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28 pages, 3611 KB  
Article
The Meta-Intelligent Child: Validating the MKIT as a Tool to Develop Metacognitive Knowledge in Early Childhood
by Onciu Oana and Prisacaru Flavia
J. Intell. 2025, 13(11), 149; https://doi.org/10.3390/jintelligence13110149 - 17 Nov 2025
Abstract
This article presents and validates the Metacognitive Knowledge Intervention for Thinking (MKIT)—an educational framework designed to assess and develop domain-general metacognitive knowledge (MK) in children aged 5 to 9. Moving beyond traditional approaches that examine metacognition within isolated subject areas, this research reconceptualizes [...] Read more.
This article presents and validates the Metacognitive Knowledge Intervention for Thinking (MKIT)—an educational framework designed to assess and develop domain-general metacognitive knowledge (MK) in children aged 5 to 9. Moving beyond traditional approaches that examine metacognition within isolated subject areas, this research reconceptualizes MK as a transferable learning resource across content domains and developmental stages. Moreover, by employing a stepped-wedge design—a rigorous but rarely used approach in education—the study introduces a methodological advancement. Simultaneously, MK is operationalized through an ecologically valid and developmentally appropriate format, using visually engaging stories, illustrated scenarios, and interactive tasks integrated within classroom routines. These adaptations enabled young learners to engage meaningfully with abstract metacognitive concepts. Therefore, across three interconnected studies (N = 458), the MKIT provided strong psychometric evidence supporting valid inferences about metacognitive knowledge, age-invariant effects, and substantial gains among children with initially low MK levels. In addition, qualitative data indicated MK transfer across contexts. Thus, these findings position MKIT as a scalable tool, supported by multiple strands of validity evidence, that makes metacognitive knowledge teachable across domains—offering a practical approach to strengthening learning, reducing early achievement gaps, and supporting the development of core components of intelligence. Full article
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18 pages, 3291 KB  
Article
Screening-Identified Oxazole-4-Carboxamide KB-2777 Exhibits In Vitro Anti-Coronavirus Activity
by Bud Jung, Woonsung Na, Minjoo Yeom, Jong-Woo Lim, Hai Quynh Do, Geonhee Jang, Min-A Ban, Ji-eun Yang, Youngjoo Byun and Daesub Song
Pharmaceutics 2025, 17(11), 1477; https://doi.org/10.3390/pharmaceutics17111477 - 16 Nov 2025
Viewed by 42
Abstract
Background/Objectives: Direct-acting antivirals vary by lineage and face rapid resistance. We identified the oxazole-4-carboxamide lead KB-2777 and aimed to define its in vitro activity across α/β-coronaviruses, time-of-addition (TOA) profile, host-response signatures, and combinability with benchmark DAAs. Methods: We tested KB-2777 (≤25 μM) against [...] Read more.
Background/Objectives: Direct-acting antivirals vary by lineage and face rapid resistance. We identified the oxazole-4-carboxamide lead KB-2777 and aimed to define its in vitro activity across α/β-coronaviruses, time-of-addition (TOA) profile, host-response signatures, and combinability with benchmark DAAs. Methods: We tested KB-2777 (≤25 μM) against HCoV-NL63 (LLC-MK2), HCoV-OC43 (Vero E6; MRC-5 for transcript profiling), and PEDV (Vero E6). We quantified extracellular viral RNA by RT-qPCR at 72 h (n = 3) and confirmed activity by spike-protein immunofluorescence (IFA), cytopathic effect (CPE) protection, and TCID50. We compared TOA regimens (full, pre, co, post), evaluated combinations with nirmatrelvir (NL63) or GS-441524 (OC43) using ZIP scores, and profiled infection-context transcripts (IL6, IFNB1, ISG15, NRF2/antioxidant, UPR). Results: KB-2777 reduced viral RNA with EC50 5.27 μM (NL63), 1.83 μM (OC43), and 1.59 μM (PEDV) without cytotoxicity in the tested range. In NL63 post-treatment, inhibition was minimal at 24 h but clear at 48–72 h (EC50 2.42 μM at 48 h; 5.25 μM at 72 h). TCID50 decreased at 48 h (12.5–25 μM, n = 