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21 pages, 632 KiB  
Review
DNA Methylation in Bladder Cancer: Diagnostic and Therapeutic Perspectives—A Narrative Review
by Dragoş Puia, Marius Ivănuță and Cătălin Pricop
Int. J. Mol. Sci. 2025, 26(15), 7507; https://doi.org/10.3390/ijms26157507 (registering DOI) - 3 Aug 2025
Viewed by 60
Abstract
Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current [...] Read more.
Bladder cancer pathogenesis is closely linked to epigenetic alterations, particularly DNA methylation and demethylation processes. Environmental carcinogens and persistent inflammatory stimuli—such as recurrent urinary tract infections—can induce aberrant DNA methylation, altering gene expression profiles and contributing to malignant transformation. This review synthesizes current evidence on the role of DNA methyltransferases (DNMT1, DNMT3a, DNMT3b) and the hypermethylation of key tumour suppressor genes, including A2BP1, NPTX2, SOX11, PENK, NKX6-2, DBC1, MYO3A, and CA10, in bladder cancer. It also evaluates the therapeutic application of DNA-demethylating agents such as 5-azacytidine and highlights the impact of chronic inflammation on epigenetic regulation. Promoter hypermethylation of tumour suppressor genes leads to transcriptional silencing and unchecked cell proliferation. Urine-based DNA methylation assays provide a sensitive and specific method for non-invasive early detection, with single-target approaches offering high diagnostic precision. Animal models are increasingly employed to validate these findings, allowing the study of methylation dynamics and gene–environment interactions in vivo. DNA methylation represents a key epigenetic mechanism in bladder cancer, with significant diagnostic, prognostic, and therapeutic implications. Integration of human and experimental data supports the use of methylation-based biomarkers for early detection and targeted treatment, paving the way for personalized approaches in bladder cancer management. Full article
(This article belongs to the Section Molecular Oncology)
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32 pages, 17593 KiB  
Review
Responsive Therapeutic Environments: A Dual-Track Review of the Research Literature and Design Case Studies in Art Therapy for Children with Autism Spectrum Disorder
by Jing Liang, Jingxuan Jiang, Jinghao Hei and Jiaqi Zhang
Buildings 2025, 15(15), 2735; https://doi.org/10.3390/buildings15152735 - 3 Aug 2025
Viewed by 76
Abstract
Art therapy serves as a crucial intervention modality for children with autism spectrum disorder (ASD), demonstrating unique value in emotional expression, sensory integration, and social communication. However, current practice presents critical challenges, including the disconnect between design expertise and clinical needs, unclear mechanisms [...] Read more.
Art therapy serves as a crucial intervention modality for children with autism spectrum disorder (ASD), demonstrating unique value in emotional expression, sensory integration, and social communication. However, current practice presents critical challenges, including the disconnect between design expertise and clinical needs, unclear mechanisms of environmental factors’ impact on therapeutic outcomes, and insufficient evidence-based support for technology integration. Purpose: This study aimed to construct an evidence-based theoretical framework for art therapy environment design for children with autism, clarifying the relationship between environmental design elements and therapeutic effectiveness. Methodology: Based on the Web of Science database, this study employed a dual-track approach comprising bibliometric analysis and micro-qualitative content analysis to systematically examine the knowledge structure and developmental trends. Research hotspots were identified through keyword co-occurrence network analysis using CiteSpace, while 24 representative design cases were analyzed to gain insights into design concepts, emerging technologies, and implementation principles. Key Findings: Through keyword network visualization analysis, this study identified ten primary research clusters that were systematically categorized into four core design elements: sensory feedback design, behavioral guidance design, emotional resonance design, and therapeutic support design. A responsive therapeutic environment conceptual framework was proposed, encompassing four interconnected components based on the ABC model from positive psychology: emotional, sensory, environmental, and behavioral dimensions. Evidence-based design principles were established emphasizing child-centeredness, the promotion of multisensory expression, the achievement of dynamic feedback, and appropriate technology integration. Research Contribution: This research establishes theoretical connections between environmental design elements and art therapy effectiveness, providing a systematic design guidance framework for interdisciplinary teams, including environmental designers, clinical practitioners, technology developers, and healthcare administrators. The framework positions technology as a therapeutic mediator rather than a driver, ensuring technological integration supports rather than interferes with children’s natural creative impulses. This contributes to creating more effective environmental spaces for art therapy activities for children with autism while aligning with SDG3 goals for promoting mental health and reducing inequalities in therapeutic access. Full article
(This article belongs to the Special Issue Art and Design for Healing and Wellness in the Built Environment)
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29 pages, 1505 KiB  
Review
Biological Macromolecule-Based Dressings for Combat Wounds: From Collagen to Growth Factors—A Review
by Wojciech Kamysz and Patrycja Kleczkowska
Med. Sci. 2025, 13(3), 106; https://doi.org/10.3390/medsci13030106 - 1 Aug 2025
Viewed by 287
Abstract
Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, [...] Read more.
