The 2023 MDPI Annual Report has
been released!
 
17 pages, 3702 KiB  
Review
Failure of Autophagy in Pompe Disease
by Hung Do, Naresh K. Meena and Nina Raben
Biomolecules 2024, 14(5), 573; https://doi.org/10.3390/biom14050573 (registering DOI) - 13 May 2024
Abstract
Autophagy is an evolutionarily conserved lysosome-dependent degradation of cytoplasmic constituents. The system operates as a critical cellular pro-survival mechanism in response to nutrient deprivation and a variety of stress conditions. On top of that, autophagy is involved in maintaining cellular homeostasis through selective [...] Read more.
Autophagy is an evolutionarily conserved lysosome-dependent degradation of cytoplasmic constituents. The system operates as a critical cellular pro-survival mechanism in response to nutrient deprivation and a variety of stress conditions. On top of that, autophagy is involved in maintaining cellular homeostasis through selective elimination of worn-out or damaged proteins and organelles. The autophagic pathway is largely responsible for the delivery of cytosolic glycogen to the lysosome where it is degraded to glucose via acid α-glucosidase. Although the physiological role of lysosomal glycogenolysis is not fully understood, its significance is highlighted by the manifestations of Pompe disease, which is caused by a deficiency of this lysosomal enzyme. Pompe disease is a severe lysosomal glycogen storage disorder that affects skeletal and cardiac muscles most. In this review, we discuss the basics of autophagy and describe its involvement in the pathogenesis of muscle damage in Pompe disease. Finally, we outline how autophagic pathology in the diseased muscles can be used as a tool to fast track the efficacy of therapeutic interventions. Full article
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16 pages, 2259 KiB  
Article
Consumers’ Perceptions for an Outdoor Ornamental Plant: Exploring the Influence of Novel Plant Diseases Diagnostics and Sustainable Nurseries Cultivation Management
by Michel Frem, Alessandro Petrontino, Vincenzo Fucilli, Barbara De Lucia, Emanuela Tria, Adele Annarita Campobasso, Federica Calderoni and Francesco Bozzo
Horticulturae 2024, 10(5), 501; https://doi.org/10.3390/horticulturae10050501 (registering DOI) - 13 May 2024
Abstract
A discrete choice experiment was conducted to assess the perceptions and willingness-to-pay of Italian consumers regarding plant diagnosis and sustainable cultivation attributes in outdoor ornamental plants, specifically Abelia × grandiflora. The results revealed that most Italian consumers place great importance on the [...] Read more.
A discrete choice experiment was conducted to assess the perceptions and willingness-to-pay of Italian consumers regarding plant diagnosis and sustainable cultivation attributes in outdoor ornamental plants, specifically Abelia × grandiflora. The results revealed that most Italian consumers place great importance on the health of ornamental plants during the purchasing process, with a preference for obtaining them from nursery facilities. Additionally, they demonstrated a willingness to pay a price premium for innovative plant diagnosis and sustainable cultivation in the production of A. × grandiflora, amounting to EUR 1.10 and EUR 0.90, respectively. These findings have significant implications for (i) nursery growers, enabling them to shape their sustainable nursery management and marketing strategies, and (ii) policymakers, facilitating the enhancement of communication strategies and the implementation of awareness campaigns aimed at promoting the sale of healthy Italian ornamental species, following the current EU regulation 2020/1201. Full article
19 pages, 1369 KiB  
Review
Insights into Calpain Activation and Rho-ROCK Signaling in Parkinson’s Disease and Aging
by Amy Gathings, Vandana Zaman, Narendra L. Banik and Azizul Haque
Biomedicines 2024, 12(5), 1074; https://doi.org/10.3390/biomedicines12051074 (registering DOI) - 13 May 2024
Abstract
Parkinson’s disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho, [...] Read more.
Parkinson’s disease (PD), a progressive neurodegenerative disease, has no cure, and current therapies are not effective at halting disease progression. The disease affects mid-brain dopaminergic neurons and, subsequently, the spinal cord, contributing to many debilitating symptoms associated with PD. The GTP-binding protein, Rho, plays a significant role in the cellular pathology of PD. The downstream effector of Rho, Rho-associated kinase (ROCK), plays multiple functions, including microglial activation and induction of inflammatory responses. Activated microglia have been implicated in the pathology of many neurodegenerative diseases, including PD, that initiate inflammatory responses, leading to neuron death. Calpain expression and activity is increased following glial activation, which triggers the Rho-ROCK pathway and induces inflammatory T cell activation and migration as well as mediates toxic α-synuclein (α-syn) aggregation and neuron death, indicating a pivotal role for calpain in the inflammatory and degenerative processes in PD. Increased calpain activity and Rho-ROCK activation may represent a new mechanism for increased oxidative damage in aging. This review will summarize calpain activation and the role of the Rho-ROCK pathway in oxidative stress and α-syn aggregation, their influence on the neurodegenerative process in PD and aging, and possible strategies and research directions for therapeutic intervention. Full article
(This article belongs to the Special Issue Neuropeptides, Dopamine and Their Interactions in Neuroscience)
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17 pages, 910 KiB  
Review
A Survey of Deep Learning Methods for Estimating the Accuracy of Protein Quaternary Structure Models
by Xiao Chen, Jian Liu, Nolan Park and Jianlin Cheng
Biomolecules 2024, 14(5), 574; https://doi.org/10.3390/biom14050574 (registering DOI) - 13 May 2024
Abstract
The quality prediction of quaternary structure models of a protein complex, in the absence of its true structure, is known as the Estimation of Model Accuracy (EMA). EMA is useful for ranking predicted protein complex structures and using them appropriately in biomedical research, [...] Read more.
