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15 pages, 2843 KB  
Article
Nucleotide Substitution Biases in Related Cancer Driver Genes
by Adam Khadre, Yifan Dou, Golrokh C. Mirzaei and Ruben C. Petreaca
Int. J. Mol. Sci. 2025, 26(24), 11903; https://doi.org/10.3390/ijms262411903 (registering DOI) - 10 Dec 2025
Abstract
Nucleotide substitutions are common in cancer cells, and they occur in both protein coding regions and non-coding regions (5′ and 3′ UTRs and introns). Although substitutions in non-coding regions have the potential to alter gene expression, it is the alteration of coding regions [...] Read more.
Nucleotide substitutions are common in cancer cells, and they occur in both protein coding regions and non-coding regions (5′ and 3′ UTRs and introns). Although substitutions in non-coding regions have the potential to alter gene expression, it is the alteration of coding regions that affects protein function and has the most drastic effect on cellular transformation. Mutations in certain genes (e.g., TP53, KRAS) are common to nearly all cancers, but most cancers are characterized by specific gene mutation signatures. In this report, we investigated nucleotide substitution signatures in coding regions of the top 25 most frequently mutated genes in multiple human cancers. The goal was to examine whether unique nucleotide substitution biases are associated with various cancers. A pan-cancer analysis showed that the most altered nucleotide is guanine, which is biased towards G->A transitions. A per-cancer analysis identified ten cancers with biased substitutions in certain genes. Some of these biases were expected (e.g., KRAS in gastrointestinal cancers or JAK2 in blood cancers). Our analysis revealed biased signature substitutions in 17 genes, of which 14 were characterized as drivers and constituted a closely related set of cell cycle regulators. We conclude that nucleotide substitution biases contribute to specific alterations in cancer genes that produce cellular transformation. Principle component analysis of nucleotide substitutions shows that most cancers cluster together, meaning that they have similar nucleotide changes. However, certain cancers, most notably lung, pancreas, and blood cancers, can be differentiated from each other based on specific nucleotide signatures. Thus, nucleotide substitution patterns can be used to differentiate between some cancers. Full article
(This article belongs to the Special Issue New Advances in Cancer Genomics)
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13 pages, 1487 KB  
Article
A Begomovirus solanumdelhiense Vector for Virus-Induced Gene Silencing in Melon
by Yufei Han, Qiansheng Liao, Ping Gao, Liqing Zhang, Bingqian Wan, Lihui Xu, Shigang Gao, Zhiwei Song, Fuming Dai and Rong Zeng
Pathogens 2025, 14(12), 1269; https://doi.org/10.3390/pathogens14121269 (registering DOI) - 10 Dec 2025
Abstract
In this study, the insert length, location within the coat protein-encoding gene, and sequence orientation of the target fragment were optimized to construct an efficient virus-induced gene silencing (VIGS) system in melon using a Begomovirus solanumdelhiense vector. Existing systems are mostly RNA viruses, [...] Read more.
In this study, the insert length, location within the coat protein-encoding gene, and sequence orientation of the target fragment were optimized to construct an efficient virus-induced gene silencing (VIGS) system in melon using a Begomovirus solanumdelhiense vector. Existing systems are mostly RNA viruses, requiring in vitro synthesis of viral strands that are prone to degradation, although they exhibit high infectivity and stability in cucurbit hosts and ease of manipulation. This vector was selected for its more stable genome structure and these advantages. The melon phytoene desaturase (CmPDS), a key gene of carotenoid biosynthesis, was selected as a reporter gene to evaluate the effects of the VIGS system. Our results revealed that the melon leaves in all the VIGS treatments exhibited a typical photobleaching phenotype at 21 days post-inoculation. Moreover, reverse transcription quantitative real-time PCR revealed a significant reduction in the mRNA levels of PDS in melon. The highest silencing efficiency (lowest PDS mRNA levels) was achieved by the VIGS vector harboring a 165 bp CmPDS fragment at the 3′ end of the AV1. These findings not only establish a more efficient VIGS protocol for melon but also provide a foundation for developing novel virus-based silencing tools applicable to functional genomics and cucurbit crop improvement, particularly for traits requiring precise gene expression modulation such as disease resistance and fruit quality. Full article
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21 pages, 2045 KB  
Review
Pathological and Molecular Insights into the Early Stage of Multiple System Atrophy
by Makoto T. Tanaka, Yasuo Miki, Tomoya Kon, Fumiaki Mori and Koichi Wakabayashi
Cells 2025, 14(24), 1966; https://doi.org/10.3390/cells14241966 (registering DOI) - 10 Dec 2025
Abstract
Recently, studies have increasingly focused on neuropathological and molecular alterations that occur in the early stages of neurodegenerative diseases to understand the primary pathogenesis. This review provides an updated overview of the early pathological and molecular changes in multiple system atrophy (MSA), a [...] Read more.
Recently, studies have increasingly focused on neuropathological and molecular alterations that occur in the early stages of neurodegenerative diseases to understand the primary pathogenesis. This review provides an updated overview of the early pathological and molecular changes in multiple system atrophy (MSA), a neurodegenerative condition characterised by the degeneration of both the striatonigral and olivopontocerebellar systems. In advanced stages of MSA, abnormal α-synuclein accumulates in the cytoplasm and nuclei of oligodendrocytes and neurones. However, in addition to these established pathological hallmarks, previous analyses of preclinical MSA cases have revealed characteristic accumulations of abnormal α-synuclein within and adjacent to the nuclear membrane. Moreover, analyses of cerebrospinal fluid and plasma from patients with MSA within 3 years of disease onset have identified alterations in various proteins and microRNAs linked to neurodegeneration and neuroinflammation. Consistent with these findings, in vitro and in vivo models of early-stage MSA have demonstrated abnormalities in neurodegeneration, neuroinflammation, and mitochondrial function. Collectively, these observations highlight the primary pathogenesis of early-stage MSA. Full article
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68 pages, 1846 KB  
Review
Oral Treatment of Obesity by GLP-1 and Its Analogs
by Natasa Holler, Ivana Ruseska, Anna-Laurence Schachner-Nedherer, Andreas Zimmer and Christina Petschacher
Pharmaceutics 2025, 17(12), 1596; https://doi.org/10.3390/pharmaceutics17121596 (registering DOI) - 10 Dec 2025
Abstract
Obesity is a multifaceted disease that significantly increases the risk of various chronic conditions. GLP-1R (co)-agonists first emerged as therapeutics for treatment of type 2 diabetes mellitus and have since become an established drug class for improving glycemic control. The interest in GLP-1 [...] Read more.