Wound care in military and combat environments poses distinct challenges that set it apart from conventional medical practice in civilian settings. The nature of injuries sustained on the battlefield—often complex, contaminated, and involving extensive tissue damage—combined with limited access to immediate medical intervention, significantly increases the risk of infection, delayed healing, and adverse outcomes. Traditional wound dressings frequently prove inadequate under such extreme conditions, as they have not been designed to address the specific physiological and logistical constraints present during armed conflicts. This review provides a comprehensive overview of recent progress in the development of advanced wound dressings tailored for use in military scenarios. Special attention has been given to multifunctional dressings that go beyond basic wound coverage by incorporating biologically active macromolecules such as collagen, chitosan, thrombin, alginate, therapeutic peptides, and growth factors. These compounds contribute to properties including moisture balance control, exudate absorption, microbial entrapment, and protection against secondary infection. This review highlights the critical role of advanced wound dressings in improving medical outcomes for injured military personnel. The potential of these technologies to reduce complications, enhance healing rates, and ultimately save lives underscores their growing importance in modern battlefield medicine. Full article
(This article belongs to the Collection Advances in Skin Wound Healing)
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26 pages, 5549 KiB  
Article
Intrusion Detection and Real-Time Adaptive Security in Medical IoT Using a Cyber-Physical System Design
by Faeiz Alserhani
Sensors 2025, 25(15), 4720; https://doi.org/10.3390/s25154720 - 31 Jul 2025
Viewed by 251
Abstract
The increasing reliance on Medical Internet of Things (MIoT) devices introduces critical cybersecurity vulnerabilities, necessitating advanced, adaptive defense mechanisms. Recent cyber incidents—such as compromised critical care systems, modified therapeutic device outputs, and fraudulent clinical data inputs—demonstrate that these threats now directly impact life-critical [...] Read more.
The increasing reliance on Medical Internet of Things (MIoT) devices introduces critical cybersecurity vulnerabilities, necessitating advanced, adaptive defense mechanisms. Recent cyber incidents—such as compromised critical care systems, modified therapeutic device outputs, and fraudulent clinical data inputs—demonstrate that these threats now directly impact life-critical aspects of patient security. In this paper, we introduce a machine learning-enabled Cognitive Cyber-Physical System (ML-CCPS), which is designed to identify and respond to cyber threats in MIoT environments through a layered cognitive architecture. The system is constructed on a feedback-looped architecture integrating hybrid feature modeling, physical behavioral analysis, and Extreme Learning Machine (ELM)-based classification to provide adaptive access control, continuous monitoring, and reliable intrusion detection. ML-CCPS is capable of outperforming benchmark classifiers with an acceptable computational cost, as evidenced by its macro F1-score of 97.8% and an AUC of 99.1% when evaluated with the ToN-IoT dataset. Alongside classification accuracy, the framework has demonstrated reliable behaviour under noisy telemetry, maintained strong efficiency in resource-constrained settings, and scaled effectively with larger numbers of connected devices. Comparative evaluations, radar-style synthesis, and ablation studies further validate its effectiveness in real-time MIoT environments and its ability to detect novel attack types with high reliability. Full article
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11 pages, 1219 KiB  
Article
The Church and Academia Model: New Paradigm for Spirituality and Mental Health Research
by Marta Illueca, Samantha M. Meints, Megan M. Miller, Dikachi Osaji and Benjamin R. Doolittle
Religions 2025, 16(8), 998; https://doi.org/10.3390/rel16080998 (registering DOI) - 31 Jul 2025
Viewed by 185
Abstract
Ongoing interest in the intersection of spirituality and health has prompted a need for integrated research. This report proposes a distinct approach in a model that allows for successful and harmonious cross-fertilization within these latter two areas of interest. Our work is especially [...] Read more.
