The 2023 MDPI Annual Report has
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16 pages, 4170 KiB  
Article
Short- and Long-Term Effects of Subchronic Stress Exposure in Male and Female Brain-Derived Neurotrophic Factor Knock-In Val66Met Mice
by Fernando Antonio Costa Xavier, Silvia Stella Barbieri, Maurizio Popoli and Alessandro Ieraci
Biology 2024, 13(5), 303; https://doi.org/10.3390/biology13050303 (registering DOI) - 27 Apr 2024
Abstract
Stress is an important risk factor for the onset of anxiety and depression. The ability to cope with stressful events varies among different subjects, probably depending on different genetic variants, sex and previous life experiences. The Val66Met variant of Brain-Derived Neurotrophic Factor (BDNF), [...] Read more.
Stress is an important risk factor for the onset of anxiety and depression. The ability to cope with stressful events varies among different subjects, probably depending on different genetic variants, sex and previous life experiences. The Val66Met variant of Brain-Derived Neurotrophic Factor (BDNF), which impairs the activity-dependent secretion of BDNF, has been associated with increased susceptibility to the development of various neuropsychiatric disorders. Adult male and female wild-type Val/Val (BDNFV/V) and heterozygous Val/Met (BDNFV/M) mice were exposed to two sessions of forced swimming stress (FSS) per day for two consecutive days. The mice were behaviorally tested 1 day (short-term effect) or 11 days (long-term effect) after the last stress session. Protein and mRNA levels were measured in the hippocampus 16 days after the end of stress exposure. Stressed mice showed a higher anxiety-like phenotype compared to non-stressed mice, regardless of the sex and genotype, when analyzed following the short period of stress. In the prolonged period, anxiety-like behavior persisted only in male BDNFV/M mice (p < 0.0001). Interestingly, recovery in male BDNFV/V mice was accompanied by an increase in pCREB (p < 0.001) and Bdnf4 (p < 0.01) transcript and a decrease in HDAC1 (p < 0.05) and Dnmt3a (p = 0.01) in the hippocampus. Overall, our results show that male and female BDNF Val66Met knock-in mice can recover from subchronic stress in different ways. Full article
(This article belongs to the Special Issue Roles and Functions of Neurotrophins and Their Receptors in the Brain)
13 pages, 2391 KiB  
Article
Comparison of Inter-Method Agreement and Reliability for Automatic Brain Volumetry Using Three Different Clinically Available Software Packages
by Kwang Ho Choi, Young Jin Heo, Hye Jin Baek, Jun-Ho Kim and Jeong Yoon Jang
Medicina 2024, 60(5), 727; https://doi.org/10.3390/medicina60050727 (registering DOI) - 27 Apr 2024
Abstract
Background and Objectives: No comparative study has evaluated the inter-method agreement and reliability between Heuron AD and other clinically available brain volumetric software packages. Hence, we aimed to investigate the inter-method agreement and reliability of three clinically available brain volumetric software packages: FreeSurfer [...] Read more.
Background and Objectives: No comparative study has evaluated the inter-method agreement and reliability between Heuron AD and other clinically available brain volumetric software packages. Hence, we aimed to investigate the inter-method agreement and reliability of three clinically available brain volumetric software packages: FreeSurfer (FS), NeuroQuant® (NQ), and Heuron AD (HAD). Materials and Methods: In this study, we retrospectively included 78 patients who underwent conventional three-dimensional (3D) T1-weighed imaging (T1WI) to evaluate their memory impairment, including 21 with normal objective cognitive function, 24 with mild cognitive impairment, and 33 with Alzheimer’s disease (AD). All 3D T1WI scans were analyzed using three different volumetric software packages. Repeated-measures analysis of variance, intraclass correlation coefficient, effect size measurements, and Bland–Altman analysis were used to evaluate the inter-method agreement and reliability. Results: The measured volumes demonstrated substantial to almost perfect agreement for most brain regions bilaterally, except for the bilateral globi pallidi. However, the volumes measured using the three software packages showed significant mean differences for most brain regions, with consistent systematic biases and wide limits of agreement in the Bland–Altman analyses. The pallidum showed the largest effect size in the comparisons between NQ and FS (5.20–6.93) and between NQ and HAD (2.01–6.17), while the cortical gray matter showed the largest effect size in the comparisons between FS and HAD (0.79–1.91). These differences and variations between the software packages were also observed in the subset analyses of 45 patients without AD and 33 patients with AD. Conclusions: Despite their favorable reliability, the software-based brain volume measurements showed significant differences and systematic biases in most regions. Thus, these volumetric measurements should be interpreted based on the type of volumetric software used, particularly for smaller structures. Moreover, users should consider the replaceability-related limitations when using these packages in real-world practice. Full article
(This article belongs to the Section Neurology)
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15 pages, 2045 KiB  
Article
Combining the Benefits of Biotin–Streptavidin Aptamer Immobilization with the Versatility of Ni-NTA Regeneration Strategies for SPR
by Eliza K. Hanson and Rebecca J. Whelan
Sensors 2024, 24(9), 2805; https://doi.org/10.3390/s24092805 (registering DOI) - 27 Apr 2024
Abstract
The high affinity of the biotin–streptavidin interaction has made this non-covalent coupling an indispensable strategy for the immobilization and enrichment of biomolecular affinity reagents. However, the irreversible nature of the biotin–streptavidin bond renders surfaces functionalized using this strategy permanently modified and not amenable [...] Read more.
