The 2023 MDPI Annual Report has
been released!
 
19 pages, 4548 KiB  
Review
The Long Journey from Animal Electricity to the Discovery of Ion Channels and the Modelling of the Human Brain
by Luigi Catacuzzeno, Antonio Michelucci and Fabio Franciolini
Biomolecules 2024, 14(6), 684; https://doi.org/10.3390/biom14060684 (registering DOI) - 12 Jun 2024
Abstract
This retrospective begins with Galvani’s experiments on frogs at the end of the 18th century and his discovery of ‘animal electricity’. It goes on to illustrate the numerous contributions to the field of physical chemistry in the second half of the 19th century [...] Read more.
This retrospective begins with Galvani’s experiments on frogs at the end of the 18th century and his discovery of ‘animal electricity’. It goes on to illustrate the numerous contributions to the field of physical chemistry in the second half of the 19th century (Nernst’s equilibrium potential, based on the work of Wilhelm Ostwald, Max Planck’s ion electrodiffusion, Einstein’s studies of Brownian motion) which led Bernstein to propose his membrane theory in the early 1900s as an explanation of Galvani’s findings and cell excitability. These processes were fully elucidated by Hodgkin and Huxley in 1952 who detailed the ionic basis of resting and action potentials, but without addressing the question of where these ions passed. The emerging question of the existence of ion channels, widely debated over the next two decades, was finally accepted and, a decade later, many of them began to be cloned. This led to the possibility of modelling the activity of individual neurons in the brain and then that of simple circuits. Taking advantage of the remarkable advances in computer science in the new millennium, together with a much deeper understanding of brain architecture, more ambitious scientific goals were dreamed of to understand the brain and how it works. The retrospective concludes by reviewing the main efforts in this direction, namely the construction of a digital brain, an in silico copy of the brain that would run on supercomputers and behave just like a real brain. Full article
(This article belongs to the Section Molecular Biophysics)
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16 pages, 374 KiB  
Article
Understanding Paul as an Antitype of Job: The Joban Allusion in 2 Corinthians 12:1–10
by Sanghwan Lee
Religions 2024, 15(6), 720; https://doi.org/10.3390/rel15060720 (registering DOI) - 12 Jun 2024
Abstract
A careful reading of 2 Corinthians 12:1–10 reveals that the passage shares several motifs with the Book of Job: (1) a supernatural adversary, (2) physical suffering, (3) an otherworldly place, (4) social adversity, (5) affluence, and (6) boasting. In light of an audience-critical [...] Read more.
A careful reading of 2 Corinthians 12:1–10 reveals that the passage shares several motifs with the Book of Job: (1) a supernatural adversary, (2) physical suffering, (3) an otherworldly place, (4) social adversity, (5) affluence, and (6) boasting. In light of an audience-critical perspective, this article proposes that the language and imagery in 2 Corinthians 12:1–10 contain a number of allusions that could direct its audience to juxtapose Paul with Job—a well-known righteous figure who demonstrated physical vulnerability but received public vindication from YHWH. According to this reading, the Joban allusion in the Corinthian passage functions as a rhetorical device that defends Paul’s apostolic authority against the super-apostles’ charge that his vulnerability evinces his lack of authority. Full article
(This article belongs to the Section Religions and Theologies)
10 pages, 708 KiB  
Article
Malnutrition and the Post-Acute Sequelae of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Multi-Institutional Population-Based Propensity Score-Matched Analysis
by Cheng-Ya Lee, Yung-Chun Liang, Wan-Hsuan Hsu, Ya-Wen Tsai, Ting-Hui Liu, Po-Yu Huang, Min-Hsiang Chuang, Kuo-Chuan Hung, Mei-Chuan Lee, Tsung Yu, Chih-Cheng Lai, Tzu-Chieh Weng and Jheng-Yan Wu
Life 2024, 14(6), 746; https://doi.org/10.3390/life14060746 (registering DOI) - 12 Jun 2024
Abstract
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health crisis, exacerbating issues like malnutrition due to increased metabolic demands and reduced intake during illness. Malnutrition, a significant risk factor, is linked to worse [...] Read more.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global health crisis, exacerbating issues like malnutrition due to increased metabolic demands and reduced intake during illness. Malnutrition, a significant risk factor, is linked to worse outcomes in patients with COVID-19, such as increased mortality and extended hospital stays. This retrospective cohort study investigated the relationship between malnutrition and clinical outcomes within 90–180 days using data obtained from the TriNetX database. Patients aged >18 years diagnosed with COVID-19 between 1 January 2022, and 31 March 2024 were enrolled in the study. The propensity score-matching (PSM) method was used to match patients with malnutrition (malnutrition group) and those without malnutrition (control group). The primary composite outcome was the cumulative hazard ratio (HR) for post-COVID-19 condition, all-cause hospitalization, and all-cause mortality between 90 days and 180 days after COVID-19 diagnosis. The secondary outcomes were the individual components of the primary outcomes. Two cohorts, each consisting of 15,004 patients with balanced baseline characteristics, were identified using PSM. During the 90–180-day follow-up period, the malnutrition group exhibited a higher incidence of all-cause hospitalization, mortality, or post-COVID-19 condition (HR = 2.315, 95% confidence interval: 2.170–2.471, p < 0.0001). Compared with patients with COVID-19 without malnutrition, those with malnutrition may be associated with a higher risk of adverse clinical outcomes. Full article
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16 pages, 8312 KiB  
Article
Temporin-GHaK Exhibits Antineoplastic Activity against Human Lung Adenocarcinoma by Inhibiting the Wnt Signaling Pathway through miRNA-4516
by Yueli Liu, Hui Liu, Jiaxin Zhang and Yingxia Zhang
Molecules 2024, 29(12), 2797; https://doi.org/10.3390/molecules29122797 (registering DOI) - 12 Jun 2024
Abstract
(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present research aims to broaden the pharmacological potential of GHaK by exploring its antineoplastic activity against human lung adenocarcinoma. [...] Read more.
