monomer, coupled with a composite photoinitiator system comprising Irgacure 819 and p-dimethylaminobenzaldehyde (DMAB). These materials were amenable to molding using an LCD light-curing 3D printer. Our findings underscored the pivotal role of triethylene glycol dimethacrylate (TEGDMA) among the array of diacrylate molecules in enhancing the mechanical properties of WCO-based 4D-printable resins. Notably, the 4D-printable material, composed of EWOA and TEGDMA in an equal mass ratio, exhibited nice mechanical strength comparable to that of mainstream petroleum-based 4D-printable materials, boasting a tensile strength of 9.17 MPa and an elongation at break of 15.39%. These figures significantly outperformed the mechanical characteristics of pure EWOA or TEGDMA resins. Furthermore, the EWOA-TEGDMA resin demonstrated impressive thermally induced shape memory performance, enabling deformation and recovery at room temperature and retaining its shape at ‒60 °C. This resin also demonstrated favorable biodegradability, with an 8.34% weight loss after 45 days of soil degradation. As a result, this 4D-printable photocurable resin derived from WCO holds immense potential for the creation of a wide spectrum of high-performance intelligent devices, brackets, mold, folding structures, and personalized products. Full article
(This article belongs to the Special Issue Advances of Oleochemistry and Its Application)
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22 pages, 3801 KiB  
Article
Evaluation of Ground Motion Damage Potential with Consideration of Compound Intensity Measures Using Principal Component Analysis and Canonical Correlation Analysis
by Tingting Liu and Dagang Lu
Buildings 2024, 14(5), 1309; https://doi.org/10.3390/buildings14051309 (registering DOI) - 06 May 2024
Abstract
The primary motivation of this study is to develop a compound intensity measure (IM) to evaluate ground motion damage potential based on principal component analysis (PCA) and canonical correlation analysis (CCA). To illustrate this, this study examines the correlation among intragroup IMs and [...] Read more.
The primary motivation of this study is to develop a compound intensity measure (IM) to evaluate ground motion damage potential based on principal component analysis (PCA) and canonical correlation analysis (CCA). To illustrate this, this study examines the correlation among intragroup IMs and intergroup IMs, as well as the correlation between various IMs and response variables. A compound IM, which can be obtained by a linear combination of ten IMs in the log-scale, is utilized to measure the ground motion damage potential. Elastoplastic, bilinear and hysteretic models are utilized to determine peak deformation and hysteretic energy as the response variables of Single-Degree-of-Freedom (SDOF) systems. On the basis of the SDOF systems, the overall structural damage index is obtained by a nonlinear time–history analysis for two reinforced concrete moment frame systems. It is clear that the developed compound IM shows significantly high-level correlation with structural response. The better the correlations, the more one can measure the earthquake damage potential. A single IM alone inadequately characterizes structural damage, highlighting the necessity of multiple IMs to estimate the possibility of structural damage. Full article
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15 pages, 486 KiB  
Review
Change in Neurocognitive Function in Patients who Receive CAR-T Cell Therapies: A Steep Hill to Climb
by Evlampia Strongyli, Paschalis Evangelidis, Ioanna Sakellari, Maria Gavriilaki and Eleni Gavriilaki
Pharmaceuticals 2024, 17(5), 591; https://doi.org/10.3390/ph17050591 (registering DOI) - 06 May 2024
Abstract
Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of [...] Read more.
Immunotherapy with chimeric antigen receptor T (CAR-T) cell therapies has brought substantial improvement in clinical outcomes in patients with relapsed/refractory B cell neoplasms. However, complications such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) limit the therapeutic efficacy of this treatment approach. ICANS can have a broad range of clinical manifestations, while various scoring systems have been developed for its grading. Cognitive decline is prevalent in CAR-T therapy recipients including impaired attention, difficulty in item naming, and writing, agraphia, and executive dysfunction. In this review, we aim to present the diagnostic methods and tests that have been used for the recognition of cognitive impairment in these patients. Moreover, up-to-date data about the duration of cognitive impairment symptoms after the infusion are presented. More research on the risk factors, pathogenesis, preventive measures, and therapy of neurocognitive impairment is crucial for better outcomes for our patients. Full article
(This article belongs to the Section Biopharmaceuticals)
14 pages, 1022 KiB  
Article
Energy Gain and Carbon Footprint in the Production of Bioelectricity and Wood Pellets in Croatia
by Zdravko Pandur, Marin Bačić, Marijan Šušnjar, Matija Landekić, Mario Šporčić and Iva Ištok
Sustainability 2024, 16(9), 3881; https://doi.org/10.3390/su16093881 (registering DOI) - 06 May 2024
Abstract
The paper presents the process of electricity and thermal energy production in a cogeneration plant and the process of wood pellet production. The aim of this study was to analyze the energy gain—EROI for energy products that are created as a product contained [...] Read more.