The high affinity of the biotin–streptavidin interaction has made this non-covalent coupling an indispensable strategy for the immobilization and enrichment of biomolecular affinity reagents. However, the irreversible nature of the biotin–streptavidin bond renders surfaces functionalized using this strategy permanently modified and not amenable to regeneration strategies that could increase assay reusability and throughput. To increase the utility of biotinylated targets, we here introduce a method for reversibly immobilizing biotinylated thrombin-binding aptamers onto a Ni-nitrilotriacetic acid (Ni-NTA) sensor chip using 6xHis-tagged streptavidin as a regenerable capture ligand. This approach enabled the reproducible immobilization of aptamers and measurements of aptamer–protein interaction in a surface plasmon resonance assay. The immobilized aptamer surface was stable during five experiments over two days, despite the reversible attachment of 6xHis-streptavidin to the Ni-NTA surface. In addition, we demonstrate the reproducibility of this immobilization method and the affinity assays performed using it. Finally, we verify the specificity of the biotin tag–streptavidin interaction and assess the efficiency of a straightforward method to regenerate and reuse the surface. The method described here will allow researchers to leverage the versatility and stability of the biotin–streptavidin interaction while increasing throughput and improving assay efficiency. Full article
(This article belongs to the Special Issue Surface Plasmon Resonance-Based Biosensor)
16 pages, 1679 KiB  
Article
Multi-Objective Optimization in 3D Floorplanning
by Zhongjie Jiang, Zhiqiang Li and Zhenjie Yao
Electronics 2024, 13(9), 1696; https://doi.org/10.3390/electronics13091696 (registering DOI) - 27 Apr 2024
Abstract
Three-dimensional integrated circuits can significantly mitigate the challenges posed by shrinking feature sizes and enable heterogeneous integration. This paper focuses on the 3D floorplanning problem. We formulate it as a multi-objective optimization issue and employ multi-objective simulated annealing to simultaneously optimize area, wirelength [...] Read more.
Three-dimensional integrated circuits can significantly mitigate the challenges posed by shrinking feature sizes and enable heterogeneous integration. This paper focuses on the 3D floorplanning problem. We formulate it as a multi-objective optimization issue and employ multi-objective simulated annealing to simultaneously optimize area, wirelength and number of vias. During the optimization process, neighboring solutions are explored in the design space through inter-layer or intra-layer perturbations, and decision criteria for the exploration process are formulated based on the dominance relationship of solutions. Test results on the GSRC benchmark demonstrate that our approach delivers superior performance in optimizing area and wirelength. Compared to 2D floorplanning, our method reduces the area by approximately 49% and the wirelength by 21%. Compared to other similar 3D floorplanning methods, we raise the success rate in satisfying the fixed-outline constraint to 100% and improve the wirelength by 3%. The multi-objective simulated annealing method proposed in this paper can effectively address the 3D floorplanning problem. Full article
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13 pages, 1613 KiB  
Article
Online Detection of Hydrogen Fluoride under Corona Discharge in Gas-Insulated Switchgear Based on Photoacoustic Spectroscopy
by Liujie Wan, Xiaohe Zhao and Kang Li
Sensors 2024, 24(9), 2806; https://doi.org/10.3390/s24092806 (registering DOI) - 27 Apr 2024
Abstract
Internal discharge and overheating faults in sulfur hexafluoride (SF6) gas-insulated electrical equipment will generate a series of characteristic gas products. Hydrogen fluoride (HF) is one of the main decomposition gases under discharge failure. Because of its extremely corrosive nature, it can [...] Read more.
Internal discharge and overheating faults in sulfur hexafluoride (SF6) gas-insulated electrical equipment will generate a series of characteristic gas products. Hydrogen fluoride (HF) is one of the main decomposition gases under discharge failure. Because of its extremely corrosive nature, it can react with other materials in gas-insulated switchgear (GIS), resulting in a short existence time, so it needs to be detected online. Resonant gas photoacoustic spectroscopy has the advantage of high sensitivity, fast response, and no sample gas consumption, and can be used for the online detection of flowing gas. In this paper, a simulated GIS corona discharge experimental platform was built, and the HF generated in the discharge was detected online by gas photoacoustic spectroscopy. The absorption peak of HF molecule near 1312.59 nm was selected as the absorption spectral line, and a resonant photoacoustic cell was designed. To improve the detection sensitivity of HF, wavelength modulation and second-harmonic detection technology were used. The online monitoring of HF in the simulated GIS corona discharge fault was successfully realized. The experimental results show that the sensitivity of the designed photoacoustic spectroscopy detection system for HF is 0.445 μV/(μL/L), and the limit of detection (LOD) is 0.611 μL/L. Full article
(This article belongs to the Special Issue Photoacoustic Sensors and Devices for Gas Detection)
31 pages, 1378 KiB  
Article
E-commerce Participation, Subjective Norms and Grassland Utilization Pressure: An Empirical Evidence of Herdsmen in Inner Mongolia, China
by Mingjun Tian and Yunhua Wu
Agriculture 2024, 14(5), 690; https://doi.org/10.3390/agriculture14050690 (registering DOI) - 27 Apr 2024
Abstract
The general requirements of China’s rural revitalization strategy are industrial prosperity, ecological livability and rich life. However, the traditional livestock breeding model has struggled to balance the dual requirements of production development and ecological protection, and it is urgent to inject new impetus [...] Read more.
