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16 pages, 1234 KiB  
Article
Genomic Insights of Emerging Multidrug-Resistant OXA-48-Producing ST135 Proteus mirabilis
by Angeliki Mavroidi, Elisavet Froukala, Nick Spanakis, Aikaterini Michelaki, Maria Orfanidou, Vasiliki Koumaki and Athanasios Tsakris
Antibiotics 2025, 14(8), 750; https://doi.org/10.3390/antibiotics14080750 - 25 Jul 2025
Abstract
Background/Objectives: Among Enterobacterales, OXA-48-like-producing Proteus mirabilis strains have been scarcely detected. Herein, we characterized a blaOXA-48-harbouring P. mirabilis strain recovered from Greece (Pm GR-1), while phylogenomics and comparative genomics analyses with previously published blaOXA-48 carriers were also assessed. [...] Read more.
Background/Objectives: Among Enterobacterales, OXA-48-like-producing Proteus mirabilis strains have been scarcely detected. Herein, we characterized a blaOXA-48-harbouring P. mirabilis strain recovered from Greece (Pm GR-1), while phylogenomics and comparative genomics analyses with previously published blaOXA-48 carriers were also assessed. Methods: Characterization of Pm GR-1 was performed by the Vitek® Compact and Mass Spectrometry systems, antimicrobial susceptibility testing, detection of beta-lactamases, multilocus-sequence typing (MLST), and whole-genome sequencing (WGS). In silico prediction of mobile genetic elements (MGEs), genomic islands (GIs), antimicrobial resistance genes (ARGs) and virulence factors (VFs), and phylogenetic, core-genome SNP and comparative genomics analyses were executed using bioinformatic tools. Results: Pm GR-1 was isolated from a urine sample of an outpatient in a Greek hospital. It exhibited a multidrug-resistant phenotype, being susceptible only to amikacin and ceftazidime/avibactam. It co-carried several beta-lactamase genes on the chromosome (blaOXA-48, blaCTX-M-14, blaTEM-1) and a plasmid (blaTEM-2) and several other ARGs, but also mutations associated with quinolone resistance in the DNA gyrase and topoisomerase IV subunits. It belonged to the international clone ST135 that has also been detected among OXA-48-producing P. mirabilis strains from Germany and the USA. Pm GR-1 was genetically related to those from Germany, sharing highly similar MGEs, GIs, ARGs and VFs, including the chromosomal blaOXA-48 genetic structure, the O-antigen locus, the flagella locus, the MR/P fimbriae operon, and the urease gene cluster. Conclusions: To our knowledge, this is the first report from Greece of a blaOXA-48-possessing P. mirabilis strain. The emergence of blaOXA-48 among P. mirabilis strains of the international clone ST135 in different geographical regions is worrying. Close monitoring of these strains is required in One Health settings. Full article
(This article belongs to the Special Issue Antimicrobial Resistance Genes: Spread and Evolution)
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22 pages, 6221 KiB  
Article
Development and Experimental Validation of a Tubular Permanent Magnet Linear Alternator for Free-Piston Engine Applications
by Parviz Famouri, Jayaram Subramanian, Fereshteh Mahmudzadeh-Ghomi, Mehar Bade, Terence Musho and Nigel Clark
Machines 2025, 13(8), 651; https://doi.org/10.3390/machines13080651 - 25 Jul 2025
Abstract
The ongoing rise in global electricity demand highlights the need for advanced, efficient, and environmentally responsible energy conversion technologies. This research presents a comprehensive design, modeling, and experimental validation of a tubular permanent magnet linear alternator (PMLA) integrated with a free piston engine [...] Read more.