The paper presents the process of electricity and thermal energy production in a cogeneration plant and the process of wood pellet production. The aim of this study was to analyze the energy gain—EROI for energy products that are created as a product contained in electrical and thermal energy and the energy contained in wood pellets. According to the obtained results, the production of only electrical energy from wood biomass in a cogeneration plant was not sustainable from an energy point of view, since the obtained electrical energy was only 1.46 times greater than the input wood energy (EROIel = 1.46), while the obtained energy of the produced wood pellets was 4.82 (EROIpel = 4.82). According to the results of equivalent carbon emission, positive net value was achieved only with cogeneration plant and pellet plant working in synergy. Wood is a renewable source of energy, and its economic use can create a significant energy gain. However, due to the trend of using renewable energy sources and the increasing need for electricity, such a process of obtaining electricity is financially profitable, although it is not justified from the energy profitability and environmental sustainability point of view. Full article
19 pages, 4593 KiB  
Article
A Novel 2-Methoxyestradiol Derivative: Disrupting Mitosis-Inhibiting Cell Motility and Inducing Apoptosis in HeLa Cells In Vitro
by Isaac Kinyua Njangiru, Noémi Bózsity-Faragó, Vivien Erzsébet Resch, Gábor Paragi, Éva Frank, György T. Balogh, István Zupkó and Renáta Minorics
Pharmaceutics 2024, 16(5), 622; https://doi.org/10.3390/pharmaceutics16050622 (registering DOI) - 06 May 2024
Abstract
The clinical application of 2-methoxyestradiol (2ME) in cancer therapy has been limited by its low solubility and rapid metabolism. Derivatives of 2ME have been synthesised to enhance bioavailability and decrease hepatic metabolism. Compound 4a, an analog of 2ME, has demonstrated exceptional pharmacological [...] Read more.
The clinical application of 2-methoxyestradiol (2ME) in cancer therapy has been limited by its low solubility and rapid metabolism. Derivatives of 2ME have been synthesised to enhance bioavailability and decrease hepatic metabolism. Compound 4a, an analog of 2ME, has demonstrated exceptional pharmacological activity, in addition to promising pharmacokinetic profile. Our study, therefore, aimed at exploring the anticancer effects of 4a on the cervical cancer cell line, HeLa. Compound 4a exhibited a significant and dose-dependent antimetastatic and antiinvasive impact on HeLa cells, as determined by wound-healing and Boyden chamber assays, respectively. Hoechst/Propidium iodide (HOPI) double staining showcased a substantial induction of apoptosis via 4a, with minimal necrotic effect. Flow cytometry revealed a significant G2/M phase arrest, accompanied by a noteworthy rise in the sub-G1 cell population, indicating apoptosis, 18 h post-treatment. Moreover, a cell-independent tubulin polymerisation assay illustrated compound 4a’s ability to stabilise microtubules by promoting tubulin polymerisation. Molecular modelling experiments depicted that 4a interacts with the colchicine-binding site, nestled between the α and β tubulin dimers. Furthermore, 4a displayed an affinity for binding to and activating ER-α, as demonstrated by the luciferase reporter assay. These findings underscore the potential of 4a in inhibiting HPV18+ cervical cancer proliferation and cellular motility. Full article
(This article belongs to the Special Issue Steroid Derivatives: Design and Pharmaceutical Application)
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57 pages, 5811 KiB  
Review
Naturally Occurring Norsteroids and Their Design and Pharmaceutical Application
by Valery M. Dembitsky
Biomedicines 2024, 12(5), 1021; https://doi.org/10.3390/biomedicines12051021 (registering DOI) - 06 May 2024
Abstract
The main focus of this review is to introduce readers to the fascinating class of lipid molecules known as norsteroids, exploring their distribution across various biotopes and their biological activities. The review provides an in-depth analysis of various modified steroids, including A, B, [...] Read more.