3, p < 0.0001), and IFA/CPE corroborated antiviral activity. TOA ranked full > pre ≈ post > co. Combinations were additive to synergistic (ZIP 5.16 with nirmatrelvir; 8.40 with GS-441524). In OC43-infected MRC-5 cells, KB-2777 attenuated IL6, IFNB1, ISG15, and selected UPR transcripts, with limited changes in uninfected cells (n = 3). Conclusions: KB-2777 shows reproducible cell-based anti-coronavirus activity across α/β lineages, a TOA signature consistent with early post-entry host modulation, and favorable, non-antagonistic combinability with DAAs. These findings support target deconvolution, SAR/ADME optimization, and evaluation in primary airway and in vivo models. Full article
(This article belongs to the Special Issue Recent Advances in Nanotechnology Therapeutics)
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24 pages, 24946 KB  
Article
Hybrid Dihydropyrimidinones Targeting AKT Signaling: Antitumor Activity in Hormone-Dependent 2D and 3D Cancer Models
by Amanda Helena Tejada, Samuel José Santos, Gabriel Tofolli Lobo, Abu-Bakr Adetayo Ariwoola, Aryel José Alves Bezerra, Giulia Rodrigues Stringhetta, Izabela Natalia Faria Gomes, Luciane Sussuchi da Silva, Rui Manuel V. Reis, Daniel D’Almeida Preto, Dennis Russowsky and Renato José Silva-Oliveira
Pharmaceutics 2025, 17(11), 1470; https://doi.org/10.3390/pharmaceutics17111470 - 14 Nov 2025
Viewed by 247
Abstract
Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a [...] Read more.
Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a lower risk of resistance. In this study, the antitumor potential and mechanisms of action of 22 novel hybrid compounds derived from xanthene and pyran scaffolds (SJ022–SJ103) were investigated. The hybrids were initially evaluated through in vitro screening in four breast, three ovarian, and two prostate cancer cell lines, followed by the selection of T-47D, OVCAR-3, and LNCaP cells for detailed assays assessing cytotoxicity, apoptosis, cell cycle distribution, DNA damage, caspase-3/7 activity, morphology, and PI3K/AKT/mTOR pathway modulation. Methods: Cytotoxicity assays were performed in the selected cell lines, while mechanistic studies included apoptosis and cell cycle analysis by flow cytometry, γH2AX detection, Western blotting for PI3K/AKT/mTOR pathway proteins, and 3D spheroid assays. Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. AKT silencing by esiRNA and molecular docking was performed to confirm target engagement. Results: SJ028 demonstrated broad activity across all tested cell lines, whereas SJ064 and SJ078 exhibited higher selectivity. Treatments induced apoptosis, S/G2-M arrest, and DNA damage, accompanied by decreased phospho-AKT levels and stable PI3K and mTOR expression. In 3D models, the hybrids increased caspase-3/7 activity and necrotic core expansion. Co-administration with hormone therapies resulted in synergistic effects in breast and ovarian cancer cells, reducing IC50 values by more than 50% in both parental and resistant models, while combinations with MK2206 were antagonistic across all tumor subtypes. AKT silencing abrogated cytotoxicity, and docking confirmed SJ028 binding to AKT. Conclusions: Xanthene- and pyran-based hybrids—particularly SJ028, SJ064, and SJ078—showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers. Full article
(This article belongs to the Special Issue Innovative Drug Delivery Strategies for Targeted Cancer Immunotherapy)
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18 pages, 4373 KB  
Article
Sensitive Detection of β-Carotene in Chromogenic and Non-Chromogenic Mycobacteria by HPLC-DAD and UHPLC-MS
by Ana Milena Murillo, Juan David Zapata Serna, Verónica Gómez Tangarife, Jaime Alberto Robledo Restrepo and Luz Elena Botero
Microbiol. Res. 2025, 16(11), 239; https://doi.org/10.3390/microbiolres16110239 - 13 Nov 2025
Viewed by 104
Abstract
Carotenoid pigments are widely distributed in nature and play a crucial role in protecting organisms from photodynamic damage. However, the characterization of carotenoid production in clinically relevant mycobacteria has been limited due to the low sensitivity of conventional detection methods. We present a [...] Read more.