The ongoing rise in global electricity demand highlights the need for advanced, efficient, and environmentally responsible energy conversion technologies. This research presents a comprehensive design, modeling, and experimental validation of a tubular permanent magnet linear alternator (PMLA) integrated with a free piston engine system. Linear alternators offer a direct conversion of linear motion to electricity, eliminating the complexity and losses associated with rotary generators and enabling higher efficiency and simplified system architecture. The study combines analytical modeling, finite element simulations, and a sensitivity-based design optimization to guide alternator and engine integration. Two prototype systems, designated as alpha and beta, were developed, modeled, and tested. The beta prototype achieved a maximum electrical output of 550 W at 57% efficiency using natural gas fuel, demonstrating reliable performance at elevated reciprocating frequencies. The design and optimization of specialized flexure springs were essential in achieving stable, high-frequency operation and improved power density. These results validate the effectiveness of the proposed design approach and highlight the scalability and adaptability of PMLA technology for sustainable power generation. Ultimately, this study demonstrates the potential of free piston linear generator systems as efficient, robust, and environmentally friendly alternatives to traditional rotary generators, with applications spanning hybrid electric vehicles, distributed energy systems, and combined heat and power. Full article
(This article belongs to the Section Electrical Machines and Drives)
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36 pages, 1354 KiB  
Review
Flavonol Technology: From the Compounds’ Chemistry to Clinical Research
by Tomasz Przybylski, Joanna Czerniel, Jakub Dobrosielski and Maciej Stawny
Molecules 2025, 30(15), 3113; https://doi.org/10.3390/molecules30153113 - 25 Jul 2025
Abstract
Flavonols, representing a subclass of flavonoids, are an important group of polyphenols. Their activity is associated with a number of beneficial properties, including hepatoprotective, senolytic, neuroprotective, and anticancer properties. They are found abundantly in many fruits, vegetables, and plant products, but flavonols’ chemistry [...] Read more.
Flavonols, representing a subclass of flavonoids, are an important group of polyphenols. Their activity is associated with a number of beneficial properties, including hepatoprotective, senolytic, neuroprotective, and anticancer properties. They are found abundantly in many fruits, vegetables, and plant products, but flavonols’ chemistry and structural properties result in their low bioavailability in vivo. In recent years, more and more studies have emerged that aim to increase the therapeutic potential of compounds belonging to this group, including by developing innovative nanoformulations. The present work focuses on the various steps, such as chemical analysis of the compounds, preformulation studies using drug delivery systems, preclinical studies, and finally clinical trials. Each of these elements is important not only for the innovation and efficacy of the therapy but most importantly for the patient’s health. There are also a limited number of studies assessing the population concentration of flavonols in the blood; therefore, this review presents an up-to-date survey of the most recent developments, using the most important compounds from the flavonol group. Full article
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17 pages, 1698 KiB  
Review
Quantifying the Diversity of Normative Positions in Conservation Sciences
by Rodrigue Castro Gbedomon, Kolawolé Valère Salako, Damien Delorme and Martin A. Schlaepfer
Conservation 2025, 5(3), 38; https://doi.org/10.3390/conservation5030038 - 25 Jul 2025
Abstract
What elements of nature do people involved in conservation projects seek to protect, and why? How do they identify and relate to nature? Answers to such fundamental questions are shaped by normative assumptions that can result in distinct conservation strategies and practices. Despite [...] Read more.