The main focus of this review is to introduce readers to the fascinating class of lipid molecules known as norsteroids, exploring their distribution across various biotopes and their biological activities. The review provides an in-depth analysis of various modified steroids, including A, B, C, and D-norsteroids, each characterized by distinct structural alterations. These modifications, which range from the removal of specific methyl groups to changes in the steroid core, result in unique molecular architectures that significantly impact their biological activity and therapeutic potential. The discussion on A, B, C, and D-norsteroids sheds light on their unique configurations and how these structural modifications influence their pharmacological properties. The review also presents examples from natural sources that produce a diverse array of steroids with distinct structures, including the aforementioned A, B, C, and D-nor variants. These compounds are sourced from marine organisms like sponges, soft corals, and starfish, as well as terrestrial entities such as plants, fungi, and bacteria. The exploration of these steroids encompasses their biosynthesis, ecological significance, and potential medical applications, highlighting a crucial area of interest in pharmacology and natural product chemistry. The review emphasizes the importance of researching these steroids for drug development, particularly in addressing diseases where conventional medications are inadequate or for conditions lacking sufficient therapeutic options. Examples of norsteroid synthesis are provided to illustrate the practical applications of this research. Full article
(This article belongs to the Special Issue Steroids and Their Derivatives as Potential Drugs for Medicine)
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20 pages, 472 KiB  
Article
Are Consumers Equally Willing to Pay More for Brands That Aim for Sustainability, Positive Societal Contribution, and Inclusivity as for Brands That Are Perceived as Exclusive? Generational, Gender, and Country Differences
by Frank Goedertier, Bert Weijters and Joeri Van den Bergh
Sustainability 2024, 16(9), 3879; https://doi.org/10.3390/su16093879 (registering DOI) - 06 May 2024
Abstract
This study explores consumer preferences for brands that emphasize sustainability and inclusivity, and for brands perceived as exclusive and trendy. Consumer data obtained via a large-scale survey involving 24,798 participants across 20 countries and one special administrative region (SAR) are used to understand [...] Read more.
This study explores consumer preferences for brands that emphasize sustainability and inclusivity, and for brands perceived as exclusive and trendy. Consumer data obtained via a large-scale survey involving 24,798 participants across 20 countries and one special administrative region (SAR) are used to understand how willingness to pay (WTP) for these brand types varies globally, accounting for demographic factors like generation, gender, and country. A substantial body of literature highlights growing consumer interest in brands that stand for sustainability and inclusivity, challenging traditional notions that luxury and exclusivity primarily drive brand value. Despite persistent skepticism among some business executives about consumers’ actual versus claimed willingness to spend more for sustainable and inclusive brands, academics and commercial researchers increasingly signal a shift in purchasing behavior that is influenced by socio-ecological factors. This research aims to provide empirical data on consumer WTP across different demographics and countries/regions, thereby contributing to academic discussions and offering insights for managerial decision making. The study frames its investigation around four research questions, to explore how consumers’ WTP for exclusive and inclusive brands varies across generations, genders, and countries/regions. It employs a robust methodological approach, using confirmatory factor analysis (CFA) and structural equation modeling (SEM) to analyze the data. This ensures that the constructs of brand inclusiveness and exclusivity are comparable across diverse cultural contexts. Significant gender, generational, and country/region differences are observed. When comparing generations, the findings indicate that GenZ consumers have a higher WTP for sustainable/inclusive brands (compared to older, GenX, and Baby Boomer generations). Similar patterns are found when considering WTP for exclusive, on-trend brands. In terms of gender, women are observed to have a higher WTP for sustainable/inclusive brands, but a lower WTP for exclusive, on-trend brands compared to men. Finally, compared to consumers originating from certain European countries, we find that consumers living in certain Asian countries/regions have a significantly higher WTP for inclusive and sustainable brands, as well as for exclusive/on-trend brands. The study underscores the complexities of consumer behavior in the global market, highlighting the coexistence of traditional preferences for exclusive, trendy brands and preferences for brands that embrace sustainability and inclusivity. Full article
29 pages, 10645 KiB  
Article
Seeds Priming with Melatonin Improves Root Hydraulic Conductivity of Wheat Varieties under Drought, Salinity, and Combined Stress
by Yuanyuan Fu, Penghui Li, Zhuanyun Si, Shoutian Ma and Yang Gao
Int. J. Mol. Sci. 2024, 25(9), 5055; https://doi.org/10.3390/ijms25095055 (registering DOI) - 06 May 2024
Abstract
Drought and salinity stress reduce root hydraulic conductivity of plant seedlings, and melatonin application positively mitigates stress-induced damage. However, the underlying effect of melatonin priming on root hydraulic conductivity of seedlings under drought–salinity combined remains greatly unclear. In the current report, we investigated [...] Read more.