Carotenoid pigments are widely distributed in nature and play a crucial role in protecting organisms from photodynamic damage. However, the characterization of carotenoid production in clinically relevant mycobacteria has been limited due to the low sensitivity of conventional detection methods. We present a descriptive analysis of carotenoid production in seven mycobacterial isolates from the scotochromogenic, photochromogenic, and non-chromogenic groups. To achieve this, we used a combination of High-performance liquid chromatography with diode-array detection (HPLC-DAD) and Ultra-high performance liquid chromatography–mass spectrometry (UHPLC-MS) to detect carotenoids pigments. Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (MB) (non-chromogenic mycobacteria) produced β-carotene when cultured in the absence of light, at levels comparable to those of photochromogenic mycobacteria such as M. marinum (MM) and M. kansasii (MK). The highest levels of carotenoids were found in scotochromogenic species M. avium (MAV) and M. gordonae (MGOR). Conversely, M. abscessus (MABS), a non-chromogenic species in which no β-carotene was detected, served as a negative control for matrix effects. As expected, the use of highly sensitive analytical techniques such as HPLC-DAD and UHPLC-MS significantly enhanced the detection of β-carotene compared to visual pigment assessment. These methods allowed the detection of basal β-carotene levels even in mycobacteria classified as non-chromogenic. The proposed analytical approach provides a robust research tool to understand the effects of different stimulus that may alter the cell physiology in terms of pigment production. Full article
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30 pages, 2372 KB  
Article
Towards Circular Biobased Materials: Enhancing Unfired Adobe with Grape Pomace—A Comprehensive Analysis
by Monica C. M. Parlato, Andrea Pezzuolo, Anna Perbellini, Edoardo Piana and Lorenzo Guerrini
Agronomy 2025, 15(11), 2605; https://doi.org/10.3390/agronomy15112605 - 12 Nov 2025
Viewed by 209
Abstract
This research pioneers the incorporation of grape pomace (GP) as a sustainable additive in unfired adobe construction materials, establishing a novel circular pathway that valorises agro-waste in zero-emission, low-energy building components. Five mix designs were developed with GP contents of 0%, 2.5%, 5%, [...] Read more.
This research pioneers the incorporation of grape pomace (GP) as a sustainable additive in unfired adobe construction materials, establishing a novel circular pathway that valorises agro-waste in zero-emission, low-energy building components. Five mix designs were developed with GP contents of 0%, 2.5%, 5%, 7.5%, and 10% by weight, using a soil matrix composed of 15% clay, 25% silt, and 60% sand with a 20% water content. Comprehensive characterization included physical properties, mechanical performance, thermal behavior, acoustic properties, and durability assessment. The incorporation of GP demonstrated dose-dependent effects on all measured properties. Bulk density decreased linearly from 1951 kg/m3 (0%GP) to 1595 kg/m3 (10%GP), representing an 18.3% reduction. Optimal mechanical performance was achieved at a 2.5–5% GP content, with compressive strength ranging from 1.51–1.64 MPa and flexural strength of 0.56–0.80 MPa, while higher GP contents resulted in significant strength reductions. Thermal conductivity improved substantially, decreasing from 0.99 to 0.25 W/Mk (66% RH) with increasing GP content, indicating enhanced insulation properties. The sound insulation performance showed a single-value sound reduction index (Rw) of 41–43 dB for all compositions, making them suitable for facade applications. Statistical analysis revealed significant correlations between GP content and material properties. The results indicate an optimal GP content of around 5%, which balances mechanical integrity, thermal performance, and durability while providing environmental benefits through the valorization of agro-waste. This research offers a sustainable approach for producing low-energy, eco-friendly building materials by incorporating grape pomace into unfired adobe, promoting waste valorization and improved thermal and acoustical insulation for green construction. Further research is needed to assess durability performance, standardize production methods, and evaluate large-scale implementation. Full article
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20 pages, 11111 KB  
Article
Long-Term Trends and Seasonally Resolved Drivers of Surface Albedo Across China Using GTWR
by Jiqiang Niu, Ziming Wang, Hao Lin, Hongrui Li, Zijian Liu, Mengyang Li, Xiaodong Deng, Bohan Wang, Tong Wu and Junkuan Zhu
Atmosphere 2025, 16(11), 1287; https://doi.org/10.3390/atmos16111287 - 12 Nov 2025
Viewed by 191
Abstract
Amid accelerating global warming, surface albedo is a key indicator and regulator of how Earth’s surface reflects solar radiation, directly affecting the planetary radiation balance and climate. In this paper, we combined MODIS shortwave albedo (MCD43A3, 500 m), MODIS NDVI (MOD13A3, 1 km; [...] Read more.