What elements of nature do people involved in conservation projects seek to protect, and why? How do they identify and relate to nature? Answers to such fundamental questions are shaped by normative assumptions that can result in distinct conservation strategies and practices. Despite their importance, normative assumptions are rarely explicitly stated in conservation sciences, possibly because an epistemology of modern science suggests that normative backgrounds are not relevant to the production of objective knowledge, or because researchers and practitioners are unaware of the diversity of positions that exist. Using a combination of qualitative and quantitative methods, we created a catalogue of existing normative positions in conservation literature and described their key characteristics. We described 72 distinctive normative positions about human–nature relationships. Each position was characterized by unique combinations of value-states belonging to one or more of the following five dimensions: ontology (the positionality of human with respect to nature), axiology (value systems and ethical frameworks), pragmatism (extent of human interventions), epistemology (knowledge sources), and agency (agents of change). We then scored each position in terms of its alignment (support, opposition, or neutrality) with respect to all value-states within each dimension. A fuzzy correspondence analysis revealed that the field of conservation is heterogeneous beyond the conventional gradient of intrinsic–instrumental–relational values. The frequency and circumstances under which stakeholders adopt different normative positions are unknown, but the list of dimensions and associated values provided in this study may serve as a checklist for scoping this diversity. Consideration of values stemming from alternative normative positions may help broaden support for conservation actions. Full article
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21 pages, 11032 KiB  
Article
Convective –Stratiform Identification Neural Network (CONSTRAINN) for the WIVERN Mission
by Federico Mustich, Alessandro Battaglia, Francesco Manconi, Pavlos Kollias and Antonio Parodi
Remote Sens. 2025, 17(15), 2590; https://doi.org/10.3390/rs17152590 - 25 Jul 2025
Abstract
The WIVERN mission promises to deliver the first global observations of the three-dimensional wind field and the associated cloud and precipitation structure in a wide range of atmospheric phenomena, including isolated thunderstorms, tropical cyclones, mid-latitude frontal systems, and polar lows. A critical element [...] Read more.
The WIVERN mission promises to deliver the first global observations of the three-dimensional wind field and the associated cloud and precipitation structure in a wide range of atmospheric phenomena, including isolated thunderstorms, tropical cyclones, mid-latitude frontal systems, and polar lows. A critical element in the development of the mission’s wind products is the differentiation between stratiform and convective regions. Convective regions are defined as those where vertical wind velocities exceed 1 m/s. This work introduces CONSTRAINN, a family of U-Net-based neural network models that utilise all of WIVERN observables—including vertical profiles of reflectivity and Doppler velocity, as well as brightness temperatures—to reconstruct convective wind activity within the Earth’s atmosphere. Results show that the retrieved convective/stratiform masks are well reconstructed, with an equitable threat score exceeding 0.6. Ablation experiments further reveal that Doppler velocity signals are the most informative for the reconstruction task. Full article
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23 pages, 6061 KiB  
Article
Genomic Insights into Emerging Multidrug-Resistant Chryseobacterium indologenes Strains: First Report from Thailand
by Orathai Yinsai, Sastra Yuantrakul, Punnaporn Srisithan, Wenting Zhou, Sorawit Chittaprapan, Natthawat Intajak, Thanakorn Kruayoo, Phadungkiat Khamnoi, Siripong Tongjai and Kwanjit Daungsonk
Antibiotics 2025, 14(8), 746; https://doi.org/10.3390/antibiotics14080746 - 24 Jul 2025
Abstract
Background: Chryseobacterium indologenes, an environmental bacterium, is increasingly recognized as an emerging nosocomial pathogen, particularly in Asia, and is often characterized by multidrug resistance. Objectives: This study aimed to investigate the genomic features of clinical C. indologenes isolates from Maharaj [...] Read more.