The general requirements of China’s rural revitalization strategy are industrial prosperity, ecological livability and rich life. However, the traditional livestock breeding model has struggled to balance the dual requirements of production development and ecological protection, and it is urgent to inject new impetus and explore new development paths. At present, e-commerce has become a bridge between pastoral areas and cities, herdsmen and consumers. E-commerce participation is not only an important starting point for herdsmen to increase the added value and profit space of livestock products, but also an effective way to change the original breeding behavior based on the premise of destroying grassland. Therefore, this paper presents an in-depth study on the issue of e-commerce enabling grassland ecological restoration, aiming to provide more scientific and effective guidance for e-commerce to be used to achieve a win–win situation in economy and ecology. Therefore, based on the data of 271 herdsmen in pastoral areas of Inner Mongolia, we used the OLS model and the two-stage least squares (2SLS) method to identify the direct impact of herdsmen’s e-commerce participation on grassland utilization pressure. The empirical results show that e-commerce participation can significantly decrease the grassland utilization pressure. The conclusion was still valid after alleviating endogeneity and conducting a robustness test. The results of a mechanism analysis suggest that the reduction effect of e-commerce participation on grassland utilization pressure is mainly due to price incentive, reputation incentive and place identity. Subjective norms can strengthen the inhibitory effect of e-commerce participation on grassland utilization pressure. Furthermore, a heterogeneity analysis demonstrates that e-commerce participation has a better, decreased impact on the grassland utilization pressure on the banners of China’s rural e-commerce demonstration county program. Under a counterfactual assumption, if herdsmen who can participate in e-commerce choose not to do this, their grassland utilization pressure will increase. Full article
16 pages, 1207 KiB  
Article
Acute Effects of Combining Weight and Elastic Resistance Exercise on Vascular Function in Older Adults
by Kampanart Paditsaeree and Witid Mitranun
Geriatrics 2024, 9(3), 56; https://doi.org/10.3390/geriatrics9030056 (registering DOI) - 27 Apr 2024
Abstract
Prior research has suggested that resistance exercise may result in a temporary decrease in vascular function, as measured by flow-mediated dilation (FMD), among untrained young individuals. However, the immediate impact of combined elastic and weight resistance training on older adults remains insufficiently explored. [...] Read more.
Prior research has suggested that resistance exercise may result in a temporary decrease in vascular function, as measured by flow-mediated dilation (FMD), among untrained young individuals. However, the immediate impact of combined elastic and weight resistance training on older adults remains insufficiently explored. We assessed vascular function before, after, and 30 min after acute exercise under three resistance conditions to evaluate whether a combination of weight and elastic resistance exercises has an acute effect on vascular function in older adults. Fourteen older adults (65.6 ± 2.9 years) executed three sets of 12 repetitions at 65% of one repetition maximum (1 RM) of the bench press (BP) exercise. Testing was performed on three separate days as follows: (1) barbell alone (BA); (2) barbell plus elastic bands (10% of 65% 1 RM) (BE10); and (3) barbell plus elastic bands (20% of 65% 1 RM) (BE20). A two-way (time × condition) repeated measures analysis of variance was employed to assess the time and condition effects on flow-mediated dilation (FMD) and pulse wave velocity (PWV). At 0 min post-exercise, FMD was significantly higher during BE10 than during BA (p < 0.05); however, at 30 min post-exercise, no significant difference (p ≥ 0.05) was observed between the three conditions. In each condition, FMD results did not differ significantly at different times (p ≥ 0.05). For FMD, the main effect of the condition (F[2,26] = 3.86, p = 0.034) and that of the time and condition (F[4,52] = 3.66, p = 0.011) were significant. For PWV, only the difference between the BA and BE10 conditions was significant at 0 min (p < 0.05). PWV increased from baseline in the BA condition (p < 0.05) but not significantly in the BE10 and BE20 conditions (p ≥ 0.05). Therefore, BA, BE10, and BE20 demonstrated various changes in vascular function. Long-term training intervention studies are needed to validate these findings. Full article
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15 pages, 764 KiB  
Review
The Role of Structural Variants in the Genetic Architecture of Parkinson’s Disease
by Abigail Miano-Burkhardt, Pilar Alvarez Jerez, Kensuke Daida, Sara Bandres Ciga and Kimberley J. Billingsley
Int. J. Mol. Sci. 2024, 25(9), 4801; https://doi.org/10.3390/ijms25094801 (registering DOI) - 27 Apr 2024
Abstract
Parkinson’s disease (PD) significantly impacts millions of individuals worldwide. Although our understanding of the genetic foundations of PD has advanced, a substantial portion of the genetic variation contributing to disease risk remains unknown. Current PD genetic studies have primarily focused on one form [...] Read more.
Parkinson’s disease (PD) significantly impacts millions of individuals worldwide. Although our understanding of the genetic foundations of PD has advanced, a substantial portion of the genetic variation contributing to disease risk remains unknown. Current PD genetic studies have primarily focused on one form of genetic variation, single nucleotide variants (SNVs), while other important forms of genetic variation, such as structural variants (SVs), are mostly ignored due to the complexity of detecting these variants with traditional sequencing methods. Yet, these forms of genetic variation play crucial roles in gene expression and regulation in the human brain and are causative of numerous neurological disorders, including forms of PD. This review aims to provide a comprehensive overview of our current understanding of the involvement of coding and noncoding SVs in the genetic architecture of PD. Full article
(This article belongs to the Special Issue Understanding the Role of Non-coding DNA in Neurodegenerative Disease)
22 pages, 992 KiB  
Review
Exploring Electrical Neuromodulation as an Alternative Therapeutic Approach in Inflammatory Bowel Diseases
by Suofeiya Dilixiati, Jiaxi Yan, De Qingzhuoga, Gengqing Song and Lei Tu
Medicina 2024, 60(5), 729; https://doi.org/10.3390/medicina60050729 (registering DOI) - 27 Apr 2024
Abstract
Background and Objectives: This review systematically evaluates the potential of electrical neuromodulation techniques—vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)—as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s Disease (CD). It aims [...] Read more.