Amid accelerating global warming, surface albedo is a key indicator and regulator of how Earth’s surface reflects solar radiation, directly affecting the planetary radiation balance and climate. In this paper, we combined MODIS shortwave albedo (MCD43A3, 500 m), MODIS NDVI (MOD13A3, 1 km; NDVI = normalized difference vegetation index) and 1-km gridded meteorological data to analyze the spatiotemporal variations of surface albedo across China during 2001–2020 at a gridded scale. Temporal trends were quantified with the Theil–Sen slope and the Mann–Kendall test, and the seasonal contributions of NDVI, air temperature, and precipitation were assessed with a geographically and temporally weighted regression (GTWR) model. China’s mean annual shortwave albedo was 0.186 and showed a significant decline. Attribution indicates NDVI is the dominant driver (~48% of total change), followed by temperature (~27%) and precipitation (~25%). Seasonally, NDVI explains ~43.94–52.02% of the variation, ~26.81–28.07% of the temperature, and ~21.17–28.57% of the precipitation. Clear spatial patterns emerge. In high-latitude and high-elevation snow-dominated regions, albedo tends to decrease with warmer conditions and increase with greater precipitation. In much of eastern China, albedo is generally positively associated with temperature and negatively with precipitation. NDVI—reflecting vegetation greenness and canopy structure—captures the effects of vegetation greening, canopy densification, and land-cover change that reduce surface reflectivity by enhancing shortwave absorption. Temperature and precipitation affect albedo primarily by regulating vegetation growth. This study goes beyond correlation mapping by combining robust trend detection (Theil–Sen + MK) with GTWR to resolve seasonally varying, non-stationary controls on albedo at 1-km over 20 years. By explicitly separating snow-covered and snow-free conditions, we quantify how NDVI, temperature, and precipitation contributions shift across climate zones and seasons, providing a reproducible, national-scale attribution that can inform ecosystem restoration and land-surface radiative management. Full article
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14 pages, 2472 KB  
Article
Molecular Epidemiology of SARS-CoV-2 in Northern Greece from the Index Case up to Early 2025 Using Nanopore Sequencing
by Georgios Meletis, Styliani Pappa, Georgia Gioula, Maria Exindari, Maria Christoforidi and Anna Papa
Epidemiologia 2025, 6(4), 78; https://doi.org/10.3390/epidemiologia6040078 - 12 Nov 2025
Viewed by 177
Abstract
Background/Objectives: Since its emergence in late 2019, SARS-CoV-2 has demonstrated remarkable genetic diversity driven by mutations and recombination events that shaped the course of the COVID-19 pandemic. Continuous genomic monitoring is essential to track viral evolution, assess the spread of variants of concern [...] Read more.
Background/Objectives: Since its emergence in late 2019, SARS-CoV-2 has demonstrated remarkable genetic diversity driven by mutations and recombination events that shaped the course of the COVID-19 pandemic. Continuous genomic monitoring is essential to track viral evolution, assess the spread of variants of concern (VOCs), and inform public health strategies. The present study aimed to characterize the molecular epidemiology of SARS-CoV-2 in northern Greece from the first national case in February 2020 through early 2025. Methods: A total of 66 respiratory samples collected from hospitalized patients across Northern Greece were subjected to whole-genome sequencing using Oxford Nanopore Technologies’ MinION Mk1C platform and the ARTIC protocol. Sequences were analyzed with PANGO, Nextclade, and GISAID nomenclature systems for lineage and clade assignment, and the WHO nomenclature for VOCs. Results: Across 66 genomes, 34 PANGO lineages were identified. Early introductions included B.1 (2/66), B.1.177 (3/66), and B.1.258 (1/66). Alpha (5/66) and Beta (5/66) circulated in February–June 2021. Delta (AY.43) was detected in early 2022 (2/66; Jan–Feb) but was rapidly displaced by Omicron and reached 100% of the sequences by May 2022. Omicron diversified into BA.1/BA.1.1 (3/66), BA.2 (6/66), BA.4/BA.5 (14/66), BF.5 (1/66), EG.5 (1/66; designated a WHO Variant of Interest in 2023), JN.1 (4/66; globally dominant lineage prompting vaccine updates in 2024–2025), KS.1 (2/66; together with KS.1.1 are recognized PANGO lineages that were tracked internationally but remained less prevalent), KP.3 (5/66; together with KP.3.1.1, prominent “FLiRT” descendants circulating in 2024), and recombinants XDK, XDD, and XEC (5/66), reported by their PANGO names in accordance with the WHO’s current framework, which reserves Greek letters only for newly designated VOCs. Conclusions: This five-year genomic analysis provides an insight into the continuous evolution of SARS-CoV-2 in northern Greece. The findings underscore the importance of sustained genomic surveillance, integrated with epidemiological data, to detect emerging variants, monitor recombination, and strengthen preparedness for future coronavirus threats. Full article
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27 pages, 4942 KB  
Article
Properties of Eco-Friendly Cement Composites Made with Recycled Cement Mortar-Based Artificial Aggregates
by Katarzyna Kalinowska-Wichrowska, Edyta Pawluczuk, Krzysztof Granatyr, Małgorzata Franus, Marta Kosior-Kazberuk, Michał Bołtryk and Adam Masłoń
Materials 2025, 18(22), 5115; https://doi.org/10.3390/ma18225115 - 11 Nov 2025
Viewed by 256
Abstract
Artificial aggregates (AAs) are man-made construction materials, and their properties greatly depend on their manufacturing process (e.g., granulation and hardening) and the raw materials used. The conducted research aimed to determine the most advantageous composition of artificial aggregates prepared based on three wastes [...] Read more.