Obesity is a multifaceted disease that significantly increases the risk of various chronic conditions. GLP-1R (co)-agonists first emerged as therapeutics for treatment of type 2 diabetes mellitus and have since become an established drug class for improving glycemic control. The interest in GLP-1 for obesity treatment has surged in 2015 after the approval of Saxenda® (liraglutide). To date, GLP-1 analogs are primarily administered by s.c. injection, which poses a significant burden on patient compliance. To address this challenge, research has focused on oral delivery. This review provides a concise overview of the techniques explored to enhance the oral delivery of GLP-1 analogs for the treatment of obesity. Relevant strategies include the following: (1) the use of permeation enhancers to increase gastrointestinal absorption of peptides; (2) micro- and nanocarriers loaded with GLP-1, including targeted delivery systems and general techniques for active drug targeting; (3) GLP-1 gene delivery; and (4) advanced microbiome systems for GLP-1 delivery. The potential for misuse and side-effects of GLP-1 analogs are also discussed. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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22 pages, 3020 KB  
Article
Metabolomic Impact of Maternal Barium Exposure on Miscarriage Risk: Identification of Metabolic Biomarkers and Construction of a Risk Prediction Model
by Xiaoyu Zhao, Ziwei Guo, Shuangshuang Zhao, Danyang Wan, Jie Xu, Yifan Xu, Yujie Liu, Haoyi Xu, Ziyang Wang and Qing Xu
Toxics 2025, 13(12), 1066; https://doi.org/10.3390/toxics13121066 (registering DOI) - 10 Dec 2025
Abstract
This study investigated the relationship between maternal barium (Ba) exposure and the risk of miscarriage using metabolomics and machine learning. Analyses were performed on samples from 183 pregnant women from Nanjing: the concentration of Ba in whole blood was measured using inductively coupled [...] Read more.
This study investigated the relationship between maternal barium (Ba) exposure and the risk of miscarriage using metabolomics and machine learning. Analyses were performed on samples from 183 pregnant women from Nanjing: the concentration of Ba in whole blood was measured using inductively coupled plasma mass spectrometry (ICP-MS), and untargeted metabolomics was performed on decidual tissue using high-resolution accurate mass spectrometry (UHPLC-QExactive HF-X). A metabolome-wide association study (MWAS) and mediation interaction effect analysis (MITM) identified metabolites and pathways linked to Ba exposure and miscarriage risk. Among 523 detected metabolites, 19 metabolites and 5 pathways were significantly associated with both Ba exposure and miscarriage, particularly glycerophospholipid metabolism. The effect of Ba exposure on miscarriage risk was mediated by five metabolites, with cuminaldehyde showing the highest share of the total mediating effect (54.74%). These metabolites, including N-acetyl-L-methionine, 4-hydroxynonenal, DG(18:0/18:3(9Z,12Z,15Z)/0:0), 10-formyldihydrofolate, and eicosadienoic acid, were used as biomarkers in a predictive model. The XGBoost model achieved an optimal AUC of 0.90 (95%CI: 0.83–0.96). This study suggests that maternal Ba exposure increases miscarriage risk, potentially through disruptions in amino acid metabolism, oxidative stress, and lipid peroxidation, and highlights the potential of metabolite biomarkers for predicting adverse birth outcomes. Full article
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17 pages, 1073 KB  
Article
Pubovesical Complex-Sparing Under Hypothermia During Robotic-Assisted Laparoscopic Radical Prostatectomy: A Single-Institution Case Series
by Chin-Heng Lu, Min-Che Tung, Chu-Shan Yuan, Yi-Sheng Lin, Li-Hua Huang, Wei-Chun Weng, Chao-Yu Hsu, Tang-Yi Tsao, Yen-Chuan Ou and Chia-Che Chang
J. Clin. Med. 2025, 14(24), 8759; https://doi.org/10.3390/jcm14248759 (registering DOI) - 10 Dec 2025
Abstract
Background/Objectives: Functional continence and potency outcomes are paramount for the pentafecta of robotic-assisted laparoscopic radical prostatectomy (RARP). We describe a modified approach of the pubovesical complex (PVC)-sparing technique under hypothermia for better continence and potency preservation. Methods: This is a retrospective single-institution case [...] Read more.
Background/Objectives: Functional continence and potency outcomes are paramount for the pentafecta of robotic-assisted laparoscopic radical prostatectomy (RARP). We describe a modified approach of the pubovesical complex (PVC)-sparing technique under hypothermia for better continence and potency preservation. Methods: This is a retrospective single-institution case series. Thirty-three PVC-sparing RARP procedures under hypothermia were performed in patients with clinically localized prostate cancer by the same experienced surgeon. The method includes four principles: (1) modified PVC-sparing technique, according to Richard Gaston et al., (2) the use of near-infrared fluorescence technology and indocyanine green to identify the benchmark artery of the neurovascular bundle and blood supply for the PVC, (3) accessory pudendal artery preservation, and (4) hypothermia to reduce tissue edema. Functional outcomes, including continence, potency, and other surgical findings, are presented. This is a feasibility case series, not a comparative or hypothesis-testing study. Results: This study enrolled 33 cases from 15 April 2020 to 31 December 2022. Four patients had positive surgical margins. The urinary continence rate was 100% after Foley removal at a mean of 6.6 days. The potency rate was 74% (17/23) at 6 months and 91.3% (21/23) at 12 months. The inclusion of a small sample of patients from a single hospital and the selection of patient conditions were the study limitations. Conclusions: The modified approach we described is technically feasible, and it can expedite the restoration of urinary function and potency preservation. No severe complications occurred, and patients achieved good oncological outcomes. Full article
(This article belongs to the Special Issue Robotic Urological Surgery: Clinical Updates for Better Outcomes)
30 pages, 643 KB  
Article
Do Institutional Investors’ ESG Commitments Affect ESG Rating Disagreement? An Empirical Analysis of UNPRI Signatory Commitment
by Yinghao Sun and Zhibin Chen
Sustainability 2025, 17(24), 11083; https://doi.org/10.3390/su172411083 (registering DOI) - 10 Dec 2025
Abstract
This study conducted a quasi-natural experiment on Chinese mutual funds that signed the United Nations Principles for Responsible Investment (UNPRI) to examine whether institutional investors’ ESG commitments reduce ESG rating disagreements among their portfolio firms. We find that firms held by UNPRI-signatory investors [...] Read more.
