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30 pages, 4892 KB  
Article
High-Precision Permanent Magnet Localization Using an Improved Artificial Lemming Algorithm Integrated with Levenberg–Marquardt Optimization
by Weihong Bi, Chunlong Zhang, Guangwei Fu, Mengye Wang and Zengjie Guo
Electronics 2026, 15(1), 135; https://doi.org/10.3390/electronics15010135 (registering DOI) - 27 Dec 2025
Abstract
Magnetic localization technology plays a significant role in medical device navigation and human–computer interaction. However, existing localization methods based on local optimization suffer from poor initial solutions and slow convergence. To address the aforementioned challenges, this paper presents a hybrid localization approach, referred [...] Read more.
Magnetic localization technology plays a significant role in medical device navigation and human–computer interaction. However, existing localization methods based on local optimization suffer from poor initial solutions and slow convergence. To address the aforementioned challenges, this paper presents a hybrid localization approach, referred to as the Improved Artificial Lemming Algorithm (IALA) Integrated with Levenberg–Marquardt (LM) Optimization. Building upon the Artificial Lemming Algorithm (ALA), the proposed method incorporates an adaptive Gaussian–Lévy hybrid mutation strategy designed to enhance search performance through improved exploration–exploitation dynamics, as quantitatively demonstrated by the diversity-based analysis where IALA maintains higher exploration percentages on multimodal functions while achieving superior optimization results on high-dimensional problems. By introducing a competitive foraging mechanism inspired by the aggressive behavior of the Tasmanian Devil Optimization (TDO) algorithm, it enhances population diversity and search initiative. Furthermore, a time-varying tracking and escape strategy is adopted to improve dynamic optimization performance in complex solution spaces. The proposed method leverages IALA to generate high-quality initial solutions, significantly accelerating the convergence speed and stability of the LM algorithm, thereby improving the overall performance of the permanent magnet localization system. The experimental results show that, using a horizontal test platform of 60 mm × 60 mm with 41 uniformly distributed test points, and acquiring data at vertical heights ranging from 15 mm to 65 mm in 5 mm increments for two distinct orientations of the permanent magnet, the IALA-LM algorithm achieves an average localization success rate of 96.9% over 902 trials, with a mean position error of 1.1 mm and a mean orientation error of 0.17°. Compared with the standard LM algorithm, the proposed IALA-LM algorithm reduces the position error by approximately 66.7% (from 3.3 mm to 1.1 mm) and the orientation error by approximately 94.3% (from 3.0° to 0.17°). Consequently, the proposed method enables high-precision, high-stability, and high-efficiency localization of permanent magnets. It can provide reliable spatial pose estimation support for demanding applications such as miniature implantable or ingestible medical devices (e.g., capsule endoscopy, intramedullary nail fixation, and tumor localization), human–computer interaction, and industrial inspection. Full article
62 pages, 1714 KB  
Review
FGFR Aberrations in Solid Tumors: Mechanistic Insights and Clinical Translation of Targeted Therapies
by Zijie He, Yizhen Chen, Genglin Li, Jintao Wang, Yuxin Wang, Pengjie Tu, Yangyun Huang, Lilan Zhao, Xiaojie Pan, Hengrui Liu and Wenshu Chen
Cancers 2026, 18(1), 89; https://doi.org/10.3390/cancers18010089 (registering DOI) - 27 Dec 2025
Abstract
Aberrations in fibroblast growth factor receptors (FGFRs) constitute a key oncogenic mechanism across multiple solid tumors, influencing tumor initiation, therapeutic response, and clinical outcomes. This review synthesizes current knowledge on the molecular biology, signaling networks, and tumor-specific distribution of FGFR alterations, including amplifications, [...] Read more.
