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Search Results (244)

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Keywords = A/B substitution

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18 pages, 3421 KiB  
Article
Bisphenol E Neurotoxicity in Zebrafish Larvae: Effects and Underlying Mechanisms
by Kaicheng Gu, Lindong Yang, Yi Jiang, Zhiqiang Wang and Jiannan Chen
Biology 2025, 14(8), 992; https://doi.org/10.3390/biology14080992 (registering DOI) - 4 Aug 2025
Abstract
As typical environmental hormones, endocrine-disrupting chemicals (EDCs) have become a global environmental health issue of high concern due to their property of interfering with the endocrine systems of organisms. As a commonly used substitute for bisphenol A (BPA), bisphenol E (BPE) has been [...] Read more.
As typical environmental hormones, endocrine-disrupting chemicals (EDCs) have become a global environmental health issue of high concern due to their property of interfering with the endocrine systems of organisms. As a commonly used substitute for bisphenol A (BPA), bisphenol E (BPE) has been frequently detected in environmental matrices such as soil and water in recent years. Existing research has unveiled the developmental and reproductive toxicity of BPE; however, only one in vitro cellular experiment has preliminarily indicated potential neurotoxic risks, with its underlying mechanisms remaining largely unelucidated in the current literature. Potential toxic mechanisms and action targets of BPE were predicted using the zebrafish model via network toxicology and molecular docking, with RT-qPCRs being simultaneously applied to uncover neurotoxic effects and associated mechanisms of BPE. A significant decrease (p < 0.05) in the frequency of embryonic spontaneous movements was observed in zebrafish at exposure concentrations ≥ 0.01 mg/L. At 72 hpf and 144 hpf, the larval body length began to shorten significantly from 0.1 mg/L to 1 mg/L, respectively (p < 0.01), accompanied by a reduced neuronal fluorescence intensity and a shortened neural axon length (p < 0.01). By 144 hpf, the motor behavior in zebrafish larvae was inhibited. Through network toxicology and molecular docking, HSP90AB1 was identified as the core target, with the cGMP/PKG signaling pathway determined to be the primary route through which BPE induces neurotoxicity in zebrafish larvae. BPE induces neuronal apoptosis and disrupts neurodevelopment by inhibiting the cGMP/PKG signaling pathway, ultimately suppressing the larval motor behavior. To further validate the experimental outcomes, we measured the expression levels of genes associated with neurodevelopment (elavl3, mbp, gap43, syn2a), serotonergic synaptic signaling (5-ht1ar, 5-ht2ar), the cGMP/PKG pathway (nos3), and apoptosis (caspase-3, caspase-9). These results offer crucial theoretical underpinnings for evaluating the ecological risks of BPE and developing environmental management plans, as well as crucial evidence for a thorough comprehension of the toxic effects and mechanisms of BPE on neurodevelopment in zebrafish larvae. Full article
(This article belongs to the Special Issue Advances in Aquatic Ecological Disasters and Toxicology)
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25 pages, 4401 KiB  
Article
Impact of High Energy Milling and Mineral Additives on a Carbonate–Quartz–Apatite System for Ecological Applications
by Vilma Petkova, Katerina Mihaylova, Ekaterina Serafimova, Rositsa Titorenkova, Liliya Tsvetanova and Andres Trikkel
Materials 2025, 18(15), 3508; https://doi.org/10.3390/ma18153508 - 26 Jul 2025
Viewed by 327
Abstract
In this study, high-energy milled (HEM) samples of natural phosphorites from Estonian deposits were investigated. The activation was performed via planetary mill with Cr-Ni grinders with a diameter of 20 mm. This method is an ecological alternative, since it eliminates the disadvantages of [...] Read more.
