The 2023 MDPI Annual Report has
been released!
 
21 pages, 2392 KiB  
Article
Integrating Machine Learning and MLOps for Wind Energy Forecasting: A Comparative Analysis and Optimization Study on Türkiye’s Wind Data
by Saadin Oyucu and Ahmet Aksöz
Appl. Sci. 2024, 14(9), 3725; https://doi.org/10.3390/app14093725 (registering DOI) - 27 Apr 2024
Abstract
This study conducted a detailed comparative analysis of various machine learning models to enhance wind energy forecasts, including linear regression, decision tree, random forest, gradient boosting machine, XGBoost, LightGBM, and CatBoost. Furthermore, it developed an end-to-end MLOps pipeline leveraging SCADA data from a [...] Read more.
This study conducted a detailed comparative analysis of various machine learning models to enhance wind energy forecasts, including linear regression, decision tree, random forest, gradient boosting machine, XGBoost, LightGBM, and CatBoost. Furthermore, it developed an end-to-end MLOps pipeline leveraging SCADA data from a wind turbine in Türkiye. This research not only compared models using the RMSE metric for selection and optimization but also explored in detail the impact of integrating machine learning with MLOps on the precision of energy production forecasts. It investigated the suitability and efficiency of ML models in predicting wind energy with MLOps integration. The study explored ways to improve LightGBM algorithm performance through hyperparameter tuning and Docker utilization. It also highlighted challenges in speeding up MLOps development and deployment processes. Model performance was assessed using the RMSE metric, conducting a comparative evaluation across different models. The findings revealed that the RMSE values among the regression models ranged from 460 kW to 192 kW. Focusing on enhancing LightGBM, the research decreased the RMSE value to 190.34 kW. Despite facing technical and operational hurdles, the implementation of MLOps was proven to enhance the speed (latency of 9 ms), reliability (through Docker encapsulation), and scalability (using Docker swarm) of machine learning endeavors. Full article
(This article belongs to the Special Issue AutoML: Advances and Applications)
24 pages, 21296 KiB  
Article
Effects of Pd Alloying and Coating on the Galvanic Corrosion between Cu Wire and Bond Pads for a Semiconductor Packaging
by Young-Ran Yoo and Young-Sik Kim
Coatings 2024, 14(5), 544; https://doi.org/10.3390/coatings14050544 (registering DOI) - 27 Apr 2024
Abstract
Semiconductor chips are packaged in a process that involves creating a path to allow for signals to be exchanged with the outside world and ultimately achieving a form to protect against various external environmental conditions such as heat and moisture. The wire bonding [...] Read more.
Semiconductor chips are packaged in a process that involves creating a path to allow for signals to be exchanged with the outside world and ultimately achieving a form to protect against various external environmental conditions such as heat and moisture. The wire bonding type of packaging is a method in which thin metal wires are bonded to pads to create an electrical connection between the chip and the lead frame. An Epoxy Molding Compound (EMC) can be applied to protect semiconductor chips from external environmental conditions such as heat, shock, and moisture. However, EMC contains halogen elements and sulfides and has hydrophilic properties, which can lead to a corrosive environment. The present study aims to evaluate the influence of chloride, which is a contaminant formed during the PCB manufacturing process. To this end, the galvanic corrosion of bonding wire materials Cu wire, Cu wire alloyed with 1% Pd, and Cu wire coated with Pd was investigated. The first ball bond was bonded to the Al pad and the second stitch bond was bonded to the Au pad of the manufacturing process, after which the galvanic corrosion behavior in the semiconductor packaging module specimen was analyzed. A model of galvanic corrosion behavior was also proposed. Full article
(This article belongs to the Special Issue Coatings for Advanced Devices)
14 pages, 270 KiB  
Article
Teachers’ Knowledge and Experiences after the Implementation of an Eating Disorder Prevention Program in the Physical Education Classroom
by Montserrat Monserrat, Ángeles Arjona, Juan Carlos Checa, Joaquín Tarifa and Darío Salguero
Educ. Sci. 2024, 14(5), 467; https://doi.org/10.3390/educsci14050467 (registering DOI) - 27 Apr 2024
Abstract
Since psychological and social factors are especially prominent among the multiple causes of eating disorders, we argue that school, a meeting place among equals and thus a locus for the transmission of values and attitudes, can play an important role in preventing these [...] Read more.
Since psychological and social factors are especially prominent among the multiple causes of eating disorders, we argue that school, a meeting place among equals and thus a locus for the transmission of values and attitudes, can play an important role in preventing these disorders. This article’s main objective is to verify whether the physical education (PE) class can become an arena for transferring and learning that prevent eating disorders, analyzing teachers’ perceptions of the program development “Psychology for Nutrition and Physical Activity in the Prevention of Eating Disorders” (P-NAF) and specifically: (1) analyzing what teachers know and believe about preventing eating disorders; (2) analyzing the relationship between PE sessions and the acquisition of skills for the prevention of eating disorders; and (3) verifying whether the strategies proposed in the program P-NAF help teachers develop skills for the prevention of eating disorders. We conducted semi-structured interviews with physical education teachers (six women and six men) from five educational institutions in southern Spain. We organized their responses into four blocks: (1) self-esteem, (2) social skills, (3) satisfaction with body image, and (4) nutrition. The results show that physical education teachers are poorly trained in eating disorders, in their detection, as well as their treatment. In particular, there is little communication between health professionals and teachers to provide the information needed to develop effective intervention programs. However, after participating in the Psychology for Nutrition and Physical Activity program, the teachers improved both their knowledge and educational tools when it comes to transmitting that knowledge. We conclude that this program is effective in its objectives and that it should be presented more widely to physical education teachers who work directly with young people. Full article
(This article belongs to the Section Curriculum and Instruction)
9 pages, 224 KiB  
Article
Conditions When the Problems of Linear Programming Are Algorithmically Unsolvable
by Viktor Chernov and Vladimir Chernov
Axioms 2024, 13(5), 293; https://doi.org/10.3390/axioms13050293 (registering DOI) - 27 Apr 2024
Abstract
We study the properties of the constructive linear programming problems. The parameters of linear functions in such problems are constructive real numbers. Solving such a problem involves finding the optimal plan with the constructive real number components. We show that it is impossible [...] Read more.