Aberrations in fibroblast growth factor receptors (FGFRs) constitute a key oncogenic mechanism across multiple solid tumors, influencing tumor initiation, therapeutic response, and clinical outcomes. This review synthesizes current knowledge on the molecular biology, signaling networks, and tumor-specific distribution of FGFR alterations, including amplifications, point mutations, and gene fusions. The mechanistic basis of FGFR-driven tumor progression is discussed, including activation of downstream signaling pathways, crosstalk with other receptor tyrosine kinases, and regulation of the tumor microenvironment, angiogenesis, and immune escape. Recent development of selective FGFR inhibitors—such as pemigatinib, erdafitinib, and futibatinib—has translated mechanistic insights into measurable clinical benefits in genomically defined patient populations. However, acquired resistance remains a major challenge, driven by secondary mutations, activation of bypass pathways, and intratumoral heterogeneity. Integration of multi-omics profiling, liquid biopsy monitoring, and biomarker-guided patient selection is essential to optimize therapeutic efficacy and overcome resistance. This review also highlights emerging therapeutic modalities, such as antibody–drug conjugates and nanotechnology-based delivery systems, which may improve target specificity and prolong therapeutic durability. By integrating molecular, translational, and clinical evidence, this review aims to establish a comprehensive framework for precision oncology strategies targeting FGFR-driven malignancies. Full article
(This article belongs to the Special Issue Novel Therapeutic Approaches for Cancer Treatment)
26 pages, 1941 KB  
Article
Unexplored Social–Ecological Trap Lens of Hilsa Fishery in Bangladesh
by Mukta Sarker, Md. Mostafa Shamsuzzaman, Khadija Akter, Anuradha Talukdar, Md. Asadujjaman and Mohammad Mojibul Hoque Mozumder
Sustainability 2026, 18(1), 295; https://doi.org/10.3390/su18010295 (registering DOI) - 27 Dec 2025
Abstract
This study aimed to assess various social–ecological traps of hilsa shad (Tenualosa ilisha) fisheries and to investigate the factors that significantly impact livelihood adaptation strategies during the ban period, based on fieldwork in coastal fishing communities. To collect empirical data, a [...] Read more.
This study aimed to assess various social–ecological traps of hilsa shad (Tenualosa ilisha) fisheries and to investigate the factors that significantly impact livelihood adaptation strategies during the ban period, based on fieldwork in coastal fishing communities. To collect empirical data, a total of 247 in-depth interviews were conducted using a semi-structured questionnaire along with six focus group discussions, oral history, and ten key informant interviews in the Chattogram and Patuakhali districts of Bangladesh. A conceptual framework derived from a strategy for reducing poverty, known as the Sustainable Livelihood Approach (SLA), is applied to determine the livelihood outcomes of hilsa fishers. The results showed that low income (<5000 BDT/month), high interest in loans from dadondar (lender) (10–12%) and aratdar (lessor of the vessel) (5%), high harvesting costs, an increasing number of hilsa fishermen, and intergenerational traps (81.78%) are creating social–ecological traps (SETs) in the hilsa fishery. The significant factors affecting the choice of adaptation strategies include family members, training facilities, home ownership, and belonging to a formal society. Apart from fighting against some extreme climate events, negative feedback comes from the absence of cold storage facilities, illegal use of fishing nets, frequent ban seasons, ignorance of conservation laws, limited opportunities for alternative occupations, and poor supply of drinking water. Hilsa fishermen in these regions depended on aratdar and dadondar for their financial support, which resulted in lower prices than the prevailing market prices. To escape from the SETs, this study identifies potential alternatives, such as government–community finance schemes, the promotion of alternative livelihoods, opportunities for technical education of their children, improvement of the local framework, and strong cooperation between local stakeholders and management authorities that are necessary to maintain the sustainability of hilsa fisheries. Full article
(This article belongs to the Section Social Ecology and Sustainability)
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35 pages, 3680 KB  
Article
A Hybrid Optimization Algorithm with Multi-Strategy Integration and Multi-Subpopulation Cooperation for Engineering Problem Solving
by Liang Kang and Weini Xia
Mathematics 2026, 14(1), 95; https://doi.org/10.3390/math14010095 (registering DOI) - 26 Dec 2025
Abstract
To solve the limitations of single optimization algorithms, such as premature convergence, insufficient global exploration, and high susceptibility to local optima, a Hybrid Optimization Algorithm (HOA) based on multi-subpopulation collaboration and multi-strategy fusion is proposed. The HOA uses Logistic chaotic mapping for population [...] Read more.