In this study, high-energy milled (HEM) samples of natural phosphorites from Estonian deposits were investigated. The activation was performed via planetary mill with Cr-Ni grinders with a diameter of 20 mm. This method is an ecological alternative, since it eliminates the disadvantages of conventional acid methods, namely the release of gaseous and solid technogenic products. The aim of the study is to determine the changes in the structure to follow the solid-state transitions and the isomorphic substitutions in the anionic sub-lattice in the structure of the main mineral apatite in the samples from Estonia, under the influence of HEM activation. It is also interesting to investigate the influence of HEM on structural-phase transformations on the structure of impurity minerals-free calcite/dolomite, pyrite, quartz, as well as to assess their influence on the thermal behavior of the main mineral apatite. The effect of HEM is monitored by using a complex of analytical methods, such as chemical analysis, powder X-ray diffraction (PXRD), wavelength-dispersive X-ray fluorescence (WD-XRF) analysis, and Fourier-transformed infrared (FTIR) analysis. The obtained results prove the correlation in the behavior of the studied samples with regard to their quartz content and bonded or non-bonded carbonate ions. After HEM activation of the raw samples, the following is established: (i) anionic isomorphism with formation of A and A-B type carbonate-apatites and hydroxyl-fluorapatite; (ii) solid-phase synthesis of calcium orthophosphate-CaHPO4 (monetite) and dicalcium diphosphate-β-Ca2P2O7; (iii) enhanced chemical reactivity by approximately three times by increasing the solubility via HEM activation. The dry milling method used is a suitable approach for solving technological projects to improve the composition and structure of soils, increasing soil fertility by introducing soluble forms of calcium phosphates. It provides a variety of application purposes depending on the composition, impurities, and processing as a soil improver, natural mineral fertilizer, or activator. Full article
(This article belongs to the Special Issue Advances in Rock and Mineral Materials—Second Edition)
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13 pages, 2775 KiB  
Article
Effects of Ti Substitution by Zr on Microstructure and Hydrogen Storage Properties of Laves Phase AB2-Type Alloy
by Xiaowei Guo, Lingxing Shi, Chuan Ma, Wentao Zhang, Chaoqun Xia and Tai Yang
Materials 2025, 18(15), 3438; https://doi.org/10.3390/ma18153438 - 22 Jul 2025
Viewed by 162
Abstract
In order to improve the hydrogen storage properties of Laves phase AB2-type alloys, a series of Ti1−xZrxMn1.0Cr0.85Fe0.1 (x = 0.1–0.5) alloys were prepared by arc melting. The effects of Zr [...] Read more.
In order to improve the hydrogen storage properties of Laves phase AB2-type alloys, a series of Ti1−xZrxMn1.0Cr0.85Fe0.1 (x = 0.1–0.5) alloys were prepared by arc melting. The effects of Zr content on microstructure and hydrogen storage properties was investigated in detail. Crystal structure characterizations confirmed that all the alloys exhibit a single-phase C14 Laves structure, and the lattice parameters increase with increasing Zr content. The hydrogen storage measurements of the alloys indicate that with increasing Zr content, the hydrogen storage capacity initially increases and then decreases. The hydrogen absorption and desorption measurements of the alloys were performed by a Sieverts-type apparatus. Pressure–composition–temperature (P-C-T) tests at various temperatures showed that all the alloys display sloped plateaus. Increasing Zr content results in a gradual decrease in hydrogen absorption and desorption plateau pressures. Moreover, these alloys exhibit varying degrees of hysteresis, which also becomes more pronounced with a rise in Zr content. In summary, the Ti0.7Zr0.3Mn1.0Cr0.85Fe0.1 alloy demonstrates the best comprehensive hydrogen storage capacity. Further investigation on the cyclic performance of the Ti0.7Zr0.3Mn1.0Cr0.85Fe0.1 alloy was conducted. It was found that the alloy particles undergo significant pulverization after hydrogenation cycles, but the alloy maintained good phase structure stability and hydrogen storage performance. Full article
(This article belongs to the Section Energy Materials)
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18 pages, 3172 KiB  
Article
Characterization of the Binding and Inhibition Mechanisms of a Novel Neutralizing Monoclonal Antibody Targeting the Stem Helix Region in the S2 Subunit of the Spike Protein of SARS-CoV-2
by Selene Si Ern Tan, Ee Hong Tam, Kah Man Lai, Yanjun Wu, Tianshu Xiao and Yee-Joo Tan
Vaccines 2025, 13(7), 688; https://doi.org/10.3390/vaccines13070688 - 26 Jun 2025
Viewed by 650
Abstract
Background/Objectives: For viral entry into host cells, the spike (S) protein of coronavirus (CoV) uses its S1 domain to bind to the host receptor and S2 domain to mediate the fusion between virion and cellular membranes. The S1 domain acquired multiple mutations as [...] Read more.