(1) Background: GHaK is derived from the antimicrobial peptide temporin-GHa by substituting the amino acid H with K to enhance its bactericidal activity. The present research aims to broaden the pharmacological potential of GHaK by exploring its antineoplastic activity against human lung adenocarcinoma. (2) Methods: The cell viability, migration, invasion, apoptosis, and cell cycle of A549 and PC-9 cells were tested after GHaK treatment. miRNA sequencing, RT-PCR, Western blotting, and luciferase reporter gene assay were further performed to reveal the potential mechanism. (3) Results: GHaK significantly suppressed cell viability, migration, and invasion; induced apoptosis; and caused cell cycle arrest in the G2/M and S phase in PC-9 and A549 cells, respectively. The miRNA sequencing results show a total of 161 up-regulated and 115 down-regulated miRNAs. Furthermore, the study identified six up-regulated miRNAs (miR-4516, miR-4284, miR-204-5p, miR-12136, miR-4463, and miR-1296-3p) and their inhibitory effects on the expressions of target genes (Wnt 8B, FZD2, DVL3, and FOSL1) caused by miR-4516 directly interacting with Wnt 8B. Western blotting revealed the down-regulation of p-GSK-3β, along with a decreased expressions of cyclin A1 and CDK2 in A549 cells and cyclin B1 and CDK1 in PC-9 cells. (4) Conclusions: Temporin-GHaK exhibits antineoplastic activity against human lung adenocarcinoma by inhibiting the Wnt signaling pathway through miRNA-4516. Full article
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15 pages, 1654 KiB  
Review
Leveraging Multi-Tissue, Single-Cell Atlases as Tools to Elucidate Shared Mechanisms of Immune-Mediated Inflammatory Diseases
by Anthony K. McLean, Gary Reynolds and Arthur G. Pratt
Biomedicines 2024, 12(6), 1297; https://doi.org/10.3390/biomedicines12061297 (registering DOI) - 12 Jun 2024
Abstract
The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis, and skin psoriasis, albeit only for subsets of individuals with each [...] Read more.
The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis, and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting “nodes” in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour before considering future directions in the field. Full article
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10 pages, 1402 KiB  
Systematic Review
Remimazolam-Induced Anaphylaxis and Cardiovascular Collapse: A Narrative Systematic Review of Eleven Cases
by Jaemoon Lee and Seong-Hyop Kim
Medicina 2024, 60(6), 971; https://doi.org/10.3390/medicina60060971 (registering DOI) - 12 Jun 2024
Abstract
Background and Objectives: Remimazolam, a novel benzodiazepine, is used for procedural sedation and general anesthesia due to its rapid onset and short duration of action. However, remimazolam-induced anaphylaxis (RIA) is a rare but severe complication. This study aimed to analyze RIA characteristics, [...] Read more.
Background and Objectives: Remimazolam, a novel benzodiazepine, is used for procedural sedation and general anesthesia due to its rapid onset and short duration of action. However, remimazolam-induced anaphylaxis (RIA) is a rare but severe complication. This study aimed to analyze RIA characteristics, focusing on cardiovascular collapse, and provide guidelines for safe remimazolam use. Methods: This study conducted a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. Research articles retrieved from PubMed on 26 May 2023, using the keywords ‘remimazolam AND anaphylaxis’ were evaluated based on the inclusion criteria of being written in English and aligning with the World Allergy Organization criteria for anaphylaxis, while studies not meeting these criteria were excluded. All published articles up to the search date were included without any date restrictions. The review analyzed factors such as age, sex, type of anesthesia, remimazolam dose (bolus/continuous), allergic symptoms and sign, epinephrine use, serum tryptase levels, and skin prick tests. Results: Among eleven cases, the mean age was 55.6 ± 19.6 years, with 81.8% male. Hypotension (81.8%) was the most common symptom, followed by bradycardia (54.5%) and desaturation (36.4%). Two patients experienced cardiac arrest. Serum tryptase levels confirmed anaphylaxis in ten cases. Epinephrine was the primary treatment, with intravenous doses ranging from 0.1 mg to 0.3 mg. Conclusions: Vigilance is crucial when administering remimazolam, adhering to recommended dosages, and promptly treating RIA with epinephrine. Further research is needed to understand the risk factors and refine the management strategies. Guidelines for safe remimazolam use are proposed. Full article
(This article belongs to the Section Intensive Care/ Anesthesiology)
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24 pages, 1301 KiB  
Article
Consumption Preferences for Truffles and Truffle-Based Products: An Application of the PLS-SEM Model
by Valentina Rosa Laganà, Fabio Lombardi, Donatella Di Gregorio and Agata Nicolosi
Sustainability 2024, 16(12), 5002; https://doi.org/10.3390/su16125002 (registering DOI) - 12 Jun 2024
Abstract
The truffle is a niche, valuable and ecological product exported and consumed all over the world. However, little is known about consumers’ preferences for truffles and truffle products. This study empirically explores the factors influencing their consumption in Italy. A PLS-SEM model was [...] Read more.