To solve the limitations of single optimization algorithms, such as premature convergence, insufficient global exploration, and high susceptibility to local optima, a Hybrid Optimization Algorithm (HOA) based on multi-subpopulation collaboration and multi-strategy fusion is proposed. The HOA uses Logistic chaotic mapping for population initialization to enhance uniformity and diversity. The population is then divided into four subpopulations; each is optimized independently using different strategies, including the genetic algorithm (GA), Gray Wolf Optimizer (GWO), self-attention mechanism, and k-nearest neighbor graph (kNN). This design leverages the strengths of individual algorithms while mitigating their respective limitations. An elite information exchange mechanism facilitates knowledge transfer by randomly reassigning elite individuals across subpopulations at fixed iteration intervals. Additionally, global optimization strategies including differential evolution (DE), Simulated Annealing (SA), Local Search (LS), and time of arrival (TOA) position adjustment are integrated to balance exploration and exploitation, thereby enhancing convergence accuracy and the ability to escape local optima. Evaluated on the CEC2017 benchmark suite and real-world engineering problems, the HOA demonstrates superior performance in convergence speed, accuracy, and robustness compared to single-algorithm approaches—notably, HOA ranks 1st in 30-dimensional CEC2017 functions. By effectively integrating multiple optimization strategies, the HOA provides an effective and reliable solution to complex optimization challenges. Full article
20 pages, 874 KB  
Systematic Review
Effectiveness of Gamification Versus Traditional Teaching Methods on Learning, Motivation, and Engagement in Undergraduate Nursing Education: A Systematic Review
by Vincenzo Andretta, Raffaele Antonio Elia, Maria Colangelo, Ivan Rubbi, Emanuela Santoro, Giovanni Boccia, Marco Cascella and Valentina Cerrone
Int. Med. Educ. 2026, 5(1), 5; https://doi.org/10.3390/ime5010005 (registering DOI) - 26 Dec 2025
Abstract
Background: Gamification is an innovative pedagogical strategy for improving learning outcomes, motivation, engagement, and knowledge retention. Nevertheless, evidence on the effectiveness of gamification remains heterogeneous. Methods: A systematic review was conducted. Searches were performed across PubMed/MEDLINE, CINAHL, PsycINFO, Scopus, Web of Science, Google [...] Read more.
Background: Gamification is an innovative pedagogical strategy for improving learning outcomes, motivation, engagement, and knowledge retention. Nevertheless, evidence on the effectiveness of gamification remains heterogeneous. Methods: A systematic review was conducted. Searches were performed across PubMed/MEDLINE, CINAHL, PsycINFO, Scopus, Web of Science, Google Scholar, and grey literature (2015–2025). Eligible studies included quantitative, qualitative, and mixed-methods research involving undergraduate nursing students exposed to gamification interventions. Data extraction and quality assessment were independently performed using RoB-2, ROBINS-I, and JBI tools. Narrative synthesis was adopted due to the heterogeneity of interventions and outcome measures. Results: A total of 48 studies were included. Gamification strategies varied widely and included interactive quizzes, gamified flipped classroom models, serious games with explicit game elements, escape rooms, digital badges, and audience-response systems. For learning outcomes, most studies reported improvements in knowledge or performance, particularly when gamification included immediate feedback and repeated practice. While the knowledge retention was evaluated less frequently (12%), it was generally maintained or improved up to 2–4 weeks and across semester assessments. Strong positive trends of motivation and engagement were found across most studies, especially with competitive quizzes, missions, and narrative-based activities. Self-efficacy and satisfaction frequently improved, particularly in gamified simulations and team-based activities. Risk of bias was variable, with many quasi-experimental and descriptive studies limiting causal inference. Evidence certainty ranged from low to moderate according to GRADE criteria. Conclusions: Gamification is a promising educational approach in undergraduate nursing programs. Effects on long-term retention and practical skills remain less clear due to methodological variability and limited follow-up data. Future research focused on standardized outcome measures and longer follow-up intervals is required to consolidate evidence and guide educational policy. Protocol registered on PROSPERO (CRD420251117719). Full article
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14 pages, 2403 KB  
Article
Evaluation of CD3 and CD20 Lymphocytes and Mast Cells in the Microenvironment of Central Giant Cell Granuloma, Peripheral Giant Cell Granuloma, and Giant Cell Tumor of Bone
by Khelan A. Fayaq and Balkees T. Gharib
Diagnostics 2026, 16(1), 90; https://doi.org/10.3390/diagnostics16010090 (registering DOI) - 26 Dec 2025
Abstract
Objective: Giant cell lesions (GCLs) share similar histopathologic features. The influence of immune involvement on the biology of giant cell lesions remains largely elusive. This study aimed to evaluate and compare lymphocyte and mast cell infiltration and distribution among three giant cell [...] Read more.