Background and Objectives: This review systematically evaluates the potential of electrical neuromodulation techniques—vagus nerve stimulation (VNS), sacral nerve stimulation (SNS), and tibial nerve stimulation (TNS)—as alternative treatments for inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s Disease (CD). It aims to synthesize current evidence on the efficacy and safety of these modalities, addressing the significant burden of IBD on patient quality of life and the limitations of existing pharmacological therapies. Materials and Methods: We conducted a comprehensive analysis of studies from PubMed, focusing on research published between 1978 and 2024. The review included animal models and clinical trials investigating the mechanisms, effectiveness, and safety of VNS, SNS, and TNS in IBD management. Special attention was given to the modulation of inflammatory responses and its impact on gastrointestinal motility and functional gastrointestinal disorders associated with IBD. Results: Preliminary findings suggest that VNS, SNS, and TNS can significantly reduce inflammatory markers and improve symptoms in IBD patients. These techniques also show potential in treating related gastrointestinal disorders during IBD remission phases. However, the specific mechanisms underlying these benefits remain to be fully elucidated, and there is considerable variability in treatment parameters. Conclusions: Electrical neuromodulation holds promise as a novel therapeutic avenue for IBD, offering an alternative to patients who do not respond to traditional treatments or experience adverse effects. The review highlights the need for further rigorous studies to optimize stimulation parameters, understand long-term outcomes, and integrate neuromodulation effectively into IBD treatment protocols. Full article
(This article belongs to the Section Gastroenterology & Hepatology)
17 pages, 4775 KiB  
Article
Altitudinal Variation in Species Diversity, Distribution, and Regeneration Status of a Secondary Picea Forest in Guandi Mountain, Northern China
by Mengtao Zhang, Zhuoyue Liu, Zhaohui Yang, Huanhuan Shen, Jin Wang and Xiaogang Wu
Forests 2024, 15(5), 771; https://doi.org/10.3390/f15050771 (registering DOI) - 27 Apr 2024
Abstract
Altitude plays a crucial role in shaping the diversity and distribution of species in forest landscapes in mountainous regions. However, existing studies often lack comprehensive analysis of the intricate relationships among environmental factors, disturbances, and species diversity. This study aims to address this [...] Read more.
Altitude plays a crucial role in shaping the diversity and distribution of species in forest landscapes in mountainous regions. However, existing studies often lack comprehensive analysis of the intricate relationships among environmental factors, disturbances, and species diversity. This study aims to address this gap by thoroughly analyzing major species’ diversity, distribution, and regeneration status, along with their influencing factors, across different altitudinal gradients (1850 to 2350 m). Field surveys were conducted to examine the major species in different vegetation layers of the secondary Picea forest in Guandi Mountain. The key findings from the study include the following: (1) the study area recorded a total of nine species of adult trees, belonging to eight genera in five families, fourteen species of shrubs from eight genera in five families, and fifty-two herb species representing forty-eight genera in twenty-six families. Dominant species varied across layers, with Picea asperata Mast. and Larix principis-rupprechtii Mayr. dominating the arborous layer, Lonicera ferdinandii Franch. and Cotoneaster acutifolius Turcz. in the shrub layer, and Poa pratensis L. and Duchesnea indica (Andrews.) Focke in the herb layer. (2) Altitude significantly influenced species diversity, with the most pronounced effects observed in the shrub and herb layers. (3) Tree species regeneration varied with altitude, with Picea asperata exhibiting the highest regeneration performance, particularly in the high-altitude zone (2250–2350 m). Regeneration parameters were significantly correlated with species diversity indices in both tree and shrub layers. (4) Redundancy analysis revealed that, apart from altitude, cutting (p = 0.015) influenced the species diversity of the tree layer, while annual precipitation (p = 0.006) and temperature (p = 0.01) determined the diversity of the shrub layer. Grazing (p = 0.042) was identified as a determining factor for species diversity in the herb layer. Overall, these findings provide valuable insights into the sustainable management of forest ecosystems in the study area and offer practical guidance for forest management in similar mountainous landscapes worldwide. Full article
15 pages, 3402 KiB  
Article
Fluorescent α-Conotoxin [Q1G, ΔR14]LvIB Identifies the Distribution of α7 Nicotinic Acetylcholine Receptor in the Rat Brain
by Hongyu Shan, Nan Wang, Xinyu Gao, Zihan Wang, Jinpeng Yu, Dongting Zhangsun, Xiaopeng Zhu and Sulan Luo
Mar. Drugs 2024, 22(5), 200; https://doi.org/10.3390/md22050200 (registering DOI) - 27 Apr 2024
Abstract
α7 nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The α7 nAChR has high Ca2+ permeability and can be quickly activated and desensitized, and is closely related to [...] Read more.
α7 nicotinic acetylcholine receptors (nAChRs) are mainly distributed in the central nervous system (CNS), including the hippocampus, striatum, and cortex of the brain. The α7 nAChR has high Ca2+ permeability and can be quickly activated and desensitized, and is closely related to Alzheimer’s disease (AD), epilepsy, schizophrenia, lung cancer, Parkinson’s disease (PD), inflammation, and other diseases. α-conotoxins from marine cone snail venom are typically short, disulfide-rich neuropeptides targeting nAChRs and can distinguish various subtypes, providing vital pharmacological tools for the functional research of nAChRs. [Q1G, ΔR14]LvΙB is a rat α7 nAChRs selective antagonist, modified from α-conotoxin LvΙB. In this study, we utilized three types of fluorescein after N-Hydroxy succinimide (NHS) activation treatment: 6-TAMRA-SE, Cy3 NHS, and BODIPY-FL NHS, labeling the N-Terminal of [Q1G, ΔR14]LvΙB under weak alkaline conditions, obtaining three fluorescent analogs: LvIB-R, LvIB-C, and LvIB-B, respectively. The potency of [Q1G, ΔR14]LvΙB fluorescent analogs was evaluated at rat α7 nAChRs expressed in Xenopus laevis oocytes. Using a two-electrode voltage clamp (TEVC), the half-maximal inhibitory concentration (IC50) values of LvIB-R, LvIB-C, and LvIB-B were 643.3 nM, 298.0 nM, and 186.9 nM, respectively. The stability of cerebrospinal fluid analysis showed that after incubation for 12 h, the retention rates of the three fluorescent analogs were 52.2%, 22.1%, and 0%, respectively. [Q1G, ΔR14]LvΙB fluorescent analogs were applied to explore the distribution of α7 nAChRs in the hippocampus and striatum of rat brain tissue and it was found that Cy3- and BODIPY FL-labeled [Q1G, ΔR14]LvΙB exhibited better imaging characteristics than 6-TAMARA-. It was also found that α7 nAChRs are widely distributed in the cerebral cortex and cerebellar lobules. Taking into account potency, imaging, and stability, [Q1G, ΔR14]LvΙB -BODIPY FL is an ideal pharmacological tool to investigate the tissue distribution and function of α7 nAChRs. Our findings not only provide a foundation for the development of conotoxins as visual pharmacological probes, but also demonstrate the distribution of α7 nAChRs in the rat brain. Full article
(This article belongs to the Section Marine Toxins)
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12 pages, 475 KiB  
Article
Assessing the Interpretation of Molecular Test Results in the Diagnosis of Bloodstream Infections
by Natalia Słabisz, Patrycja Leśnik, Katarzyna Żybura-Wszoła, Ruth Dudek-Wicher, Urszula Nawrot and Jacek Majda
Diagnostics 2024, 14(9), 915; https://doi.org/10.3390/diagnostics14090915 (registering DOI) - 27 Apr 2024
Abstract
A retrospective study at the 4th Military Clinical Hospital in Wroclaw, Poland, assessed PCR testing alongside blood cultures to guide antimicrobial therapy decisions in hospitalized patients, to determine how much time the results of the molecular tests preceded conventional methods. Among 118 patients, [...] Read more.