Ongoing interest in the intersection of spirituality and health has prompted a need for integrated research. This report proposes a distinct approach in a model that allows for successful and harmonious cross-fertilization within these latter two areas of interest. Our work is especially pertinent to inquiries around the role of spirituality in mental health, with special attention to chronic pain conditions. The latter have become an open channel for novel avenues to explore the field of spirituality-based interventions within the arena of psychological inquiry. To address this, the authors developed and implemented the Church and Academia Model, a prototype for an innovative collaborative research project, with the aim of exploring the role of devotional practices, and their potential to be used as therapeutic co-adjuvants or tools to enhance the coping skills of patients with chronic pain. Keeping in mind that the church presents a rich landscape for clinical inquiry with broad relevance for clinicians and society at large, we created a unique hybrid research model. This is a new paradigm that focuses on distinct and well-defined studies where the funding, protocol writing, study design, and implementation are shared by experts from both the pastoral and clinical spaces. A team of theologians, researchers, and healthcare providers, including clinical pain psychologists, built a coalition leveraging their respective skill sets. Each expert is housed in their own environs, creating a functional network that has proven academically productive and pastorally effective. Key outputs include the creation and validation of a new psychometric measure, the Pain-related PRAYER Scale (PPRAYERS), an associated bedside prayer tool and a full-scale dissemination strategy through journal publications and specialty society conferences. This collaborative prototype is also an ideal fit for integrated knowledge translation platforms, and it is a promising paradigm for future collaborative projects focused on spirituality and mental health. Full article
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9 pages, 2757 KiB  
Article
Externally Triggered Activation of Nanostructure-Masked Cell-Penetrating Peptides
by Gayong Shim
Molecules 2025, 30(15), 3205; https://doi.org/10.3390/molecules30153205 - 30 Jul 2025
Viewed by 279
Abstract
Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon [...] Read more.
Cell-penetrating peptides offer a promising strategy for intracellular delivery; however, non-specific uptake and off-target cytotoxicity limit their clinical utility. To address these limitations, a cold atmospheric plasma-responsive delivery platform was developed in which the membrane activity of a peptide was transiently suppressed upon complexation with a DNA-based nanostructure. Upon localized plasma exposure, DNA masking was disrupted, restoring the biological functions of the peptides. Transmission electron microscopy revealed that the synthesized DNA nanoflower structures were approximately 150–250 nm in size. Structural and functional analyses confirmed that the system remained inert under physiological conditions and was rapidly activated by plasma treatment. Fluorescence recovery, cellular uptake assays, and cytotoxicity measurements demonstrated that the peptide activity could be precisely controlled in both monolayer and three-dimensional spheroid models. This externally activatable nanomaterial-based system enables the spatial and temporal regulation of peptide function without requiring biochemical triggers or permanent chemical modifications. This platform provides a modular strategy for the development of potential peptide therapeutics that require precise control of activation in complex biological environments. Full article
(This article belongs to the Special Issue Nanomaterials for Advanced Biomedical Applications, 2nd Edition)
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14 pages, 2566 KiB  
Review
Improved Biomass Production and Secondary Metabolism: A Critical Review of Grafting in Cannabis sativa
by S. M. Ahsan, Md. Injamum-Ul-Hoque, Md. Mezanur Rahman, Sang-Mo Kang, In-Jung Lee and Hyong Woo Choi
Plants 2025, 14(15), 2347; https://doi.org/10.3390/plants14152347 - 30 Jul 2025
Viewed by 433
Abstract
Cannabis sativa L. is a versatile plant with applications in various sectors such as agriculture, medicine, food, and cosmetics. The therapeutic properties of cannabis are often linked to its secondary compounds. The worldwide cannabis market is undergoing swift changes due to varying legal [...] Read more.