This study conducted a quasi-natural experiment on Chinese mutual funds that signed the United Nations Principles for Responsible Investment (UNPRI) to examine whether institutional investors’ ESG commitments reduce ESG rating disagreements among their portfolio firms. We find that firms held by UNPRI-signatory investors exhibit significantly less ESG rating disagreement than those held by non-UNPRI investors. We further demonstrate that this effect operates through two channels: improved ESG disclosure quality and increased external ESG attention. Corporate governance and industry ESG sensitivity positively moderates the relationship between institutional investors’ ESG commitments and ESG rating disagreement. Moreover, the mitigating effect is more pronounced for domestic rating agencies. This study not only provides evidence for the role of institutional investors in ESG development but also identifies potential pathways to reduce ESG rating discrepancies, offering insights into enhancing the reliability of ESG rating outcomes. Full article
(This article belongs to the Section Social Ecology and Sustainability)
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39 pages, 6763 KB  
Article
An Estimate of the Economic Value of the Marine and Coastal Ecosystem Services of Algoa Bay, South Africa
by Matthew Orolowitz, James Blignaut, Chase Lourens, Matthew Bentley, Twesigye Twekye, Pablo Rees, Estee Miltz, Rozanne Peacock, Bernadette Snow and Amanda T. Lombard
Sustainability 2025, 17(24), 11055; https://doi.org/10.3390/su172411055 (registering DOI) - 10 Dec 2025
Abstract
Ecosystem services provided by coastal and marine environments are increasingly recognised as of paramount importance for human wellbeing. To inform marine spatial planning and its implementation, as well as to manage conflicts between marine resource beneficiaries, we developed a comprehensive estimate of the [...] Read more.
Ecosystem services provided by coastal and marine environments are increasingly recognised as of paramount importance for human wellbeing. To inform marine spatial planning and its implementation, as well as to manage conflicts between marine resource beneficiaries, we developed a comprehensive estimate of the economic value of the ecosystem services of Algoa Bay (AB) from 2000 to 2019. This is to assist in the development of effective policies concerning the management of marine resources. We quantified and assessed the monetary value by integrating 15 ecosystem services (ES) across five ecosystems using a range of economic valuation techniques and four scenarios. The scenarios differentiate between the local and global beneficiaries of the services and a conservative and alternative valuation estimate. These latter two valuation benefits are calculated using different sets of valuation estimates. We identified that onshore ecosystems, and recreation and tourism services, hold the most value. We estimated that the value grew from USD 613.4 million to USD 1695.9 million for local beneficiaries and from USD 1127.7 million to USD 2787.9 million for global beneficiaries between 2000 and 2019. The local values are roughly equivalent to the municipal budget, implying that the value of the ES is at least equal to that of the combined value of public service delivery. This highlights the significant economic contributions of marine and coastal ecosystems to local economies. This valuation provides a framework to make explicit the value that beneficiaries derive from marine ecosystems and provides a novel perspective on the valuation of ES in the coastal and marine ecosystems. This framework can be replicated elsewhere where there is a need to develop the ocean economy in an equitable and sustainable way. Full article
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13 pages, 691 KB  
Review
Global Perspectives on Patient Safety: The Central Role of Nursing Management
by Robert L. Anders
Healthcare 2025, 13(24), 3240; https://doi.org/10.3390/healthcare13243240 (registering DOI) - 10 Dec 2025
Abstract
Background: Unsafe care remains a major global health challenge, contributing to millions of preventable deaths and ranking among the top ten causes of mortality and disability worldwide. The World Health Organization’s Global Patient Safety Action Plan 2021–2030 emphasizes the need for strong leadership [...] Read more.
Background: Unsafe care remains a major global health challenge, contributing to millions of preventable deaths and ranking among the top ten causes of mortality and disability worldwide. The World Health Organization’s Global Patient Safety Action Plan 2021–2030 emphasizes the need for strong leadership and system-wide engagement to eliminate avoidable harm. As the largest component of the global healthcare workforce, nurses—especially those in management roles—are essential to achieving these goals. Objective: This narrative review synthesizes global evidence on how nursing management practices, particularly leadership, staffing, and safety culture, influence patient safety outcomes across diverse health systems. Methods: A purposive narrative review was conducted using PubMed, CINAHL, Scopus, and Web of Science databases. Peer-reviewed studies and organizational reports published between 2020 and 2025 were evaluated. A thematic synthesis approach was used to identify patterns related to leadership style, staffing ratios, workplace conditions, and organizational resilience. Quality appraisal followed adapted Critical Appraisal Skills Programme (CASP) and Joanna Briggs Institute (JBI) guidance. Results: A total of 37 peer-reviewed empirical studies were included in the narrative synthesis, along with key global policy and foundational framework documents used to contextualize findings. Evidence consistently demonstrated that transformational leadership, adequate nurse staffing, positive safety culture, and organizational learning structures are strongly associated with improved patient outcomes, reduced errors, and enhanced workforce well-being. Most studies exhibited moderate to high methodological rigor. Conclusions: Nursing management plays a decisive role in advancing global patient safety. Policies that strengthen leadership capacity, ensure safe staffing, promote just culture, and support nurse well-being are critical to achieving WHO’s 2030 safety objectives. Empowering nurse leaders across all regions is essential for building safer, more resilient health systems. Full article
4 pages, 169 KB  
Editorial
Ceramics in the Circular Economy for a Sustainable World
by Pardeep Kumar Gianchandani, Enrico Fabrizio, Bartolomeo Megna, Manuela Ceraulo and Francesco Baino
Ceramics 2025, 8(4), 151; https://doi.org/10.3390/ceramics8040151 (registering DOI) - 10 Dec 2025
Abstract
The transition toward a circular economy is one of the most pressing challenges and opportunities of our time, requiring fundamental shifts in how we produce, consume, and manage materials [...] Full article
(This article belongs to the Special Issue Ceramics in the Circular Economy for a Sustainable World)
32 pages, 1608 KB  
Article
Common Eigenvalues of Vertex-Decorated Regular Graphs
by Vladimir R. Rosenfeld
Axioms 2025, 14(12), 907; https://doi.org/10.3390/axioms14120907 (registering DOI) - 10 Dec 2025
Abstract
Let G=(V,E) be a simple graph with the vertex set V and the edge set E|V|=n,|E|=m. An example of a vertex-decorated graph DG is [...] Read more.