Artificial aggregates (AAs) are man-made construction materials, and their properties greatly depend on their manufacturing process (e.g., granulation and hardening) and the raw materials used. The conducted research aimed to determine the most advantageous composition of artificial aggregates prepared based on three wastes simultaneously: municipal waste incineration ash (MWIA), sediment from the bottom of a water reservoir (SBWR), recycled cement mortar (RCM)- which was the main waste. A production process of such aggregates was also developed, with the setting of the hardening temperature (20 °C, 200 °C, 400 °C). The X-ray diffractometry (XRD), differential thermal analysis (DTA), and thermogravimetry analysis (TGA) were used to characterize the waste. Then, the properties of cementitious composites prepared with artificial aggregate with the best strength parameters of 0–100% of the natural aggregate were determined. Carbon footprint calculations were performed for the production of artificial aggregate, depending on its composition and for cementitious composites. Full article
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23 pages, 3873 KB  
Article
Toward Sustainable 3D Concrete Printing: Assessment of SCM–Superplasticizer Interactions on Rheology and Buildability
by Mai Megahed and Mohamed AbouZeid
Constr. Mater. 2025, 5(4), 80; https://doi.org/10.3390/constrmater5040080 - 11 Nov 2025
Viewed by 220
Abstract
Three-dimensional concrete printing (3DCP) requires mixtures that develop sufficient early buildability while preserving open time for reliable interlayer bonding. This study investigates the time-dependent evolution of static yield stress for printable concretes incorporating three supplementary cementitious materials—metakaolin (MK), silica fume (SF), and biochar [...] Read more.
Three-dimensional concrete printing (3DCP) requires mixtures that develop sufficient early buildability while preserving open time for reliable interlayer bonding. This study investigates the time-dependent evolution of static yield stress for printable concretes incorporating three supplementary cementitious materials—metakaolin (MK), silica fume (SF), and biochar (BC)—used with either a polycarboxylate ether- (PCE) or naphthalene-based superplasticizer. Static yield stress was measured at 15, 30, and 45 min of concrete age using the stress-growth method with a shear vane apparatus. Performance targets were τs (15 min) ≤ 2.8 kPa, reflecting extrudability/pumpability; τs (30 min) ≤ 3.1 kPa, representing printability/open time; and τs (45 min) ≥ 3.4 kPa, representing buildability. Pooled Type-II ANOVA showed a highly significant SP effect (p < 0.001), a significant SCM × SP interaction (p = 0.031), and a significant time effect (p = 0.005), whereas SCM (p = 0.709) and SCM% (p = 0.914) were non-significant once interaction and time were included. Across SCMs, SNF–PCE gaps are ~0.2–0.8 kPa at 30 min (+7–30%) and ~0.4–1.3 kPa at 45 min (+12–45%), with the largest gaps in SF, intermediate in MK, and smallest in BC. Full article
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32 pages, 5848 KB  
Article
Porous Refractories Synthesized Using Rice Husk and Rice Husk Processing Products
by Svetlana Yefremova, Sergey Yermishin, Askhat Kablanbekov, Baimakhan Satbaev, Nurgali Shalabaev and Serik Satbaev
Materials 2025, 18(21), 5063; https://doi.org/10.3390/ma18215063 - 6 Nov 2025
Viewed by 480
Abstract
In recent years, research in the field of the sustainable production of refractory ceramics has become topical. Significant attention has been paid to the use of secondary raw materials for obtaining high-quality materials. The purpose of the current study was to develop new [...] Read more.