Background/Objectives: For viral entry into host cells, the spike (S) protein of coronavirus (CoV) uses its S1 domain to bind to the host receptor and S2 domain to mediate the fusion between virion and cellular membranes. The S1 domain acquired multiple mutations as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolved to give rise to Variant of Concerns (VOCs) but the S2 domain has limited changes. In particular, the stem helix in S2 did not change significantly and it is fairly well-conserved across multiple beta-CoVs. In this study, we generated a murine mAb 7B2 binding to the stem helix of SARS-CoV-2. Methods: MAb 7B2 was isolated from immunized mouse and its neutralization activity was evaluated using microneutralization, plaque reduction and cell–cell fusion assays. Bio-layer interferometry was used to measure binding affinity and AlphaFold3 was used to model the antibody–antigen interface. Results: MAb 7B2 has lower virus neutralizing and membrane block activities when compared to a previously reported stem helix-binding human mAb S2P6. Alanine scanning and AlphaFold3 modeling reveals that residues K1149 and D1153 in S form a network of polar interactions with the heavy chain of 7B2. Conversely, S2P6 binding to S is not affected by alanine substitution at K1149 and D1153 as indicated by the high ipTM scores in the predicted S2P6-stem helix structure. Conclusions: Our detailed characterization of the mechanism of inhibition of 7B2 reveals its distinctive binding model from S2P6 and yields insights on multiple neutralizing and highly conserved epitopes in the S2 domain which could be key components for pan-CoV vaccine development. Full article
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12 pages, 1752 KiB  
Proceeding Paper
Ab Initio Life-Cycle Analysis Assisting the Selection of Eco-Friendly Additives in Bio-Based Coatings
by Pieter Samyn, Patrick Cosemans and Thomas Vandenhaute
Eng. Proc. 2025, 87(1), 76; https://doi.org/10.3390/engproc2025087076 - 11 Jun 2025
Viewed by 380
Abstract
The formulation of eco-friendly coatings with protective properties against corrosion and/or mechanical degradation requires the selection of appropriate bio-based binders and functional additives. Although the concentration of additives remains limited, the replacement of fossil-based additives with bio-based additives may deliver an important contribution [...] Read more.
The formulation of eco-friendly coatings with protective properties against corrosion and/or mechanical degradation requires the selection of appropriate bio-based binders and functional additives. Although the concentration of additives remains limited, the replacement of fossil-based additives with bio-based additives may deliver an important contribution to improving the carbon footprint of a coating, in parallel with their influences on coating performance, lifetime, and processing. However, the role of bio-based additives in life-cycle analysis (LCA) is often neglected and minorly considered in current literature. Reasons for this include the complexity of the full system, together with a lack of data, methodological inconveniences, and appropriate design of realistic scenarios. Within this work, an approach of simplified LCA is followed by ab initio cradle-to-gate analysis of coating formulations focusing on the replacement of specific fossil additives (e.g., carbon black, silicates, and calcium carbonate) with bio-based additives (e.g., biochar, bio-based wax, recovered calcium carbonate, and nanocellulose). The different environmental impact parameters (human health, eco-toxicity, resource scarcity, and carbon footprint) for bio-based additives and coating formulations are calculated from eco-cost analysis (Idemat 2024 v2.2 database), indicating a 15 to 30% gain in carbon footprint for coatings with bio-based additives. In a particular case study for improving coating performance by substituting cellulosic additives into nanocellulose from different sources, the reduction in environmental impact parameters is positively associated with their high performance at low concentration. The need for intermediate processing of bio-based additives is a main parameter contributing to their environmental impact, but environmental benefits are abundantly compensated by their carbon storage credit and performance improvement. Full article
(This article belongs to the Proceedings of The 5th International Electronic Conference on Applied Sciences)
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29 pages, 7563 KiB  
Article
Influence of Fluorine Doping on Rutile TiO2 Nanostructures for Visible-Light-Driven Photocatalysis: A DFT + U Study
by Fikadu Takele Geldasa and Francis Birhanu Dejene
Nanomaterials 2025, 15(9), 694; https://doi.org/10.3390/nano15090694 - 5 May 2025
Cited by 2 | Viewed by 547
Abstract
In this work, a density functional theory (DFT) with Hubbard correction (U) approaches implemented through the Quantum ESPRESSO code is utilized to investigate the effects of fluorine (F) doping on the structural, electronic, and optical properties of rutile TiO2. Rutile TiO [...] Read more.