Let G=(V,E) be a simple graph with the vertex set V and the edge set E|V|=n,|E|=m. An example of a vertex-decorated graph DG is a vertex-quadrangulated graph QG. The vertex quadrangulation QG of 4-regular graph G visually looks like a graph whose vertices are depicted as empty squares, and the connecting edges are attached to the corners of the squares. If we contract each quadrangle of QG to a point that takes over the incidence of the four edges that were previously joined to this quadrangle, then we can again get the original graph G. Any connected graph H that provides (some of) its vertices for external connections can play the role of a decorating graph, and any graph G with vertices of valency no greater than the number of contact vertices in H can be decorated with it. Herein, we consider the case when G is a regular graph. Since the decoration also depends on the way the edges are attached to the decorating graph, we clearly stipulate it. We show that all similarly decorated regular graphs DG that meet our conditions have at least |V(H)| predicted common eigenvalues. A number of related results are proven. As possible applications of these results in chemistry, cases of simplified findings of eigenvalues of a molecular graph even in the absence of the usual symmetry of the molecule may be of interest. This, in particular, can somewhat expand the possibilities of applying the simple Hückel method for large molecules. Full article
(This article belongs to the Section Algebra and Number Theory)
24 pages, 1409 KB  
Review
Temporary Anchorage Devices in Orthodontics: A Narrative Review of Biomechanical Foundations, Clinical Protocols, and Technological Advances
by Teodora Consuela Bungau, Ruxandra Cristina Marin, Adriana Țenț and Gabriela Ciavoi
Appl. Sci. 2025, 15(24), 13035; https://doi.org/10.3390/app152413035 (registering DOI) - 10 Dec 2025
Abstract
Temporary anchorage devices (TADs) have become integral in contemporary orthodontic biomechanics, providing reliable skeletal anchorage independent of dental support or patient compliance. This narrative review synthesizes the current evidence regarding TADs classification, design parameters, biomechanical principles, clinical insertion protocols, complication management, and technological [...] Read more.
Temporary anchorage devices (TADs) have become integral in contemporary orthodontic biomechanics, providing reliable skeletal anchorage independent of dental support or patient compliance. This narrative review synthesizes the current evidence regarding TADs classification, design parameters, biomechanical principles, clinical insertion protocols, complication management, and technological innovations. We reviewed foundational literature and recent clinical studies with emphasis on factors affecting primary and secondary stability, including insertion torque, angulation, cortical bone characteristics, and soft-tissue considerations. Self-drilling techniques are generally preferred for maxillary sites, while pre-drilling remains indicated in dense mandibular bone to reduce thermal risk and torque overload. Clinical success is optimized when insertion torque is maintained between 5 and 10 N·cm and site-specific anatomy is respected. Reported survival rates exceed 85–95% when proper protocols are followed. While TADs are associated with relatively low complication rates, failures are usually early and linked to excessive torque, poor hygiene, or inflammation. New technologies such as cone-beam computed tomography-guided placement, 3D-printed surgical guides, and AI-based planning tools offer promising avenues for safer and more individualized treatment. In conclusion, TADs represent a predictable and versatile option for skeletal anchorage in orthodontics, provided that mechanical design, biological adaptation, and clinical handling are coherently integrated into patient-specific strategies. Full article
(This article belongs to the Special Issue Advances in Dental Materials, Instruments, and Their New Applications)
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29 pages, 7158 KB  
Review
Marine Lifecycle Carbon Footprint Toward Carbon Neutrality: Recent Progress and Prospects
by Yuhang Chang, Dai Liu, Feixiang Chang, Chang Zhai, Long Liu, Hongliang Luo, Meiqi Yu, Juncong Ge and Keiya Nishida
Processes 2025, 13(12), 3997; https://doi.org/10.3390/pr13123997 (registering DOI) - 10 Dec 2025
Abstract
The problem of global climate change is becoming increasingly serious, drawing worldwide attention to the need for carbon emissions reduction. As a primary mode of transport, maritime shipping accounts for 2% of global carbon emissions. Therefore, researchers have turned their attention to marine [...] Read more.