The truffle is a niche, valuable and ecological product exported and consumed all over the world. However, little is known about consumers’ preferences for truffles and truffle products. This study empirically explores the factors influencing their consumption in Italy. A PLS-SEM model was implemented and validated using an extended version of the theory of planned behavior, including consumers’ food-specific curiosity as an additional construct to basic constructs such as attitude, subjective norms and perceived behavioral control. The analysis allowed us to examine and verify the significance of the relationships between the factors and what impact they have on intentions to consume fresh and truffle-based products. The processing concerns of consumers were reached through face-to-face consultation with a semi-structured questionnaire. The results obtained suggested that consumers’ intentions in using truffles involve several factors, such as consumers’ personal experiences, organoleptic characteristics (aroma and taste), food safety, trust in the seller/brand, traceability information, the aspect of green products and, more generally, the protection of the environment and forests. The findings provided novel insights for researchers to understand the aspects of truffle consumption, and also represent a guideline for marketers to develop appropriate marketing tactics to grow the truffle business. Full article
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12 pages, 996 KiB  
Article
Characterizing Complex Spatiotemporal Patterns from Entropy Measures
by Luan Orion Barauna, Rubens Andreas Sautter, Reinaldo Roberto Rosa, Erico Luiz Rempel and Alejandro C. Frery
Entropy 2024, 26(6), 508; https://doi.org/10.3390/e26060508 (registering DOI) - 12 Jun 2024
Abstract
In addition to their importance in statistical thermodynamics, probabilistic entropy measurements are crucial for understanding and analyzing complex systems, with diverse applications in time series and one-dimensional profiles. However, extending these methods to two- and three-dimensional data still requires further development. In this [...] Read more.
In addition to their importance in statistical thermodynamics, probabilistic entropy measurements are crucial for understanding and analyzing complex systems, with diverse applications in time series and one-dimensional profiles. However, extending these methods to two- and three-dimensional data still requires further development. In this study, we present a new method for classifying spatiotemporal processes based on entropy measurements. To test and validate the method, we selected five classes of similar processes related to the evolution of random patterns: (i) white noise; (ii) red noise; (iii) weak turbulence from reaction to diffusion; (iv) hydrodynamic fully developed turbulence; and (v) plasma turbulence from MHD. Considering seven possible ways to measure entropy from a matrix, we present the method as a parameter space composed of the two best separating measures of the five selected classes. The results highlight better combined performance of Shannon permutation entropy (SHp) and a new approach based on Tsallis Spectral Permutation Entropy (Sqs). Notably, our observations reveal the segregation of reaction terms in this SHp×Sqs space, a result that identifies specific sectors for each class of dynamic process, and it can be used to train machine learning models for the automatic classification of complex spatiotemporal patterns. Full article
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18 pages, 867 KiB  
Article
On Least Squares Support Vector Regression for Predicting Mechanical Properties of Steel Rebars
by Renan Bessa, Guilherme Alencar Barreto, David Nascimento Coelho, Elineudo Pinho de Moura and Raphaella Hermont Fonseca Murta
Metals 2024, 14(6), 695; https://doi.org/10.3390/met14060695 (registering DOI) - 12 Jun 2024
Abstract
Aiming at ensuring the quality of the product and reducing the cost of steel manufacturing, an increasing number of studies have been developing nonlinear regression models for the prediction of the mechanical properties of steel rebars using machine learning techniques. Bearing this in [...] Read more.
Aiming at ensuring the quality of the product and reducing the cost of steel manufacturing, an increasing number of studies have been developing nonlinear regression models for the prediction of the mechanical properties of steel rebars using machine learning techniques. Bearing this in mind, we revisit this problem by developing a design methodology that amalgamates two powerful concepts in parsimonious model building: (i) sparsity, in the sense that few support vectors are required for building the predictive model, and (ii) locality, in the sense that simpler models can be fitted to smaller data partitions. In this regard, two regression models based on the Least Squares Support Vector Regression (LSSVR) model are developed. The first one is an improved sparse version of the one introduced in a previous work. The second one is a novel local LSSVR-based regression model. The task of interest is the prediction of four output variables (the mechanical properties YS, UTS, UTS/YS, and PE) based on information about its chemical composition (12 variables) and the parameters of the heat treatment rolling (6 variables). The proposed LSSVR-based regression models are evaluated using real-world data collected from steel rebar manufacturing and compared with the global LSSVR model. The local sparse LSSVR approach was able to consistently outperform the standard single regression model approach in the task of interest, achieving improvements in the average R2 from previous studies: 5.04% for UTS, 5.19% for YS, 1.96% for UTS/YS, and 3.41% for PE. Furthermore, the sparsification of the dataset and the local modeling approach significantly reduce the number of SV operations on average, utilizing 34.0% of the total SVs available for UTS estimation, 44.0% for YS, 31.3% for UTS/YS, and 32.8% for PE. Full article
(This article belongs to the Special Issue Machine Learning Models in Metals)
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16 pages, 1044 KiB  
Article
Development of an LC-HRMS/MS Method for Quantifying Steroids and Thyroid Hormones in Capillary Blood: A Potential Tool for Assessing Relative Energy Deficiency in Sport (RED-S)
by Chiara Tuma, Andreas Thomas, Hans Braun and Mario Thevis
Metabolites 2024, 14(6), 328; https://doi.org/10.3390/metabo14060328 (registering DOI) - 12 Jun 2024
Abstract
Relative energy deficiency in sport (RED-S) is a condition that arises from persistent low energy availability (LEA), which affects the hypothalamic–pituitary axis and results in alterations of several hormones in both male and female athletes. As frequent blood hormone status determinations using venipuncture [...] Read more.