In recent years, research in the field of the sustainable production of refractory ceramics has become topical. Significant attention has been paid to the use of secondary raw materials for obtaining high-quality materials. The purpose of the current study was to develop new high-temperature porous materials based on the magnesium sulfate-refractory clay–chamotte–aluminum system using environmentally friendly raw components. To synthesize porous refractories, rice husk and the by-products of its thermal processing were used as substitutes for ingredients usually introduced into the composition of high-temperature materials. Ground rice husk was used as both a burnout additive and a silica source. It was added to the mixture instead of chamotte. An organic condensate from rice husk pyrolysis was used as a binder. A sodium silicate solution, after activating pyrolyzed rice husk with alkali, was also tested as a binder. These liquid ingredients served as replacements for lignosulfonate and liquid glass. The new raw material components and the porous refractories obtained with their use were studied using methods of chemical analysis, XRD, GC-MS, TA, SEM, and EDS. Standard methods for studying the properties of refractories were used to evaluate the physicomechanical and thermal characteristics of the experimental materials. The sample with the maximum content of rice husk (14.4 wt.%) and organic condensate from its pyrolysis (10.5 wt.%) demonstrated promising properties as a light porous refractory: an apparent porosity of 44%, a volumetric weight of 1.1 g·cm−3, compressive strength of 2.1 MPa, tensile strength in bending of 4.5 MPa, bond strength of 0.01 MPa, thermal shock resistance of 155 thermal cycles, and thermal conductivity of 0.05 W (m·K)−1. It can be used as a prospective thermal insulating material. Full article
(This article belongs to the Section Advanced and Functional Ceramics and Glasses)
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14 pages, 3017 KB  
Article
Swelling Behaviour of Sulfate Soil Treated with Lime–Metakaolin at Different Curing Ages
by Mansour Ebailila, Khaled Ehwailat and Jonathan Oti
Ceramics 2025, 8(4), 133; https://doi.org/10.3390/ceramics8040133 - 6 Nov 2025
Viewed by 221
Abstract
Sulfate soil stabilisation, while offering technical benefits for infrastructure, is a challenging process, complicated by the nucleation of ettringite, an expansive mineral that can cause soil deterioration. This study was undertaken to elucidate the synergistic effect of lime and metakaolin on the physico-mechanical [...] Read more.
Sulfate soil stabilisation, while offering technical benefits for infrastructure, is a challenging process, complicated by the nucleation of ettringite, an expansive mineral that can cause soil deterioration. This study was undertaken to elucidate the synergistic effect of lime and metakaolin on the physico-mechanical performance of high-sulfate-bearing soil. The binder content in the stabilised specimens was fixed at 20 wt%, and metakaolin was used to partially substitute lime at different substitution levels. The physico-mechanical investigation revealed that supplementation of lime with metakaolin had a promotional effect on the unconfined compressive strength and swelling potential. The threshold of this effect was obtained by a binary blend of 7.5L–12.5MK, where the UCS was increased fourfold, while the swelling potential was reduced to a near-zero magnitude of 0.33%. This superior performance is due to the fineness and high reactivity of metakaolin, as both limit the nucleation of ettringite and promote the neoformation of further hydrated compounds, thus yielding a denser interlocked system and increasing its resistance to water soaking. Full article
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18 pages, 2638 KB  
Article
Repurposing MK-8245 as a Quorum Sensing Inhibitor to Suppress Virulence and Potentiate Antibiotic Activity in Pseudomonas aeruginosa
by Giulia Bernabè, Giovanni Marzaro, Mahmoud Elsayed Mosaad Shalata, Daniela Iosob, Valentina Inglima, Massimo Bellato, Ignazio Castagliuolo and Paola Brun
Antibiotics 2025, 14(11), 1116; https://doi.org/10.3390/antibiotics14111116 - 5 Nov 2025
Viewed by 322
Abstract
Background/Objectives: The rise in multidrug-resistant pathogens such as Pseudomonas aeruginosa (PA), coupled with declining antibiotic development, underscores the need for innovative therapeutic strategies. Repurposing approved drugs provides advantages of safety and rapid development. Since quorum sensing (QS) controls key virulence traits in [...] Read more.