The problem of global climate change is becoming increasingly serious, drawing worldwide attention to the need for carbon emissions reduction. As a primary mode of transport, maritime shipping accounts for 2% of global carbon emissions. Therefore, researchers have turned their attention to marine carbon emissions. Specifically, lifecycle assessment (LCA) has attracted wide attention due to its comprehensiveness and objectivity. This article reviews alternate fuels like biodiesel, liquefied natural gas (LNG), methanol, ammonia, and hydrogen. These fuels generate fewer Tank-to-Wake (TTW) carbon emissions than conventional diesel but higher emissions in the Well-to-Tank (WTT) stage owing to production-related emissions, resulting in varying overall carbon footprints. Most carbon emissions in marine transportation come from fuel consumption. Selecting the shortest route can cut fuel use and emissions. Port greening and electrification are vital for emission cuts. Current marine LCA research exhibits key gaps, including fragmented case studies, a lack of methodological standardization, and insufficient dynamic predictive capacity, severely constraining its guiding value for industry decarbonization pathways. This study systematically reviews and categorizes marine LCA research from the past decade in both Chinese and English from the Web of Science and CNKI databases through a Ship-Route-Port framework. Specifically, 34 papers underwent quantitative or qualitative analysis, comprehensively comparing the full lifecycles of six mainstream marine alternative fuels: biodiesel, LNG, methanol, ammonia, hydrogen, and electricity. This study also underscores the need for unified standards to boost low-carbon fuel use and explores the unique challenges and uncertainties involved in applying LCA to the marine sector. LCA applied to the maritime sector shows promise as a valuable tool for guiding low-carbon transition strategies. Full article
(This article belongs to the Topic Marine Energy)
24 pages, 6129 KB  
Review
Research Situation and Prospect Analysis of Corrosion of Rubber Materials: A Study Based on Bibliometric Mapping
by Jingning Zhang, Kan Jin, Shanjie Zhao, Shun Wang, Luojia Ding and Di Xu
Processes 2025, 13(12), 3996; https://doi.org/10.3390/pr13123996 (registering DOI) - 10 Dec 2025
Abstract
Rubber materials are widely used in industrial sectors such as petrochemicals and energy due to their excellent elasticity, flexibility, and sealing properties. However, in complex and demanding service environments, rubber is susceptible to swelling or dissolution caused by medium corrosion, leading to seal [...] Read more.
Rubber materials are widely used in industrial sectors such as petrochemicals and energy due to their excellent elasticity, flexibility, and sealing properties. However, in complex and demanding service environments, rubber is susceptible to swelling or dissolution caused by medium corrosion, leading to seal failure or structural damage and ultimately resulting in safety incidents. To systematically review research progress and trends in this field, this paper employs 729 literature samples from the Web of Science core database (2008–2025) and utilizes VOSviewer and Citespace knowledge mapping tools to conduct a bibliometric analysis of corrosion research on rubber materials. This reveals existing knowledge gaps, technological challenges, hot trends, and future demands. Findings indicate that China, the United States, and India lead in publication volume. Research spans multiple disciplines including multidisciplinary materials science, applied physics, and polymer science, reflecting a cross-disciplinary nature. Current rubber corrosion studies focus on three key areas: fundamental properties and performance of rubber materials, corrosion mechanisms, and protective/corrosion-resistant technologies. Key international challenges include unclear mechanisms of complex media interactions, insufficient multi-scale characterization and life prediction, and limited adaptability to service environments. Future development trends will concentrate on three aspects: systematic research on novel multi-media coupling effects, precision in micro-mechanism and life prediction, and highly reliable advancement in green modification and high-performance protection. Full article
(This article belongs to the Section Materials Processes)
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3 pages, 131 KB  
Editorial
Advances in Lithium-Ion Battery Safety and Fire Prevention
by Zhi Wang
Batteries 2025, 11(12), 455; https://doi.org/10.3390/batteries11120455 (registering DOI) - 10 Dec 2025
Abstract
With the rapid development of new energy technologies, lithium-ion batteries (LIBs) have become one of the core technologies in modern energy storage and electric mobility [...] Full article
(This article belongs to the Special Issue Advances in Lithium-Ion Battery Safety and Fire)
20 pages, 4488 KB  
Article
Molecular Characterization of Oral Epithelial Dysplasia and Oral Squamous Cell Carcinoma Using EGFR, CDKN2A, and HRAS Alterations
by Satoshi Okubo, Satoru Miyabe, Masahiro Fukumura, Jun Sasaki, Hitoshi Fujii, Fumitaka Terasawa, Satoshi Watanabe, Soma Okada, Megumi Miyabe, Katsuyuki Miyabe, Yoshihiko Sugita, Hatsuhiko Maeda, Sanako Nakaya, Kaori Sakane, Seiji Yamada, Nitin Bhola, Saman Warnakulasuriya, Toru Nagao and Mitsuo Goto
Cancers 2025, 17(24), 3949; https://doi.org/10.3390/cancers17243949 (registering DOI) - 10 Dec 2025
Abstract
Background/Objectives: Oral squamous cell carcinoma (OSCC) often presents at an advanced stage; therefore, the early detection of precursor lesions is crucial. However, the risk assessment of precursor lesions such as oral epithelial dysplasia (OED) remains challenging because of the subjectivity of histopathological grading. [...] Read more.
Background/Objectives: Oral squamous cell carcinoma (OSCC) often presents at an advanced stage; therefore, the early detection of precursor lesions is crucial. However, the risk assessment of precursor lesions such as oral epithelial dysplasia (OED) remains challenging because of the subjectivity of histopathological grading. We aimed to identify molecular markers that enhance the diagnostic accuracy and prognostic stratification of OSCC and explore the differences in the molecular characterization of OED and OSCC using a few selected markers. Methods: A two-step diagnostic workflow was applied: (1) FISH evaluation of EGFR amplification and CDKN2A deletion to distinguish OED from OSCC and identify EGFR-dependent tumors, and (2) HRAS immunohistochemistry performed exclusively in EGFR-negative OSCCs to stratify EGFR-independent cases. Fluorescence in situ hybridization (FISH) was used to assess seven EGFR/cell cycle-related genes (CCND1, CDKN2A, EGFR, PIK3CA, PTEN, TP53, and 1p36 locus) in 117 formalin-fixed paraffin-embedded samples (66 OED and 51 OSCC) and 10 normal mucosa samples. HRAS expression was evaluated using immunohistochemistry (IHC) in 36 EGFR amplification-negative OSCCs samples. Results: EGFR amplification was frequent in OSCC, whereas CDKN2A deletion was common in OED. The EGFR-amplified/ CDKN2A-intact profile showed high specificity for OSCC and improved diagnostic performance (area under the curve = 0.77) when combined with the Ki-67 labeling index. It also predicted poor disease-free survival (hazard ratio [HR] = 5.08, p = 0.016) and overall survival (HR = 6.10, p = 0.047). Among EGFR-negative OSCCs, HRAS overexpression was associated with advanced-stage disease and a poor prognosis (HR = 6.15, p = 0.043). Conclusions: EGFR amplification was frequent in OSCC, and CDKN2A deletion was prevalent in OED, supporting their use as molecular markers for differential diagnoses. FISH for EGFR/CDKN2A and HRAS IHC can stratify OSCC by diagnosis and prognosis, enabling practical molecular subclassification, including EGFR-negative cases. Full article
(This article belongs to the Special Issue Molecular Mechanisms in Head and Neck Cancer)
40 pages, 731 KB  
Article
Local Linear Regression for Functional Ergodic Data with Missing at Random Responses
by Yassine Baghli, Oussama Bouanani and Salim Bouzebda
Mathematics 2025, 13(24), 3941; https://doi.org/10.3390/math13243941 (registering DOI) - 10 Dec 2025
Abstract
In this article, we develop a novel kernel-based estimation framework for functional regression models in the presence of missing responses, with particular emphasis on the Missing At Random (MAR) mechanism. The analysis is carried out in the setting of stationary and ergodic functional [...] Read more.