In this work, a density functional theory (DFT) with Hubbard correction (U) approaches implemented through the Quantum ESPRESSO code is utilized to investigate the effects of fluorine (F) doping on the structural, electronic, and optical properties of rutile TiO2. Rutile TiO2 is a promising material for renewable energy production and environmental remediation, but its wide bandgap limits its application to the UV spectrum, which is narrow and expensive. To extend the absorption edge of TiO2 into the visible light range, different concentrations of F were substituted at oxygen atom sites. The structural analysis reveals that the lattice constants and bond lengths of TiO2 increased with F concentrations. Ab initio molecular dynamics simulations (AIMD) at 1000 K confirm that both pristine and F-doped rutile TiO2 maintains structural integrity, indicating excellent thermal stability essential for high-temperature photocatalytic applications. Band structure calculations show that pure rutile TiO2 has a bandgap of 3.0 eV, which increases as the F concentration rises, with the 0.25 F-doped structures exhibiting an even larger bandgap, preventing it from responding to visible light. The absorption edge of doped TiO2 shifts towards the visible region, as shown by the imaginary part of the dielectric function. This research provides valuable insights for experimentalists, helping them understand how varying F concentrations influence the properties of rutile TiO2 for photocatalytic applications. Full article
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13 pages, 7137 KiB  
Communication
Co-Doping Effects on the Electronic and Optical Properties of β-Ga2O3: A First-Principles Investigation
by Ya-Rui Wang and Su-Zhen Luan
Materials 2025, 18(9), 2005; https://doi.org/10.3390/ma18092005 - 28 Apr 2025
Viewed by 608
Abstract
To meet the demands for functional layers in inverted flexible perovskite solar cells, high-performance formamidinium-based perovskite solar cells, and high-performance photodetectors in future applications, it is crucial to appropriately reduce the bandgap of third-generation wide-bandgap semiconductor materials. In this study, we first optimized [...] Read more.
To meet the demands for functional layers in inverted flexible perovskite solar cells, high-performance formamidinium-based perovskite solar cells, and high-performance photodetectors in future applications, it is crucial to appropriately reduce the bandgap of third-generation wide-bandgap semiconductor materials. In this study, we first optimized doping sites through Ag-Cl and Ag-S configurations to establish stable substitution patterns, followed by density functional theory (DFT) calculations using the Generalized Gradient Approximation with the Perdew–Burke–Ernzerhof (GGA-PBE) functional, implemented in the Vienna Ab initio Simulation Package (VASP). A plane-wave basis set with a cutoff energy of 450 eV and a 3 × 4 × 3 Γ-centered k-mesh were adopted to investigate the effects of Mg-Cl, Mg-S, Zn-Cl, and Zn-S co-doping on the structural stability, electronic properties, and optical characteristics of β-Ga2O3. Based on structural symmetry, six doping sites were considered, with Ag-S/Cl systems revealing preferential occupation at octahedral Ga(1) sites through site formation energy analysis. The results demonstrate that Mg-Cl, Mg-S, Zn-Cl, and Zn-S co-doped systems exhibit thermodynamic stability. The bandgap of pristine β-Ga2O3 was calculated to be 2.08 eV. Notably, Zn-Cl co-doping achieves the lowest bandgap reduction to 1.81 eV. Importantly, all co-doping configurations, including Mg-Cl, Mg-S, Zn-Cl, and Zn-S, effectively reduce the bandgap of β-Ga2O3. Furthermore, the co-doped systems show enhanced visible light absorption (30% increase at 500 nm) and improved optical storage performance compared to the pristine material. Full article
(This article belongs to the Section Optical and Photonic Materials)
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27 pages, 764 KiB  
Article
Effects of Carnosine Supplementation on Cognitive Outcomes in Prediabetes and Well-Controlled Type 2 Diabetes: A Randomised Placebo-Controlled Clinical Trial
by Rohit Hariharan, Aya Mousa, Kirthi Menon, Jack Feehan, Barbara Ukropcová, Jozef Ukropec, Martin Schön, Arshad Majid, Giancarlo Aldini, Maximilian de Courten, James Cameron, Simon M. Bell and Barbora de Courten
Pharmaceuticals 2025, 18(5), 630; https://doi.org/10.3390/ph18050630 - 26 Apr 2025
Viewed by 1271
Abstract
Background: Trends in global ageing underscore the rising burden of age-related cognitive decline and concomitant cardiometabolic diseases, including type 2 diabetes mellitus (T2DM). Carnosine, a naturally occurring dipeptide with anti-inflammatory, antioxidant and anti-glycating properties, has shown promise in animal models and limited human [...] Read more.