We study the properties of the constructive linear programming problems. The parameters of linear functions in such problems are constructive real numbers. Solving such a problem involves finding the optimal plan with the constructive real number components. We show that it is impossible to have an algorithm that solves an arbitrary constructive real programming problem. Full article
(This article belongs to the Special Issue Advances in Linear Algebra with Applications)
20 pages, 5292 KiB  
Article
Ovine and Caprine Strains of Corynebacterium pseudotuberculosis on Czech Farms—A Comparative Study
by Jirina Markova, Denisa Langova, Vladimir Babak and Iveta Kostovova
Microorganisms 2024, 12(5), 875; https://doi.org/10.3390/microorganisms12050875 (registering DOI) - 27 Apr 2024
Abstract
Caseous lymphadenitis (CLA) is a worldwide disease of small ruminants caused by Corynebacterium pseudotuberculosis, a facultative intracellular pathogen that is able to survive and multiply in certain white blood cells of the host. In this study, 33 strains of C. pseudotuberculosis were [...] Read more.
Caseous lymphadenitis (CLA) is a worldwide disease of small ruminants caused by Corynebacterium pseudotuberculosis, a facultative intracellular pathogen that is able to survive and multiply in certain white blood cells of the host. In this study, 33 strains of C. pseudotuberculosis were isolated from sheep and goats suffering from CLA on nine farms in the Czech Republic. All these strains were tested for their antibiotic susceptibility, ability to form a biofilm and resistance to the effects of commonly used disinfectant agents. To better understand the virulence of C. pseudotuberculosis, the genomes of strains were sequenced and comparative genomic analysis was performed with another 123 genomes of the same species, including ovis and equi biovars, downloaded from the NCBI. The genetic determinants for the virulence factors responsible for adherence and virulence factors specialized for iron uptake and exotoxin phospholipase D were revealed in every analyzed genome. Carbohydrate-Active Enzymes were compared, revealing the presence of genetic determinants encoding exo-α-sialidase (GH33) and the CP40 protein in most of the analyzed genomes. Thirty-three Czech strains of C. pseudotuberculosis were identified as the biovar ovis on the basis of comparative genome analysis. All the compared genomes of the biovar ovis strains were highly similar regardless of their country of origin or host, reflecting their clonal behavior. Full article
(This article belongs to the Special Issue Bacterial Infections and Antimicrobial Resistance in Animals)
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12 pages, 9469 KiB  
Article
Optimized Field Emission from Graphene Sheets with Rare Earth Oxides
by ZhiJianMuCuo Dong, Jianlong Liu, Dayang Wang, Guoling Zhong, Xingyue Xiang and Baoqing Zeng
Coatings 2024, 14(5), 545; https://doi.org/10.3390/coatings14050545 (registering DOI) - 27 Apr 2024
Abstract
This paper demonstrates a simple method to improve the field emission of graphene sheets (GSs) by coating them with thin films of rare earth oxides. The rare earth oxide films are coated on GS using drop coating, without changing the surface morphology, resulting [...] Read more.
This paper demonstrates a simple method to improve the field emission of graphene sheets (GSs) by coating them with thin films of rare earth oxides. The rare earth oxide films are coated on GS using drop coating, without changing the surface morphology, resulting in a remarkable improvement in the field emission properties of GSs. The field emission property of GSs is tunable and can be optimized by applying various rare earth oxide films at the appropriate level. It is found that the turn-on field of GSs is reduced from 4.2 V/mm to 1.7 V/mm by Gd2O3 and to 2.2 V/mm by La2O3. The threshold field of GS is also reduced from 7.8 V/mm to 3.4 V/mm and 4.8 V/mm, respectively. Field emission results indicate that the improvement is due to the low work function surface and more effective emission sites generated around the GS surface after coating. The field emission test and the emission pattern suggest that the field emission performance of GS can be significantly enhanced through the application of La2O3 and Gd2O3 coating, as well as by optimizing the concentration of rare earth oxides in the coating. Hence, the rare earth-coated GS can serve as a potential field emitter. Full article
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14 pages, 3465 KiB  
Article
Characterization of Escherichia coli Strains for Novel Production of Plasmodium ovale Lactate Dehydrogenase
by Jae-Won Choi, Sang-Oh Ha, Yeon-Jun Kim, Jun-Seop Shin, Min-Ji Choi, Si-Eun Yu, Junghun Han, Eun-Ji Park, Kyoung Sik Park and Jung Hoon Kang
Microorganisms 2024, 12(5), 876; https://doi.org/10.3390/microorganisms12050876 (registering DOI) - 27 Apr 2024
Abstract
Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, Plasmodium ovale morphologically resembles P. vivax, resulting in misidentification and confusion in diagnosis, and is responsible for malarial disease relapse [...] Read more.