Background/Objectives: The rise in multidrug-resistant pathogens such as Pseudomonas aeruginosa (PA), coupled with declining antibiotic development, underscores the need for innovative therapeutic strategies. Repurposing approved drugs provides advantages of safety and rapid development. Since quorum sensing (QS) controls key virulence traits in PA, targeting this pathway represents a promising antivirulence approach. This study aimed to identify and repurpose existing drugs as QS inhibitors. Methods: An in silico docking screen of 3000 FDA-approved or clinically tested compounds was performed against the C4-HSL receptor RhlR. Seventeen candidates were tested in the laboratory strain PAO1 for lactone-dependent signaling inhibition. The most active compound, MK-8245, was further evaluated for effects on growth, cytotoxicity, lactone release, biofilm formation, pyocyanin, elastase, rhamnolipids, and swarming motility. Its activity was also assessed in 20 clinical PA isolates. Results: MK-8245 (40 µM) reduced QS-regulated gene expression by ~60% without affecting viability. In PAO1, it inhibited rhamnolipids (60%), pyocyanin (40%), elastase (25%), biofilm formation, and swarming motility (25%). MK-8245 also enhanced the efficacy of imipenem against biofilms. In clinical isolates, it consistently decreased lactone release (~60%), pyocyanin (~50%), rhamnolipids (~40%), biofilm formation (~30%), and swarming motility (~25%). Conclusions: MK-8245 emerges as a promising antivirulence candidate against P. aeruginosa. By disrupting QS signaling and impairing multiple virulence factors, it attenuates pathogenicity without bactericidal pressure. Its synergy with standard antibiotics and consistent activity in clinical isolates highlight its translational potential and warrant further preclinical evaluation. Full article
(This article belongs to the Special Issue New Inhibitors for Overcoming Antimicrobial Resistance)
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17 pages, 3563 KB  
Article
Using Sphere Symmetry Breaking to Calculate SCHENBERG’s Antenna Quadrupolar Frequencies
by Natan Vanelli Garcia, Fabio da Silva Bortoli, Nadja Simao Magalhaes, Sergio Turano de Souza and Carlos Frajuca
Symmetry 2025, 17(11), 1871; https://doi.org/10.3390/sym17111871 - 5 Nov 2025
Viewed by 163
Abstract
Gravitational waves (GW) play an important role in the understanding of several astrophysical objects, like neutron stars and black holes. One technology used to detect them involves massive objects that vibrate as GW cross it, and the detectors built are, accordingly, of the [...] Read more.
Gravitational waves (GW) play an important role in the understanding of several astrophysical objects, like neutron stars and black holes. One technology used to detect them involves massive objects that vibrate as GW cross it, and the detectors built are, accordingly, of the resonant-mass type. SCHENBERG is a resonant-mass GW detector, built in Brazil, whose antenna is a spherical, 65 cm in diameter mass made of a CuAl alloy, and its quadrupole vibrational modes would be excited by GW, as predicted by general relativity. The chosen alloy can be cooled down to mK temperatures with a good mechanical quality factor. The quadrupole mode frequencies were measured at 4K, and a frequency band of about 67.5 Hz was found, but when the antenna was simulated in SolidWorks FEM software version 2010–2011 (as well as in Ansys SpaceClaimTM), the band obtained for a free sphere was different—around 30 Hz. When the holes for the suspension were included in the simulation, the same discrepancy persisted. In this work, gravity was included in the FEM simulation, and we show that the bandwidth results are even smaller. We were then able to obtain a bandwidth close to the measured one by including a small deviation from the vertical axle, as well as variations on the sphere microstructure, which are assumptions that break the symmetry of a perfect, homogeneous free sphere. We believe that the microstructure variations are due to differences in the cooling time during the sphere casting. As for a good mechanical quality factor, the sphere was not submitted to homogenization. With these additions to the FEM simulation, a reasonable frequency distribution was found, consistent with the one measured for SCHENBERG’s antenna. Full article
(This article belongs to the Section Physics)
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13 pages, 274 KB  
Article
The Strains Enterococcus faecalis as Contaminants of Raw Goat Milk and Their Treatment with Postbiotic Active Substances Produced by Autochthonous Lactococci
by Andrea Lauková, Eva Bino, Natália Zábolyová, Marián Maďar and Monika Pogány Simonová
Processes 2025, 13(11), 3552; https://doi.org/10.3390/pr13113552 - 4 Nov 2025
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Abstract
Enterococci from raw goat milk were taxonomically allotted in the species Enterococcus faecalis using sequencing (16S rRNA and BLASTn analysis) with a percentage identity up to 99.91%. The virulence factor gene gelE was found in the strains EE/K3, EE/G3, and EE/G6. The agg [...] Read more.