Background: Chryseobacterium indologenes, an environmental bacterium, is increasingly recognized as an emerging nosocomial pathogen, particularly in Asia, and is often characterized by multidrug resistance. Objectives: This study aimed to investigate the genomic features of clinical C. indologenes isolates from Maharaj Nakorn Chiang Mai Hospital, Thailand, to understand their mechanisms of multidrug resistance, virulence factors, and mobile genetic elements (MGEs). Methods: Twelve C. indologenes isolates were identified, and their antibiotic susceptibility profiles were determined. Whole genome sequencing (WGS) was performed using a hybrid approach combining Illumina short-reads and Oxford Nanopore long-reads to generate complete bacterial genomes. The hybrid assembled genomes were subsequently analyzed to detect antimicrobial resistance (AMR) genes, virulence factors, and MGEs. Results: C. indologenes isolates were primarily recovered from urine samples of hospitalized elderly male patients with underlying conditions. These isolates generally exhibited extensive drug resistance, which was subsequently explored and correlated with genomic determinants. With one exception, CMCI13 showed a lower resistance profile (Multidrug resistance, MDR). Genomic analysis revealed isolates with genome sizes of 4.83–5.00 Mb and GC content of 37.15–37.35%. Genomic characterization identified conserved resistance genes (blaIND-2, blaCIA-4, adeF, vanT, and qacG) and various virulence factors. Phylogenetic and pangenome analysis showed 11 isolates clustering closely with Chinese strain 3125, while one isolate (CMCI13) formed a distinct branch. Importantly, each isolate, except CMCI13, harbored a large genomic island (approximately 94–100 kb) carrying significant resistance genes (blaOXA-347, tetX, aadS, and ermF). The absence of this genomic island in CMCI13 correlated with its less resistant phenotype. No plasmids, integrons, or CRISPR-Cas systems were detected in any isolate. Conclusions: This study highlights the alarming emergence of multidrug-resistant C. indologenes in a hospital setting in Thailand. The genomic insights into specific resistance mechanisms, virulence factors, and potential horizontal gene transfer (HGT) events, particularly the association of a large genomic island with the XDR phenotype, underscore the critical need for continuous genomic surveillance to monitor transmission patterns and develop effective treatment strategies for this emerging pathogen. Full article
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18 pages, 27645 KiB  
Article
Innovative Pedagogies for Industry 4.0: Teaching RFID with Serious Games in a Project-Based Learning Environment
by Pascal Vrignat, Manuel Avila, Florent Duculty, Christophe Bardet, Stéphane Begot and Pascale Marangé
Educ. Sci. 2025, 15(8), 953; https://doi.org/10.3390/educsci15080953 - 24 Jul 2025
Abstract
This work was conducted within the framework of French university reforms undertaken since 2022. Regardless of learning level and target audience, project-based learning has proved its effectiveness as a teaching strategy for many years. The novelty of the present contribution lies in the [...] Read more.
This work was conducted within the framework of French university reforms undertaken since 2022. Regardless of learning level and target audience, project-based learning has proved its effectiveness as a teaching strategy for many years. The novelty of the present contribution lies in the gamification of this learning method. A popular game, Trivial Pursuit, was adapted to enable students to acquire knowledge in a playful manner while preparing for upcoming technical challenges. Various technical subjects were chosen to create new cards for the game. A total of 180 questions and their answers were created. The colored tokens were then used to trace manufactured products. This teaching experiment was conducted as part of a project-based learning program with third-year Bachelor students (Electrical Engineering and Industrial Computing Department). The game components associated with the challenge proposed to the students comprised six key elements: objectives, challenges, mechanics, components, rules, and environment. Within the framework of the Industry 4.0 concept, this pedagogical activity focused on the knowledge, understanding, development, and application of an RFID (Radio Frequency Identification) system demonstrating the capabilities of this technology. This contribution outlines the various stages of the work assigned to the students. An industrial partner was also involved in this work. Full article
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22 pages, 1285 KiB  
Article
Stage-Specific Transcriptomic Insights into Seed Germination and Early Development in Camellia oleifera Abel.
by Zhen Zhang, Caixia Liu, Ying Zhang, Zhilong He, Longsheng Chen, Chengfeng Xun, Yushen Ma, Xiaokang Yuan, Yanming Xu and Rui Wang
Plants 2025, 14(15), 2283; https://doi.org/10.3390/plants14152283 - 24 Jul 2025
Abstract
Seed germination is a critical phase in the plant lifecycle of Camellia oleifera (oil tea), directly influencing seedling establishment and crop reproduction. In this study, we examined transcriptomic and physiological changes across five defined germination stages (G0–G4), from radicle dormancy to cotyledon emergence. [...] Read more.