Cannabis sativa L. is a versatile plant with applications in various sectors such as agriculture, medicine, food, and cosmetics. The therapeutic properties of cannabis are often linked to its secondary compounds. The worldwide cannabis market is undergoing swift changes due to varying legal frameworks. Medicinal cannabis (as a heterozygous and dioecious species) is distinct from most annual crops grown in controlled environments, typically propagated through stem cutting rather than seeds to ensure genetic uniformity. Consequently, as with any commercially cultivated crop, biomass yield plays a crucial role in overall productivity. The key factors involved in cultivation conditions, such as successful root establishment, stress tolerance, and the production cycle duration, are critical for safeguarding, improving, and optimizing plant yield. Grafting is a long-established horticultural practice that mechanically joins the scion and rootstock of distinct genetic origins by merging their vascular systems. This approach can mitigate undesirable traits by leveraging the strengths of particular plants, proving beneficial to various applications. Grafting is not used commercially in Cannabis. Only three very recent investigations suggest that grafting holds significant promise for enhancing both the agronomic and medicinal potential of Cannabis. This review critically examines the latest advancements in cannabis grafting and explores prospects for improving biomass (stem, root, flower, etc.) yield and secondary metabolite production. Full article
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21 pages, 2831 KiB  
Review
IL-20 Subfamily Biological Effects: Mechanistic Insights and Therapeutic Perspectives in Cancer
by Valentina Maggisano, Maria D’Amico, Saveria Aquila, Francesca Giordano, Anna Martina Battaglia, Adele Chimento, Flavia Biamonte, Diego Russo, Vincenzo Pezzi, Stefania Bulotta and Francesca De Amicis
Int. J. Mol. Sci. 2025, 26(15), 7320; https://doi.org/10.3390/ijms26157320 - 29 Jul 2025
Viewed by 154
Abstract
The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert [...] Read more.
The interleukin-20 (IL-20) cytokine subfamily, a subset of the IL-10 superfamily, includes IL-19, IL-20, IL-22, IL-24, and IL-26. Recently, their involvement in cancer biology has gained attention, particularly due to their impact on the tumor microenvironment (TME). Notably, IL-20 subfamily cytokines can exert both pro-tumorigenic and anti-tumorigenic effects, depending on the context. For example, IL-22 promotes tumor growth by enhancing cancer cell proliferation and protecting against apoptosis, whereas IL-24 demonstrates anti-tumor activity by inducing cancer cell death and inhibiting metastasis. Additionally, these cytokines influence macrophage polarization—an essential factor in the immune landscape of tumors—thereby modulating the inflammatory environment and immune evasion strategies. Understanding the dual role of IL-20 subfamily cytokines within the TME and their interactions with cancer cell hallmarks presents a promising avenue for therapeutic development. Interleukin-20 receptor antagonists are being researched for their role in cancer therapy, since they potentially inhibit tumor growth and progression. This review explores the relationship between IL-20 cytokines and key cancer-related processes, including growth and proliferative advantages, angiogenesis, invasion, metastasis, and TME support. Further research is necessary to unravel the specific mechanisms underlying their contributions to tumor progression and to determine their potential for targeted therapeutic strategies. Full article
(This article belongs to the Special Issue Advanced Research on Immune Cells and Cytokines (2nd Edition))
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33 pages, 4819 KiB  
Review
Hydrogels Modulating the Microbiome: Therapies for Tissue Regeneration with Infection Control
by Germán Reynaldo Jiménez-Gastelum, Carlos Esteban Villegas-Mercado, Juan Luis Cota-Quintero, Silvia Ivonne Arzola-Rodríguez, Rosalío Ramos-Payán and Mercedes Bermúdez
Gels 2025, 11(8), 584; https://doi.org/10.3390/gels11080584 - 29 Jul 2025
Viewed by 414
Abstract
This review explores the emerging role of functionalized hydrogels in modulating the microbiome for therapeutic applications in tissue regeneration and infection control. The skin and gut microbiomes play crucial roles in maintaining tissue homeostasis, regulating immune responses, and influencing the healing process. Disruptions [...] Read more.