The quality prediction of quaternary structure models of a protein complex, in the absence of its true structure, is known as the Estimation of Model Accuracy (EMA). EMA is useful for ranking predicted protein complex structures and using them appropriately in biomedical research, such as protein–protein interaction studies, protein design, and drug discovery. With the advent of more accurate protein complex (multimer) prediction tools, such as AlphaFold2-Multimer and ESMFold, the estimation of the accuracy of protein complex structures has attracted increasing attention. Many deep learning methods have been developed to tackle this problem; however, there is a noticeable absence of a comprehensive overview of these methods to facilitate future development. Addressing this gap, we present a review of deep learning EMA methods for protein complex structures developed in the past several years, analyzing their methodologies, data and feature construction. We also provide a prospective summary of some potential new developments for further improving the accuracy of the EMA methods. Full article
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22 pages, 18159 KiB  
Article
Kinematics-Based Design Method and Experimental Validation of Internal Meshing Screw for High-Viscosity Fluid Mixing
by Fang Guo, Genhao Liu, Yinghai Hao, Yu Ma, Guifang Wu, Zhanfeng Hou, Na Li and Xiwen Li
Appl. Sci. 2024, 14(10), 4119; https://doi.org/10.3390/app14104119 (registering DOI) - 13 May 2024
Abstract
The challenge of mixing high-viscosity materials is a common issue encountered in the manufacturing process of food materials. The advantages of the internal meshing screw mixer have led to its adoption in various manufacturing processes, but it has yet to be implemented in [...] Read more.
The challenge of mixing high-viscosity materials is a common issue encountered in the manufacturing process of food materials. The advantages of the internal meshing screw mixer have led to its adoption in various manufacturing processes, but it has yet to be implemented in the food industry. The paper presents a design method for an internal meshing screw mixer based on kinematic principles. The mixer features a helical chamber created by alternating volumes formed by the stator and rotor, establishing an extension-dominated environment for mixing high-viscosity fluids. A kinematic model based on the internal cycloid principle was established, providing trajectories and equations for key points on the rotor, simulating both its rotation and revolution processes, and revealing the velocity variations at different points on the rotor. Based on the kinematic analysis results, a stator and rotor design method was developed according to relevant functional divisions. To achieve the desired motion effects, transmission and support devices were designed, and the relationship between the transmission device and the internal cycloid surface of the fixed rotor was established. The mixer’s application and mixing effectiveness in the food industry were validated using corn syrup and flour. Experimental results showed that the extensional mixer described in the paper effectively mixed high-viscosity fluids while also efficiently blending fine powders. Slurry viscosity was tested with a rheometer at different speeds with an eccentric rotor mixer. Results showed that viscosity decreased with increasing shear rate, with a more pronounced decrease at higher shear rates. The apparent viscosity trend remained consistent at different speeds, although variations were observed at lower shear rates, especially concerning speed. The non-Newtonian fluid index exhibited minimal variations at different speeds, while the consistency coefficient showed significant fluctuations. The mixing uniformity index of the slurry was used to evaluate the mixing uniformity and dispersion uniformity of this extensional mixer. At different rotational speeds, the density of the slurry changes little. The uniformity index of mixing decreases gradually with the increase of rotational speed, reaching its maximum at 15 r/min. The overall trend of the uniformity index decreases with increasing rotational speed, indicating a decrease in density uniformity. A peak appears at 45 r/min, possibly due to the maximum values of elongation rate and shear rate at this speed. As the rotational speed increases, the residence time of the material in the mixer decreases, which may be the main reason for the decrease in mixing uniformity. These findings provide valuable insights into the design and utilization of extension-dominated screw mixers within the food industry, laying a solid foundation for future research and practical applications in this field. Full article
(This article belongs to the Section Mechanical Engineering)
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11 pages, 247 KiB  
Article
Anemia in Dogs with Acute Kidney Injury
by Ilaria Lippi, Francesca Perondi, Giulia Ghiselli, Sara Santini, Verena Habermaass and Veronica Marchetti
Vet. Sci. 2024, 11(5), 212; https://doi.org/10.3390/vetsci11050212 (registering DOI) - 13 May 2024
Abstract
Anemia is a well-known complication in CKD dogs, but its frequency in AKI dogs has been poorly investigated. The aim of the present study was to retrospectively evaluate frequency, degree of severity, and regeneration rate of anemia in relation to IRIS grade, etiology, [...] Read more.