Seed germination is a critical phase in the plant lifecycle of Camellia oleifera (oil tea), directly influencing seedling establishment and crop reproduction. In this study, we examined transcriptomic and physiological changes across five defined germination stages (G0–G4), from radicle dormancy to cotyledon emergence. Using RNA sequencing (RNA-seq), we assembled 169,652 unigenes and identified differentially expressed genes (DEGs) at each stage compared to G0, increasing from 1708 in G1 to 10,250 in G4. Functional enrichment analysis revealed upregulation of genes associated with cell wall organization, glucan metabolism, and Photosystem II assembly. Key genes involved in cell wall remodeling, including cellulose synthase (CESA), phenylalanine ammonia-lyase (PAL), 4-coumarate-CoA ligase (4CL), caffeoyl-CoA O-methyltransferase (COMT), and peroxidase (POD) showed progressive activation during germination. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed dynamic regulation of phenylpropanoid and flavonoid biosynthesis, photosynthesis, carbohydrate metabolism, and hormone signaling pathways. Transcription factors such as indole-3-acetic acid (IAA), ABA-responsive element binding factor (ABF), and basic helix–loop–helix (bHLH) were upregulated, suggesting hormone-mediated regulation of dormancy release and seedling development. Physiologically, cytokinin (CTK) and IAA levels peaked in G4, antioxidant enzyme activities were highest in G2, and starch content increased toward later stages. These findings provide new insights into the molecular mechanisms underlying seed germination in C. oleifera and identify candidate genes relevant to rootstock breeding and nursery propagation. Full article
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12 pages, 782 KiB  
Review
Primary Sequence-Intrinsic Immune Evasion by Viral Proteins Guides CTL-Based Vaccine Strategies
by Li Wan, Masahiro Shuda, Yuan Chang and Patrick S. Moore
Viruses 2025, 17(8), 1035; https://doi.org/10.3390/v17081035 - 24 Jul 2025
Abstract
Viruses use a range of sophisticated strategies to evade detection by cytotoxic T-lymphocytes (CTLs) within host cells. Beyond elaborating dedicated viral proteins that disrupt the MHC class I antigen-presentation machinery, some viruses possess intrinsic, cis-acting genome-encoded elements that interfere with antigen processing and [...] Read more.
Viruses use a range of sophisticated strategies to evade detection by cytotoxic T-lymphocytes (CTLs) within host cells. Beyond elaborating dedicated viral proteins that disrupt the MHC class I antigen-presentation machinery, some viruses possess intrinsic, cis-acting genome-encoded elements that interfere with antigen processing and display. These protein features, including G-quadruplex motifs, repetitive peptide sequences, and rare-codon usage, counterintuitively limit production of proteins critical to virus survival, particularly during latency. By slowing viral protein synthesis, these features reduce antigen production and proteosomal degradation, ultimately limiting the generation of peptides for MHC I presentation. These built-in evasion tactics enable viruses to remain “invisible” to CTLs during latency. While these primary sequence intrinsic immune evasion (PSI) mechanisms are well-described in select herpesviruses, emerging evidence suggests that they may also play a critical role in RNA viruses. How these proteins are made, rather than what they functionally target, determines their immune evasion properties. Understanding PSI mechanisms could rationally inform the design of engineered viral antigens with altered or removed evasion elements to restore antigen CTL priming and activation. Such vaccine strategies have the potential to enhance immune recognition, improve clearance of chronically infected cells, and contribute to the treatment of persistent viral infections and virus-associated cancers. Full article
(This article belongs to the Special Issue 15-Year Anniversary of Viruses)
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18 pages, 8415 KiB  
Article
Genome-Wide Identification of the UGT Gene Family in Poplar Populus euphratica and Functional Analysis of PeUGT110 Under Drought Stress
by Jilong An, Qing He, Jinfeng Xi, Jing Li and Gaini Wang
Forests 2025, 16(8), 1214; https://doi.org/10.3390/f16081214 - 24 Jul 2025
Abstract
UDP-glycosyltransferases (UGTs) play essential roles in various biological processes, such as phytohormone homeostasis, abiotic stress adaptation, and secondary metabolite biosynthesis. Populus euphratica is a model species for investigating stress adaptation; however, the PeUGT gene family has yet to be systematically characterized. Here, we [...] Read more.