This review explores the emerging role of functionalized hydrogels in modulating the microbiome for therapeutic applications in tissue regeneration and infection control. The skin and gut microbiomes play crucial roles in maintaining tissue homeostasis, regulating immune responses, and influencing the healing process. Disruptions in microbial balance—such as those observed in chronic wounds, autoimmune conditions, or post-surgical environments—can impair regeneration and increase susceptibility to infection. Hydrogels, due to their tunable physical and chemical properties, serve as versatile platforms for delivering probiotics, prebiotics, antimicrobials, and immune-modulatory agents. The encapsulation of beneficial bacteria, such as Lactobacillus plantarum or Prevotella histicola, within hydrogels could enhance bacterial viability, targeted delivery, and immune tolerance. Additionally, hydrogels functionalized with silver nanoparticles, nitric oxide donors, and bacteriocins have demonstrated effective biofilm disruption and pathogen clearance. These systems also promote favorable immune responses, such as M2 macrophage polarization and the induction of regulatory T cells, which are essential for tissue repair. Innovative approaches, including 3D bioprinting, self-healing materials, and photothermal-responsive hydrogels, expand the clinical versatility of these systems. Full article
(This article belongs to the Special Issue Hydrogel for Tissue Engineering and Biomedical Therapeutics)
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33 pages, 8681 KiB  
Review
AI-Empowered Electrochemical Sensors for Biomedical Applications: Technological Advances and Future Challenges
by Yafeng Liu, Xiaohui Liu, Xuemei Wang and Hui Jiang
Biosensors 2025, 15(8), 487; https://doi.org/10.3390/bios15080487 - 28 Jul 2025
Viewed by 291
Abstract
Biomarkers play a pivotal role in disease diagnosis, therapeutic efficacy evaluation, prognostic assessment, and drug screening. However, the trace concentrations of these markers in complex physiological environments pose significant challenges to efficient detection. It is necessary to avoid interference from non-specific signals, which [...] Read more.
Biomarkers play a pivotal role in disease diagnosis, therapeutic efficacy evaluation, prognostic assessment, and drug screening. However, the trace concentrations of these markers in complex physiological environments pose significant challenges to efficient detection. It is necessary to avoid interference from non-specific signals, which may lead to misjudgment of other substances as biomarkers and affect the accuracy of detection results. With the rapid advancements in electrochemical technologies and artificial intelligence (AI) algorithms, intelligent electrochemical biosensors have emerged as a promising approach for biomedical detection, offering speed, specificity, high sensitivity, and accuracy. This review focuses on elaborating the latest applications of AI-empowered electrochemical biosensors in the biomedical field, including disease diagnosis, treatment monitoring, drug development, and wearable devices. AI algorithms can further improve the accuracy, sensitivity, and repeatability of electrochemical sensors through the screening and performance prediction of sensor materials, as well as the feature extraction and noise reduction suppression of sensing signals. Even in complex physiological microenvironments, they can effectively address common issues such as electrode fouling, poor signal-to-noise ratio, chemical interference, and matrix effects. This work may provide novel insights for the development of next-generation intelligent biosensors for precision medicine. Full article
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15 pages, 239 KiB  
Article
Examining Puppetry’s Contribution to the Learning, Social and Therapeutic Support of Students with Complex Educational and Psychosocial Needs in Special School Settings: A Phenomenological Study
by Konstantinos Mastrothanasis, Angelos Gkontelos, Maria Kladaki and Eleni Papouli
Disabilities 2025, 5(3), 67; https://doi.org/10.3390/disabilities5030067 - 28 Jul 2025
Viewed by 1240
Abstract
The present study focuses on investigating the contribution of puppetry as a pedagogical and psychosocial tool in special education, addressing the literature gap in the systematic documentation of the experiences of special education teachers, concerning its use in daily teaching practice. The main [...] Read more.