Relative energy deficiency in sport (RED-S) is a condition that arises from persistent low energy availability (LEA), which affects the hypothalamic–pituitary axis and results in alterations of several hormones in both male and female athletes. As frequent blood hormone status determinations using venipuncture are rare in sports practice, microsampling offers promising possibilities for preventing and assessing RED-S. Therefore, this study aimed at developing a liquid chromatography–high-resolution tandem mass spectrometry (LC-HRMS/MS) method for quantifying relevant steroids and thyroid hormones in 30 μL of capillary blood obtained using Mitra® devices with volumetric absorptive microsampling technology (VAMS®). The results of the study showed that all validation criteria were met, including a storage stability of more than 28 days in a frozen state (−18 °C) and 14 days at room temperature (20 °C). The validated assay provided precise (<12%) and accurate (<13%) results for all the target analytes. Furthermore, as a proof of concept, autonomously collected VAMS® samples from 50 female and male, healthy, active adults were analyzed. The sensitivity of all analytes was adequate to quantify the decreased hormone concentrations in the RED-S state, as all authentic samples could be measured accordingly. These findings suggest that self-collected VAMS® samples offer a practical opportunity for regular hormone measurements in athletes and can be used for early RED-S assessment and progress monitoring during RED-S recovery. Full article
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27 pages, 992 KiB  
Article
Natural Disasters and Human Development in Asia–Pacific: The Role of External Debt
by Markus Brueckner, Sudyumna Dahal and Haiyan Lin
J. Risk Financial Manag. 2024, 17(6), 246; https://doi.org/10.3390/jrfm17060246 (registering DOI) - 12 Jun 2024
Abstract
The average country in Asia–Pacific experiences more natural disasters than average countries of other developing regions. This paper presents stylized facts on natural disasters, human development, and external debt in Asia–Pacific. The paper also contains estimates of the effects that natural disasters have [...] Read more.
The average country in Asia–Pacific experiences more natural disasters than average countries of other developing regions. This paper presents stylized facts on natural disasters, human development, and external debt in Asia–Pacific. The paper also contains estimates of the effects that natural disasters have on human development. Controlling for country- and time-fixed effects, the dynamic panel model estimates show that external debt has a mitigating effect on the adverse impacts that natural disasters have on human development; in countries with low external debt-to-GDP ratios, natural disasters significantly decrease the human development index, but not so in countries with high external debt-to-GDP ratios. External debt (i.e., borrowing from abroad) is a financial contract for obtaining resources from abroad (i.e., imports of goods and services). When a country experiencing a natural disaster borrows from abroad to increase imports of goods and services, the population suffers less when a natural disaster strikes. Natural disasters destroy goods and capital (e.g., food, machinery, buildings, and roads) in the countries in which they occur. If imports of goods and services do not increase, then the population has less goods and services to consume following a natural disaster. By increasing imports, which are mirrored on the financial side by an increase in external debt, the population of a country that was struck by a natural disaster can experience consumption smoothing. As the incidence of natural disasters increases globally, a policy recommendation for disaster-prone countries, supported by the empirical results of this paper, is the need for deeper and innovative mechanisms of access to international financing, including reforms in both domestic and international financial systems. The paper’s most significant contribution is the unique lens through which it analyzes the often-studied subject of natural disasters. Rather than looking at disasters as merely adverse events and debt as an unwelcome obligation in isolation, it connects the two and uncovers the paradoxically positive and beneficial role a healthy level of external debt can play in mitigating the adverse effects of these disasters. It provides a fresh perspective, a shift in thinking that may immensely benefit external debt and disaster management policies. Full article
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14 pages, 1973 KiB  
Article
3D Chromatin Alteration by Disrupting β-Catenin/CBP Interaction Is Enriched with Insulin Signaling in Pancreatic Cancer
by Yufan Zhou, Zhijing He, Tian Li, Lavanya Choppavarapu, Xiaohui Hu, Ruifeng Cao, Gustavo W. Leone, Michael Kahn and Victor X. Jin
Cancers 2024, 16(12), 2202; https://doi.org/10.3390/cancers16122202 (registering DOI) - 12 Jun 2024
Abstract
The therapeutic potential of targeting the β-catenin/CBP interaction has been demonstrated in a variety of preclinical tumor models with a small molecule inhibitor, ICG-001, characterized as a β-catenin/CBP antagonist. Despite the high binding specificity of ICG-001 for the N-terminus of CBP, this β-catenin/CBP [...] Read more.
The therapeutic potential of targeting the β-catenin/CBP interaction has been demonstrated in a variety of preclinical tumor models with a small molecule inhibitor, ICG-001, characterized as a β-catenin/CBP antagonist. Despite the high binding specificity of ICG-001 for the N-terminus of CBP, this β-catenin/CBP antagonist exhibits pleiotropic effects. Our recent studies found global changes in three-dimensional (3D) chromatin architecture in response to disruption of the β-catenin/CBP interaction in pancreatic cancer cells. However, an understanding of how the functional crosstalk between the antagonist and the β-catenin/CBP interaction affects changes in 3D chromatin architecture and, thereby, gene expression and downstream effects remains to be elucidated. Here, we perform Hi-C analyses on canonical and patient-derived pancreatic cancer cells before and after treatment with ICG-001. In addition to global alteration of 3D chromatin domains, we unexpectedly identify insulin signaling genes enriched in the altered chromatin domains. We further demonstrate that the chromatin loops associated with insulin signaling genes are significantly weakened after ICG-001 treatment. We finally elicit the deletion of a looping of IRS1—a key insulin signaling gene—significantly impeding pancreatic cancer cell growth, indicating that looping-mediated insulin signaling might act as an oncogenic pathway to promote pancreatic cancer progression. Our work shows that targeting aberrant insulin chromatin looping in pancreatic cancer might provide a therapeutic benefit. Full article
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17 pages, 3956 KiB  
Article
Investigating the Free Volumes as Nanospaces in Human Stratum Corneum Lipid Bilayers Using Positron Annihilation Lifetime Spectroscopy (PALS)
by Krystyna Mojsiewicz-Pieńkowska, Dagmara Bazar, Jacek Filipecki and Kordian Chamerski
Int. J. Mol. Sci. 2024, 25(12), 6472; https://doi.org/10.3390/ijms25126472 (registering DOI) - 12 Jun 2024
Abstract
This work is the first one that provides not only evidence for the existence of free volumes in the human stratum corneum but also focuses on comparing these experimental data, obtained through the unique positron annihilation lifetime spectroscopy (PALS) method, with theoretical values [...] Read more.