UDP-glycosyltransferases (UGTs) play essential roles in various biological processes, such as phytohormone homeostasis, abiotic stress adaptation, and secondary metabolite biosynthesis. Populus euphratica is a model species for investigating stress adaptation; however, the PeUGT gene family has yet to be systematically characterized. Here, we identified 134 UGT genes in P. euphratica. Phylogenetic analysis classified these genes into 16 major groups (A–P), and UGT genes within the same groups showed similar structural characteristics. Tandem duplication events were identified as the predominant mechanism driving the expansion of the PeUGT family. Cis-acting element analysis revealed an enrichment of motifs associated with developmental regulation, light response, phytohormone signaling, and abiotic stress in the promoters of PeUGT genes. Expression profiling demonstrated spatiotemporal regulation of the PeUGT genes under drought stress. Among them, PeUGT110 was significantly induced by PEG treatment in the leaf, root, and stem tissues of P. euphratica. Overexpression of PeUGT110 enhanced drought tolerance in transgenic Arabidopsis. Furthermore, the PeUGT110-OE lines exhibited reduced malonaldehyde accumulation, elevated proline content, higher superoxide dismutase activity, and upregulated expression of stress-related genes under drought stress. The results demonstrated that PeUGT110 plays a critical role in plant drought resistance. These findings establish a foundation for elucidating the function of PeUGT genes. Full article
(This article belongs to the Section Genetics and Molecular Biology)
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15 pages, 1787 KiB  
Article
Flow Regime Impacts on Chemical Pollution in the Water and Sediments of the Moopetsi River and Human Health Risk in South Africa
by Abraham Addo-Bediako, Thato Matita and Wilmien Luus-Powell
Water 2025, 17(15), 2200; https://doi.org/10.3390/w17152200 - 23 Jul 2025
Viewed by 55
Abstract
Many effluents from human activities discharged into freshwater ecosystems cause chemical pollution. Chemical pollution in rivers is a serious threat to freshwater ecosystems due to the associated potential human health risks. This study determined the extent of chemical pollution, identified potential sources of [...] Read more.
Many effluents from human activities discharged into freshwater ecosystems cause chemical pollution. Chemical pollution in rivers is a serious threat to freshwater ecosystems due to the associated potential human health risks. This study determined the extent of chemical pollution, identified potential sources of pollution and assessed human health risk in the Moopetsi River, an intermittent river in the Limpopo Province of South Africa. Chemical analyses were conducted on water and sediment samples collected during high-flow, low-flow and intermittent-flow regimes. The findings showed seasonal variations in the chemical pollution levels in the sediments and the highest contamination was measured during intermittent flow. The enrichment factor and geoaccumulation index values identified chromium and nickel as major contributors to sediment contamination. The mean arsenic, chromium and nickel levels exceeded the established guideline values. An evaluation of human health risk was conducted using ingestion and dermal absorption pathways. The results showed that ingestion has greater non-carcinogenic and carcinogenic risks than dermal exposure, especially for children during intermittent flow. The elements of great concern for non-carcinogenic risk were chromium, manganese and nickel and for carcinogenic risk, they were arsenic, chromium, nickel and lead. The outcome of this study is useful for waste management and conservation to reduce environmental degradation and human health risk. Full article
(This article belongs to the Special Issue Advances in Metal Removal and Recovery from Water)
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16 pages, 3400 KiB  
Article
Antimicrobial Resistance Genotypes and Mobile Genetic Elements of Poultry-Derived Escherichia coli: A Retrospective Genomic Study from the United States
by Sohyun Cho, Hazem Ramadan, Lari M. Hiott, Jonathan G. Frye and Charlene R. Jackson
Pathogens 2025, 14(8), 726; https://doi.org/10.3390/pathogens14080726 - 23 Jul 2025
Viewed by 120
Abstract
The presence of antibiotic resistance in commensal bacteria may be an influential factor in the persistence of resistance in pathogens. This is especially critical for Escherichia coli that consumers may be exposed to through the consumption of uncooked meat. In this study, E. [...] Read more.