A retrospective study at the 4th Military Clinical Hospital in Wroclaw, Poland, assessed PCR testing alongside blood cultures to guide antimicrobial therapy decisions in hospitalized patients, to determine how much time the results of the molecular tests preceded conventional methods. Among 118 patients, Staphylococcus aureus (37%) and Escherichia coli (21%) were the most common bloodstream infection agents. Blood cultures utilized the BacT/ALERT 3D system, and molecular diagnostics were conducted using the FilmArray platform with the BIOFIRE BCID2 panel. Methicillin susceptibility was observed in 66% of S. aureus strains, while 26% of Gram-negative bacilli exhibited an ESBL phenotype. Therapeutic decisions based on molecular test results were often incorrect for S. aureus infections, particularly MSSA (64.5%), but generally accurate for Gram-negative bacilli. The median times from positive blood culture to BCID2 and pathogen identification/susceptibility were 10 h and 52 h, respectively. Molecular diagnostics facilitated faster initiation of appropriate antibiotic therapy, highlighting the need to educate medical staff on proper interpretation. Consulting within an antimicrobial stewardship program (ASP) could enhance the benefits of implementing molecular methods in bloodstream infection diagnostics. Full article
(This article belongs to the Section Diagnostic Microbiology and Infectious Disease)
17 pages, 3531 KiB  
Article
Adjoint Solver-Based Analysis of Mouth–Tongue Morphologies on Vapor Deposition in the Upper Airway
by Mohamed Talaat, Xiuhua Si and Jinxiang Xi
Fluids 2024, 9(5), 104; https://doi.org/10.3390/fluids9050104 (registering DOI) - 27 Apr 2024
Abstract
Even though inhalation dosimetry is determined by three factors (i.e., breathing, aerosols, and the respiratory tract), the first two categories have been more widely studied than the last. Both breathing and aerosols are quantitative variables that can be easily changed, while respiratory airway [...] Read more.
Even though inhalation dosimetry is determined by three factors (i.e., breathing, aerosols, and the respiratory tract), the first two categories have been more widely studied than the last. Both breathing and aerosols are quantitative variables that can be easily changed, while respiratory airway morphologies are difficult to reconstruct, modify, and quantify. Although several methods are available for model reconstruction and modification, developing an anatomically accurate airway model and morphing it to various physiological conditions remains labor-intensive and technically challenging. The objective of this study is to explore the feasibility of using an adjoint–CFD model to understand airway shape effects on vapor deposition and control vapor flux into the lung. A mouth–throat model was used, with the shape of the mouth and tongue being automatically varied via adjoint morphing and the vapor transport being simulated using ANSYS Fluent coupled with a wall absorption model. Two chemicals with varying adsorption rates, Acetaldehyde and Benzene, were considered, which exhibited large differences in dosimetry sensitivity to airway shapes. For both chemicals, the maximal possible morphing was first identified and then morphology parametric studies were conducted. Results show that changing the mouth–tongue shape can alter the oral filtration by 3.2% for Acetaldehyde and 0.27% for Benzene under a given inhalation condition. The front tongue exerts a significant impact on all cases considered, while the impact of other regions varies among cases. This study demonstrates that the hybrid adjoint–CFD approach can be a practical and efficient method to investigate morphology-associated variability in the dosimetry of vapors and nanomedicines under steady inhalation. Full article
(This article belongs to the Special Issue Advances in Hemodynamics and Related Biological Flows)
16 pages, 2565 KiB  
Article
Synthesis and Characterization of Novel Cobalt Carbonyl Phosphorus and Arsenic Clusters
by Mehdi Elsayed Moussa, Susanne Bauer, Christian Graßl, Christoph Riesinger, Gábor Balázs and Manfred Scheer
Molecules 2024, 29(9), 2025; https://doi.org/10.3390/molecules29092025 (registering DOI) - 27 Apr 2024
Abstract
Phosphorus- and arsenic-containing cobalt clusters are an interesting class of compounds that continue to provide new structures with captivating bonding patterns. Although the first members of this family were reported 45 years ago, the number of such species is still limited within the [...] Read more.