Drought and salinity stress reduce root hydraulic conductivity of plant seedlings, and melatonin application positively mitigates stress-induced damage. However, the underlying effect of melatonin priming on root hydraulic conductivity of seedlings under drought–salinity combined remains greatly unclear. In the current report, we investigated the influence of seeds of three wheat lines’ 12 h priming with 100 μM of melatonin on root hydraulic conductivity (Lpr) and relevant physiological indicators of seedlings under PEG, NaCl, and PEG + NaCl combined stress. A previous study found that the combined PEG and NaCl stress remarkably reduced the Lpr of three wheat varieties, and its value could not be detected. Melatonin priming mitigated the adverse effects of combined PEG + NaCl stress on Lpr of H4399, Y1212, and X19 to 0.0071 mL·h−1·MPa−1, 0.2477 mL·h−1·MPa−1, and 0.4444 mL·h−1·MPa−1, respectively, by modulating translation levels of aquaporin genes and contributed root elongation and seedlings growth. The root length of H4399, Y1212, and X19 was increased by 129.07%, 141.64%, and 497.58%, respectively, after seeds pre-treatment with melatonin under PEG + NaCl combined stress. Melatonin -priming appreciably regulated antioxidant enzyme activities, reduced accumulation of osmotic regulators, decreased levels of malondialdehyde (MDA), and increased K+ content in stems and root of H4399, Y1212, and X19 under PEG + NaCl stress. The path investigation displayed that seeds primed with melatonin altered the modification of the path relationship between Lpr and leaf area under stress. The present study suggested that melatonin priming was a strategy as regards the enhancement of root hydraulic conductivity under PEG, NaCl, and PEG + NaCl stress, which efficiently enhanced wheat resistant to drought–salinity stress. Full article
(This article belongs to the Special Issue Plant Adaptation Mechanism to Stress)
19 pages, 2883 KiB  
Article
Genetic Variability and Genetic Differentiation of Populations in the Grooved Carpet Shell Clam (Ruditapes decussatus) Based on Intron Polymorphisms
by Carlos Saavedra and David Cordero
Oceans 2024, 5(2), 257-275; https://doi.org/10.3390/oceans5020016 (registering DOI) - 06 May 2024
Abstract
The grooved carpet-shell clam is one of the most economically relevant shellfish species living in the Mediterranean and nearby Atlantic coasts. Previous studies using different types of genetic markers showed a remarkable genetic divergence of the eastern Mediterranean, western Mediterranean, and Atlantic populations, [...] Read more.
The grooved carpet-shell clam is one of the most economically relevant shellfish species living in the Mediterranean and nearby Atlantic coasts. Previous studies using different types of genetic markers showed a remarkable genetic divergence of the eastern Mediterranean, western Mediterranean, and Atlantic populations, but important details remained unclear. Here, data from six nuclear introns scored for restriction fragment size polymorphisms in eight populations that have not been studied before have been pooled for the analysis with data scattered through three previous studies, totaling 32 samples from 29 locations. The results show lower levels of heterozygosity, higher mean number of alleles, and alleles with restricted distribution in the Mediterranean populations, suggesting the existence of a large, isolated population in the eastern Mediterranean at the middle Pleistocene. The data also confirm the similarity of populations from Tunisia to Western Mediterranean populations. Finally, a genetic mosaic is apparent in the Atlantic coasts of the Iberian Peninsula, with a divergence of Rias Baixas populations from more northern populations and Central Portugal populations. The effects of oceanic fronts, seasonal upwellings, river plumes, and/or fishery management operations could explain this and other features of the Atlantic populations. Full article
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9 pages, 374 KiB  
Article
Effect of Fluid Intake on Acute Changes in Plasma Volume: A Randomized Controlled Crossover Pilot Trial
by Janis Schierbauer, Sabrina Sanfilippo, Auguste Grothoff, Ulrich Fehr, Nadine Wachsmuth, Thomas Voit, Paul Zimmermann and Othmar Moser
Metabolites 2024, 14(5), 263; https://doi.org/10.3390/metabo14050263 (registering DOI) - 06 May 2024
Abstract
Plasma volume (PV) undergoes constant and dynamic changes, leading to a large intra-day variability in healthy individuals. Hydration is known to induce PV changes; however, the response to the intake of osmotically different fluids is still not fully understood. In a randomized controlled [...] Read more.