Objective: Giant cell lesions (GCLs) share similar histopathologic features. The influence of immune involvement on the biology of giant cell lesions remains largely elusive. This study aimed to evaluate and compare lymphocyte and mast cell infiltration and distribution among three giant cell lesions. Study design: A total of 30 FFPE tissue blocks, comprising 10 PGCGs, 10 CGCGs (aggressive and nonaggressive), and 10 GCTs (aggressive and nonaggressive) of bone, were subjected to IHC staining for CD3 and CD20 lymphocyte markers and toluidine blue staining for mast cells. The mean count of positively stained cells was calculated and categorized into three scores, along with a group for negative cases. Statistical analysis was conducted to assess significance at p < 0.05. Result: Lymphocyte infiltration was observed across all lesions. CD3+ and CD20+ cell counts were significantly elevated in PGCGs, followed by CGCGs, and were lowest in GCTs of bone. In contrast, mast cell counts were high in GCTs of bone and CGCGs and low in PGCGs. Aggressive giant cell lesions of bone showed a significantly low number of CD3+ and CD20+ cells (Mann–Whitney U test; p = 0.05, 0.004) and a high number of mast cells (Mann–Whitney U test; p < 0.001) compared with nonaggressive lesions of bone. PGCGs and nonaggressive CGCGs showed comparable CD3 expression, with no significant difference between them (p = 0.59). CD20 levels were higher in nonaggressive CGCGs but did not reach statistical significance (Mann–Whitney U test; p = 0.07). Mast cell density was significantly lower in PGCGs compared with intraosseous nonaggressive CGCGs. Conclusions: The present study shows that GCTs of bone, CGCGs, and PGCGs possess distinct immune microenvironmental profiles. Aggressive lesions demonstrate reduced lymphocyte infiltration and increased mast cell density, a pattern particularly evident in GCTs of bone. This imbalance may contribute to their aggressive behavior by enabling them to escape host immune regulation. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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19 pages, 1806 KB  
Communication
Unraveling Resistance Mechanisms to Gαq Pathway Inhibition in Uveal Melanoma: Insights from Signacardenas-Alcoserling-Activation Library Screening
by Simone Lubrano, Rodolfo Daniel Cervantes-Villagrana, Nadia Arang, Elena Sofia Cardenas-Alcoser, Kuniaki Sato, Gabriela Cuesta-Margolles, Justine S. Paradis, Monica Acosta and J. Silvio Gutkind
Cancers 2026, 18(1), 74; https://doi.org/10.3390/cancers18010074 - 25 Dec 2025
Abstract
Background/Objectives: Uveal melanoma (UVM), the leading primary intraocular cancer in adults, is driven by GNAQ/GNA11 mutations, encoding the active forms of Gαq proteins. While local treatments like surgery or radiation can control primary tumors, nearly half of patients die from metastasis. [...] Read more.
Background/Objectives: Uveal melanoma (UVM), the leading primary intraocular cancer in adults, is driven by GNAQ/GNA11 mutations, encoding the active forms of Gαq proteins. While local treatments like surgery or radiation can control primary tumors, nearly half of patients die from metastasis. Our aim was identifying potential pathways involved in resistance to targeted therapy in UVM. Methods: Here, we screened 100 pathway-activating mutant complementary DNAs by lentiviral overexpression to identify those that enhance the survival of cancer cells in the presence of clinically relevant targeted therapies, using BAP1 wild-type UVM cells and validated the most significant results in BAP1-mutant cells. Results: This revealed JAK/STAT activation, overexpression of anti-apoptotic BCL2/BCL-XL, and dysregulated PI3K/mTOR or Hippo pathways as escape routes under MEK-ERK or FAK inhibition. Bioinformatic analysis of UVM transcriptome in TCGA further showed that high expression of the hallmark PI3K/AKT/mTOR pathway and IL6/JAK/STAT signaling correlates with poor prognosis. A similar correlation was shown by YAP and anti-apoptotic signatures. The analysis of individual representative genes from these signatures revealed that MTOR, BCL2L1 (BCL-XL), and TEAD4 gene expression are linked to poorer survival, underscoring the potential clinical impact of these adaptive pathways. Proliferation and apoptosis assay demonstrated that aberrant activation of AKT and YAP promotes resistance to FAK and MEK inhibitors. Conclusions: These findings support the adaptability of UVM lesions and suggest rational combination therapies targeting both primary GNAQ/GNA11-driven oncogenic signals and their compensatory networks as a more effective, personalized treatment approach for advanced UVM. Full article
(This article belongs to the Special Issue Advances in Uveal Melanoma)
27 pages, 1714 KB  
Article
Beyond Escapism: The Positive Role of Cosplay in Gender Expression, Mental Health, and Cultural Consumption in Japan
by Moqiao Liu
Soc. Sci. 2026, 15(1), 10; https://doi.org/10.3390/socsci15010010 - 25 Dec 2025
Viewed by 26
Abstract
With the promotion and development of anime, manga, and video games in Japan and beyond, a substantial number of fans have been attracted. These people began to dress up as their favorite characters. Cosplay has found applications in different fields. This essay argues [...] Read more.