The presence of antibiotic resistance in commensal bacteria may be an influential factor in the persistence of resistance in pathogens. This is especially critical for Escherichia coli that consumers may be exposed to through the consumption of uncooked meat. In this study, E. coli isolates previously recovered from poultry in the US between 2001 and 2012 were whole-genome sequenced to identify their antibiotic resistance genes and mobile genetic elements. The genomes of 98 E. coli isolates from poultry carcass rinsates and 2 isolates from poultry diagnostic samples with multidrug resistance or potential extended-spectrum β-lactam (ESBL)-producing phenotypes as well as the genetic variabilities among the E. coli were assessed. All E. coli isolates were positive for at least one antibiotic resistance gene and plasmid replicon, with 37 resistance genes and 27 plasmid replicons detected among the isolates. While no ESBL genes were detected, blaCMY-2 was the most common β-lactamase gene, and blaTEM and blaCARB-2 were also identified. Most isolates (95%) harbored at least one intact phage, and as many as seven intact phages were identified in one isolate. These results show the occurrence of antibiotic resistance genes and mobile genetic elements in these 100 poultry-associated E. coli isolates, which may be responsible for the resistance phenotypes exhibited by the isolates. This retrospective study also enables comparisons of resistance genes and mobile genetic elements from more recent E. coli isolates associated with poultry to aid in understanding the trends of both antibiotic resistance phenotypes and genotypes in the poultry setting over time. Full article
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22 pages, 4133 KiB  
Article
Multiomics Signature Reveals Network Regulatory Mechanisms in a CRC Continuum
by Juan Carlos Higareda-Almaraz, Francesco Mattia Mancuso, Pol Canal-Noguer, Kristi Kruusmaa and Arianna Bertossi
Int. J. Mol. Sci. 2025, 26(15), 7077; https://doi.org/10.3390/ijms26157077 - 23 Jul 2025
Viewed by 67
Abstract
Sporadic colorectal cancer (CRC), the third leading cause of cancer-related death globally, arises through a continuum from normal tissue to adenomas, progressing from low-grade (LGD) to high-grade dysplasia (HGD); yet, the early epigenetic drivers of this transition remain unclear. To investigate these events, [...] Read more.
Sporadic colorectal cancer (CRC), the third leading cause of cancer-related death globally, arises through a continuum from normal tissue to adenomas, progressing from low-grade (LGD) to high-grade dysplasia (HGD); yet, the early epigenetic drivers of this transition remain unclear. To investigate these events, we profiled LGD and HGD adenomas using EM-seq, and identified a consensus differential methylation signature (DMS) of 626 regions through two independent bioinformatics pipelines. This signature effectively distinguished LGD from HGD in both tissue and plasma-derived cell-free DNA (cfDNA), highlighting specific methylation patterns. Functional annotation indicated enrichment for regulatory elements associated with transcription factor activity and cell signaling. Applying the DMS to the TCGA CRC dataset revealed three tumor subtypes with increasing hypermethylation and one normal cluster. The most hypermethylated subtype exhibited poor survival, high mutation burden, and disrupted transcriptional networks. While overlapping with classical CpG Island Methylator Phenotype (CIMP) categories, the DMS captured a broader spectrum of methylation alterations. These findings suggest that the DMS captures functionally relevant, antecedent epigenetic alterations in CRC progression, enabling the robust stratification of dysplasia severity and tumor subtypes. This signature holds promise for enhancing preclinical detection and molecular classification, and warrants further evaluation in larger prospective cohorts. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapeutic Strategies of Colorectal Cancer)
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15 pages, 1307 KiB  
Article
Shear Bond Strength and Finite Element Stress Analysis of Composite Repair Using Various Adhesive Strategies With and Without Silane Application
by Elif Ercan Devrimci, Hande Kemaloglu, Cem Peskersoy, Tijen Pamir and Murat Turkun
Appl. Sci. 2025, 15(15), 8159; https://doi.org/10.3390/app15158159 - 22 Jul 2025
Viewed by 88
Abstract
This study evaluated the effect of various adhesive systems, particularly silane application, on the repair bond strength of a nanofill resin composite and associated stress distribution using finite element analysis (FEA). A total of 105 composite specimens (4 × 6 mm) were aged [...] Read more.