This work is the first one that provides not only evidence for the existence of free volumes in the human stratum corneum but also focuses on comparing these experimental data, obtained through the unique positron annihilation lifetime spectroscopy (PALS) method, with theoretical values published in earlier works. The mean free volume of 0.269 nm was slightly lower than the theoretical value of 0.4 nm. The lifetime τ3 (1.83 ns with a coefficient of variation CV of 3.21%) is dependent on the size of open sites in the skin. This information was used to calculate the free volume radius R (0.269 nm with CV 2.14%), free volume size Vf (0.081 nm3 with CV 4.69%), and the intensity I3 (9.01% with CV 10.94%) to estimate the relative fractional free volume fv (1.32 a.u. with CV 13.68%) in human skin ex vivo. The relation between the lifetime of o-Ps (τ3) and the radius of free volume (R) was formulated using the Tao–Eldrup model, which assumes spherical voids and applies to sites with radii smaller than 1 nm. The results indicate that PALS is a powerful tool for confirming the existence of free volumes and determining their size. The studies also focused on describing the probable locations of these nanospaces in SC lipid bilayers. According to the theory, these play an essential role in dynamic processes in biological systems, including the diffusion of low-molecular-weight hydrophobic and moderately hydrophilic molecules. The mechanism of their formation has been determined by the molecular dynamics of the lipid chains. Full article
(This article belongs to the Collection Feature Papers in “Molecular Biology”)
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23 pages, 3508 KiB  
Article
Optic Disc Segmentation in Human Retina Images Using a Meta Heuristic Optimization Method and Disease Diagnosis with Deep Learning
by Hamida Almeshrky and Abdulkadir Karacı
Appl. Sci. 2024, 14(12), 5103; https://doi.org/10.3390/app14125103 (registering DOI) - 12 Jun 2024
Abstract
Glaucoma is a common eye disease that damages the optic nerve and leads to loss of vision. The disease shows few symptoms in the early stages, making its identification a complex task. To overcome the challenges associated with this task, this study aimed [...] Read more.
Glaucoma is a common eye disease that damages the optic nerve and leads to loss of vision. The disease shows few symptoms in the early stages, making its identification a complex task. To overcome the challenges associated with this task, this study aimed to tackle the localization and segmentation of the optic disc, as well as the classification of glaucoma. For the optic disc segmentation, we propose a novel metaheuristic approach called Grey Wolf Optimization (GWO). Two different approaches are used for glaucoma classification: a one-stage approach, in which the whole image without cropping is used for classification, and a two-stage approach. In the two-stage approach, the optic disc region is detected using the You Only Look Once (YOLO) detection algorithm. Once the optic disc region of interest (ROI) is identified, glaucoma classification is performed using pre-trained convolutional neural networks (CNNs) and vision transformation techniques. In addition, both the one-stage and the two-stage approaches are applied in combination with the pre-trained CNN using the Random Forest algorithm. In segmentation, GWO achieved an average sensitivity of 96.04%, a specificity of 99.58%, an accuracy of 99.39%, a DICE coefficient of 94.15%, and a Jaccard index of 90.4% on the Drishti-GS dataset. For classification, the proposed method achieved remarkable results with a high-test accuracy of 100% and 88.18% for hold-out validation and three-fold cross-validation for the Drishti-GS dataset, and 96.15% and 93.84% for ORIGA with hold-out and five-fold cross-validation, respectively. Comparing the results with previous studies, the proposed CNN model outperforms them. In addition, the use of the Swin transformer shows its effectiveness in classifying glaucoma in different subsets of the data. Full article
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22 pages, 11192 KiB  
Article
Identification and Characterization of Critical Processing Parameters in the Fabrication of Double-Emulsion Poly(lactic-co-glycolic) Acid Microparticles
by Elizabeth R. Bentley, Stacia Subick, Michael Pezzillo, Stephen C. Balmert, Aidan Herbert and Steven R. Little
Pharmaceutics 2024, 16(6), 796; https://doi.org/10.3390/pharmaceutics16060796 (registering DOI) - 12 Jun 2024
Abstract
In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved [...] Read more.
In the past several decades, polymeric microparticles (MPs) have emerged as viable solutions to address the limitations of standard pharmaceuticals and their corresponding delivery methods. While there are many preclinical studies that utilize polymeric MPs as a delivery vehicle, there are limited FDA-approved products. One potential barrier to the clinical translation of these technologies is a lack of understanding with regard to the manufacturing process, hindering batch scale-up. To address this knowledge gap, we sought to first identify critical processing parameters in the manufacturing process of blank (no therapeutic drug) and protein-loaded double-emulsion poly(lactic-co-glycolic) acid MPs through a quality by design approach. We then utilized the design of experiments as a tool to systematically investigate the impact of these parameters on critical quality attributes (e.g., size, surface morphology, release kinetics, inner occlusion size, etc.) of blank and protein-loaded MPs. Our results elucidate that some of the most significant CPPs impacting many CQAs of double-emulsion MPs are those within the primary or single-emulsion process (e.g., inner aqueous phase volume, solvent volume, etc.) and their interactions. Furthermore, our results indicate that microparticle internal structure (e.g., inner occlusion size, interconnectivity, etc.) can heavily influence protein release kinetics from double-emulsion MPs, suggesting it is a crucial CQA to understand. Altogether, this study identifies several important considerations in the manufacturing and characterization of double-emulsion MPs, potentially enhancing their translation. Full article
(This article belongs to the Section Nanomedicine and Nanotechnology)
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32 pages, 2880 KiB  
Systematic Review
Enteric Infection-Associated Reactive Arthritis: A Systematic Review and Meta-Analysis
by Darya Shafiee, Zhandos Salpynov, Arnur Gusmanov, Yerkhanat Khuanbai, Zhussipbek Mukhatayev and Jeannette Kunz
J. Clin. Med. 2024, 13(12), 3433; https://doi.org/10.3390/jcm13123433 (registering DOI) - 12 Jun 2024
Abstract
Background. The objective of this systematic review and meta-analysis was to estimate the proportions of individuals infected with Campylobacter, Escherichia, Salmonella, Shigella, or Yersinia who develop reactive arthritis. Methods. A systematic review was conducted, encompassing English-language articles published before [...] Read more.