Background: Trends in global ageing underscore the rising burden of age-related cognitive decline and concomitant cardiometabolic diseases, including type 2 diabetes mellitus (T2DM). Carnosine, a naturally occurring dipeptide with anti-inflammatory, antioxidant and anti-glycating properties, has shown promise in animal models and limited human studies for improving cognitive function, insulin resistance and T2DM, but its therapeutic effects on cognition remain unclear. The aim of this study is to assess the effects of carnosine on cognitive function in individuals with prediabetes or well-controlled T2DM. Methods: This is a secondary analysis of a double-blind randomised controlled trial (RCT), whereby 49 adults with prediabetes or early-stage well-controlled T2DM were randomised to receive 2 g of carnosine or identical placebo daily for 14 weeks. At baseline and follow-up, cognitive function was assessed as a secondary outcome using the Digit-Symbol Substitution Test, Stroop test, Trail Making Tests A & B, and the Cambridge Automated Neuropsychological Test Battery (CANTAB). Results: In total, 42 adults (23 males and 19 females) completed the trial. There were no differences in participant anthropometry or cognitive functioning between carnosine and placebo groups at baseline (all p > 0.1). After the 14-week supplementation period, there were no differences between carnosine and placebo groups in change and follow-up values for any cognitive measures including Stroop, Digit Symbol Substitution Sest, Trail Making A/B or CANTAB (all p > 0.05). Adjustments for baseline cognitive scores, diabetic status, level of education, age or interaction effects with participants’ sex did not change the results. Conclusions: Carnosine supplementation did not improve cognitive measures in individuals with prediabetes or T2DM in this study. While larger trials may provide further insights, alternative factors—such as the relatively young and healthy profile of our cohort—may have contributed to the lack of observed effect. Future research should examine individuals with existing cognitive impairment or those at higher risk of cognitive decline to better define the therapeutic potential of carnosine in this context. Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Products in Internal Diseases)
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20 pages, 5173 KiB  
Article
Scarf Adhesive Bonding of 3D-Printed Polymer Structures
by Tiago F. R. Ribeiro, Raul D. S. G. Campilho, Ricardo F. R. Pinto and Ricardo J. B. Rocha
J. Manuf. Mater. Process. 2025, 9(4), 115; https://doi.org/10.3390/jmmp9040115 - 2 Apr 2025
Viewed by 621
Abstract
Additive manufacturing (AM) has swiftly emerged as a substitute for conventional methods such as machining and injection moulding. Its appeal is attributed to accelerated prototyping, improved sustainability, and the capacity to fabricate intricate shapes. Nonetheless, the size constraints of additive manufacturing components require [...] Read more.
Additive manufacturing (AM) has swiftly emerged as a substitute for conventional methods such as machining and injection moulding. Its appeal is attributed to accelerated prototyping, improved sustainability, and the capacity to fabricate intricate shapes. Nonetheless, the size constraints of additive manufacturing components require the assembly of smaller 3D-printed elements to create larger structures. This study investigates the tensile properties of scarf joints (SJs) created from several polymers, including ABS, PETG, and PLA, adhered with Araldite® 2015 and Sikaforce® 7752 adhesives. The characteristics of the adherends were assessed prior to examining the adhesive efficacy in the SJ configuration. Experimental evaluations quantified failure modes, joint strength, assembly stiffness, and energy at failure, comparing findings with predictions from a cohesive zone model (CZM). The objective was to determine the ideal combination of materials and adhesives for enhanced joint performance. Results indicated that joint performance is greatly affected by the adherend material, adhesive selection, and scarf angle. PLA and Araldite® 2015 typically exhibited optimal strength and stiffness, but Sikaforce® 7752 demonstrated enhanced energy absorption for extended bonding lengths. Full article
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11 pages, 14052 KiB  
Article
Effect of Cr and Mo Substitution of Fe on Activation and Hydrogen Ab-/Desorption Properties of TiFe Hydrogen Storage Alloy
by Yuehai Li, Houqun Xiao, Minglong Zhong and Qingjun Chen
Metals 2025, 15(2), 200; https://doi.org/10.3390/met15020200 - 14 Feb 2025
Cited by 1 | Viewed by 912
Abstract
In this study, a series of quaternary TiFe-based alloys, Ti1.05Fe0.85Cr0.1−xMox (x = 0, 0.03, 0.05, 0.07, 0.1), were designed to investigate the activation and hydrogen ab-/desorption properties of TiFe hydrogen storage alloys through the [...] Read more.