Anemia is a well-known complication in CKD dogs, but its frequency in AKI dogs has been poorly investigated. The aim of the present study was to retrospectively evaluate frequency, degree of severity, and regeneration rate of anemia in relation to IRIS grade, etiology, therapy, and outcome. Medical records of dogs (2017–2023) with historical, laboratory, and ultrasound findings consistent with AKI were retrospectively reviewed. According to etiology, AKI was classified as ischemic/inflammatory (IS), infectious (INF), nephrotoxic (NEP), obstructive (OBS), and unknown (UK). AKI dogs were also classified according to therapeutical management (medical vs. hemodialysis), survival to discharge (survivors vs. non-survivors). Anemia was defined as HCT < 37% and classified as mild (HCT 30–37%), moderate (HCT 20–29%), severe (13–19%), or very severe (<13%). Anemia was classified as microcytic (MCV < 61 fL), normocytic (61 and 73 fL), and macrocytic (>73 fL). Anemia was considered hypochromic (MCHC< 32 g/dL), normochromic (32 and 38 g/dL), and hyperchromic (>38 g/dL). Regeneration rate was considered absent (RET ≤ 60,000/μL), mild 61,000–150,000/μL), and moderate (>150,000/μL). A total of 120 AKI dogs were included in the study, and anemia was found in 86/120 dogs (72%). The severity of anemia was mild in 32/86 dogs (37%), moderate in 40/86 dogs (47%), severe in 11/86 dogs (13%), and very severe in 3/86 (3%). Anemia was normochromic in 71/86 dogs (83%), hyperchromic in 12/86 dogs (14%), and hypochromic in 3/86 dogs (3%). Normocytic anemia was present in 56/86 dogs (65%), microcytic anemia in 27/86 dogs (31%), and macrocytic anemia in 3/86 dogs (4%). Non-regenerative anemia was found in 76/86 dogs (88%). The frequency of anemia increased significantly (p < 0.0001) with the progression of IRIS grade, although no significant difference in the severity of anemia was found among the IRIS grades. The frequency of non-regenerative forms of anemia was significantly higher than regenerative forms (p < 0.0001) in all IRIS grades. In our population of AKI dogs, anemia was a very frequent finding, in agreement with current findings in human nephrology. Full article
12 pages, 2227 KiB  
Article
Ocular Biometry Percentile Curves and Their Relation to Myopia Development in Indian Children
by Aparna Gopalakrishnan, Viswanathan Sivaraman, Jameel Rizwana Hussaindeen, Meenakshi Swaminathan, Alex Gentle, James A. Armitage and Simon Backhouse
J. Clin. Med. 2024, 13(10), 2867; https://doi.org/10.3390/jcm13102867 (registering DOI) - 13 May 2024
Abstract
Background: The aim of the present study was to provide ocular biometry percentile values for Indian children between the ages of 6 and 12 and to validate the usefulness of centiles in predicting myopia development. Methods: The study was part of a longitudinal [...] Read more.
Background: The aim of the present study was to provide ocular biometry percentile values for Indian children between the ages of 6 and 12 and to validate the usefulness of centiles in predicting myopia development. Methods: The study was part of a longitudinal study—the Sankara Nethralaya Tamil Nadu Essilor Myopia Study (STEM), where objective refraction and ocular biometry were measured for children studying in grades 1, 4, and 6 at baseline (2019–2020). These data were used to generate ocular biometry percentile curves (both for axial length (AL) and AL/corneal curvature (AL/CR) ratios). The usefulness of percentile values in predicting myopia development was estimated from follow-up data (2022). Results: The total number of children in the three grades at baseline was 4514 (age range 6 to 12). Boys represented 54% (n = 2442) of the overall sample. The prevalence of myopia at baseline was 11.7% (95% CI from 10.8 to 12.7%) in these three grades. Both the AL and AL/CR ratio centiles showed a linear trend with an increase in AL and AL/CR with increasing grades (p < 0.001) for all percentiles (2, 5, 10, 25, 50, 75, 90, 95, 98, and 99) when stratified by sex. In the follow-up data (n = 377), the 75th and 50th percentiles of the AL/CR ratio had an area under the curve (AUC) of 0.79 and 0.72 to predict myopia onset for grade 4 and 6 children at baseline. Combining baseline AL with the centile shift in follow-up as a predictor increased the AUC to 0.83. Conclusions: The present study has provided centile values specific for Indian children between the ages of 6 and 12 to monitor and intervene where children are at a higher risk of myopia development. Full article
(This article belongs to the Special Issue Multifactorial Causation and Therapies of Myopia)
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20 pages, 6005 KiB  
Article
Exploring the Interplay between Tribocorrosion and Surface Chemistry of the ASTM F139 Surgical Stainless Steel in Phosphate-Buffered Saline Solution
by Marcelo de Matos Macedo, Marcela Bergamaschi Tercini, Renato Altobelli Antunes and Mara Cristina Lopes de Oliveira
Materials 2024, 17(10), 2295; https://doi.org/10.3390/ma17102295 (registering DOI) - 13 May 2024
Abstract
Surgical ASTM F139 stainless steel is used for temporary fixtures in the biomedical field. Tribocorrosion is a major concern in this application. The aim of the present work was to study the interplay between tribocorrosion behavior and the surface chemistry of the ASTM [...] Read more.
Surgical ASTM F139 stainless steel is used for temporary fixtures in the biomedical field. Tribocorrosion is a major concern in this application. The aim of the present work was to study the interplay between tribocorrosion behavior and the surface chemistry of the ASTM F139 stainless steel in phosphate-buffered saline solution (PBS). Sliding wear tests were conducted against alumina balls at different electrochemical potentials: open circuit potential (OCP), cathodic potential (−100 mV versus the OCP), and anodic potentials (+200 mVAg/AgCl and +700 mVAg/AgCl). The normal load was 20 N. The wear volume was estimated based on micrographs obtained from the wear tracks using confocal laser scanning microscopy. Moreover, the wear tracks were also examined by scanning electron microscopy (SEM). The surface chemistry of the ASTM F139 specimens was analyzed by X-ray photoelectron spectroscopy (XPS). The wear volume was dependent on the electrochemical potential, being maximized at +700 mVAg/AgCl. Delamination areas and grooves were observed in the wear tracks. Detailed assessment of the surface chemistry inside the wear tracks allowed identification of the main chemical species and their relative quantities, thus enabling correlation of the passive film composition with the observed tribocorrosion behavior. Full article
(This article belongs to the Special Issue Advances in Surface Corrosion Protection of Alloys)
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24 pages, 5816 KiB  
Review
Functionalized Calcium Carbonate-Based Microparticles as a Versatile Tool for Targeted Drug Delivery and Cancer Treatment
by Lara Biny, Evgeniia Gerasimovich, Alexander Karaulov, Alyona Sukhanova and Igor Nabiev
Pharmaceutics 2024, 16(5), 653; https://doi.org/10.3390/pharmaceutics16050653 (registering DOI) - 13 May 2024
Abstract
Nano- and microparticles are increasingly widely used in biomedical research and applications, particularly as specific labels and targeted delivery vehicles. Silica has long been considered the best material for such vehicles, but it has some disadvantages limiting its potential, such as the proneness [...] Read more.