Plasma volume (PV) undergoes constant and dynamic changes, leading to a large intra-day variability in healthy individuals. Hydration is known to induce PV changes; however, the response to the intake of osmotically different fluids is still not fully understood. In a randomized controlled crossover trial, 18 healthy individuals (10 females) orally received an individual amount of an isotonic sodium-chloride (ISO), Ringer (RIN), or glucose (GLU) solution. Hemoglobin mass (Hbmass) was determined with the optimized carbon monoxide re-breathing method. Fluid-induced changes in PV were subsequently calculated based on capillary hemoglobin concentration ([Hb]) and hematocrit (Hct) before and then every 10 minutes until 120 min (t0–120) after the fluid intake and compared to a control trial arm (CON), where no fluid was administered. Within GLU and CON trial arms, no statistically significant differences from baseline until t120 were found (p > 0.05). In the ISO trial arm, PV was significantly increased at t70 (+138 mL, p = 0.01), t80 (+191 mL, p < 0.01), and t110 (+182 mL, p = 0.01) when compared to t0. Moreover, PV in the ISO trial arm was significantly higher at t70 (p = 0.02), t110 (p = 0.04), and t120 (p = 0.01) when compared to the same time points in the CON trial arm. Within the RIN trial arm, PV was significantly higher between t70 and t90 (+183 mL, p = 0.01) and between t110 (+194 mL, p = 0.03) and t120 (+186 mL, p < 0.01) when compared to t0. These results demonstrated that fluids with a higher content of osmotically active particles lead to acute hemodilution, which is associated with a decrease in [Hb] and Hct. These findings underpin the importance of the hydration state on PV and especially on PV constituent levels in healthy individuals. Full article
28 pages, 4708 KiB  
Article
Neural Network Approximation of Helicopter Turboshaft Engine Parameters for Improved Efficiency
by Serhii Vladov, Ruslan Yakovliev, Maryna Bulakh and Victoria Vysotska
Energies 2024, 17(9), 2233; https://doi.org/10.3390/en17092233 (registering DOI) - 06 May 2024
Abstract
The work is devoted to the development of a method for neural network approximation of helicopter turboshaft engine parameters, which is the basis for researching engine energy characteristics to improve efficiency, reliability, and flight safety. It is proposed to use a three-layer direct [...] Read more.
The work is devoted to the development of a method for neural network approximation of helicopter turboshaft engine parameters, which is the basis for researching engine energy characteristics to improve efficiency, reliability, and flight safety. It is proposed to use a three-layer direct propagation neural network with linear neurons in the output layer for training in which the scale conjugate gradient algorithm is modified by introducing a moment coefficient into the analytical expression. This modification helps in calculating new model parameters to avoid falling into a local minimum. The dependence of the energy released during helicopter turboshaft engine compressor rotation on the gas-generator rotor r.p.m. was obtained. This enables the determination of the optimal gas-generator rotor r.p.m. region for a specific type of helicopter turboshaft engine. The optimal ratio of energy consumption and compressor operating efficiency is achieved, thereby ensuring helicopter turboshaft engines’ optimal performance and reliability. Experimental data support the high efficiency of using a three-layer feed-forward neural network with linear neurons in the output layer, trained using a modified scale conjugate gradient algorithm, for approximating parameters of helicopter turboshaft engines compared to the analogues. Specifically, this method better predicts the relations between the energy release during compressor rotation and gas-generator rotor r.p.m. The efficiency coefficient of the proposed method was 0.994, which exceeded that of the closest analogue (0.914) by 1.09 times. Full article
(This article belongs to the Section I2: Energy and Combustion Science)
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11 pages, 7896 KiB  
Case Report
Lichen Amyloidosis in an Atopic Patient Treated with Dupilumab: A New Therapeutic Option
by Benedetta Tirone, Gerardo Cazzato, Francesca Ambrogio, Caterina Foti and Marco Bellino
Diseases 2024, 12(5), 94; https://doi.org/10.3390/diseases12050094 (registering DOI) - 06 May 2024
Abstract
Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been [...] Read more.