In this study, a series of quaternary TiFe-based alloys, Ti1.05Fe0.85Cr0.1−xMox (x = 0, 0.03, 0.05, 0.07, 0.1), were designed to investigate the activation and hydrogen ab-/desorption properties of TiFe hydrogen storage alloys through the substitution of Fe with Cr and Mo. The incorporation of Cr and Mo significantly enhanced the activation performance of TiFe hydrogen storage alloys, enabling activation at room temperature. This improvement in activation was accompanied by the maintenance of a high maximum hydrogen storage capacity and an elevated effective hydrogen storage capacity. As the Mo content increased, the lattice parameters increased slightly, further boosting the activation performance and reducing the optimal operating temperature from 90 to 75 °C, which can be readily matched using the waste heat from fuel cells. The addition of Mo also resulted in a flatter hydrogen absorption plateau, making the hydrogen storage and release process more stable. Among the alloys, Ti1.05Fe0.85Cr0.05Mo0.05 exhibited the best performance, with a maximum hydrogen storage capacity of 2.00 wt.%, an effective hydrogen storage capacity of 1.81 wt.%, and a relatively flat hydrogen ab-/desorption plateau. After 200 cycles, the hydrogen storage capacity decreased by only 0.50%, indicating promising application prospects in related fields. Full article
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21 pages, 2416 KiB  
Article
Preparation and Transformations of Acetophenone-Derived Enamino Ketones, BF2-β-Ketoiminates, and BF2-β-Diketonates
by Helena Brodnik, Luka Ciber, Uroš Grošelj, Nejc Petek, Bogdan Štefane and Jurij Svete
Molecules 2025, 30(3), 601; https://doi.org/10.3390/molecules30030601 - 29 Jan 2025
Viewed by 1199
Abstract
A series of differently substituted β-enaminones 2a,b, 4ai, 8ad, and 913, their BF2-β-ketoiminate complexes 5ad, and BF2-β-diketonate complexes 6ad were prepared as [...] Read more.
A series of differently substituted β-enaminones 2a,b, 4ai, 8ad, and 913, their BF2-β-ketoiminate complexes 5ad, and BF2-β-diketonate complexes 6ad were prepared as model substrates for photochemical transformations. The attempted photochemical transformations of enaminones 2, 4, 8 and BF2-β-ketoiminate complexes 5 failed. On the other hand, irradiation of mixtures of BF2-β-diketonate complexes 6ad and cycloalkanes with UV-A light (365 nm) gave the corresponding De Mayo reaction products 7af in 9–30% yields. The photochemical ring-expansion of acetyl tetralone-derived BF2-complex 6d gave novel diannulated cyclooctane derivatives 7e and 7f, which would be difficult to obtain using conventional cyclization methods. Full article
(This article belongs to the Section Organic Chemistry)
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14 pages, 2557 KiB  
Article
Detection of Delafloxacin Resistance Mechanisms in Multidrug-Resistant Klebsiella pneumoniae
by András Kubicskó, János Juhász, Katalin Kamotsay, Dora Szabo and Béla Kocsis
Antibiotics 2025, 14(1), 62; https://doi.org/10.3390/antibiotics14010062 - 9 Jan 2025
Cited by 2 | Viewed by 1410
Abstract
Background: In this study, the mechanisms implicated in delafloxacin resistance in Klebsiella pneumoniae strains were investigated. Delafloxacin is a novel, broad-spectrum fluoroquinolone that has been approved for clinical application. Methods: In our study, 43 K. pneumoniae strains were assessed, antimicrobial susceptibility testing was [...] Read more.