Nano- and microparticles are increasingly widely used in biomedical research and applications, particularly as specific labels and targeted delivery vehicles. Silica has long been considered the best material for such vehicles, but it has some disadvantages limiting its potential, such as the proneness of silica-based carriers to spontaneous drug release. Calcium carbonate (CaCO3) is an emerging alternative, being an easily available, cost-effective, and biocompatible material with high porosity and surface reactivity, which makes it an attractive choice for targeted drug delivery. CaCO3 particles are used in this field in the form of either bare CaCO3 microbeads or core/shell microparticles representing polymer-coated CaCO3 cores. In addition, they serve as removable templates for obtaining hollow polymer microcapsules. Each of these types of particles has its specific advantages in terms of biomedical applications. CaCO3 microbeads are primarily used due to their capacity for carrying pharmaceutics, whereas core/shell systems ensure better protection of the drug-loaded core from the environment. Hollow polymer capsules are particularly attractive because they can encapsulate large amounts of pharmaceutical agents and can be so designed as to release their contents in the target site in response to specific stimuli. This review focuses first on the chemistry of the CaCO3 cores, core/shell microbeads, and polymer microcapsules. Then, systems using these structures for the delivery of therapeutic agents, including drugs, proteins, and DNA, are outlined. The results of the systematic analysis of available data are presented. They show that the encapsulation of various therapeutic agents in CaCO3-based microbeads or polymer microcapsules is a promising technique of drug delivery, especially in cancer therapy, enhancing drug bioavailability and specific targeting of cancer cells while reducing side effects. To date, research in CaCO3-based microparticles and polymer microcapsules assembled on CaCO3 templates has mainly dealt with their properties in vitro, whereas their in vivo behavior still remains poorly studied. However, the enormous potential of these highly biocompatible carriers for in vivo applications is undoubted. This last issue is addressed in depth in the Conclusions and Outlook sections of the review. Full article
(This article belongs to the Topic Recent Advances in Anticancer Strategies)
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21 pages, 3983 KiB  
Article
Deep Reinforcement Learning for Ecological and Distributed Urban Traffic Signal Control with Multi-Agent Equilibrium Decision Making
by Liping Yan and Jing Wang
Electronics 2024, 13(10), 1910; https://doi.org/10.3390/electronics13101910 (registering DOI) - 13 May 2024
Abstract
Multi-Agent Reinforcement Learning (MARL) has shown strong advantages in urban multi-intersection traffic signal control, but it also suffers from the problems of non-smooth environment and inter-agent coordination. However, most of the existing research on MARL traffic signal control has focused on designing efficient [...] Read more.
Multi-Agent Reinforcement Learning (MARL) has shown strong advantages in urban multi-intersection traffic signal control, but it also suffers from the problems of non-smooth environment and inter-agent coordination. However, most of the existing research on MARL traffic signal control has focused on designing efficient communication to solve the environment non-smoothness problem, while neglecting the coordination between agents. In order to coordinate among agents, this paper combines MARL and the regional mixed-strategy Nash equilibrium to construct a Deep Convolutional Nash Policy Gradient Traffic Signal Control (DCNPG-TSC) model, which enables agents to perceive the traffic environment in a wider range and achieves effective agent communication and collaboration. Additionally, a Multi-Agent Distributional Nash Policy Gradient (MADNPG) algorithm is proposed in this model, which is the first time the mixed-strategy Nash equilibrium is used for the improvement in the Multi-Agent Deep Deterministic Policy Gradient algorithm traffic signal control strategy to provide the optimal signal phase for each intersection. In addition, the eco-mobility concept is integrated into MARL traffic signal control to reduce pollutant emissions at intersections. Finally, simulation results in synthetic and real-world traffic road networks show that DCNPG-TSC outperforms other state-of-the-art MARL traffic signal control methods in almost all performance metrics, because it can aggregate the information of neighboring agents and optimize the agent’s decisions through gaming to find an optimal joint equilibrium strategy for the traffic road network. Full article
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12 pages, 3461 KiB  
Article
Synthetic ShK-Like Peptide from the Jellyfish Nemopilema nomurai Has Human Voltage-Gated Potassium-Channel-Blocking Activity
by Ye-Ji Kim, Yejin Jo, Seung Eun Lee, Jungeun Kim, Jae-Pil Choi, Nayoung Lee, Hyokyoung Won, Dong Ho Woo and Seungshic Yum
Mar. Drugs 2024, 22(5), 217; https://doi.org/10.3390/md22050217 (registering DOI) - 13 May 2024
Abstract
We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is [...] Read more.