Malaria is one of the most prevalent diseases worldwide with high incidence and mortality. Among the five species that can infect humans, Plasmodium ovale morphologically resembles P. vivax, resulting in misidentification and confusion in diagnosis, and is responsible for malarial disease relapse due to the formation of hypnozoites. P. ovale receives relatively less attention compared to other major parasites, such as P. falciparum and P. vivax, primarily due to its lower pathogenicity, mortality rates, and prevalence rates. To efficiently produce lactate dehydrogenase (LDH), a major target for diagnosing malaria, this study used three Escherichia coli strains, BL21(DE3), BL21(DE3)pLysS, and Rosetta(DE3), commonly used for recombinant protein production. These strains were characterized to select the optimal strain for P. ovale LDH (PoLDH) production. Gene cloning for recombinant PoLDH production and transformation of the three strains for protein expression were performed. The optimal PoLDH overexpression and washing buffer conditions in nickel-based affinity chromatography were established to ensure high-purity PoLDH. The yields of PoLDH expressed by the three strains were as follows: BL21(DE3), 7.6 mg/L; BL21(DE3)pLysS, 7.4 mg/L; and Rosetta(DE3), 9.5 mg/L. These findings are expected to be highly useful for PoLDH-specific diagnosis and development of antimalarial therapeutics. Full article
(This article belongs to the Special Issue Advances in Microbial Cell Factories, 2nd Edition)
17 pages, 2411 KiB  
Review
Mitochondria-Derived Vesicles, Sterile Inflammation, and Pyroptosis in Liver Cancer: Partners in Crime or Innocent Bystanders?
by Flora Guerra, Francesca Romana Ponziani, Ferdinando Cardone, Cecilia Bucci, Emanuele Marzetti and Anna Picca
Int. J. Mol. Sci. 2024, 25(9), 4783; https://doi.org/10.3390/ijms25094783 (registering DOI) - 27 Apr 2024
Abstract
Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon tissue injury and the ensuing sterile inflammation have also been attributed a role in HCC pathogenesis. Cargoes of extracellular vesicles [...] Read more.
Alterations in cellular signaling, chronic inflammation, and tissue remodeling contribute to hepatocellular carcinoma (HCC) development. The release of damage-associated molecular patterns (DAMPs) upon tissue injury and the ensuing sterile inflammation have also been attributed a role in HCC pathogenesis. Cargoes of extracellular vesicles (EVs) and/or EVs themselves have been listed among circulating DAMPs but only partially investigated in HCC. Mitochondria-derived vesicles (MDVs), a subpopulation of EVs, are another missing link in the comprehension of the molecular mechanisms underlying the onset and progression of HCC biology. EVs have been involved in HCC growth, dissemination, angiogenesis, and immunosurveillance escape. The contribution of MDVs to these processes is presently unclear. Pyroptosis triggers systemic inflammation through caspase-dependent apoptotic cell death and is implicated in tumor immunity. The analysis of this process, together with MDV characterization, may help capture the relationship among HCC development, mitochondrial quality control, and inflammation. The combination of immune checkpoint inhibitors (i.e., atezolizumab and bevacizumab) has been approved as a synergistic first-line systemic treatment for unresectable or advanced HCC. The lack of biomarkers that may allow prediction of treatment response and, therefore, patient selection, is a major unmet need. Herein, we overview the molecular mechanisms linking mitochondrial dysfunction, inflammation, and pyroptosis, and discuss how immunotherapy targets, at least partly, these routes. Full article
(This article belongs to the Special Issue Emerging Role of Immunogenic Cell Death in Cancer Therapy)
16 pages, 2068 KiB  
Technical Note
Fourier Domain Adaptation for the Identification of Grape Leaf Diseases
by Jing Wang, Qiufeng Wu, Tianci Liu, Yuqi Wang, Pengxian Li, Tianhao Yuan and Ziyang Ji
Appl. Sci. 2024, 14(9), 3727; https://doi.org/10.3390/app14093727 (registering DOI) - 27 Apr 2024
Abstract
With the application of computer vision in the field of agricultural disease recognition, the convolutional neural network is widely used in grape leaf disease recognition and has achieved remarkable results. However, most of the grape leaf disease recognition models have the problem of [...] Read more.
With the application of computer vision in the field of agricultural disease recognition, the convolutional neural network is widely used in grape leaf disease recognition and has achieved remarkable results. However, most of the grape leaf disease recognition models have the problem of weak generalization ability. In order to overcome this challenge, this paper proposes an image identification method for grape leaf diseases in different domains based on Fourier domain adaptation. Firstly, Fourier domain adaptation is performed on the labeled source domain data and the unlabeled target domain data. To decrease the gap in distribution between the source domain data and the target domain data, the low-frequency spectrum of the source domain data and the target domain data is swapped. Then, three convolutional neural networks (AlexNet, VGG13, and ResNet101) were used to train the images after style changes and the unlabeled target domain images were classified. The highest accuracy of the three networks can reach 94.6%, 96.7%, and 91.8%, respectively, higher than that of the model without Fourier transform image training. In order to reduce the impact of randomness, when selecting the transformed image, we propose using farthest point sampling to select the image with low feature correlation for the Fourier transform. The final identification result is also higher than the accuracy of the network model trained without transformation. Experimental results showed that Fourier domain adaptation can improve the generalization ability of the model and obtain a more accurate grape leaf disease recognition model. Full article
21 pages, 1871 KiB  
Article
Combination Mechanism of Soil Dissolved Organic Matter and Cu2+ in Vegetable Fields, Forests and Dry Farmland in Lujiang County
by Youru Yao, Jingyi Zhang, Kang Ma, Jing Li, Xin Hu, Yusi Wang, Yuesheng Lin, Fengman Fang and Shiyin Li
Agriculture 2024, 14(5), 684; https://doi.org/10.3390/agriculture14050684 (registering DOI) - 27 Apr 2024
Abstract
Dissolved organic matter (DOM) serves as a critical link in the migration and transformation of heavy metals at the soil–solid interface, influencing the migration behaviour and transformation processes of Cu2+ in soil. There have been studies on the combination mechanisms between DOM [...] Read more.