Background: In this study, the mechanisms implicated in delafloxacin resistance in Klebsiella pneumoniae strains were investigated. Delafloxacin is a novel, broad-spectrum fluoroquinolone that has been approved for clinical application. Methods: In our study, 43 K. pneumoniae strains were assessed, antimicrobial susceptibility testing was performed via the broth microdilution method, and the minimum inhibitory concentration (MIC) values for ciprofloxacin, delafloxacin, levofloxacin, moxifloxacin, ceftazidime, cefotaxime, and imipenem were determined. Four delafloxacin-resistant K. pneumoniae strains were selected for whole-genome sequencing (WGS). Results: The MIC50 values for the 43 K. pneumoniae strains were as follows: ciprofloxacin 0.5 mg/L, levofloxacin 0.25 mg/L, moxifloxacin 0.5 mg/L, and delafloxacin 0.25 mg/L. All four selected delafloxacin-resistant K. pneumoniae strains showed extended-spectrum beta-lactamase production, and one strain exhibited carbapenem resistance. WGS enabled us to determine the sequence types (STs) of these strains, namely, ST307 (two strains), ST377, and ST147. Multiple mutations in quinolone-resistance-determining regions (QRDRs) were detected in all the delafloxacin-resistant K. pneumoniae strains; specifically, gyrA Ser83Ile and parC Ser80Ile were uniformly present in the strains of ST307 and ST147. However, in the ST377 strain, gyrA Ser83Tyr, Asp87Ala, and parC Ser80Ile, amino acid substitutions were detected. We also identified OqxAB and AcrAB efflux pumps in all delafloxacin-resistant K. pneumoniae strains. The association between beta-lactamase production and delafloxacin resistance was determined; specifically, CTX-M-15 production was detected in the ST147, ST307, and ST377 strains. Moreover, NDM-1 was detected in ST147. Conclusions: We conclude that multiple mutations in QRDRs, in combination with OqxAB and AcrAB efflux pumps, achieved delafloxacin resistance in K. pneumoniae. In our study, we report on NDM-1-producing K. pneumoniae ST147 in Hungary. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Genes: Spread and Evolution)
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17 pages, 2636 KiB  
Article
Development of Peptide Mimics of the Human Acetylcholine Receptor Main Immunogenic Region for Treating Myasthenia Gravis
by Vu B. Trinh and Robert H. Fairclough
Int. J. Mol. Sci. 2025, 26(1), 229; https://doi.org/10.3390/ijms26010229 - 30 Dec 2024
Cited by 1 | Viewed by 978
Abstract
We have designed and produced 39 amino acid peptide mimics of the Torpedo and human acetylcholine receptors’ (AChRs) main immunogenic regions (MIRs). These conformationally sensitive regions consist of three non-contiguous segments of the AChR α-subunits and are the target of 50–70% of the [...] Read more.
We have designed and produced 39 amino acid peptide mimics of the Torpedo and human acetylcholine receptors’ (AChRs) main immunogenic regions (MIRs). These conformationally sensitive regions consist of three non-contiguous segments of the AChR α-subunits and are the target of 50–70% of the anti-AChR autoantibodies (Abs) in human myasthenic serum and in the serum of rats with a model of that disease, experimental autoimmune myasthenia gravis (EAMG), induced by immunizing the rats with the Torpedo electric organ AChR. These MIR segments covalently joined together bind a significant fraction of the monoclonal antibodies (mAbs) raised in rats against electric organ AChR. Many of these mAbs cross react with the rat neuromuscular AChR MIR and induce myasthenic symptoms when injected into naïve rats. The human MIR mimic peptide (H39MIR) is evolutionarily related to that of the Torpedo electric organ MIR mimic peptide (T39MIR) with eight amino acid differences between the two MIR mimics. The mAbs raised to the electric organ AChR MIR cross react with the human and scores of other species’ neuromuscular AChRs. However, the mAbs do not cross react with the H39MIR mimic attached to the N-terminus of an intein–chitin-binding domain (H39MIR-IChBD) even though they do bind to the T39MIR-IChBD construct. To account for this difference in binding anti-MIR mAbs, each of the eight human amino acids was substituted individually into the T39MIR-IChBD, and four of them were found to weaken mAb recognition. Substituting the corresponding four Torpedo amino acids individually and in combination into the homologous positions in H39MIR-IChBD makes chimeric human MIR mimic peptides (T/H39MIR), some of which bind anti-MIR mAbs and anti-MIR Abs from rat EAMG and human MG sera. The best mAb binding chimeric peptide constructs may potentially serve as the basis of a diagnostic anti-MIR Ab titer assay that is both prognostic and predictive of disease severity. Furthermore, the best peptides may also serve as the targeting element of a non-steroidal antigen-specific treatment of MG to remove anti-AChR MIR Abs, either as fused to the N-terminals of the human immunoglobin Fc fragment or as the targeting component of a T cell chimeric autoantibody receptor (CAAR) directed to anti-MIR memory B cells for elimination. Full article