The present study focuses on investigating the contribution of puppetry as a pedagogical and psychosocial tool in special education, addressing the literature gap in the systematic documentation of the experiences of special education teachers, concerning its use in daily teaching practice. The main objective is to capture the way in which puppetry enhances the learning, social and therapeutic support of students with complex educational and psychosocial needs. The study employs a qualitative phenomenological approach, conducting semi-structured interviews with eleven special education teachers who integrate puppetry into their teaching. Qualitative data were analyzed using thematic analysis. The findings highlight that puppetry significantly enhances cognitive function, concentration, memory and language development, while promoting the active participation, cooperation, social inclusion and self-expression of students. In addition, the use of the puppet acts as a means of psycho-emotional empowerment, supporting positive behavior and helping students cope with stress and behavioral difficulties. Participants identified peer support, material adequacy and training as key factors for effective implementation, while conversely, a lack of resources and time is cited as a key obstacle. The integration of puppetry in everyday school life seems to ameliorate a more personalized, supportive and experiential learning environment, responding to the diverse and complex profiles of students attending special schools. Continuous training for teachers, along with strengthening the collaboration between the arts and special education, is essential for the effective use of puppetry in the classroom. Full article
14 pages, 1450 KiB  
Article
Characterization and Complete Genomic Analysis of a Novel Bacteriophage BUCT775 for Acinetobacter baumannii and Its Elimination Efficiency in the Environment
by Yuxuan Liu, Yunfei Huang, Dongxiang Zhu, Lefei Zhang, Jianwei Zhang, Yigang Tong and Mengzhe Li
Int. J. Mol. Sci. 2025, 26(15), 7279; https://doi.org/10.3390/ijms26157279 - 28 Jul 2025
Viewed by 201
Abstract
Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen responsible for a range of severe infections and nosocomial outbreaks. Phage-based therapy and biocontrol represent effective strategies to combat the prevalence of A. baumannii. This study reports a novel phage, BUCT775, capable [...] Read more.
Acinetobacter baumannii (A. baumannii) is an opportunistic pathogen responsible for a range of severe infections and nosocomial outbreaks. Phage-based therapy and biocontrol represent effective strategies to combat the prevalence of A. baumannii. This study reports a novel phage, BUCT775, capable of specifically lysing A. baumannii, and investigates its physiological properties, genomic characteristics, in vivo therapeutic efficacy, and environmental disinfection performance. Phage BUCT775 is a podovirus that forms clear, well-defined plaques with an average diameter of 2.5 ± 0.52 mm. It exhibits a broad range of temperature stability (4–55 °C) and pH stability (pH 3–12). The optimal multiplicity of infection (MOI) for phage BUCT775 is 0.01. At an MOI of 0.01, it demonstrates a latent period of approximately 10 min and exhibits a high burst size. Genomic sequencing and bioinformatics analysis revealed that phage BUCT775 belongs to the order Caudoviricetes and the family Autographiviridae. Its genome has a G + C content of 39.3% and is not known to contain virulence genes or antibiotic resistance genes. Phage BUCT775 exhibited significant therapeutic effects on A. baumannii-infected G. mellonella larvae, increasing the 120 h survival rate of the larvae by 20%. Additionally, phage BUCT775 efficiently eliminated A. baumannii in the environment, with an average clearance rate exceeding 98% within 3 h. These studies suggest that phage BUCT775 holds significant potential for application in phage therapy and environmental disinfection. Full article
(This article belongs to the Section Molecular Genetics and Genomics)
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29 pages, 646 KiB  
Systematic Review
Connected by Boredom: A Systematic Review of the Role of Trait Boredom in Problematic Technology Use
by Ginevra Tagliaferri, Manuel Martí-Vilar, Francesca Valeria Frisari, Alessandro Quaglieri, Emanuela Mari, Jessica Burrai, Anna Maria Giannini and Clarissa Cricenti
Brain Sci. 2025, 15(8), 794; https://doi.org/10.3390/brainsci15080794 - 25 Jul 2025
Viewed by 623
Abstract
Background/Objectives: In an increasingly pervasive digital environment, trait boredom has been identified as a key psychological factor in the onset and maintenance of problematic digital technology use. This systematic review aims to investigate the role of trait boredom in digital behavioral addictions, including [...] Read more.