Phosphorus- and arsenic-containing cobalt clusters are an interesting class of compounds that continue to provide new structures with captivating bonding patterns. Although the first members of this family were reported 45 years ago, the number of such species is still limited within the broad family of transition metal complexes bearing pnictogen atoms. Herein, we present the reaction of Co2(CO)8 as a cobalt source with a number of phosphorus- and arsenic-containing compounds under variable reaction conditions. These reactions result in various known and novel cobalt phosphorus and cobalt arsenic clusters in which different nuclearity ratios between P/As and Co exist. All those clusters were characterized by X-ray structural analysis and partly by IR, 31P{1H} NMR, EI-MS and elemental analysis. This comprehensive study is the first detailed study in this field that reveals the richness of compounds that could be obtained only by modifying the ratio of used reactants and the involved reaction conditions. Full article
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17 pages, 28860 KiB  
Review
Platelet Biorheology and Mechanobiology in Thrombosis and Hemostasis: Perspectives from Multiscale Computation
by Rukiye Tuna, Wenjuan Yi, Esmeralda Crespo Cruz, JP Romero, Yi Ren, Jingjiao Guan, Yan Li, Yuefan Deng, Danny Bluestein, Zixiang Leonardo Liu and Jawaad Sheriff
Int. J. Mol. Sci. 2024, 25(9), 4800; https://doi.org/10.3390/ijms25094800 (registering DOI) - 27 Apr 2024
Abstract
Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s1) relies on platelet activation and coagulation. Thrombosis at elevated [...] Read more.
Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modeling informed by biology can provide new pathophysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to the better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine. Full article
28 pages, 5720 KiB  
Article
Vine Copula-Based Multivariate Distribution of Rainfall Intensity, Wind Speed, and Wind Direction for Optimizing Qatari Meteorological Stations
by Hassan Qasem, Niels-Erik Joergensen, Ataur Rahman, Husam Abdullah Samman, Sharouq Al Malki and Abdulrahman Saleh Al Ansari
Water 2024, 16(9), 1257; https://doi.org/10.3390/w16091257 (registering DOI) - 27 Apr 2024
Abstract
This study employs copula functions to establish the dependency structure of the joint distribution among rainfall intensity, wind speed, and wind direction in Qatar. Based on a Vine Copula, the trivariate distribution between rainfall intensity, wind speed, and wind direction is found to [...] Read more.
This study employs copula functions to establish the dependency structure of the joint distribution among rainfall intensity, wind speed, and wind direction in Qatar. Based on a Vine Copula, the trivariate distribution between rainfall intensity, wind speed, and wind direction is found to exhibit a root-mean-square error (RMSE) of 0.0072 on the observed vs. modeled cumulative probabilities using ranked normalized observations. It is also found that the winter Shamal winds are most pronounced during rainfall. However, a secondary component of easterly winds known as the Kaus winds is also found to exert an important influence. This wind pattern is observable during rainfall at all the selected stations, albeit with minor variations. It is also found that rainfall stations where the rainfall is obstructed in any way from northwest to north and from east to southeast significantly influence the rainfall measurements. Specific rain gauges in Qatar are found to be situated in disrupted surroundings, such as meteorological stations close to passing traffic, where road spray could infiltrate the rain gauge funnel, impacting the accuracy of rainfall measurements. The study results necessitated the relocation of approximately half of these roadside gauges to mitigate wind-induced biases from road spray. An evaluation of operations is recommended for approximately 80 meteorological stations responsible for measuring rainfall in Qatar. The methodology devised in this study holds potential for application to other Middle Eastern countries and regions with similar climates. Full article
(This article belongs to the Section Water and Climate Change)
35 pages, 949 KiB  
Review
From Eye Care to Hair Growth: Bimatoprost
by Marco Zeppieri, Caterina Gagliano, Leopoldo Spadea, Carlo Salati, Ekele Caleb Chukwuyem, Ehimare Samuel Enaholo, Fabiana D’Esposito and Mutali Musa
Pharmaceuticals 2024, 17(5), 561; https://doi.org/10.3390/ph17050561 (registering DOI) - 27 Apr 2024
Abstract
Background: Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and beyond. Originally developed as an ocular hypotensive agent, it has proven highly effective in treating glaucoma and ocular [...] Read more.
Background: Bimatoprost has emerged as a significant medication in the field of medicine over the past several decades, with diverse applications in ophthalmology, dermatology, and beyond. Originally developed as an ocular hypotensive agent, it has proven highly effective in treating glaucoma and ocular hypertension. Its ability to reduce intraocular pressure has established it as a first-line treatment option, improving management and preventing vision loss. In dermatology, bimatoprost has shown promising results in the promotion of hair growth, particularly in the treatment of alopecia and hypotrichosis. Its mechanism of action, stimulating the hair cycle and prolonging the growth phase, has led to the development of bimatoprost-containing solutions for enhancing eyelash growth. Aim: The aim of our review is to provide a brief description, overview, and studies in the current literature regarding the versatile clinical use of bimatoprost in recent years. This can help clinicians determine the most suitable individualized therapy to meet the needs of each patient. Methods: Our methods involve a comprehensive review of the latest advancements reported in the literature in bimatoprost formulations, which range from traditional eye drops to sustained-release implants. These innovations offer extended drug delivery, enhance patient compliance, and minimize side effects. Results: The vast literature published on PubMed has confirmed the clinical usefulness of bimatoprost in lowering intraocular pressure and in managing patients with glaucoma. Numerous studies have shown promising results in dermatology and esthetics in promoting hair growth, particularly in treating alopecia and hypotrichosis. Its mechanism of action involves stimulating the hair cycle and prolonging the growth phase, leading to the development of solutions that enhance eyelash growth. The global use of bimatoprost has expanded significantly, with applications growing beyond its initial indications. Ongoing research is exploring its potential in glaucoma surgery, neuroprotection, and cosmetic procedures. Conclusions: Bimatoprost has shown immense potential for addressing a wide range of therapeutic needs through various formulations and advancements. Promising future perspectives include the exploration of novel delivery systems such as contact lenses and microneedles to further enhance drug efficacy and patient comfort. Ongoing research and future perspectives continue to shape its role in medicine, promising further advancements and improved patient outcomes. Full article
(This article belongs to the Special Issue Ophthalmic Pharmacology)
20 pages, 6538 KiB  
Article
An Enzymatic and Proteomic Analysis of Panus lecomtei during Biodegradation of Gossypol in Cottonseed
by Clemente Batista Soares Neto, Taísa Godoy Gomes, Edivaldo Ximenes Ferreira Filho, Wagner Fontes, Carlos André Ornelas Ricart, João Ricardo Moreira de Almeida, Félix Gonçalves de Siqueira and Robert Neil Gerard Miller
J. Fungi 2024, 10(5), 321; https://doi.org/10.3390/jof10050321 (registering DOI) - 27 Apr 2024
Abstract
Cotton is an important plant-based protein. Cottonseed cake, a byproduct of the biodiesel industry, offers potential in animal supplementation, although the presence of the antinutritional sesquiterpenoid gossypol limits utilization. The macrofungus Panus lecomtei offers potential in detoxification of antinutritional factors. Through an enzymatic [...] Read more.