Background. The objective of this systematic review and meta-analysis was to estimate the proportions of individuals infected with Campylobacter, Escherichia, Salmonella, Shigella, or Yersinia who develop reactive arthritis. Methods. A systematic review was conducted, encompassing English-language articles published before January 2024, sourced from the Embase, PubMed, Scopus, and Web of Science databases. This review included observational studies that reported the occurrence of reactive arthritis (ReA) among patients with Campylobacter, Escherichia, Salmonella, Shigella, or Yersinia infections. Data extraction was carried out independently by two reviewers. Subsequently, a random-effects meta-analysis was performed, with heterogeneity assessed using the I2 value. Additionally, meta-regression was employed to investigate the potential influence of study-level variables on the observed heterogeneity. Results. A total of 87 studies were identified; 23 reported on ReA development after Campylobacter infection, 7 reported on ReA after Escherichia infection, 30 reported ReA onset after salmonellosis, 14 reported ReA after shigellosis, and 13 reported ReA after Yersinia infection. The proportion of Campylobacter patients who developed ReA was 0.03 (95% CI [0.01, 0.06], I2 = 97.62%); the proportion of Escherichia patients who developed ReA was 0.01 (95% CI [0.00, 0.06], I2 = 92.78%); the proportion of Salmonella patients was 0.04 (95% CI [0.02, 0.08], I2 = 97.67%); the proportion of Shigella patients was 0.01 (95% CI [0.01, 0.03], I2 = 90.64%); and the proportion of Yersinia patients who developed ReA was 0.05 (95% CI [0.02, 0.13], I2 = 96%). Conclusion. A significant proportion of Salmonella, Shigella, and Yersinia cases resulted in ReA. Nonetheless, it is important to interpret the findings cautiously due to the substantial heterogeneity observed between studies. Full article
(This article belongs to the Section Immunology)
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13 pages, 1215 KiB  
Article
Antiviral Activities of Mastoparan-L-Derived Peptides against Human Alphaherpesvirus 1
by Liana Costa Pereira Vilas Boas, Danieli Fernanda Buccini, Rhayfa Lorrayne Araújo Berlanda, Bruno de Paula Oliveira Santos, Mariana Rocha Maximiano, Luciano Morais Lião, Sónia Gonçalves, Nuno C. Santos and Octávio Luiz Franco
Viruses 2024, 16(6), 948; https://doi.org/10.3390/v16060948 (registering DOI) - 12 Jun 2024
Abstract
Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective [...] Read more.
Human alphaherpesvirus 1 (HSV-1) is a significantly widespread viral pathogen causing recurrent infections that are currently incurable despite available treatment protocols. Studies have highlighted the potential of antimicrobial peptides sourced from Vespula lewisii venom, particularly those belonging to the mastoparan family, as effective against HSV-1. This study aimed to demonstrate the antiviral properties of mastoparans, including mastoparan-L [I5, R8], mastoparan-MO, and [I5, R8] mastoparan, against HSV-1. Initially, Vero cell viability was assessed in the presence of these peptides, followed by the determination of antiviral activity, mechanism of action, and dose-response curves through plaque assays. Structural analyses via circular dichroism and nuclear magnetic resonance were conducted, along with evaluating membrane fluidity changes induced by [I5, R8] mastoparan using fluorescence-labeled lipid vesicles. Cytotoxic assays revealed high cell viability (>80%) at concentrations of 200 µg/mL for mastoparan-L and mastoparan-MO and 50 µg/mL for [I5, R8] mastoparan. Mastoparan-MO and [I5, R8] mastoparan exhibited over 80% HSV-1 inhibition, with up to 99% viral replication inhibition, particularly in the early infection stages. Structural analysis indicated an α-helical structure for [I5, R8] mastoparan, suggesting effective viral particle disruption before cell attachment. Mastoparans present promising prospects for HSV-1 infection control, although further investigation into their mechanisms is warranted. Full article
(This article belongs to the Special Issue Antiviral Peptide)
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16 pages, 6124 KiB  
Article
Structural Optimization of Scarfing Machine with Acceleration Profile and Multi-Objective Genetic Algorithm Approach
by Sangbin Lee, Yoonjae Lee, Byeonghui Park and Changwoo Lee
Machines 2024, 12(6), 398; https://doi.org/10.3390/machines12060398 (registering DOI) - 12 Jun 2024
Abstract
Scarfing is a type of flame treatment used to improve the quality of metal generated during steelmaking. It employs the principles of gas cutting to remove impurities and defects. Due to the high-temperature conditions and the need for uniform metal treatment, mechanical scarfing [...] Read more.