We identified a new human voltage-gated potassium channel blocker, NnK-1, in the jellyfish Nemopilema nomurai based on its genomic information. The gene sequence encoding NnK-1 contains 5408 base pairs, with five introns and six exons. The coding sequence of the NnK-1 precursor is 894 nucleotides long and encodes 297 amino acids containing five presumptive ShK-like peptides. An electrophysiological assay demonstrated that the fifth peptide, NnK-1, which was chemically synthesized, is an effective blocker of hKv1.3, hKv1.4, and hKv1.5. Multiple-sequence alignment with cnidarian Shk-like peptides, which have Kv1.3-blocking activity, revealed that three residues (3Asp, 25Lys, and 34Thr) of NnK-1, together with six cysteine residues, were conserved. Therefore, we hypothesized that these three residues are crucial for the binding of the toxin to voltage-gated potassium channels. This notion was confirmed by an electrophysiological assay with a synthetic peptide (NnK-1 mu) where these three peptides were substituted with 3Glu, 25Arg, and 34Met. In conclusion, we successfully identified and characterized a new voltage-gated potassium channel blocker in jellyfish that interacts with three different voltage-gated potassium channels. A peptide that interacts with multiple voltage-gated potassium channels has many therapeutic applications in various physiological and pathophysiological contexts. Full article
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13 pages, 678 KiB  
Article
Bariatric Surgery: An Opportunity to Improve Quality of Life and Healthy Habits
by Beatriz Vanessa Díaz-González, Inmaculada Bautista-Castaño, Elisabeth Hernández García, Judith Cornejo Torre, Juan Ramón Hernández Hernández and Lluis Serra-Majem
Nutrients 2024, 16(10), 1466; https://doi.org/10.3390/nu16101466 (registering DOI) - 13 May 2024
Abstract
Bariatric surgery therapy (BST) is an effective treatment for obesity; however, little is known about its impacts on health-related quality of life (HRQoL) and related factors. This study aimed to evaluate changes in HRQoL and its relationship with weight loss, depression status, physical [...] Read more.
Bariatric surgery therapy (BST) is an effective treatment for obesity; however, little is known about its impacts on health-related quality of life (HRQoL) and related factors. This study aimed to evaluate changes in HRQoL and its relationship with weight loss, depression status, physical activity (PA), and nutritional habits after BST. Data were obtained before and 18 months postprocedure from 56 obese patients who underwent BST. We administered four questionnaires: Short Form-36 health survey for HRQoL, 14-item MedDiet adherence questionnaire, Rapid Assessment of PA (RAPA) questionnaire, and Beck’s Depression Inventory-II. Multivariable linear regression analysis was used to identify factors associated with improvement in HRQoL. After the surgery, MedDiet adherence and HRQoL improved significantly, especially in the physical component. No changes in PA were found. Patients without previous depression have better mental quality of life, and patients who lost more than 25% of %TBWL have better results in physical and mental quality of life. In the multivariable analysis, we found that %TBWL and initial PCS (inversely) were related to the improvement in PCS and initial MCS (inversely) with the MCS change. In conclusion, BST is an effective intervention for obesity, resulting in significant weight loss and improvements in HRQoL and nutritional habits. Full article
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12 pages, 1080 KiB  
Review
Voltage Sensors Embedded in G Protein-Coupled Receptors
by Merav Tauber and Yair Ben-Chaim
Int. J. Mol. Sci. 2024, 25(10), 5295; https://doi.org/10.3390/ijms25105295 (registering DOI) - 13 May 2024
Abstract
Some signaling processes mediated by G protein-coupled receptors (GPCRs) are modulated by membrane potential. In recent years, increasing evidence that GPCRs are intrinsically voltage-dependent has accumulated. A recent publication challenged the view that voltage sensors are embedded in muscarinic receptors. Herein, we briefly [...] Read more.
Some signaling processes mediated by G protein-coupled receptors (GPCRs) are modulated by membrane potential. In recent years, increasing evidence that GPCRs are intrinsically voltage-dependent has accumulated. A recent publication challenged the view that voltage sensors are embedded in muscarinic receptors. Herein, we briefly discuss the evidence that supports the notion that GPCRs themselves are voltage-sensitive proteins and an alternative mechanism that suggests that voltage-gated sodium channels are the voltage-sensing molecules involved in such processes. Full article
(This article belongs to the Special Issue Cellular Responses to Environmental Changes)
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13 pages, 1335 KiB  
Article
One-Year Evaluation of High-Power Rapid Curing on Dentin Bond Strength
by Eva Klarić, Josipa Vukelja Bosnić, Matej Par, Zrinka Tarle and Danijela Marovic
Materials 2024, 17(10), 2297; https://doi.org/10.3390/ma17102297 (registering DOI) - 13 May 2024
Abstract
This study investigated the effect of 3 s light-curing with a high-power LED curing unit on the shear bond strength of bulk-fill composites. Four bulk-fill composites were bonded to dentin with a universal adhesive (Scotchbond Universal Plus): two materials designed for rapid curing [...] Read more.
This study investigated the effect of 3 s light-curing with a high-power LED curing unit on the shear bond strength of bulk-fill composites. Four bulk-fill composites were bonded to dentin with a universal adhesive (Scotchbond Universal Plus): two materials designed for rapid curing (Tetric PowerFill and Tetric PowerFlow) and two controls (Filtek One Bulk Fill Restorative and SDR Plus Bulk Fill Flowable). The 4 mm composite layer was light-cured with Bluephase PowerCure for 20 s at 1000 mW/cm2 (“20 s”) or for 3 s at 3000 mW/cm2 (“3 s”). The samples were stored at 37 °C in distilled water and tested after 1, 6 and 12 months. The samples polymerised in the “3 s” mode had statistically similar or higher bond strength than the samples cured in “20 s” mode, except for the Tetric PowerFlow (1 month) and SDR+ (6 month). The flowable materials Tetric PowerFlow and SDR Plus initially showed the highest values in the “3 s” and “20 s” groups, which decreased after 12 months. The bond strength was statistically similar for all materials and curing protocols after 12 months, except for Tetric PowerFill cured with the “3 s” protocol (21.22 ± 5.0 MPa), which showed the highest value. Tetric PowerFill showed the highest long-term bond strength. While “3 s” curing resulted in equal or better shear bond strength, its use can only be recommended for a material with an AFCT agent such as Tetric PowerFill. Full article
(This article belongs to the Special Issue Novel Dental Restorative Materials (Volume II))
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19 pages, 6813 KiB  
Article
Physiological and Transcriptome Analyses Reveal the Protective Effect of Exogenous Trehalose in Response to Heat Stress in Tea Plant (Camellia sinensis)
by Shizhong Zheng, Chufei Liu, Ziwei Zhou, Liyi Xu and Zhongxiong Lai
Plants 2024, 13(10), 1339; https://doi.org/10.3390/plants13101339 (registering DOI) - 13 May 2024
Abstract
It is well known that application of exogenous trehalose can enhance the heat resistance of plants. To investigate the underlying molecular mechanisms by which exogenous trehalose induces heat resistance in C. sinensis, a combination of physiological and transcriptome analyses was conducted. The [...] Read more.