With the promotion and development of anime, manga, and video games in Japan and beyond, a substantial number of fans have been attracted. These people began to dress up as their favorite characters. Cosplay has found applications in different fields. This essay argues that cosplay has played a positive role in promoting gender expression, enhancing mental health, and fostering cultural consumption that transcends mere escapism. Cosplay provides a safe environment for gender expression, challenging traditional gender norms, embracing diversity of gender expression, and allowing cosplayers to showcase their gender identities. Cosplay helps cosplayers not only overcome mental pressure in real life by enabling them to play superheroes and build their resilience, but also brings them a sense of achievement and cultivates their problem-solving abilities through the creation of costumes. Cosplayers utilize these characters for cultural consumption, promoting the cosplay-related economic industry in Japan. Cosplayers, audiences, and organizers of anime conventions form a sustainable consumption cycle by making or purchasing costumes, spending money on merchandise, and organizing comic conventions. Cosplay has driven economic benefits in the catering, photography, and venue rental industries by incorporating anime themes and catering to the demands of three major consumer groups. Full article
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20 pages, 505 KB  
Review
Expression and Clinical Significance of CD47 in Colorectal Cancer: A Review
by Qijie Li, Paola Vignali, Donghao Tang, Giulia Martinelli, Beatrice Fuochi, Rebecca Sparavelli, Anello Marcello Poma, Rossella Bruno, Elisabetta Macerola and Clara Ugolini
Cancers 2026, 18(1), 54; https://doi.org/10.3390/cancers18010054 - 24 Dec 2025
Viewed by 83
Abstract
Cluster of Differentiation 47 (CD47), an innate immune checkpoint, facilitates immune escape by binding signal regulatory protein alpha (SIRPα) to inhibit macrophage phagocytosis. Its significance in colorectal cancer (CRC) has garnered heightened interest. This review summarizes five immunohistochemistry (IHC) studies and complementary transcriptomic [...] Read more.
Cluster of Differentiation 47 (CD47), an innate immune checkpoint, facilitates immune escape by binding signal regulatory protein alpha (SIRPα) to inhibit macrophage phagocytosis. Its significance in colorectal cancer (CRC) has garnered heightened interest. This review summarizes five immunohistochemistry (IHC) studies and complementary transcriptomic analyses assessing CD47 in CRC. IHC results consistently indicated membrane overexpression, though positivity rates varied widely (16–91%) due to methodological heterogeneity. Transcriptomic results confirmed CD47 upregulation, especially in Consensus Molecular Subtype 1 (CMS1) and CMS4 subtypes and revealed co-expression with immune checkpoints and oncogenic pathways. Clinically, high CD47 levels were associated with advanced TNM stage, metastasis, poor differentiation, and altered immune infiltration; however, the prognostic significance varied among cohorts. Overall, CD47 appears to be a promising biomarker and therapeutic target, but clinical translation requires standardized evaluation, including harmonized antibody selection and scoring cut-offs, and prospective validation. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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24 pages, 6486 KB  
Article
Resistance Mutations to Broadly Neutralizing Antibodies Destabilize Hemagglutinin and Attenuate H1N1 Influenza Virus
by Guohua Yang, Po-Ling Chen, Samuel W. Rovito, Karine Minari, Haley N. Writt, Jennifer DeBeauchamp, Jeri Carol Crumpton, Lisa Kercher, Rebecca M. DuBois, Richard J. Webby and Charles J. Russell
Viruses 2026, 18(1), 32; https://doi.org/10.3390/v18010032 - 24 Dec 2025
Viewed by 111
Abstract
Because antigenic drift primarily generates amino-acid changes in the membrane-distal hemagglutinin (HA) head, broadly neutralizing antibodies (bNAbs) are being developed to target conserved epitopes in the membrane-proximal stem. Mutations to HA2 residue A44, a buried residue beneath the central stem epitope, in 2009 [...] Read more.