(This article belongs to the Special Issue Autoimmune Diseases: From Molecular Basis to Therapy)
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12 pages, 7952 KiB  
Article
Electro-Thermal Co-Optimization Design of GaN MMIC PA
by Xinhuang Chen, Bin Li, Fengyuan Mao and Zhaohui Wu
Electronics 2024, 13(23), 4796; https://doi.org/10.3390/electronics13234796 - 5 Dec 2024
Viewed by 1132
Abstract
A method of electro-thermal co-optimization design for the Gallium nitride (GaN) monolithic microwave integrated circuit (MMIC) power amplifier (PA) is introduced in this paper. Due to the self-heating effect of the GaN high electron mobility transistor (HEMT), it is necessary to pay attention [...] Read more.
A method of electro-thermal co-optimization design for the Gallium nitride (GaN) monolithic microwave integrated circuit (MMIC) power amplifier (PA) is introduced in this paper. Due to the self-heating effect of the GaN high electron mobility transistor (HEMT), it is necessary to pay attention to the influence of thermal resistance change on circuit performance when designing a high-power RF PA. For this purpose, a three-dimensional finite element analysis model of GaN multi-gate HEMT is developed. The thermal resistance and junction temperature of the device under a RF dynamic current are extracted by heat transfer simulation and can be substituted into the temperature node of the transistor model for PA circuit simulation design. To verify the proposed method, a Class AB MMIC PA was designed and tested using a 0.15-μm GaN-on-SiC process. Through the application of the above methods, the designed PA performance is optimized and achieves the performance of over 60% power-added efficiency (PAE) and 38 dBm saturation power (Psat) within a compact area of 1.6 mm × 2.2 mm. It is demonstrated that the proposed method can effectively improve the consistency of simulation results and measurement results, which can be a valuable reference for high-power MMIC PA design. Full article
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7 pages, 827 KiB  
Proceeding Paper
Enhancing Safety-Critical Brake System Testing with Vector SIL over Complex Vector HIL
by János Májer, Dénes Fodor, Péter Panyi, Félix Tivadar Nagy and Balázs István Németh
Eng. Proc. 2024, 79(1), 34; https://doi.org/10.3390/engproc2024079034 - 5 Nov 2024
Viewed by 781
Abstract
Advanced vehicle technologies that substitute or assist the driver are crucial and safety-critical elements, including independently acting electronic control units. A key element of vehicle road safety is its behavior on the road, influenced by various factors such as adhesion and physical forces. [...] Read more.
Advanced vehicle technologies that substitute or assist the driver are crucial and safety-critical elements, including independently acting electronic control units. A key element of vehicle road safety is its behavior on the road, influenced by various factors such as adhesion and physical forces. Self-activating brake systems, including related sensors and processing units, are vital for modern autonomous vehicles. The complexity of software in vehicle electronic control units (ECUs) has significantly increased, making traditional testing methods inadequate. This paper explores the use of Software-in-the-Loop (SIL) and Hardware-in-the-Loop (HIL) testing methods in an automated test environment to enhance software development and testing processes. It can be demonstrated that there is interoperability between the HIL and SIL systems using the same test case implementation in the Vector CANoe simulation environment. As a result, it can be demonstrated that in the case of a safety-critical function, such as an ABS (anti-lock brake system) control intervention, the ECU control software behaves the same in both the HIL and SIL simulation environments. Full article
(This article belongs to the Proceedings of The Sustainable Mobility and Transportation Symposium 2024)
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