Dissolved organic matter (DOM) serves as a critical link in the migration and transformation of heavy metals at the soil–solid interface, influencing the migration behaviour and transformation processes of Cu2+ in soil. There have been studies on the combination mechanisms between DOM and Cu2+ in paddy soils. However, the adsorption/complexation and redox processes between DOM and Cu2+ in other agricultural soil types (such as dry farmland and vegetable fields) are unclear. In order to reveal the combination process of DOM with Cu in different agricultural soil types and the dynamic changes in chemical behaviour that occur, this study analysed the variability of DOM components and structure in three soils using three-dimensional fluorescence spectroscopy and X-ray photoelectron spectroscopy. In addition, the priority order of different DOM compounds in combination with Cu and the change process in relation to the Cu valence state in the soil of Lujiang County, Anhui Province, was revealed based on laboratory experiments. The results showed that the composition of soil DOM was mainly composed of humic-like and fulvic-like substances with a clear terrestrial origin and that the organic matter showed a high degree of decomposition characteristics. The results indicated that the composition of soil DOM is mainly composed of humic and fulvic acid-like substances, and they have obvious characteristics of terrestrial origin. In addition, the soil organic matter showed high decomposition characteristics. The complex stability constants (lgKM) of humic acid-like substances with Cu2+ follow the order of forest land (lgKM = 5.21), vegetable land (lgKM = 4.90), and dry farmland (lgKM = 4.88). The lgKM of fulvic acid-like substances with Cu2+ is in the order of dry farmland (lgKM = 4.51) and vegetable land (lgKM = 4.39). Humic acid-like substances in soil DOM combine preferentially with Cu2+, showing a stronger chelating affinity than fulvic acid-like substances. Cu2+ complexes mainly include hydroxyl, phenolic hydroxyl and amino functional groups are included in soil DOM, accompanied by redox reactions. In comparison to dry farmland, the soil DOM in forest and vegetable fields undergoes more intense redox reactions simultaneously with the chelation of Cu2+. Therefore, the application of organic fertilisers to vegetable and forest soils may lead to uncertainties concerning the fate of heavy metals with variable chemical valence. These results contribute to a deeper understanding of the interaction mechanisms between DOM and Cu2+ in agricultural soils. Full article
12 pages, 916 KiB  
Article
Human Impact on the Twenty-Four-Hour Patterns of Steller Sea Lions’ Use of a Haulout in Hokkaido, Japan
by Yuko Chayahara, Yumiko Nakanowataru, Sara Abe, Runa Kurosawa, Sayuki Suma, Nana Murasato, Rin Oyamada, Natsuki Ebashi, Masatoshi Tsunokawa, Mayu Sakurama and Takanori Kooriyama
Animals 2024, 14(9), 1312; https://doi.org/10.3390/ani14091312 (registering DOI) - 27 Apr 2024
Abstract
Steller sea lions (SSLs) migrate to the Hokkaido coast to spend the winter there, leading to conflicts arising with fishermen over herring. This study analyzed the trends in the SSLs’ use of a haulout as a rest site under human pressure. From January [...] Read more.
Steller sea lions (SSLs) migrate to the Hokkaido coast to spend the winter there, leading to conflicts arising with fishermen over herring. This study analyzed the trends in the SSLs’ use of a haulout as a rest site under human pressure. From January to March in 2017, 2018, and 2019, we recorded the SSL behavior at the haulout site off Otaru City, Hokkaido, for 24 h a day using a fixed-point video recorder. We investigated three years of data to analyze the relationships between the SSL behaviors (attendance/landing–entry timings/remaining on land) and herring caught. We also monitored the SSL behaviors during changes in weather conditions and under human pressure. Throughout the three years, the SSLs used the haulout site during harsher weather or under human pressure. In 2017 and 2018, there was a correlation between the herring caught and the maximum number of SSLs on the haulout, but not in 2019. The number of SSLs on the haulout increased from evening to night; most individuals entered the water in the morning. The SSLs probably return to the water around sunrise not only for foraging but also to avoid anthropogenic pressure. The damage caused to the herring fishery by the SSLs was severe, but it is also clear that human pressure changed their behavior in response. Full article
(This article belongs to the Special Issue Research on Relationship between Marine Mammal Ecology and Human)
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15 pages, 3410 KiB  
Article
Physicochemical Properties of Inorganic and Hybrid Hydroxyapatite-Based Granules Modified with Citric Acid or Polyethylene Glycol
by Ewelina Cichoń, Karolina Kosowska, Piotr Pańtak, Joanna P. Czechowska, Aneta Zima and Anna Ślósarczyk
Molecules 2024, 29(9), 2018; https://doi.org/10.3390/molecules29092018 (registering DOI) - 27 Apr 2024
Abstract
This study delves into the physicochemical properties of inorganic hydroxyapatite (HAp) and hybrid hydroxyapatite–chitosan (HAp-CTS) granules, also gold-enriched, which can be used as aggregates in biomicroconcrete-type materials. The impact of granules’ surface modifications with citric acid (CA) or polyethylene glycol (PEG) was assessed. [...] Read more.
This study delves into the physicochemical properties of inorganic hydroxyapatite (HAp) and hybrid hydroxyapatite–chitosan (HAp-CTS) granules, also gold-enriched, which can be used as aggregates in biomicroconcrete-type materials. The impact of granules’ surface modifications with citric acid (CA) or polyethylene glycol (PEG) was assessed. Citric acid modification induced increased specific surface area and porosity in inorganic granules, contrasting with reduced parameters in hybrid granules. PEG modification resulted in a slight increase in specific surface area for inorganic granules and a substantial rise for hybrid granules with gold nanoparticles. Varied effects on open porosity were observed based on granule type. Microstructural analysis revealed increased roughness for inorganic granules post CA modification, while hybrid granules exhibited smoother surfaces. Novel biomicroconcretes, based on α-tricalcium phosphate (α-TCP) calcium phosphate cement and developed granules as aggregates within, were evaluated for compressive strength. Compressive strength assessments showcased significant enhancement with PEG modification, emphasizing its positive impact. Citric acid modification demonstrated variable effects, depending on granule composition. The incorporation of gold nanoparticles further enriched the multifaceted approach to enhancing calcium phosphate-based biomaterials for potential biomedical applications. This study demonstrates the pivotal role of surface modifications in tailoring the physicochemical properties of granules, paving the way for advanced biomicroconcretes with improved compressive strength for diverse biomedical applications. Full article
(This article belongs to the Special Issue Biomaterials Based on Calcium Phosphates and Their Modifications)
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12 pages, 1241 KiB  
Review
Genetic Mechanisms Driving Uterine Leiomyoma Pathobiology, Epidemiology, and Treatment
by Malini S. Ramaiyer, Eslam Saad, Irem Kurt and Mostafa A. Borahay
Genes 2024, 15(5), 558; https://doi.org/10.3390/genes15050558 (registering DOI) - 27 Apr 2024
Abstract
Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly [...] Read more.