Because antigenic drift primarily generates amino-acid changes in the membrane-distal hemagglutinin (HA) head, broadly neutralizing antibodies (bNAbs) are being developed to target conserved epitopes in the membrane-proximal stem. Mutations to HA2 residue A44, a buried residue beneath the central stem epitope, in 2009 H1N1 viruses have been shown to cause resistance to stem-binding bNAbs. Here, we introduced A44V and A44T mutations into A/Tennessee/1-560/2009 (TN09) and A/Puerto Rico/15/2018 (PR18) and investigated their effects in cell culture, mice, and ferrets. In both virus strains, the mutations decreased HA and virus stability and decreased bNAb binding and neutralization in vitro. The mutations reduced pathogenicity and lung replication in DBA/2J mice. Ferrets were inoculated with PR18 wild-type (WT) or A44V virus, and the A44V mutation reduced day-1 and peak nasal virus titers. Airborne transmission in the A44V group occurred only after genotypic reversion (HA2-V44A) or acquisition of a distal re-stabilizing mutation (HA2-I77M). Compared to WT, an engineered PR18 virus containing both HA2 mutations (A44V and I77M) had similar growth and pathogenicity in mice in addition to decreased binding and neutralization by bNAbs. Overall, this work provides insight into the role of HA stability during HA stem-epitope remodeling that results in virus resistance to stem-binding bNAbs. Full article
(This article belongs to the Section Viral Immunology, Vaccines, and Antivirals)
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18 pages, 3937 KB  
Article
A Novel SPH-Based Approach to Predicting Explosion-Induced Failure and Containment in 18650 Battery Systems
by Murat Demiral, Erol Gültekin and Murat Otkur
Appl. Sci. 2026, 16(1), 153; https://doi.org/10.3390/app16010153 - 23 Dec 2025
Viewed by 79
Abstract
This study presents a comprehensive smoothed particle hydrodynamics (SPH) framework developed to investigate the thermomechanical response and failure behavior of cylindrical 18650-type lithium-ion battery cans under explosion conditions. The model captures the coupled evolution of gas pressure, temperature, and particle dynamics, as well [...] Read more.
This study presents a comprehensive smoothed particle hydrodynamics (SPH) framework developed to investigate the thermomechanical response and failure behavior of cylindrical 18650-type lithium-ion battery cans under explosion conditions. The model captures the coupled evolution of gas pressure, temperature, and particle dynamics, as well as the resulting deformation and fracture of the metallic enclosure. Parametric analyses were conducted to evaluate the influence of the internal gas domain geometry, can wall thickness, and initial pressure on the structural response, along with the subsequent post-explosion interaction between the escaping gas and external protective coverage. The results demonstrate the strong dependence of failure initiation on gas confinement geometry and highlight the existence of transient thermodynamic asymmetries within the gas domain that govern the impulse transferred to the can wall. The proposed modeling approach provides a physically consistent means of reproducing the key stages of battery explosion—from internal pressurization to external gas impact—and offers valuable insights for designing safer and more resilient energy storage enclosures. Full article
(This article belongs to the Special Issue Advances in Structural Integrity and Failure Analysis)
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13 pages, 1222 KB  
Article
Multifaceted Adaptive Strategies of Alternanthera philoxeroides in Response to Soil Copper Contamination
by Ling Wang, Kun Li, Xun Huang, Xiaoping Xin, Alan Wright, Zhaohua Li and Liya Zhao
Land 2026, 15(1), 31; https://doi.org/10.3390/land15010031 - 23 Dec 2025
Viewed by 134
Abstract
Excessive copper (Cu) content in soil can affect plant growth and also cause damage to the soil ecosystem, making it one of the risk control projects for agricultural land soil pollution in China. Alternanthera philoxeroides exhibits stronger colonization ability in heavy metal-contaminated soil, [...] Read more.