Enterococci from raw goat milk were taxonomically allotted in the species Enterococcus faecalis using sequencing (16S rRNA and BLASTn analysis) with a percentage identity up to 99.91%. The virulence factor gene gelE was found in the strains EE/K3, EE/G3, and EE/G6. The agg gene was detected in the strain EE/G6, and the esp gene was detected in the strains EE/K5 and EE/G7. Each strain possessed at least one virulence factor gene. In the strain EE/G6, the gelE and esp genes were found. The strains EE/G6 and EE/G3 showed resistance to tetracycline and vancomycin. EE/G7 was resistant to vancomycin and gentamicin. All strains possessed low-grade biofilm-forming ability (0.1 < A570 ≤ 1.0). They possessed genes for biofilm formation (bopD, srt, and/or ace). They also produced esterase (20–40 nmo/L), esterase lipase, and α-chymotrypsin (10–40 nmoL). The values of acid phosphatase reached 20–40 nmoL. The strains EE/G3, EE/G6, and EE/G7 were observed to possess the most pathogenicity. However, all strains were susceptible to postbiotic active substances produced by two autochthonous lactococci, MK2/8 and MK1/3 (inhibitory activity up to 400 AU/mL). These postbiotic substances provide a new potential alternative to reducing contaminants in milk. Full article
(This article belongs to the Section Food Process Engineering)
28 pages, 6216 KB  
Article
An Investigation of Changes in the New Thornthwaite Climate Classification Based on Temperature, Rainfall, and Evapotranspiration over Thailand, Using CMIP 5 for the Mid-21st Century Period
by Nutthakarn Phumkokrux and Panu Trivej
Appl. Sci. 2025, 15(21), 11731; https://doi.org/10.3390/app152111731 - 3 Nov 2025
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Abstract
This study aims (1) to study the trend and characteristics of monthly air temperature, monthly rainfall, and potential evapotranspiration (PET) in Thailand over the mid-21st century (2022–2060) period, and (2) to create a climate pattern map using the New Thornthwaite Climate Classification in [...] Read more.
This study aims (1) to study the trend and characteristics of monthly air temperature, monthly rainfall, and potential evapotranspiration (PET) in Thailand over the mid-21st century (2022–2060) period, and (2) to create a climate pattern map using the New Thornthwaite Climate Classification in Thailand over the same period under RCP4.5 and RCP8.5 scenarios using CSIRO-Mk3 in the CMIP5 dataset with Empirical Quantile Mapping (EQM) statistical downscaling. Spatial analyses of temperature and PET reveal significant warming trends, with temperatures rising by approximately 0.033 °C/year and PET rising by about 10 mm/year, especially in the Bangkok Metropolitan Region due to the urban heat island effect, with temperature values under RCP8.5 remaining consistently higher than those under RCP4.5. Rainfall projections show relatively stable spatial patterns across both scenarios, with higher concentrations along the Andaman coast, the eastern peninsula, and northeastern Thailand; these are areas influenced by the southwest monsoon and tropical cyclones. Central Thailand, however, exhibits persistently low rainfall, likely due to rain-shadow effects. PET patterns mirror early 21st-century observations, with the highest values projected in central Thailand and increasing trends under both scenarios, suggesting heightened drought risks. By 2060, The New Thornthwaite Climate Classification indicates that Moist climate zones are projected to disappear nationwide, with Semi-arid and Dry climates dominating under both RCP4.5 and RCP8.5 scenarios. Annual mean temperature will rise by 0.033 °C/year and PET by ~10 mm/year, while rainfall trends remain nearly stable. The classification’s reliance on minimal parameters—temperature, precipitation, and PET—provides a practical tool for climate monitoring and policy development. Full article
(This article belongs to the Special Issue Geographic Information System (GIS) for Various Applications)
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