Background/Objectives: In an increasingly pervasive digital environment, trait boredom has been identified as a key psychological factor in the onset and maintenance of problematic digital technology use. This systematic review aims to investigate the role of trait boredom in digital behavioral addictions, including problematic smartphone use, Internet and social media overuse, and gaming addiction, through theoretical models such as the I-PACE model and the Compensatory Internet Use Theory (CIUT). Methods: A systematic literature search was conducted across multiple scientific databases (PsycINFO, Web of Science, PubMed, and Scopus), yielding a total of 4603 records. Following the PRISMA guidelines after duplicate removal and screening based on title and abstract, 152 articles were assessed for full-text eligibility, and 28 studies met the predefined inclusion and exclusion criteria and were included in the final review. Results: Findings reveal that trait boredom functions as both a direct and indirect factor in problematic technology use. It serves as a mediator and moderator in the relationship between psychological vulnerabilities (e.g., depression, alexithymia, vulnerable narcissism) and dysfunctional digital behaviors. Furthermore, as an independent variable, it has an influence on technological variables through Fear of Missing Out (FoMO), loneliness, low self-regulation, and dysfunctional metacognitions, while protective factors such as mindfulness and attentional control mitigate its impact. Conclusions: Boredom represents a central psychological lever for understanding behavioral addictions in the digital age and should be considered a key target in preventive and therapeutic interventions focused on enhancing self-regulation and meaningful engagement with free time. Full article
(This article belongs to the Special Issue Psychiatry and Addiction: A Multi-Faceted Issue)
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24 pages, 528 KiB  
Review
Therapeutic and Prognostic Relevance of Cancer Stem Cell Populations in Endometrial Cancer: A Narrative Review
by Ioana Cristina Rotar, Elena Bernad, Liviu Moraru, Viviana Ivan, Adrian Apostol, Sandor Ianos Bernad, Daniel Muresan and Melinda-Ildiko Mitranovici
Diagnostics 2025, 15(15), 1872; https://doi.org/10.3390/diagnostics15151872 - 25 Jul 2025
Viewed by 231
Abstract
The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are [...] Read more.
The biggest challenge in cancer therapy is tumor resistance to the classical approach. Thus, research interest has shifted toward the cancer stem cell population (CSC). CSCs are a small subpopulation of cancer cells within tumors with self-renewal, differentiation, and metastasis/malignant potential. They are involved in tumor initiation and development, metastasis, and recurrence. Method. A narrative review of significant scientific publications related to the topic and its applicability in endometrial cancer (EC) was performed with the aim of identifying current knowledge about the identification of CSC populations in endometrial cancer, their biological significance, prognostic impact, and therapeutic targeting. Results: Therapy against the tumor population alone has no or negligible effect on CSCs. CSCs, due to their stemness and therapeutic resistance, cause tumor relapse. They target CSCs that may lead to noticeable persistent tumoral regression. Also, they can be used as a predictive marker for poor prognosis. Reverse transcription–polymerase chain reaction (RT-PCR) demonstrated that the cultured cells strongly expressed stemness-related genes, such as SOX-2 (sex-determining region Y-box 2), NANOG (Nanog homeobox), and Oct 4 (octamer-binding protein 4). The expression of surface markers CD133+ and CD44+ was found on CSC as stemness markers. Along with surface markers, transcription factors such as NF-kB, HIF-1a, and b-catenin were also considered therapeutic targets. Hypoxia is another vital feature of the tumor environment and aids in the maintenance of the stemness of CSCs. This involves the hypoxic activation of the WNT/b-catenin pathway, which promotes tumor survival and metastasis. Specific antibodies have been investigated against CSC markers; for example, anti-CD44 antibodies have been demonstrated to have potential against different CSCs in preclinical investigations. Anti-CD-133 antibodies have also been developed. Targeting the CSC microenvironment is a possible drug target for CSCs. Focusing on stemness-related genes, such as the transcription pluripotency factors SOX2, NANOG, and OCT4, is another therapeutic option. Conclusions: Stemness surface and gene markers can be potential prognostic biomarkers and management approaches for cases with drug-resistant endometrial cancers. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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23 pages, 19687 KiB  
Article
Intranasal Mitochondrial Transplantation Restores Mitochondrial Function and Modulates Glial–Neuronal Interactions in a Genetic Parkinson’s Disease Model of UQCRC1 Mutation
by Jui-Chih Chang, Chin-Hsien Lin, Cheng-Yi Yeh, Mei-Fang Cheng, Yi-Chieh Chen, Chi-Han Wu, Hui-Ju Chang and Chin-San Liu
Cells 2025, 14(15), 1148; https://doi.org/10.3390/cells14151148 - 25 Jul 2025
Viewed by 554
Abstract
The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in [...] Read more.
The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article
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