In this article, we develop a novel kernel-based estimation framework for functional regression models in the presence of missing responses, with particular emphasis on the Missing At Random (MAR) mechanism. The analysis is carried out in the setting of stationary and ergodic functional data, where we introduce apparently for the first time a local linear estimator of the regression operator. The principal theoretical contributions of the paper may be summarized as follows. First, we establish almost sure uniform rates of convergence for the proposed estimator, thereby quantifying its asymptotic accuracy in a strong sense. Second, we prove its asymptotic normality, which provides the foundation for distributional approximations and subsequent inference. Third, we derive explicit closed-form expressions for the associated asymptotic variance, yielding a precise characterization of the limiting law. These results are obtained under standard structural assumptions on the relevant functional classes and under mild regularity conditions on the underlying model, ensuring broad applicability of the theory. On the methodological side, the asymptotic analysis is exploited to construct pointwise confidence regions for the regression operator, thereby enabling valid statistical inference. Furthermore, a comprehensive set of simulation experiments is conducted, demonstrating that the proposed estimator exhibits superior finite-sample predictive performance when compared to existing procedures, while simultaneously retaining robustness in the presence of missingness governed by MAR mechanisms. Full article
(This article belongs to the Section D1: Probability and Statistics)
55 pages, 4222 KB  
Review
A Comprehensive Review of Data-Driven and Physics-Based Models for Energy Performance in Non-Domestic Buildings
by Lukumba Phiri, Thomas O. Olwal and Topside E. Mathonsi
Energies 2025, 18(24), 6481; https://doi.org/10.3390/en18246481 (registering DOI) - 10 Dec 2025
Abstract
The building sector accounts for a significant portion of the global energy consumption and carbon dioxide (CO2) emissions, making it a critical area for improving energy efficiency. In Africa, the rapid energy demand and costs have further emphasized the urgency of [...] Read more.
The building sector accounts for a significant portion of the global energy consumption and carbon dioxide (CO2) emissions, making it a critical area for improving energy efficiency. In Africa, the rapid energy demand and costs have further emphasized the urgency of developing effective solutions for reducing building energy use. This paper presents a comprehensive review of data-driven and physics-based modeling approaches for forecasting and optimizing energy performance in non-domestic buildings. The review highlights the evolution of statistical models, classical machine learning methods, deep learning, and hybrid approaches across various application scenarios. Emphasis is placed on the role of data pre-processing techniques, including data fusion and transfer learning, as strategies to address data limitations and improve model generalization. Furthermore, the study evaluates the strengths and limitations of different modeling methods in terms of accuracy, scalability, and applicability in real-world contexts. By integrating insights from recent literature, this paper identifies key research gaps such as the need for standard datasets, physics-informed hybrid modeling, and policy-oriented frameworks. The findings aim to guide building managers, policymakers, and researchers toward adopting robust data-driven solutions that enhance energy resilience, reduce operational costs, and support environmental sustainability in the built environment. The review also justifies the importance of these models for practical applications like energy benchmarking, retrofit planning, and CO2 reduction, providing a clear link between research and industry implementation. Full article
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3 pages, 163 KB  
Editorial
Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics—A Summary of Key Findings and Insights from the Special Issue
by Stamatia Tsoupra and Karolina Akinosoglou
Viruses 2025, 17(12), 1601; https://doi.org/10.3390/v17121601 (registering DOI) - 10 Dec 2025
Abstract
Viral sepsis has gained increasing clinical and scientific attention as it represents a complex, life-threatening condition driven by a dysregulated host response to viral pathogens [...] Full article
(This article belongs to the Special Issue Viral Sepsis: Pathogenesis, Diagnostics and Therapeutics)
24 pages, 621 KB  
Article
The Regress of Uncertainty and the Forecasting Paradox
by Nassim Nicholas Taleb and Pasquale Cirillo
Risks 2025, 13(12), 247; https://doi.org/10.3390/risks13120247 (registering DOI) - 10 Dec 2025
Abstract
We show that epistemic uncertainty–our iterated ignorance about our own ignorance–inevitably thickens statistical tails, even under perceived thin-tailed environments from past realizations. Any claim of precise risk carries a margin of error, and that margin itself is uncertain, in an infinite regress of [...] Read more.