Uterine leiomyomas (ULs) are the most common benign tumor of the uterus. They can be associated with symptoms including abnormal uterine bleeding, pelvic pain, urinary frequency, and pregnancy complications. Despite the high prevalence of UL, its underlying pathophysiology mechanisms have historically been poorly understood. Several mechanisms of pathogenesis have been suggested, implicating various genes, growth factors, cytokines, chemokines, and microRNA aberrations. The purpose of this study is to summarize the current research on the relationship of genetics with UL. Specifically, we performed a literature review of published studies to identify how genetic aberrations drive pathophysiology, epidemiology, and therapeutic approaches of UL. With regards to pathophysiology, research has identified MED12 mutations, HMGA2 overexpression, fumarate hydratase deficiency, and cytogenetic abnormalities as contributors to the development of UL. Additionally, epigenetic modifications, such as histone acetylation and DNA methylation, have been identified as contributing to UL tumorigenesis. Specifically, UL stem cells have been found to contain a unique DNA methylation pattern compared to more differentiated UL cells, suggesting that DNA methylation has a role in tumorigenesis. On a population level, genome-wide association studies (GWASs) and epidemiologic analyses have identified 23 genetic loci associated with younger age at menarche and UL growth. Additionally, various GWASs have investigated genetic loci as potential drivers of racial disparities in UL incidence. For example, decreased expression of Cytohesin 4 in African Americans has been associated with increased UL risk. Recent studies have investigated various therapeutic options, including ten-eleven translocation proteins mediating DNA methylation, adenovirus vectors for drug delivery, and “suicide gene therapy” to induce apoptosis. Overall, improved understanding of the genetic and epigenetic drivers of UL on an individual and population level can propel the discovery of novel therapeutic options. Full article
(This article belongs to the Special Issue Genetics and Genomics of Female Reproduction)
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21 pages, 4884 KiB  
Article
Cell Instructive Behavior of Composite Scaffolds in a Co-Culture of Human Mesenchymal Stem Cells and Peripheral Blood Mononuclear Cells
by Georgia-Ioanna Kontogianni, Amedeo Franco Bonatti, Carmelo De Maria, Raasti Naseem, Catarina Coelho, Kalliopi Alpantaki, Aristea Batsali, Charalampos Pontikoglou, Paulo Quadros, Kenneth Dalgarno, Giovanni Vozzi, Chiara Vitale-Brovarone and Maria Chatzinikolaidou
J. Funct. Biomater. 2024, 15(5), 116; https://doi.org/10.3390/jfb15050116 (registering DOI) - 27 Apr 2024
Abstract
The in vitro evaluation of 3D scaffolds for bone tissue engineering in mono-cultures is a common practice; however, it does not represent the native complex nature of bone tissue. Co-cultures of osteoblasts and osteoclasts, without the addition of stimulating agents for monitoring cellular [...] Read more.
The in vitro evaluation of 3D scaffolds for bone tissue engineering in mono-cultures is a common practice; however, it does not represent the native complex nature of bone tissue. Co-cultures of osteoblasts and osteoclasts, without the addition of stimulating agents for monitoring cellular cross-talk, remains a challenge. In this study, a growth factor-free co-culture of human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and human peripheral blood mononuclear cells (hPBMCs) has been established and used for the evaluation of 3D-printed scaffolds for bone tissue engineering. The scaffolds were produced from PLLA/PCL/PHBV polymeric blends, with two composite materials produced through the addition of 2.5% w/v nanohydroxyapatite (nHA) or strontium-substituted nanohydroxyapatite (Sr-nHA). Cell morphology data showed that hPBMCs remained undifferentiated in co-culture, while no obvious differences were observed in the mono- and co-cultures of hBM-MSCs. A significantly increased alkaline phosphatase (ALP) activity and osteogenic gene expression was observed in co-culture on Sr-nHA-containing scaffolds. Tartrate-resistant acid phosphatase (TRAP) activity and osteoclastogenic gene expression displayed significantly suppressed levels in co-culture on Sr-nHA-containing scaffolds. Interestingly, mono-cultures of hPBMCs on Sr-nHA-containing scaffolds indicated a delay in osteoclasts formation, as evidenced from TRAP activity and gene expression, demonstrating that strontium acts as an osteoclastogenesis inhibitor. This co-culture study presents an effective 3D model to evaluate the regenerative capacity of scaffolds for bone tissue engineering, thus minimizing time-consuming and costly in vivo experiments. Full article
(This article belongs to the Special Issue Advanced Biopolymers in Biomedical Application)
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11 pages, 393 KiB  
Article
The Short-Term Efficacy of a Three-Week Pulmonary Rehabilitation Program among Patients with Obstructive Lung Diseases
by Magdalena K. Klimczak, Hubert A. Krzepkowski, Wojciech J. Piotrowski and Adam J. Białas
J. Clin. Med. 2024, 13(9), 2576; https://doi.org/10.3390/jcm13092576 (registering DOI) - 27 Apr 2024
Abstract
Introduction: The recommended duration for pulmonary rehabilitation stands at a minimum of six weeks; however, this stipulation may pose constraints in various countries due to financial limitations imposed by insurance companies and/or national health funds, as is the case in Poland. Consequently, [...] Read more.