It is well known that application of exogenous trehalose can enhance the heat resistance of plants. To investigate the underlying molecular mechanisms by which exogenous trehalose induces heat resistance in C. sinensis, a combination of physiological and transcriptome analyses was conducted. The findings revealed a significant increase in the activity of superoxide dismutase (SOD) and peroxidase (POD) upon treatment with 5.0 mM trehalose at different time points. Moreover, the contents of proline (PRO), endogenous trehalose, and soluble sugar exhibited a significant increase, while malondialdehyde (MDA) content decreased following treatment with 5.0 mM trehalose under 24 h high-temperature stress (38 °C/29 °C, 12 h/12 h). RNA-seq analysis demonstrated that the differentially expressed genes (DEGs) were significantly enriched in the MAPK pathway, plant hormone signal transduction, phenylpropanoid biosynthesis, flavone and flavonol biosynthesis, flavonoid biosynthesis, and the galactose metabolism pathway. The capability to scavenge free radicals was enhanced, and the expression of a heat shock factor gene (HSFB2B) and two heat shock protein genes (HSP18.1 and HSP26.5) were upregulated in the tea plant. Consequently, it was concluded that exogenous trehalose contributes to alleviating heat stress in C. sinensis. Furthermore, it regulates the expression of genes involved in diverse pathways crucial for C. sinensis under heat-stress conditions. These findings provide novel insights into the molecular mechanisms underlying the alleviation of heat stress in C. sinensis with trehalose. Full article
(This article belongs to the Special Issue Recent Advances in Plant Genomics and Transcriptome Analysis)
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12 pages, 1946 KiB  
Article
HotCFuzz: Enhancing Vulnerability Detection through Fuzzing and Hotspot Code Coverage Analysis
by Chunlai Du, Yanhui Guo, Yifan Feng and Shijie Zheng
Electronics 2024, 13(10), 1909; https://doi.org/10.3390/electronics13101909 (registering DOI) - 13 May 2024
Abstract
Software vulnerabilities present a significant cybersecurity threat, particularly as software code grows in size and complexity. Traditional vulnerability-mining techniques face challenges in keeping pace with this complexity. Fuzzing, a key automated vulnerability-mining approach, typically focuses on code branch coverage, overlooking syntactic and semantic [...] Read more.
Software vulnerabilities present a significant cybersecurity threat, particularly as software code grows in size and complexity. Traditional vulnerability-mining techniques face challenges in keeping pace with this complexity. Fuzzing, a key automated vulnerability-mining approach, typically focuses on code branch coverage, overlooking syntactic and semantic elements of the code. In this paper, we introduce HotCFuzz, a novel vulnerability-mining model centered on the coverage of hot code blocks. Leveraging vulnerability syntactic features to identify these hot code blocks, we devise a seed selection algorithm based on their coverage and integrate it into the established fuzzing test framework AFL. Experimental results demonstrate that HotCFuzz surpasses AFL, AFLGo, Beacon, and FairFuzz in terms of efficiency and time savings. Full article
(This article belongs to the Special Issue Machine Learning for Cybersecurity: Threat Detection and Mitigation)
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15 pages, 783 KiB  
Review
AMPs as Host-Directed Immunomodulatory Agents against Skin Infections Caused by Opportunistic Bacterial Pathogens
by Subhasree Saha, Devashish Barik and Debabrata Biswas
Antibiotics 2024, 13(5), 439; https://doi.org/10.3390/antibiotics13050439 (registering DOI) - 13 May 2024
Abstract
Skin is the primary and largest protective organ of the human body. It produces a number of highly evolved arsenal of factors to counter the continuous assault of foreign materials and pathogens from the environment. One such potent factor is the repertoire of [...] Read more.
Skin is the primary and largest protective organ of the human body. It produces a number of highly evolved arsenal of factors to counter the continuous assault of foreign materials and pathogens from the environment. One such potent factor is the repertoire of Antimicrobial Peptides (AMPs) that not only directly destroys invading pathogens, but also optimally modulate the immune functions of the body to counter the establishment and spread of infections. The canonical direct antimicrobial functions of these AMPs have been in focus for a long time to design principles for enhanced therapeutics, especially against the multi-drug resistant pathogens. However, in recent times the immunomodulatory functions performed by these peptides at sub-microbicidal concentrations have been a point of major focus in the field of host-directed therapeutics. Such strategies have the added benefit of not having the pathogens develop resistance against the immunomodulatory pathways, since the pathogens exploit these signaling pathways to obtain and survive within the host. Thus, this review summarizes the potent immunomodulatory effect of these AMPs on, specifically, the different host immune cells with the view of providing a platform of information that might help in designing studies to exploit and formulate effective host-directed adjunct therapeutic strategies that would synergies with drug regimens to counter the current diversity of drug-resistant skin opportunistic pathogens. Full article
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26 pages, 413 KiB  
Review
John Cunningham Virus and Progressive Multifocal Leukoencephalopathy: A Falsely Played Diagnosis
by Dimitra S. Mouliou
Diseases 2024, 12(5), 100; https://doi.org/10.3390/diseases12050100 (registering DOI) - 13 May 2024
Abstract
Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple [...] Read more.