We show that epistemic uncertainty–our iterated ignorance about our own ignorance–inevitably thickens statistical tails, even under perceived thin-tailed environments from past realizations. Any claim of precise risk carries a margin of error, and that margin itself is uncertain, in an infinite regress of doubt. This “errors-on-errors” mechanism rules out thin-tailed certainty: predictive laws must be heavier-tailed than their in-sample counterparts. The result is the Forecasting Paradox: the future is structurally more extreme than the past. This insight collapses branching scenarios into a single heavy-tailed forecast, with direct implications for risk management, scientific modeling, and AI safety. Full article
(This article belongs to the Special Issue Innovative Quantitative Methods for Financial Risk Management)
28 pages, 4794 KB  
Article
Regional Lessons to Support Local Guidelines: Adaptive Housing Solutions from the Baltic Sea Region for Climate-Sensitive Waterfronts in Gdańsk
by Bahaa Bou Kalfouni, Anna Rubczak, Olga Wiszniewska, Piotr Warżała, Filip Lasota and Dorota Kamrowska-Załuska
Sustainability 2025, 17(24), 11082; https://doi.org/10.3390/su172411082 (registering DOI) - 10 Dec 2025
Abstract
Across the Baltic Sea region, areas situated in climate-sensitive water zones are increasingly exposed to environmental and socio-economic challenges. Gdańsk, Poland, is a prominent example where the rising threat of climate-related hazards, particularly connected with flooding, coincides with growing demand for resilient and [...] Read more.
Across the Baltic Sea region, areas situated in climate-sensitive water zones are increasingly exposed to environmental and socio-economic challenges. Gdańsk, Poland, is a prominent example where the rising threat of climate-related hazards, particularly connected with flooding, coincides with growing demand for resilient and adaptive housing solutions. Located in the Vistula Delta, the city’s vulnerability is heightened by its low-lying terrain, polder-based land systems, and extensive waterfronts. These geographic conditions underscore the urgent need for flexible, climate-responsive design strategies that support long-term adaptation while safeguarding the urban fabric and the well-being of local communities. This study provides evidence-based guidance for adaptive housing solutions tailored to Gdańsk’s waterfronts. It draws on successful architectural and urban interventions across the Baltic Sea region, selected for their environmental, social, and cultural relevance, to inform development approaches that strengthen resilience and social cohesion. To achieve this, an exploratory case study methodology was employed, supported by desk research and qualitative content analysis of strategic planning documents, academic literature, and project reports. A structured five-step framework, comprising project identification, document selection, qualitative assessment, data extraction, and analysis, was applied to examine three adaptive housing projects: Hammarby Sjöstad (Stockholm), Kalasataman Huvilat (Helsinki), and Urban Rigger (Copenhagen). Findings indicate measurable differences across nine sustainability indicators (1–5 scale): Hammarby Sjöstad excels in environmental integration (5/5 in carbon reduction and renewable energy), Kalasataman Huvilat demonstrates strong modular and human-scaled adaptability (3–5/5 across social and housing flexibility), and Urban Rigger leads in climate adaptability and material efficiency (4–5/5). Key adaptive measures include flexible spatial design, integrated environmental management, and community engagement. The study concludes with practical recommendations for local planning guidelines. The guidelines developed through the Gdańsk case study show strong potential for broader application in cities facing similar challenges. Although rooted in Gdańsk’s specific conditions, the model’s principles are transferable and adaptable, making the framework relevant to water sensitivity, flexible housing, and inclusive, resilient urban strategies. It offers transversal value to both urban scholars and practitioners in planning, policy, and community development. Full article
8 pages, 529 KB  
Communication
Synthesis of 3,5-Diamino-Substituted Dithieno[3,2-b:2′,3′-d]thiophene Derivatives
by Roman A. Irgashev and Nikita A. Kazin
Molbank 2025, 2025(4), M2109; https://doi.org/10.3390/M2109 (registering DOI) - 10 Dec 2025
Abstract
We report the first synthesis of 3,5-diamino-substituted dithieno[3,2-b:2′,3′-d]thiophene derivatives, bearing alkoxycarbonyl or acetyl groups at C-2 and C-6 positions. The target compounds were prepared via the reaction of 3,4-dibromothiophene-2,5-dicarbonitrile with alkyl thioglycolates or mercaptoacetone in the presence of DBU [...] Read more.
We report the first synthesis of 3,5-diamino-substituted dithieno[3,2-b:2′,3′-d]thiophene derivatives, bearing alkoxycarbonyl or acetyl groups at C-2 and C-6 positions. The target compounds were prepared via the reaction of 3,4-dibromothiophene-2,5-dicarbonitrile with alkyl thioglycolates or mercaptoacetone in the presence of DBU and isolated in 67–87% yield. The key dinitrile was synthesized in 76% yield from 3,4-dibromothiophene-2,5-dicarbaldehyde. In turn, this dialdehyde was prepared on a multigram scale from commercially available 2,5-dimethylthiophene in three steps. The resulting dithieno[3,2-b:2′,3′-d]thiophenes serve as valuable building blocks for materials chemistry, offering multiple reactive sites for further structural elaboration and property tuning. Full article
(This article belongs to the Section Organic Synthesis and Biosynthesis)
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27 pages, 1169 KB  
Article
Mitigating Load Shedding in South Africa Through Optimized Hybrid Solar–Battery Deployment: A Techno-Economic Assessment
by Ginevra Vittoria and Rui Castro
Energies 2025, 18(24), 6480; https://doi.org/10.3390/en18246480 (registering DOI) - 10 Dec 2025
Abstract
South Africa’s persistent electricity shortages and recurrent load shedding remain among the most pressing challenges to national economic growth and social stability. This paper presents a techno-economic framework to assess how optimized deployment of photovoltaic (PV) and battery energy storage systems (BESSs) can [...] Read more.