Introduction: The recommended duration for pulmonary rehabilitation stands at a minimum of six weeks; however, this stipulation may pose constraints in various countries due to financial limitations imposed by insurance companies and/or national health funds, as is the case in Poland. Consequently, our study endeavors to analyze the short-term outcomes stemming from a condensed three-week PR regimen administered to patients diagnosed with chronic obstructive pulmonary disease (COPD), asthma, and the concomitance of these conditions (COPD-A)—this is an approach that is standard in the rehabilitation protocols endorsed by our national health fund. Methods: Patients diagnosed with COPD, asthma, and COPD-A, referred to the PR program, underwent retrospective analysis to evaluate the short-term efficacy of a three-week PR program. Patients underwent comprehensive assessment by respiratory physicians and rehabilitation consultants, leading to individualized PR programs. Clinical evaluations occurred at program onset and completion. Results: 125 patients participated: 37 COPD, 61 asthma, and 27 COPD-A. Significant improvements were observed in the COPD Assessment Test (CAT), the consensus-based GINA symptom control tool (GINA-SCT), the Modified Medical Research Council (mMRC) scale, forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and the 6-min walk test (6 MWT) distance, as well as in the St. George’s Respiratory Questionnaire (SGRQ) scores. All groups experienced reduced dyspnea severity and improved exercise tolerance. FEV1 and FVC improved in asthma and COPD-A, but not significantly in COPD. Multivariable logistic regression identified predictive factors for PR response. Conclusions: The study supports the short-term efficacy of the three-week PR program in improving clinical outcomes, exercise tolerance, and quality of life in COPD and asthma patients. Tailoring interventions based on predictors of PR response can optimize outcomes. Further research, particularly of the COPD-A group, is needed for individualized approaches. Larger sample sizes are necessary to confirm our findings. Full article
(This article belongs to the Special Issue Advances in Pulmonary Rehabilitation)
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17 pages, 11790 KiB  
Article
Meibum Lipidomic Analysis in Evaporative Dry Eye Subjects
by Jacobo Garcia-Queiruga, Hugo Pena-Verdeal, Belen Sabucedo-Villamarin, Monica Paz-Tarrio, Esteban Guitian-Fernandez, Carlos Garcia-Resua, Eva Yebra-Pimentel and Maria J. Giraldez
Int. J. Mol. Sci. 2024, 25(9), 4782; https://doi.org/10.3390/ijms25094782 (registering DOI) - 27 Apr 2024
Abstract
Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in [...] Read more.
Meibomian Glands (MG) are sebaceous glands responsible for the production of meibum, the main component of the Tear Film Lipid Layer (TFLL). The TFLL facilitates the spread of the tear film over the ocular surface, provides stability and reduces tear evaporation. Alterations in meibum composition lead to different ocular alterations like Meibomian Gland Dysfunction (MGD) and subsequent Evaporative Dry Eye (EDE). The aim of the present study was to investigate the composition and abundance of meibum lipids and their relationship with eyelid margin abnormalities, lipid layer patterns and MG status. The study utilizes a lipidomic approach to identify and quantify lipids in meibum samples using an Elute UHPLC system. This system considered all four dimensions (mass/charge, retention time, ion mobility and intensity) to provide the accurate identification of lipid species. Samples were categorized as healthy or low/no signs of alteration (group 1) or severe signs of alteration or EDE/MGD (group 2). The current investigation found differences in Variable Importance in Projection lipid abundance between both groups for the MGD signs studied. Changes in meibum composition occur and are related to higher scores in eyelid margin hyperaemia, eyelid margin irregularity, MG orifice plugging, MG loss and lipid layer pattern. Full article
(This article belongs to the Special Issue Molecular Advances in Dry Eye Syndrome)
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19 pages, 6804 KiB  
Article
Integrated Transcriptomics and Metabolomics Analysis Reveal the Regulatory Mechanisms Underlying Sodium Butyrate-Induced Carotenoid Biosynthesis in Rhodotorula glutinis
by Xingyu Huang, Jingdie Fan, Caina Guo, Yuan Chen, Jingwen Qiu and Qi Zhang
J. Fungi 2024, 10(5), 320; https://doi.org/10.3390/jof10050320 (registering DOI) - 27 Apr 2024
Abstract
Sodium butyrate (SB) is a histone deacetylase inhibitor that can induce changes in gene expression and secondary metabolite titers by inhibiting histone deacetylation. Our preliminary analysis also indicated that SB significantly enhanced the biosynthesis of carotenoids in the Rhodotorula glutinis strain YM25079, although [...] Read more.
Sodium butyrate (SB) is a histone deacetylase inhibitor that can induce changes in gene expression and secondary metabolite titers by inhibiting histone deacetylation. Our preliminary analysis also indicated that SB significantly enhanced the biosynthesis of carotenoids in the Rhodotorula glutinis strain YM25079, although the underlying regulatory mechanisms remained unclear. Based on an integrated analysis of transcriptomics and metabolomics, this study revealed changes in cell membrane stability, DNA and protein methylation levels, amino acid metabolism, and oxidative stress in the strain YM25079 under SB exposure. Among them, the upregulation of oxidative stress may be a contributing factor for the increase in carotenoid biosynthesis, subsequently enhancing the strain resistance to oxidative stress and maintaining the membrane fluidity and function for normal cell growth. To summarize, our results showed that SB promoted carotenoid synthesis in the Rhodotorula glutinis strain YM25079 and increased the levels of the key metabolites and regulators involved in the stress response of yeast cells. Additionally, epigenetic modifiers were applied to produce fungal carotenoid, providing a novel and promising strategy for the biosynthesis of yeast-based carotenoids. Full article
(This article belongs to the Special Issue New Trends in Yeast Metabolic Engineering)
38 pages, 1099 KiB  
Review
A Review on the Potential Use of Medicinal Plants from the Apiaceae and the Rosaceae Families in Cardiovascular Diseases—Experimental Evidence and Traditional Applications
by Rafał Celiński, Barbara Krzemińska, Anna Grzywa-Celińska, Gabriela Szewczyk and Katarzyna Dos Santos Szewczyk
Appl. Sci. 2024, 14(9), 3728; https://doi.org/10.3390/app14093728 (registering DOI) - 27 Apr 2024
Abstract
Cardiovascular diseases are the leading cause of mortality worldwide. The World Health Organization has presented alarming data stating that in 2019, 17.9 million people globally died due to cardiovascular diseases, constituting 32% of all deaths. Despite increasingly advanced pharmacological and procedural treatment methods [...] Read more.