Scarfing is a type of flame treatment used to improve the quality of metal generated during steelmaking. It employs the principles of gas cutting to remove impurities and defects. Due to the high-temperature conditions and the need for uniform metal treatment, mechanical scarfing performed via a frame is preferred over manual hand scarfing. To achieve stable mechanical scarfing, a properly designed frame is essential. Generally, while using more material can create stable equipment, it also increases costs. Therefore, this study proposed a design method that selects an acceleration profile to minimize the shock on the frame during scarfing equipment operation while using a multi-objective genetic algorithm to minimize weight and maximize rigidity. Because modifying existing scarfing equipment based on the optimization results would incur additional costs and time, pre-optimizing through simulation before equipment fabrication is crucial. Optimization was achieved via the dimensional optimization of the existing frame equipment. As a result, the weight of each part and the deformation decreased by an average of 17.05 kg and 3.93%, respectively. Full article
(This article belongs to the Special Issue Optimization and Design of Compliant Mechanisms)
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17 pages, 5085 KiB  
Article
Effect of Chemical Composition of Metal–Organic Crosslinker on the Properties of Fracturing Fluid in High-Temperature Reservoir
by Shenglong Shi, Jinsheng Sun, Shanbo Mu, Kaihe Lv, Jingping Liu, Yingrui Bai, Jintang Wang, Xianbin Huang, Jiafeng Jin and Jian Li
Molecules 2024, 29(12), 2798; https://doi.org/10.3390/molecules29122798 (registering DOI) - 12 Jun 2024
Abstract
To investigate the effect of the chemical composition of a metal–organic crosslinker on the performances of fracturing fluid in high-temperature conditions, four zirconium (Zr) crosslinkers and one aluminum–zirconium (Al-Zr) crosslinker with a polyacrylamide were used. The crosslinkers possessed the same Zr concentration, but [...] Read more.
To investigate the effect of the chemical composition of a metal–organic crosslinker on the performances of fracturing fluid in high-temperature conditions, four zirconium (Zr) crosslinkers and one aluminum–zirconium (Al-Zr) crosslinker with a polyacrylamide were used. The crosslinkers possessed the same Zr concentration, but they differed in component amounts and the order of the addition of the crosslinker components, leading to different chemical compositions in the crosslinkers. The fracturing fluids prepared by different tested crosslinkers were compared in terms of properties of rheological behavior, sand-carrying ability, microstructure, and gel breaking characteristics. The results showed that the fracturing fluids prepared by zirconium lactic acid, ethanediamine, and sorbitol crosslinkers offered the slowest viscosity development and highest final viscosity compared to the zirconium lactic acid crosslinker and the zirconium lactic acid and ethanediamine crosslinker. The zirconium sorbitol, lactic acid, and ethanediamine crosslinker exhibited a faster crosslinking rate and a higher final viscosity than the zirconium lactic acid, ethanediamine, and sorbitol crosslinker; the crosslinker showed crosslinking density and crosslinking reactivity, resulting in more crosslinking sites and a higher strength in the fracturing fluid. The Al-Zr-based crosslinker possessed better properties in temperature and shear resistance, viscoelasticity, shear recovery, and sand-carrying ability than the Zr-based crosslinker due to the synergistic crosslinking effect of aluminum and zirconium ions. The tertiary release gelation mechanism of the Al-Zr-based fracturing fluid achieved a temperature resistance performance in the form of continuous crosslinking, avoiding the excessive crosslinking dehydration and reducing viscosity loss caused by early shear damage. These results indicated that the chemical compositions of metal–organic crosslinkers were important factors in determining the properties of fracturing fluids. Therefore, the appropriate type of crosslinker could save costs without adding the additional components required for high-temperature reservoirs. Full article
(This article belongs to the Section Macromolecular Chemistry)
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11 pages, 553 KiB  
Article
Synergistic Effects of Combined Flavourzyme and Floating Electrode–Dielectric Barrier Discharge Plasma on Reduction of Escherichia coli Biofilms in Squid (Todarodes pacificus)
by So Hee Kim, Pantu Kumar Roy and Shin Young Park
Microorganisms 2024, 12(6), 1188; https://doi.org/10.3390/microorganisms12061188 (registering DOI) - 12 Jun 2024
Abstract
This study investigated the synergistic effect of combining flavourzyme, a natural enzyme, and floating electrode–dielectric barrier discharge (FE-DBD) plasma (1.1 kV, 43 kHz, N2 1.5 m/s) treatment, a non-thermal decontamination technology, against Escherichia coli biofilms in squid. E. coli (ATCC 35150 and ATCC [...] Read more.
This study investigated the synergistic effect of combining flavourzyme, a natural enzyme, and floating electrode–dielectric barrier discharge (FE-DBD) plasma (1.1 kV, 43 kHz, N2 1.5 m/s) treatment, a non-thermal decontamination technology, against Escherichia coli biofilms in squid. E. coli (ATCC 35150 and ATCC 14301) biofilms were formed on the surface of squid and treated with different minimum inhibitory concentrations (MICs) of flavourzyme (1/8; 31.25 μL/mL, 1/4; 62.5 μL/mL, 2/4; 125 μL/mL, and 3/4 MIC; 250 μL/mL) and FE-DBD plasma (5, 10, 30, and 60 min). Independently, flavourzyme and FE-DBD plasma treatment decreased by 0.26–1.71 and 0.19–1.03 log CFU/cm2, respectively. The most effective synergistic combination against E. coli biofilms was observed at 3/4 MIC flavourzyme + 60 min FE-DBD plasma exposure, resulting in a reduction of 1.55 log CFU/cm2. Furthermore, the combined treatment exhibited higher efficacy in E. coli biofilm inactivation in squid compared to individual treatments. The pH values of the synergistic combinations were not significantly different from those of the untreated samples. The outcomes indicate that the combined treatment with flavourzyme and FE-DBD plasma can effectively provide effective control of E. coli biofilms without causing pH changes in squid. Therefore, our study suggests a new microbial control method for microbial safety in the seafood industry. Full article
(This article belongs to the Special Issue Advance Research on Bacterial Biofilm)
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12 pages, 326 KiB  
Article
The Influence of Kindergarten Environment on the Development of Preschool Children’s Physical Fitness
by Alice Haav, Leila Oja and Jaanika Piksööt
Int. J. Environ. Res. Public Health 2024, 21(6), 761; https://doi.org/10.3390/ijerph21060761 (registering DOI) - 12 Jun 2024
Abstract
The aim of this research is to find out to what extent the special qualifications of physical education teachers and the physical environment of kindergartens influence the physical development of preschoolers. Forty-four kindergartens across Estonia participated in the study, half of which had [...] Read more.