South Africa’s persistent electricity shortages and recurrent load shedding remain among the most pressing challenges to national economic growth and social stability. This paper presents a techno-economic framework to assess how optimized deployment of photovoltaic (PV) and battery energy storage systems (BESSs) can mitigate these disruptions under realistic grid and regulatory constraints. Despite recent operational improvements at Eskom—including a 10-month period without load shedding in 2024—energy insecurity persists due to aging coal assets, limited transmission capacity, and slow renewable integration. Using hourly demand and solar-resource data for 2023, combined with Eskom’s load-reduction records, a Particle Swarm Optimization (PSO) model identifies cost-optimal hybrid system configurations that minimize the Levelized Cost of Electricity (LCOE) while maximizing coverage of unserved energy. Three deployment scenarios are analyzed: (i) constrained regional grid capacity, (ii) flexible redistribution of capacity across six provinces, and (iii) unconstrained national deployment. Results indicate that constrained deployment covers about 86% of curtailed load at 1.88 USD kWh−1, whereas flexible and unconstrained scenarios achieve over 99% coverage at ≈0.58 USD kWh−1. The findings demonstrate that targeted PV–BESS expansion, coupled with selective grid reinforcement, can effectively eliminate load shedding and accelerate South Africa’s transition toward a resilient, low-carbon electricity system. Full article
22 pages, 1175 KB  
Review
A Review of Recent Advances in Multivalent Ion Batteries for Next Generation Energy Storage
by Raj Shah, Kate Marussich and Vikram Mittal
Electrochem 2025, 6(4), 44; https://doi.org/10.3390/electrochem6040044 (registering DOI) - 10 Dec 2025
Abstract
As demand for high-performance energy storage grows across grid and mobility sectors, multivalent ion batteries (MVIBs) have emerged as promising alternatives to lithium-based systems due to their potential for higher volumetric energy density and material abundance. This review comprehensively examines recent breakthroughs in [...] Read more.
As demand for high-performance energy storage grows across grid and mobility sectors, multivalent ion batteries (MVIBs) have emerged as promising alternatives to lithium-based systems due to their potential for higher volumetric energy density and material abundance. This review comprehensively examines recent breakthroughs in magnesium, zinc, aluminum, and calcium-based battery chemistries, with a focus on overcoming barriers related to slow ion transport, limited reversibility, and electrode degradation. Advances in aqueous and non-aqueous electrolyte formulations, including solvation shell engineering, interfacial passivation, and dual-zone ion transport, are discussed for their role in improving compatibility and cycling stability. Particular focus is placed on three high-impact innovations: solvation-optimized Mg-ion systems for improved mobility and retention, interface-engineered Zn-ion batteries enabling dendrite-free operation, and sustainable Al-ion technologies targeting grid-scale deployment with eco-friendly electrolytes and recyclable materials. Cross-cutting insights from operando characterization techniques and AI-guided materials discovery are also evaluated for their role in accelerating MVIB development. By integrating fundamental materials innovation with practical system design, multivalent ion batteries offer a compelling path toward next-generation, safer, and more sustainable energy storage platforms. Full article
22 pages, 462 KB  
Review
Artificial Intelligence in Tetralogy of Fallot: From Prenatal Diagnosis to Lifelong Management: A Narrative Review
by Tiziana Fragasso, Davide Passaro, Alessandra Toscano, Antonio Amodeo, Alberto Eugenio Tozzi and Giorgia Grutter
Bioengineering 2025, 12(12), 1349; https://doi.org/10.3390/bioengineering12121349 (registering DOI) - 10 Dec 2025
Abstract
Artificial intelligence (AI) is rapidly transforming cardiovascular medicine, with profound implications for congenital heart disease (CHD). Tetralogy of Fallot (ToF), the most common cyanotic disease, requires lifelong surveillance and complex management because of late complications such as pulmonary regurgitation, arrhythmias, and right ventricular [...] Read more.
Artificial intelligence (AI) is rapidly transforming cardiovascular medicine, with profound implications for congenital heart disease (CHD). Tetralogy of Fallot (ToF), the most common cyanotic disease, requires lifelong surveillance and complex management because of late complications such as pulmonary regurgitation, arrhythmias, and right ventricular dysfunction. This review synthesizes current evidence on AI applications across the continuum of ToF care—from prenatal diagnosis to adulthood follow-up. We examine advances in imaging, perioperative planning, intraoperative monitoring, intensive care, and long-term surveillance, including wearable and implantable technologies. Machine learning (ML), deep learning (DL), and natural language processing (NLP) are revolutionizing diagnostic accuracy, risk stratification, surgical decision-making, and personalized long-term care. The future lies in the integration of multimodal data, including imaging, electronic health records (EHRs), genomic information, and continuous monitoring, to support precision medicine. Challenges remain regarding dataset limitations, interpretability, regulatory standards, and ethical concerns. Nevertheless, ongoing innovation and collaboration between clinicians, engineers, and regulators promise a new era in congenital cardiology. By embedding AI throughout the patient journey, healthcare systems may improve outcomes and quality of life for individuals with ToF. Full article
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34 pages, 8108 KB  
Article
Tuning Scaffold Properties of New 1,4-Substituted Pyrrolo[3,2-c]quinoline Derivatives Endowed with Anticancer Potential, New Biological and In Silico Insights
by Francesco Mingoia, Caterina Di Sano, Claudia D’Anna, Marco Fazzari, Alessia Bono, Gabriele La Monica, Annamaria Martorana and Antonino Lauria
Biomolecules 2025, 15(12), 1718; https://doi.org/10.3390/biom15121718 (registering DOI) - 10 Dec 2025
Abstract
A new series of angular tricyclic pyrrolo[3,2-c]quinoline derivatives (PQs) was designed and synthesized to further explore the previously promising antiproliferative activity exhibited by the 4-benzodioxole-substituted hit 7d. Accordingly, several structural modifications mainly focused on the benzodioxole moiety were introduced, allowing us to [...] Read more.
A new series of angular tricyclic pyrrolo[3,2-c]quinoline derivatives (PQs) was designed and synthesized to further explore the previously promising antiproliferative activity exhibited by the 4-benzodioxole-substituted hit 7d. Accordingly, several structural modifications mainly focused on the benzodioxole moiety were introduced, allowing us to gain new insights into the activity and biological profile. NCI antiproliferative screening (SRB colorimetric assay), together with MTS-based assay against six other tumour cell lines, enabled us a deeper understanding of the selectivity and potency patterns. This led to the identification of a new promising hit, compound 7p, which exhibited cytotoxic activity in the low micromolar range against MCF-7 and HeLa cells. Further biological evaluations, including apoptosis induction, clonogenic, and scratch tests, provided additional biological insights into the anticancer potential of these compounds, supporting the subsequent lead optimization process for more potent anticancer activity. The integrated in silico docking results evidenced a clear multi-target profile, as testified by the broad anticancer activity, and suggest a good potential for rational polypharmacology. Full article
(This article belongs to the Section Chemical Biology)
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