Cardiovascular diseases are the leading cause of mortality worldwide. The World Health Organization has presented alarming data stating that in 2019, 17.9 million people globally died due to cardiovascular diseases, constituting 32% of all deaths. Despite increasingly advanced pharmacological and procedural treatment methods for these diseases, there is still a quest for new therapeutic possibilities that promise even greater efficacy and safety. The overriding purpose of this study is to provide an insight into the traditional uses of species from the Apiaceae and Rosaceae families as well as to systematize knowledge regarding their scientifically proven cardiovascular activities (animal studies and clinical trials). The review is intended to indicate knowledge gaps for future studies concerning plants used in traditional medicine but without scientific research. As a result, various plant species from both Apiaceae and Rosaceae family have been collected and described based on their study that has proven their effectiveness and uses in cardiovascular diseases. Most of these plants have a hypotensive effect, followed by anti-hyperlipidemic, vasorelaxant, antithrombotic, and diuretic activity. These are the mechanisms that contribute to various cardiovascular diseases, such as heart attack, coronary heart disease, hypertension, and stroke. Full article
18 pages, 1990 KiB  
Article
Cyanotoxin Occurrence and Diversity in 98 Cyanobacterial Blooms from Swedish Lakes and the Baltic Sea
by Caroline Dirks, Paolo Cappelli, Maria Blomqvist, Susanne Ekroth, Malin Johansson, Max Persson, Stina Drakare, Heidi Pekar and Aida Zuberovic Muratovic
Mar. Drugs 2024, 22(5), 199; https://doi.org/10.3390/md22050199 (registering DOI) - 27 Apr 2024
Abstract
The Drinking Water Directive (EU) 2020/2184 includes the parameter microcystin LR, a cyanotoxin, which drinking water producers need to analyze if the water source has potential for cyanobacterial blooms. In light of the increasing occurrences of cyanobacterial blooms worldwide and given that more [...] Read more.
The Drinking Water Directive (EU) 2020/2184 includes the parameter microcystin LR, a cyanotoxin, which drinking water producers need to analyze if the water source has potential for cyanobacterial blooms. In light of the increasing occurrences of cyanobacterial blooms worldwide and given that more than 50 percent of the drinking water in Sweden is produced from surface water, both fresh and brackish, the need for improved knowledge about cyanotoxin occurrence and cyanobacterial diversity has increased. In this study, a total of 98 cyanobacterial blooms were sampled in 2016–2017 and identified based on their toxin production and taxonomical compositions. The surface water samples from freshwater lakes throughout Sweden including brackish water from eight east coast locations along the Baltic Sea were analyzed for their toxin content with LC-MS/MS and taxonomic composition with 16S rRNA amplicon sequencing. Both the extracellular and the total toxin content were analyzed. Microcystin’s prevalence was highest with presence in 82% of blooms, of which as a free toxin in 39% of blooms. Saxitoxins were found in 36% of blooms in which the congener decarbamoylsaxitoxin (dcSTX) was detected for the first time in Swedish surface waters at four sampling sites. Anatoxins were most rarely detected, followed by cylindrospermopsin, which were found in 6% and 10% of samples, respectively. As expected, nodularin was detected in samples collected from the Baltic Sea only. The cyanobacterial operational taxonomic units (OTUs) with the highest abundance and prevalence could be annotated to Aphanizomenon NIES-81 and the second most profuse cyanobacterial taxon to Microcystis PCC 7914. In addition, two correlations were found, one between Aphanizomenon NIES-81 and saxitoxins and another between Microcystis PCC 7914 and microcystins. This study is of value to drinking water management and scientists involved in recognizing and controlling toxic cyanobacteria blooms. Full article
(This article belongs to the Section Marine Toxins)
20 pages, 5688 KiB  
Review
Preparation and Application of Carbon Dots Nanozymes
by Jichuan Kong and Feng Zhou
Antioxidants 2024, 13(5), 535; https://doi.org/10.3390/antiox13050535 (registering DOI) - 27 Apr 2024
Abstract
Carbon dot (CD) nanozymes have enzyme-like activity. Compared with natural enzymes, CD nanozymes offer several advantages, including simple preparation, easy preservation, good stability and recycling, which has made them a popular research topic in various fields. In recent years, researchers have prepared a [...] Read more.
Carbon dot (CD) nanozymes have enzyme-like activity. Compared with natural enzymes, CD nanozymes offer several advantages, including simple preparation, easy preservation, good stability and recycling, which has made them a popular research topic in various fields. In recent years, researchers have prepared a variety of CD nanozymes for biosensing detection, medicine and tumor therapy, and many of them are based on oxidative stress regulation and reactive oxygen species clearance. Particularly to expand their potential applications, elemental doping has been utilized to enhance the catalytic capabilities and other properties of CD nanozymes. This review discusses the prevalent techniques utilized in the synthesis of CD nanozymes and presents the diverse applications of CD nanozymes based on their doping characteristics. Finally, the challenges encountered in the current utilization of CD nanozymes are presented. The latest research progress of synthesis, application and the challenges outlined in the review can help and encourage the researchers for the future research on preparation, application and other related researches of CD nanozymes. Full article
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20 pages, 7266 KiB  
Article
Computational Insights into the Interaction between Neprilysin and α-Bisabolol: Proteolytic Activity against Beta-Amyloid Aggregates in Alzheimer’s Disease
by Jonathan Elias Rodrigues Martins, José Ednésio da Cruz Freire, Francisco Sérgio Lopes Vasconcelos-Filho, Diego da Silva de Almeida, Vânia Marilande Ceccatto and Bruno Lopes de Sousa
Processes 2024, 12(5), 885; https://doi.org/10.3390/pr12050885 (registering DOI) - 27 Apr 2024
Abstract
(1) Background: Alzheimer’s disease (AD) is an irreversible disorder of the central nervous system associated with beta-amyloid protein (Aβ) deposition and accumulation. Current treatments can only act on symptoms and not the etiologic agent. Neprilysin and α-bisabolol have been shown to reduce the [...] Read more.