Progressive Multifocal Leukoencephalopathy (PML) is a possibly fatal demyelinating disease and John Cunningham Polyomavirus (JCPyV) is believed to cause this condition. The so-called JCPyV was initially reported in lymphoma and Human Immunodeficiency Virus (HIV) cases, whereas nowadays, its incidence is increasing in Multiple Sclerosis (MS) cases treated with natalizumab (Tysabri). However, there are conflicting literature data on its pathology and diagnosis, whereas some misdiagnosed reports exist, giving rise to further questions towards the topic. In reality, the so-called PML and the supposed JCPyV are not what they seem to be. In addition, novel and more frequent PML-like conditions may be reported, especially after the Coronavirus Disease 2019 (COVID-19) pandemic. Full article
13 pages, 2016 KiB  
Article
Towards the Optimization of a Photovoltaic/Membrane Distillation System for the Production of Pure Water
by Dufei Fang, Damian M. Amiruddin, Imin Kao, Devinder Mahajan, Xuming Chen and Benjamin S. Hsiao
Membranes 2024, 14(5), 110; https://doi.org/10.3390/membranes14050110 (registering DOI) - 13 May 2024
Abstract
The production of pure water plays a pivotal role in enabling sustainable green hydrogen production through electrolysis. The current industrial approach for generating pure water relies on energy-intensive techniques such as reverse osmosis. This study unveils a straightforward method to produce pure water, [...] Read more.
The production of pure water plays a pivotal role in enabling sustainable green hydrogen production through electrolysis. The current industrial approach for generating pure water relies on energy-intensive techniques such as reverse osmosis. This study unveils a straightforward method to produce pure water, employing real-world units derived from previously simulated and developed laboratory devices. This demonstrated system is cost-effective and boasts low energy consumption, utilizing membrane distillation (MD) driven by the waste heat harnessed from photovoltaic (PV) panels. In a previous study, modeling simulations were conducted to optimize the multi-layered MD system, serving as a blueprint for the construction of prototype devices with a suitable selection of materials, enabling the construction of field-testable units. The most efficient PV-MD device, featuring evaporation and condensation zones constructed from steel sheets and polytetrafluoroethylene (PTFE) membranes, is capable of yielding high-purity water with conductivity levels below 145 μS with high flux rates. Full article
(This article belongs to the Collection Feature Papers in Membrane Engineering and Applications)
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21 pages, 7283 KiB  
Article
Nature-Based Solutions for Optimizing the Water–Ecosystem–Food Nexus in Mediterranean Countries
by Silvia Vanino, Valentina Baratella, Tiziana Pirelli, Donato Ferrari, Antonella Di Fonzo, Fabrizio Pucci, Nikolaos P. Nikolaidis, Maria A. Lilli, Zübeyde Albayram Doğan, Tuncay Topdemir, Sami Awabdeh, Luna Al-Hadidi, Nabeel Bani Hani, Andreas Panagopoulos, Vassilios Pisinaras, Anna Chatzi, Estrella López, Christina Papadaskalopoulou, Dimitris Tassopoulos, Efstathia Chatzitheodorou, Alessandro Pagano, Raffaele Giordano, Ivan Portoghese, Esteban Henao, Anna Osann and Stefano Fabianiadd Show full author list remove Hide full author list
Sustainability 2024, 16(10), 4064; https://doi.org/10.3390/su16104064 (registering DOI) - 13 May 2024
Abstract
Nature-based solutions (NBSs), defined as actions that work with and enhance nature, providing environmental, social, and economic benefits, play a pivotal role in accomplishing multiple objectives within the Water–Ecosystem–Food Nexus domain. They contribute to facilitating the transition to more resilient agrifood systems and [...] Read more.
Nature-based solutions (NBSs), defined as actions that work with and enhance nature, providing environmental, social, and economic benefits, play a pivotal role in accomplishing multiple objectives within the Water–Ecosystem–Food Nexus domain. They contribute to facilitating the transition to more resilient agrifood systems and providing an evidence base for a broader Nexus policy dialogue. This paper describes the stepwise methodology developed in the EU-funded LENSES project to carry out a comprehensive analysis of NBSs in six pilot areas in five Mediterranean countries and presents the results of NBS implementation in four pilot areas, highlighting obstacles and opportunities. The methodology includes the development of an analytical evaluation framework and a comprehensive catalogue of Nexus-related NBSs, whose suitability needs to be assessed at the local level to achieve better use of protected/natural ecosystems, increase the sustainability and multifunctionality of managed ecosystems, and design and manage novel ecosystems. Subsequently, in a collective learning process that supported the operationalisation of the WEF Nexus, NBSs were identified that address specific contextual vulnerabilities, improve water distribution, and enhance food security while preserving ecosystems and supporting adaptation to climate change. The added value of the proposed methodology lies in the multi-stakeholder participatory approach to gain in-depth knowledge of local agri-food systems, including their main WEF-related challenges, and to facilitate overcoming barriers to NBS implementation. Finally, a final survey was conducted among a small group of purposively selected stakeholders to gain some insight into their perceptions of the impact of NBS and to gather some opinions on the main barriers and opportunities. Full article
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19 pages, 3164 KiB  
Article
A New Approach to Landscape Visual Quality Assessment from a Fine-Tuning Perspective
by Rong Fan, Yingze Chen and Ken P. Yocom
Land 2024, 13(5), 673; https://doi.org/10.3390/land13050673 (registering DOI) - 13 May 2024
Abstract
Various methods for evaluating the visual quality of landscapes have been continuously studied. In the era of the rapid development of big data, methods to obtain evaluation data efficiently and accurately have received attention. However, few studies have been conducted to optimize the [...] Read more.