Cotton is an important plant-based protein. Cottonseed cake, a byproduct of the biodiesel industry, offers potential in animal supplementation, although the presence of the antinutritional sesquiterpenoid gossypol limits utilization. The macrofungus Panus lecomtei offers potential in detoxification of antinutritional factors. Through an enzymatic and proteomic analysis of P. lecomtei strain BRM044603, grown on crushed whole cottonseed contrasting in the presence of free gossypol (FG), this study investigated FG biodegradation over a 15-day cultivation period. Fungal growth reduced FG to levels at 100 μg/g, with a complex adaptive response observed, involving primary metabolism and activation of oxidative enzymes for metabolism of xenobiotics. Increasing activity of secreted laccases correlated with a reduction in FG, with enzyme fractions degrading synthetic gossypol to trace levels. A total of 143 and 49 differentially abundant proteins were observed across the two contrasting growth conditions after 6 and 12 days of cultivation, respectively, revealing a dynamic protein profile during FG degradation, initially related to constitutive metabolism, then later associated with responses to oxidative stress. The findings advance our understanding of the mechanisms involved in gossypol degradation and highlight the potential of P. lecomtei BRM044603 in cotton waste biotreatment, relevant for animal supplementation, sustainable resource utilization, and bioremediation. Full article
(This article belongs to the Special Issue Fungal-Related Proteomics in Biotechnology and Health)
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33 pages, 7650 KiB  
Article
Elevational Earth-Sheltered Buildings with Horizontal Overhang Photovoltaic-Integrated Panels—New Energy-Plus Building Concept in the Territory of Serbia
by Aleksandar Nešović, Robert Kowalik, Milan Bojović, Agata Janaszek and Stanisław Adamczak
Energies 2024, 17(9), 2100; https://doi.org/10.3390/en17092100 (registering DOI) - 27 Apr 2024
Abstract
The global scientific community is intensively promoting energy-plus buildings. Following the leading world trends, this paper presents a new energy-plus building concept—elevational earth-sheltered buildings with three different types of horizontal overhang photovoltaic-integrated panels: wooden support columns covered with clay tiles, steel pipes as [...] Read more.
The global scientific community is intensively promoting energy-plus buildings. Following the leading world trends, this paper presents a new energy-plus building concept—elevational earth-sheltered buildings with three different types of horizontal overhang photovoltaic-integrated panels: wooden support columns covered with clay tiles, steel pipes as support columns covered with sheet steel, and concrete support columns with concrete coverage. In this instance, the specific multi-numerical case study building model for the city of Kragujevac (located in central Serbia with favorable climatic conditions) was performed over 7 months (from 1 October to 30 April), taking into account the soil temperature, the effects of solar shading, the performance of the heating system—a ground source heat pump—and the characteristics of the artificial and automatic lighting control system. The simulation results show that the optimal depth of a horizontal overhang (energy-plus status) depends on the occupant’s habits, in addition to meteorological conditions. The presented methodology can be used for any other location, both in Europe and the world. Full article
(This article belongs to the Special Issue Energy Efficiency of the Buildings III)
23 pages, 741 KiB  
Article
An Effective Modification Strategy to Build Multifunctional Peptides Based on a Trypsin Inhibitory Peptide of the Kunitz Family
by Ying Wang, Daning Shi, Wanchen Zou, Yangyang Jiang, Tao Wang, Xiaoling Chen, Chengbang Ma, Wei Li, Tianbao Chen, James F. Burrows, Lei Wang and Mei Zhou
Pharmaceutics 2024, 16(5), 597; https://doi.org/10.3390/pharmaceutics16050597 (registering DOI) - 27 Apr 2024
Abstract
Peptides with antimicrobial activity or protease inhibitory activity are potential candidates to supplement traditional antibiotics or cancer chemotherapies. However, the potential of many peptides are limited by drawbacks such as cytotoxicity or susceptibility to hydrolysis. Therefore, strategies to modify the structure of promising [...] Read more.