(1) Background: Alzheimer’s disease (AD) is an irreversible disorder of the central nervous system associated with beta-amyloid protein (Aβ) deposition and accumulation. Current treatments can only act on symptoms and not the etiologic agent. Neprilysin and α-bisabolol have been shown to reduce the aggregation of Aβ, suggesting a potential interaction between both molecules, leading to increased proteolytic activity on Aβ aggregates. (2) Methods: Computational simulations were conducted to explore the interaction between murine neprilysin [NEP(m)] and α-bisabolol and their effects on enzymatic activity. NEP(m) structure was predicted using comparative modeling, and the binding pattern to α-bisabolol and its effects on leu-enkephalin binding were explored through docking calculations and molecular dynamics simulations, respectively. (3) Results: The findings suggest that α-bisabolol stabilizes the Val481-Pro488 segment of NEP2(m), which directly interacts with the peptide substrate, enabling an optimized alignment between the catalytic residue Glu525 and leu-enkephalin. (4) Conclusions: This computational evidence strongly supports the notion that α-bisabolol stabilizes peptide substrates at the NEP2(m) catalytic site, leading to the positive modulation of enzymatic activity. Full article
(This article belongs to the Section Pharmaceutical Processes)
11 pages, 399 KiB  
Article
Calcitonin Gene-Related Peptide Level in Cystic Fibrosis Patients
by Sabina Galiniak, Marek Biesiadecki, Iwona Rościszewska-Żukowska and Marta Rachel
Life 2024, 14(5), 565; https://doi.org/10.3390/life14050565 (registering DOI) - 27 Apr 2024
Abstract
Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the [...] Read more.
Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the gene responsible for encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, there are not many data in the literature about the role of CGRP in CF. The serum level of αCGRP was estimated using the enzyme-linked immunosorbent assay among 64 patients with CF and 31 healthy controls. The αCGRP concentration in the CF group was 62.51 ± 15.45 pg/mL, while in the control group it was 47.43 ± 8.06 pg/mL (p < 0.001). We also compared the level of αCGRP in CF patients according to the type of CFTR mutation. Homozygotes for ΔF508 had higher αCGRP levels than heterozygotes (67.9 ± 10.2 vs. 54.5 ± 18.3 pg/mL, p < 0.01). The level of this neuropeptide was statistically higher in patients with severe disease than in those with mild CF (p = 0.003) when patients were divided into three groups by spirometry results. αCGRP concentration was not correlated with age, sex, clinical parameters, and pulmonary function test results in the study participants. The results of our study suggest a significant increase in the concentration of αCGRP in the serum of patients with CF compared to the control group. This observation opens interesting possibilities for understanding the role of αCGRP in the context of CF pathophysiology. Full article
(This article belongs to the Special Issue Cystic Fibrosis: A Disease with a New Face)
20 pages, 8289 KiB  
Article
Optimizing Solar Heating for Thangka Exhibition Halls: A Case Study in Malkang Cultural Village
by Wenyang Han, Yan Bai, Miao Du, Yujie Tao, Yin Zhang and Qianru Yang
Energies 2024, 17(9), 2091; https://doi.org/10.3390/en17092091 (registering DOI) - 27 Apr 2024
Abstract
With the continuous development of rural revitalization and urbanization in China, the sustainable transformation of traditional rural architecture has become increasingly important. This study takes the Thangka exhibition hall in rural Malkang, Sichuan Province, as the research object and proposes a Thangka exhibition [...] Read more.
With the continuous development of rural revitalization and urbanization in China, the sustainable transformation of traditional rural architecture has become increasingly important. This study takes the Thangka exhibition hall in rural Malkang, Sichuan Province, as the research object and proposes a Thangka exhibition hall architectural design centered around solar heating and aiming for near-zero energy consumption. The research method involves establishing a solar energy system model on the roof of the exhibition hall and utilizing solar angle and area calculation formulas along with simulation software to calculate the optimal installation angle and area of solar panels, with the aim of achieving indoor temperatures that meet Thangka protection requirements while achieving zero-energy heating. Preliminary results indicate that this solar-centric near-zero energy architectural design can effectively promote the increase in indoor temperature through solar thermal conversion. Additionally, through calculation and simulation, the optimal installation angle for the solar panels achieving zero-energy heating is determined to be 24.25 with an azimuth angle of −1.2. The optimum installation area for solar panels is 8.2 square meters in the showroom and 2.7 square meters in the storeroom. Among these, the solar panel area for the Thangka exhibition hall constitutes 4.12% of the total area and is required for maintaining Thangka protection temperature requirements throughout the year, while the solar panel area for the storage room constitutes 1.88% and is also needed for the same purpose. Studying the optimal installation angle and area of solar panels can transform the exhibition hall into a near-zero-energy building, meeting the temperature requirements for Thangka preservation and human thermal comfort, while also achieving optimal economic benefits. This provides guidance and a reference for promoting near-zero-energy buildings in rural areas. Full article
(This article belongs to the Special Issue Development of Energy-Efficient Solutions for Smart Buildings)
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