Excessive copper (Cu) content in soil can affect plant growth and also cause damage to the soil ecosystem, making it one of the risk control projects for agricultural land soil pollution in China. Alternanthera philoxeroides exhibits stronger colonization ability in heavy metal-contaminated soil, but its physiological and ecological mechanisms of tolerance to excessive Cu remain unclear. A greenhouse incubation experiment was conducted to study the multifaced responses of A. philoxeroides to Cu stress at artificially augmented concentrations of 0, 250, 500, and 1000 mg kg−1. The results showed that A. philoxeroides exhibited high tolerance to Cu2+, with a tolerance index (TI) exceeding 60%. As the Cu concentration increased from 0 mg kg−1 to 500 mg kg−1, root biomass and Cu concentration in the root increased. Additionally, soluble sugar (SS) and malondialdehyde (MDA) contents, and catalase (CAT) and peroxidase (POD) activities of A. philoxeroides continued to increase, whereas superoxide dismutase (SOD) enzyme activity, branch number, leaf area, and net photosynthetic rate kept declining. However, the trend of these indicators was opposite when Cu2+ concentrations were above 500 mg kg−1, while the canopy area and underground root system of A. philoxeroides increased. These results suggested A. philoxeroides displayed a standing “silent” tolerance strategy to survive when soil copper was lower than 500 mg kg−1 concentrations, and an “escape” strategy to avoid high copper stress by expanding the above- and below-ground areas of plants when soil copper concentrations were higher than 500 mg kg−1. This study recommends the controlled utilization of A. philoxeroides for pollution remediation in Cu-contaminated soil areas where most local native plants are unable to survive. Full article
(This article belongs to the Topic Water-Soil Pollution Control and Environmental Management)
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17 pages, 1088 KB  
Review
The Need for a Systems Biology Approach in Cancer Explained
by Hehuan Zhu, Xi Zhang, Ehsan Nazemalhosseini-Mojarad, Jessica Roelands, Lysanne D. A. N. de Muynck, Cor J. Ravensbergen, Rachel Hoorntje, Imke Stouten, Marianne Hokland, Alexander L. Vahrmeijer, Rob A. E. M. Tollenaar, Edwin Koster and Peter J. K. Kuppen
Int. J. Mol. Sci. 2026, 27(1), 141; https://doi.org/10.3390/ijms27010141 - 22 Dec 2025
Viewed by 124
Abstract
Traditionally, scientists tend to approach cancer research in a reductionistic way: aiming at uncovering underlying, separate components in malignant processes. And indeed, great progress has been made by reducing the development of a tumor to single, specific genes and mutations. For instance, familial [...] Read more.
Traditionally, scientists tend to approach cancer research in a reductionistic way: aiming at uncovering underlying, separate components in malignant processes. And indeed, great progress has been made by reducing the development of a tumor to single, specific genes and mutations. For instance, familial adenomatous polyposis (FAP) could be reduced to a germline mutation in the Adenomatous Polyposis Coli (APC) gene. The escape of tumor cells from immune surveillance could be reduced to the tumor expression of immune checkpoints, resulting in new approaches in tumor therapy by applying immune checkpoint inhibitors. However, a germline mutation in APC is not 1:1 related to colorectal cancer (CRC), and only some patients respond to immune checkpoint inhibitors. The point here is that biological systems, also comprising cancer, have properties that cannot be reduced to single components. The cooperation of the single components results in new, emergent properties. The outcome of an interaction in a complex network, like the immune system, depends on the many cell types involved and the numerous molecules that interact and activate or inhibit pathways. The way the composing elements are organized is a causal factor in itself for any emergent property. The rise of genomic analysis at the end of the previous century, enabling us to sequence a full genome at the DNA and RNA levels, has initiated an awareness of the need for ‘systems biology’: to consider a full system and how it is organized, in all of its aspects, to understand biological pathways and their outcomes. In this review, we outline the prospects and limitations of systems biology in cancer research and propose a causal framework that integrates upward and downward causation and multiple realizability to understand the emergent properties of tumors that determine the dynamics of tumor development. Full article
(This article belongs to the Special Issue 25th Anniversary of IJMS: Updates and Advances in Molecular Oncology)
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18 pages, 2670 KB  
Article
Effects of Polysaccharide Coating on Cell-Surface Association and Endocytic Uptake of PLGA Nanomicelles in MCF-7 Cells
by Abdulkadir Bahadir Alkan, Esma Nur Develi Arslanhan, Fatemeh Bahadori, Muhammed Zahid Kasapoglu, Fahri Akbas, Seda Susgun, Zahra Eskandari and Ebru Toksoy Oner
Pharmaceutics 2026, 18(1), 17; https://doi.org/10.3390/pharmaceutics18010017 - 22 Dec 2025
Viewed by 202
Abstract
Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of [...] Read more.