Peptides with antimicrobial activity or protease inhibitory activity are potential candidates to supplement traditional antibiotics or cancer chemotherapies. However, the potential of many peptides are limited by drawbacks such as cytotoxicity or susceptibility to hydrolysis. Therefore, strategies to modify the structure of promising peptides may represent an effective approach for developing more promising clinical candidates. In this study, the mature peptide OSTI−1949, a Kunitz-type inhibitor from Odorrana schmackeri, and four designed analogues were successfully synthesised. In contrast to the parent peptide, the analogues showed impressive multi-functionality including antimicrobial, anticancer, and trypsin inhibitory activities. In terms of safety, there were no obvious changes observed in the haemolytic activity at the highest tested concentration, and the analogue OSTI−2461 showed an increase in activity against cancer cell lines without cytotoxicity to normal cells (HaCaT). In summary, through structural modification of a natural Kunitz-type peptide, the biological activity of analogues was improved whilst retaining low cytotoxicity. The strategy of helicity enhancement by forming an artificial α-helix and ß-sheet structure provides a promising way to develop original bioactive peptides for clinical therapeutics. Full article
25 pages, 1716 KiB  
Article
A Spacecraft Onboard Autonomous Task Scheduling Method Based on Hierarchical Task Network-Timeline
by Junwei Zhang and Liangqing Lyu
Aerospace 2024, 11(5), 350; https://doi.org/10.3390/aerospace11050350 (registering DOI) - 27 Apr 2024
Abstract
To address the inherent challenges of deep space exploration, such as communication delays and the unpredictability of spacecraft environments, this study focuses on enhancing spacecraft adaptability and autonomy, which are essential for Autonomous Space Scientific Exploration. A pivotal aspect of this endeavor is [...] Read more.
To address the inherent challenges of deep space exploration, such as communication delays and the unpredictability of spacecraft environments, this study focuses on enhancing spacecraft adaptability and autonomy, which are essential for Autonomous Space Scientific Exploration. A pivotal aspect of this endeavor is the advancement of spacecraft task scheduling, which is integral to increasing spacecraft autonomy. Current research in this domain predominantly revolves around mission timing planning and is primarily executed from ground stations. However, these plans often lack the granularity required for direct implementation by spacecraft. In response, our study proposes an innovative approach to augment spacecraft autonomy, introducing a method that articulately describes mission objectives and resource information. We designed a novel hierarchical task network-timeline (HTN-T) algorithm, an amalgamation of the HTN scheduling method and the distinctive elements of existing research. This algorithm addresses time constraints through horizontal and vertical expansions, building upon the resolution of logical constraints found in conventional planning methods. Furthermore, it introduces a priority-based strategy for resolving resource conflicts in spacecraft tasks. This algorithm is substantiated through validation, including proof-of-principle demonstrations and assessments within a Space–ground Collaborative Management and Control System encompassing both ground and spacecraft operations. The findings indicate that our proposed algorithm achieves high rates of scheduling success and operational efficiency within a feasible timeframe, thus effectively navigating the complexities of autonomous spacecraft task scheduling. Full article
(This article belongs to the Section Astronautics & Space Science)
17 pages, 3862 KiB  
Article
Flexural-Gravity Waves in a Channel with a Compressed Ice Cover
by Evgeniy Batyaev and Tatiana Khabakhpasheva
Water 2024, 16(9), 1255; https://doi.org/10.3390/w16091255 (registering DOI) - 27 Apr 2024
Abstract
The characteristics of linear hydroelastic waves propagating in a channel covered with compressed ice are investigated. The channel has a rectangular cross-section and is assumed to be infinite in length. The fluid in the channel is non-viscous and incompressible; its flow is potential. [...] Read more.
The characteristics of linear hydroelastic waves propagating in a channel covered with compressed ice are investigated. The channel has a rectangular cross-section and is assumed to be infinite in length. The fluid in the channel is non-viscous and incompressible; its flow is potential. The ice cover is modelled by an elastic plate of constant thickness frozen to the channel walls. Principal attention is paid to the investigation of the influence of ice compression on the parameters of hydroelastic waves. The problem is solved in a coupled hydroelastic formulation. The profiles of propagating waves in the channel are sought in the form of series on the normal modes of a dry plate. The modes are defined analytically through trigonometric and hyperbolic functions. It is shown that compression in the longitudinal and transverse directions has different effects on the dispersion relations of these hydroelastic waves, their shape and phase, as well as on the critical velocities and strains distribution. Full article
(This article belongs to the Special Issue Hydraulic and Transient Performances of Pumped-Storage Units)
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23 pages, 865 KiB  
Review
Long Non-Coding RNAs as Determinants of Thyroid Cancer Phenotypes: Investigating Differential Gene Expression Patterns and Novel Biomarker Discovery
by Nicole R. DeSouza, Tara Jarboe, Michelle Carnazza, Danielle Quaranto, Humayun K. Islam, Raj K. Tiwari and Jan Geliebter
Biology 2024, 13(5), 304; https://doi.org/10.3390/biology13050304 (registering DOI) - 27 Apr 2024
Abstract
Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of [...] Read more.
Thyroid Cancer (TC) is the most common endocrine malignancy, with increasing incidence globally. Papillary thyroid cancer (PTC), a differentiated form of TC, accounts for approximately 90% of TC and occurs predominantly in women of childbearing age. Although responsive to current treatments, recurrence of PTC by middle age is common and is much more refractive to treatment. Undifferentiated TC, particularly anaplastic thyroid cancer (ATC), is the most aggressive TC subtype, characterized by it being resistant and unresponsive to all therapeutic and surgical interventions. Further, ATC is one of the most aggressive and lethal malignancies across all cancer types. Despite the differences in therapeutic needs in differentiated vs. undifferentiated TC subtypes, there is a critical unmet need for the identification of molecular biomarkers that can aid in early diagnosis, prognosis, and actionable therapeutic targets for intervention. Advances in the field of cancer genomics have enabled for the elucidation of differential gene expression patterns between tumors and healthy tissue. A novel category of molecules, known as non-coding RNAs, can themselves be differentially expressed, and extensively contribute to the up- and downregulation of protein coding genes, serving as master orchestrators of regulated and dysregulated gene expression patterns. These non-coding RNAs have been identified for their roles in driving carcinogenic patterns at various stages of tumor development and have become attractive targets for study. The identification of specific genes that are differentially expressed can give insight into mechanisms that drive carcinogenic patterns, filling the gaps of deciphering molecular and cellular processes that modulate TC subtypes, outside of well-known driver mutations. Full article
(This article belongs to the Section Biochemistry and Molecular Biology)

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