Various methods for evaluating the visual quality of landscapes have been continuously studied. In the era of the rapid development of big data, methods to obtain evaluation data efficiently and accurately have received attention. However, few studies have been conducted to optimize the evaluation methods for landscape visual quality. Here, we aim to develop an evaluation model that is model fine-tuned using Scenic Beauty Evaluation (SBE) results. In elucidating the methodology, it is imperative to delve into the intricacies of refining the evaluation process. First, fine-tuning the model can be initiated with a scoring test on a small population, serving as an efficient starting point. Second, determining the optimal hyperparameter settings necessitates establishing intervals within a threshold range tailored to the characteristics of the dataset. Third, from the pool of fine-tuned models, selecting the one exhibiting optimal performance is crucial for accurately predicting the visual quality of the landscape within the study population. Lastly, through the interpolation process, discernible differences in landscape aesthetics within the core monitoring area can be visually distinguished, thereby reinforcing the reliability and practicality of the new method. In order to demonstrate the efficiency and practicality of the new method, we chose the core section of the famous Beijing–Hangzhou Grand Canal in Wujiang District, China, as a case study. The results show the following: (1) Fine-tuning the model can start with a scoring test on a small population. (2) The optimal hyperparameter setting intervals of the model need to be set in a threshold range according to different dataset characteristics. (3) The model with optimal performance is selected among the four fine-tuning models for predicting the visual quality of the landscape in the study population. (4) After the interpolation process, the differences in landscape aesthetics within the core monitoring area can be visually distinguished. We believe that the new method is efficient, accurate, and practically applicable for improving landscape visual quality evaluation. Full article
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20 pages, 4786 KiB  
Article
VIS-SLAM: A Real-Time Dynamic SLAM Algorithm Based on the Fusion of Visual, Inertial, and Semantic Information
by Yinglong Wang, Xiaoxiong Liu, Minkun Zhao and Xinlong Xu
ISPRS Int. J. Geo-Inf. 2024, 13(5), 163; https://doi.org/10.3390/ijgi13050163 (registering DOI) - 13 May 2024
Abstract
A deep learning-based Visual Inertial SLAM technique is proposed in this paper to ensure accurate autonomous localization of mobile robots in environments with dynamic objects. Addressing the limitations of real-time performance in deep learning algorithms and the poor robustness of pure visual geometry [...] Read more.
A deep learning-based Visual Inertial SLAM technique is proposed in this paper to ensure accurate autonomous localization of mobile robots in environments with dynamic objects. Addressing the limitations of real-time performance in deep learning algorithms and the poor robustness of pure visual geometry algorithms, this paper presents a deep learning-based Visual Inertial SLAM technique. Firstly, a non-blocking model is designed to extract semantic information from images. Then, a motion probability hierarchy model is proposed to obtain prior motion probabilities of feature points. For image frames without semantic information, a motion probability propagation model is designed to determine the prior motion probabilities of feature points. Furthermore, considering that the output of inertial measurements is unaffected by dynamic objects, this paper integrates inertial measurement information to improve the estimation accuracy of feature point motion probabilities. An adaptive threshold-based motion probability estimation method is proposed, and finally, the positioning accuracy is enhanced by eliminating feature points with excessively high motion probabilities. Experimental results demonstrate that the proposed algorithm achieves accurate localization in dynamic environments while maintaining real-time performance. Full article
(This article belongs to the Topic Artificial Intelligence in Navigation)
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15 pages, 3629 KiB  
Article
Characterization of FOLH1 Expression in Renal Cell Carcinoma
by Eric Ovruchesky, Elizabeth Pan, Melis Guer, Andrew Elliott, Shankar Siva, Praful Ravi, Bradley McGregor, Aditya Bagrodia, Ithaar Derweesh, Pedro Barata, Elisabeth I. Heath, Emmanuel S. Antonarakis, Sourat Darabi, Dave S. B. Hoon, Amir Mortazavi, Toni K. Choueiri, Chadi Nabhan, Shuanzeng Wei and Rana R. McKay
Cancers 2024, 16(10), 1855; https://doi.org/10.3390/cancers16101855 (registering DOI) - 13 May 2024
Abstract
Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation [...] Read more.
Purpose: Given the emergence of PSMA-targeted diagnostic agents and therapeutics, we sought to investigate patterns of FOLH1 expression in RCC and their impacts on RCC outcomes. Methods: We conducted a pooled multi-institutional analysis of patients with RCC having undergone DNA and RNA next-generation sequencing. FOLH1-high/low expression was defined as the ≥75th/<25th percentile of RNA transcripts per million (TPM). Angiogenic, T-effector, and myeloid expression signatures were calculated using previously defined gene sets. Kaplan–Meier estimates were calculated from the time of tissue collection or therapy start. Results: We included 1,724 patients in the analysis. FOLH1 expression was significantly higher in clear cell (71%) compared to non-clear cell RCC tumors (19.0 versus 3.3 TPM, p < 0.001) and varied by specimen site (45% primary kidney/55% metastasis, 13.6 versus 9.9 TPM, p < 0.001). FOLH1 expression was correlated with angiogenic gene expression (Spearman = 0.76, p < 0.001) and endothelial cell abundance (Spearman = 0.76, p < 0.001). While OS was similar in patients with FOLH1-high versus -low ccRCC, patients with FOLH1-high clear cell tumors experienced a longer time on cabozantinib treatment (9.7 versus 4.6 months, respectively, HR 0.57, 95% CI 0.35–0.93, p < 0.05). Conclusions: We observed differential patterns of FOLH1 expression based on histology and tumor site in RCC. FOLH1 was correlated with angiogenic gene expression, increased OS, and a longer duration of cabozantinib treatment. Full article
(This article belongs to the Special Issue Renal Cell Carcinoma: From Pathology to Therapeutic Strategies)
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