Background: Targeting cancer tumors using PLGA (Poly(D, L-lactide-co-glycolide)) nanoparticles (NPs) requires clathrin-mediated endocytosis (CME) and lysosomal degradation to provide release within cancer cells. However, Caveolae-mediated endocytosis (CavME) provides lysosomal escape, which is favorable in oral applications. Macropinocytosis (MPC) is a non-targeted way of endocytosis, used by immune cells. Methods: In this proof-of-concept study, we investigated how polysaccharide surface coatings modulate the endocytic uptake of FITC-labeled PLGA nanomicelles (FPM) in MCF-7 breast cancer cells using spectrophotometry. This research involved the surface modification of FPM using polysaccharides: cellulose (FPCM) as a polyglucan and Halomonas Levan (FPLM) as a polyfructan, to modify the NP and cell-surface association. Results: MPC was found to be the major internalization pathway for the nanomicelles ~200 nm. However, after surface modification, FPCM and FPM remained highly MPC-dependent with additional CavME/CME involvement, whereas FPLM showed relatively reduced MPC dependence and a higher CME contribution. Conclusion: Overall, the results indicate that simple polysaccharide coatings can bias the relative use of MPC, CME, and CavME for PLGA nanomicelles in MCF-7 cells, providing a basis for pathway-oriented nanocarrier design. Validation by flow cytometry, studies in additional breast cancer cell lines, and transporter-level investigations will be needed to generalize and refine these findings. Full article
(This article belongs to the Special Issue PLGA Micro/Nanoparticles in Drug Delivery)
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Article
Activating KRAS Mutations Expressed in 3D Endothelial Spheroids Induce Blebbing Morphologies Associated with Amoeboid-like Migration
by Lucinda S. McRobb, Vivienne S. Lee and Marcus A. Stoodley
Cells 2026, 15(1), 22; https://doi.org/10.3390/cells15010022 - 22 Dec 2025
Viewed by 185
Abstract
Introduction: A 3D endothelial spheroid model expressing mosaic gain-of-function KRAS mutations was established to further understand the molecular changes associated with sporadic brain arteriovenous malformations (AVMs). Methods: Repellent 96-well U-bottom plates were seeded with human cerebral microvascular endothelial cells and resultant spheroids transduced [...] Read more.
Introduction: A 3D endothelial spheroid model expressing mosaic gain-of-function KRAS mutations was established to further understand the molecular changes associated with sporadic brain arteriovenous malformations (AVMs). Methods: Repellent 96-well U-bottom plates were seeded with human cerebral microvascular endothelial cells and resultant spheroids transduced with recombinant adeno-associated virus expressing KRASG12V. Spheroids were monitored using live-cell imaging for extended culture periods. Results: In the early growth period, KRASG12V expression increased spheroid growth rates and enhanced spheroid sprouting on gel matrices consistent with known AVM characteristics. With extended culture, novel endothelial characteristics were observed. KRASG12V-expressing spheroids displayed dynamic blebbing associated with the formation of rounded, hypertrophic cells disposed to engage in spheroid escape. These cells displayed reduced cell–cell adherence with rapid plasma membrane blebbing characteristic of amoeboid-like migration and mesenchymal-to-amoeboid transition. Spheroid growth and blebbing were reversed with MEK and mTOR inhibitors; Rho/ROCK inhibition specifically targeted the blebbing phenotype. Conclusions: Endothelial spheroids expressing KRASG12V exhibit characteristic features associated with abnormal vessel development in brain AVMs as well as novel phenotypes not previously observed in 2D monolayers. The ability to extend culture periods in this simple 3D model may allow further phenotypic exploration of important AVM driver mutations. Full article
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