The aim of this research is to find out to what extent the special qualifications of physical education teachers and the physical environment of kindergartens influence the physical development of preschoolers. Forty-four kindergartens across Estonia participated in the study, half of which had a physical education teacher (PEt), whereas the remaining 22 kindergartens were taught by non-qualified kindergarten teachers (NoPEt). Six Eurofit fitness tests were used to assess the physical development of children (n = 704; aged 6–7 years old, with an average age of 6.55 ± 0.5 years). An analysis of variance was used to compare the mean values of the fitness test results of the two groups. Linear regression analysis was applied to clarify the influence of individual and environmental factors on children’s fitness scores. In kindergartens where the position of a PEt had been created, the results of children’s physical fitness were statistically significantly better, more specifically in handgrip strength (m = 12.0, 95% CI = 11.8–12.3 vs. m = 11.5, 95% CI = 11.2–11.7) and in speed tests (m = 23.0, 95% CI = 22.8–23.2 vs. m = 23.6, 95% CI = 23.3–23.8). According to the teacher interviews, these kindergartens also had more rooms and areas specially created for physical exercises. The study revealed that the physical development of children is, when controlling for other individual and environmental factors, influenced by the professional qualification of the PE teacher (95% CI = 0.06–0.56) as well as children’s participation in sports training (95% CI = 0.29–0.83). These findings are important for preschool institutions and municipalities in designing the optimal physical environment for facilitating children’s physical fitness. Full article
(This article belongs to the Special Issue Exercise and Physical Activity in Health Promotion)
17 pages, 9433 KiB  
Article
Cloning, Expression, Enzymatic Characterization and Mechanistic Studies of M13 Mutant Acetohydroxyacid Synthase That Rescues Valine Feedback Inhibition
by Yaqing Tan, Xingxing Gao, Zhiqiang An, Nan Wang, Yaqian Ma and Hailing Zhang
Fermentation 2024, 10(6), 311; https://doi.org/10.3390/fermentation10060311 (registering DOI) - 12 Jun 2024
Abstract
Acetohydroxyacid synthase (AHAS) is a key enzyme in the first step of the branched-chain amino acid synthesis pathway, and the production of acetohydroxybutyrate from one molecule of 2-ketobutyric acid and one molecule of pyruvate. AHAS is inhibited by feedback from L-valine, L- [...] Read more.
Acetohydroxyacid synthase (AHAS) is a key enzyme in the first step of the branched-chain amino acid synthesis pathway, and the production of acetohydroxybutyrate from one molecule of 2-ketobutyric acid and one molecule of pyruvate. AHAS is inhibited by feedback from L-valine, L-leucine, and L-isoleucine, and the expression of ilvBN, the gene encoding AHAS, is regulated by all three branched-chain amino acids. A change in amino acids 20–22 on the regulatory subunit (M13 mutation) removes the feedback inhibition by valine. We cloned the gene encoding AHAS (ilvBN) into a vector and then transfected it into Escherichia coli BL21 for expression with targeted changes in amino acids 20–22 on the regulatory subunit, and then determined the activity of the mutated AHAS and its inhibitory effects on valine, isoleucine, and leucine. The enzyme containing the M13 mutation was feedback resistant to all three amino acids. Previous studies have suggested that the binding sites for the three branched-chain amino acids may be at the same variable center. We investigated the enzymatic properties of wild-type and mutant AHAS, modeled their crystal structures, and resolved the mechanism of feedback inhibition induced by mutant M13, which will be useful for continuing the modification of AHAS and the design of broad-spectrum herbicides. Full article
(This article belongs to the Section Microbial Metabolism, Physiology & Genetics)
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10 pages, 2387 KiB  
Article
Monte Carlo Simulation of Quantum-Cutting Nanocrystals as the Luminophore in Luminescent Solar Concentrators
by Qi Nie, Wenqing Li and Xiao Luo
Photonics 2024, 11(6), 553; https://doi.org/10.3390/photonics11060553 (registering DOI) - 12 Jun 2024
Abstract
Quantum-cutting luminescent solar concentrators (QC-LSCs) have great potential to serve as large-area solar windows. These QC nanocrystals can realize a photoluminescence quantum yield (PLQY) of as high as 200% with virtually zero self-absorption loss. Based on our previous work, we have constructed a [...] Read more.
Quantum-cutting luminescent solar concentrators (QC-LSCs) have great potential to serve as large-area solar windows. These QC nanocrystals can realize a photoluminescence quantum yield (PLQY) of as high as 200% with virtually zero self-absorption loss. Based on our previous work, we have constructed a Monte Carlo simulation model that is suitable to simulate the performance of the QC-LSCs, which can take into account the band-edge emissions and near-infrared emissions of the QC-materials. Under ideal PLQY conditions, CsPbClxBr3−x:Yb3+-based LSCs can reach 12% of the size-independent external quantum efficiency (ηext). Even if LSCs have a certain scattering factor, the CsPbClxBr3−x:Yb3+-based LSCs can still obtain an ηext exceeding 6% in the window size (>1 m2). The flux gain (FG) of the CsPbClxBr3−x:Yb3+-based LSC-PV system can reach 14 in the window size, which is a very encouraging result. Full article
(This article belongs to the Special Issue New Insights in Low-Dimensional Optoelectronic Materials and Devices)
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