This study evaluated the effect of various adhesive systems, particularly silane application, on the repair bond strength of a nanofill resin composite and associated stress distribution using finite element analysis (FEA). A total of 105 composite specimens (4 × 6 mm) were aged by thermal cycling (10,000 cycles), roughened, etched with phosphoric acid, and assigned to seven groups (n = 15): G1. control—no adhesive; G2. Single Bond Universal Adhesive; G3. composite primer; G4. PQ1; G5. Silane + PQ1; G6. Clearfil Universal Bond; G7. All-Bond Universal. Shear bond strength was measured using a universal testing machine (1 mm/min), and failure modes were microscopically classified. FEA was conducted under static and fatigue conditions using 3D models built in Fusion-360. Mechanical properties were obtained from technical data and the literature. A 300 N load was applied and contact detection (0.05 mm) and constraint zones were defined. Statistical analysis was performed using one-way ANOVA and Tukey’s HSD (p = 0.05). Pearson’s correlation was used to assess the relationship between bond strength and von Mises stress. The highest bond strength was found in G2 (21.54 MPa) while G1 showed the lowest (8.86 MPa). Silane-treated groups exhibited favorable stress distribution and a strong correlation between experimental and simulated outcomes. Silane applications significantly enhance composite repair performance. Full article
(This article belongs to the Special Issue Dental Materials: Latest Advances and Prospects, Third Edition)
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35 pages, 2334 KiB  
Article
Identification of Critical Exposed Elements and Strategies for Mitigating Secondary Hazards in Flood-Induced Coal Mine Accidents
by Xue Yang, Chen Liu, Langxuan Pan, Xiaona Su, Ke He and Ziyu Mao
Water 2025, 17(15), 2181; https://doi.org/10.3390/w17152181 - 22 Jul 2025
Viewed by 90
Abstract
Natech events, involving multi-hazard coupling and cascading effects, pose serious threats to coal mine safety. This paper addresses flood-induced Natech scenarios in coal mining and introduces a two-stage cascading analysis framework based on hazard systems theory. A tri-layered network—comprising natural hazards, exposed elements, [...] Read more.
Natech events, involving multi-hazard coupling and cascading effects, pose serious threats to coal mine safety. This paper addresses flood-induced Natech scenarios in coal mining and introduces a two-stage cascading analysis framework based on hazard systems theory. A tri-layered network—comprising natural hazards, exposed elements, and secondary hazards—models hazard propagation. In Stage 1, an improved adjacency information entropy algorithm with multi-hazard coupling coefficients identifies critical exposed elements. In Stage 2, Dijkstra’s algorithm extracts key risk transmission paths. A dual-dimensional classification method, based on entropy and transmission risk, is then applied to prioritize emergency responses. This method integrates the criticality of exposed elements with the risk levels associated with secondary disaster propagation paths. Case studies validate the framework, revealing: (1) Hierarchical heterogeneity in the network, with surface facilities and surrounding hydrological systems as central hubs; shaft and tunnel systems and surrounding geological systems are significantly affected by propagation from these core nodes, exhibiting marked instability. (2) Strong risk polarization in secondary hazard propagation, with core-node-originated paths being more efficient and urgent. (3) The entropy-risk classification enables targeted hazard control, improving efficiency. The study proposes chain-breaking strategies for precise, hierarchical, and timely emergency management, enhancing coal mine resilience to flood-induced Natech events. Full article
(This article belongs to the Topic Natural Hazards and Disaster Risks Reduction, 2nd Edition)
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