Lichen amyloidosis (LA) is a type of cutaneous amyloidosis characterized by brownish hyperkeratotic and itchy papules on the lower leg, back, forearm, or thigh. It is associated with itching and atopic dermatitis (AD) according to an etiopathogenetic mechanism that has not yet been fully elucidated. Currently, the available therapies for this condition include oral antihistamines, laser, cyclosporine, topical corticosteroids, and phototherapy, but, in light of the overlap with AD, Dupilumab may also be indicated. We report the case of a female, 52 years old, who had been suffering from AD and LA for about 27 years. She had lesions attributable to both diseases on the trunk and lower limbs associated with severe itching and had proved resistant to cyclosporine therapy. It was decided to opt for Dupilumab with the induction of 2 fl of 300 mg and maintenance with 1 fl every other week. The therapy proved to be effective, returning a total resolution of both diseases one year after the beginning of the treatment. Dupilumab demonstrated efficacy and safety in the LA related to AD and led to clinical and quality of life improvements in this patient. Therefore, Dupilumab should be considered when treating LA. Further studies should be conducted focusing on the efficacy of the drug on LA (whether or not related to AD), changes in the skin lesions after discontinuation, and the safety of long-term application. Full article
17 pages, 379 KiB  
Article
Can Crisis Periods Affect the ESG Reporting Scope? The Portuguese Euronext Entities Case
by Catarina Cepeda
J. Risk Financial Manag. 2024, 17(5), 191; https://doi.org/10.3390/jrfm17050191 (registering DOI) - 06 May 2024
Abstract
Portuguese companies are increasingly responding to the demand of stakeholders for transparent information about companies’ environmental, social, and governance (ESG) performance by issuing non-financial reports (NFRs). While the number of NFRs published annually has been increasing over the last two decades, their quality [...] Read more.
Portuguese companies are increasingly responding to the demand of stakeholders for transparent information about companies’ environmental, social, and governance (ESG) performance by issuing non-financial reports (NFRs). While the number of NFRs published annually has been increasing over the last two decades, their quality and companies’ ESG performance have been questioned, especially in times of crisis. To address these concerns, several jurisdictions have introduced mandatory NFR rules, such as the European Directive 2014/95/EU. Employing an institutional theory lens, this paper’s research objective is to evaluate whether the last decade’s crises and whether the fact that NFRs became mandatory for certain entities positively affected companies’ activities covered in the ESG reporting scope. We used panel data regression models on 45 listed companies in Portugal during the period 2008–2021. Our results show that the ESG reporting scope is not positively influenced by the transition from NFRs to a mandatory and global financial crisis (GFC). However, the COVID-19 crisis positively affected NFR quality. These results have major implications for practitioners, reflecting the importance of promoting these tools in an organization to improve non-financial performance and companies’ sustainability. Full article
(This article belongs to the Special Issue Financial Reporting and Auditing)
20 pages, 663 KiB  
Review
BCM-7: Opioid-like Peptide with Potential Role in Disease Mechanisms
by Ecem Bolat, Furkan Eker, Selin Yılmaz, Sercan Karav, Emel Oz, Charles Brennan, Charalampos Proestos, Maomao Zeng and Fatih Oz
Molecules 2024, 29(9), 2161; https://doi.org/10.3390/molecules29092161 (registering DOI) - 06 May 2024
Abstract
Bovine milk is an essential supplement due to its rich energy- and nutrient-rich qualities. Caseins constitute the vast majority of the proteins in milk. Among these, β-casein comprises around 37% of all caseins, and it is an important type of casein with several [...] Read more.
Bovine milk is an essential supplement due to its rich energy- and nutrient-rich qualities. Caseins constitute the vast majority of the proteins in milk. Among these, β-casein comprises around 37% of all caseins, and it is an important type of casein with several different variants. The A1 and A2 variants of β-casein are the most researched genotypes due to the changes in their composition. It is accepted that the A2 variant is ancestral, while a point mutation in the 67th amino acid created the A1 variant. The digestion derived of both A1 and A2 milk is BCM-7. Digestion of A2 milk in the human intestine also forms BCM-9 peptide molecule. The opioid-like characteristics of BCM-7 are highlighted for their potential triggering effect on several diseases. Most research has been focused on gastrointestinal-related diseases; however other metabolic and nervous system-based diseases are also potentially triggered. By manipulating the mechanisms of these diseases, BCM-7 can induce certain situations, such as conformational changes, reduction in protein activity, and the creation of undesired activity in the biological system. Furthermore, the genotype of casein can also play a role in bone health, such as altering fracture rates, and calcium contents can change the characteristics of dietary products. The context between opioid molecules and BCM-7 points to a potential triggering mechanism for the central nervous system and other metabolic diseases discussed. Full article
(This article belongs to the Section Food Chemistry)
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