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2025
Photodynamic therapy (PDT) involves the use of photosensitizers (PSs) that, upon activation by specific wavelengths of light, generate reactive oxygen species (ROS), including singlet oxygen (1O2) and hydroxyl radicals (·OH), within the targeted tissue, typically tumor cells. The generated ROS induces cellular damage, disrupts cellular processes, and ultimately leads to apoptosis or necrosis of the tumor cells. However, the clinical application of PDT is significantly hindered by the limited tissue penetration ability of light. To address this limitation, laser-free self-luminescent photosensitive systems have emerged as potential solutions for achieving deep-tissue PDT and imaging. This review provides a comprehensive analysis of various laser-independent photosensitive systems, with a particular emphasis on those based on resonance energy transfer (RET), chemically induced electron exchange luminescence (CIEEL), and Cherenkov radiation energy transfer (CRET). The aim is to offer a theoretical framework for the development of novel photodynamic systems and to reassess the application potential of certain previously overlooked photosensitizers (PSs).- Book : 26(4)
- Pub. Date : 2025
- Page : pp.1437-1437
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2025
Abstract
Determining stress and strain in a component of a fusion power plant involves defining boundary conditions for the mechanical equilibrium equations, which implies the availability of a full reactor model for defining those conditions. To address this fundamental challenge of reactor design, a finite element method (FEM) model for the Mega-Ampere Spherical Tokamak Upgrade (MAST-U) fusion tokamak, operating at the Culham Campus of UKAEA, has been developed and applied to assess mechanical deformations, strain, and stress in the full tokamak structure, taken as a proxy for a fusion power plant. The model, handling 127 million finite elements using about 800 processors in parallel, illustrates the level of fidelity of structural simulations of a complex nuclear device made possible by the modern supercomputing systems. The model predicts gravitational and atmospheric pressure-induced deformations in broad agreement with observations, and enables computing the spectrum of acoustic vibrations of a tokamak, arising from mechanical disturbances like an earthquake or a plasma disruption. We introduce the notion of the {\it density of stress} to characterise the distribution of stress in the entire tokamak structure, and to predict the magnitude and locations of stress concentrations. The model enables defining computational requirements for simulating a whole operating fusion power plant, and provides a digital foundation for the assessment of reactor performance as well as for specifying the relevant materials testing programme.- Book : ()
- Pub. Date : 2025
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2025
- Book : 1073()
- Pub. Date : 2025
- Page : pp.170285-170285
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2025
- Book : ()
- Pub. Date : 2025
- Page : pp.e42607-e42607
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2025
AbstractBackground and PurposeMalignant melanoma is the most lethal form of skin cancer, characterised by a poor survival rate. One of the key factors driving the aggressive growth of melanoma cells is the elevated expression of the proto‐oncogene Bcl‐3. This study aims to optimise, evaluate and characterise a second‐generation Bcl‐3 inhibitor, using melanoma as a model to demonstrate its potential therapeutic efficacy.Experimental ApproachWe synthesised and screened a series of structural analogues and selected A27, the most promising candidate for further investigation. We assessed whether A27 disrupted the interaction between Bcl‐3 and its binding partner, p50, and examined the subsequent effects on cyclin D1 expression. Additionally, we evaluated the impact of A27 on melanoma cell proliferation and migration in vitro, as well as its therapeutic efficacy in various in vivo melanoma models.Key ResultsNuclear magnetic resonance (NMR) confirmed that A27 directly binds to Bcl‐3, effectively inhibiting its function. By disrupting the Bcl‐3/p50 interaction, A27 led to a significant down‐regulation of cyclin D1 expression. In cellular assays, A27 markedly reduced proliferation and migration of melanoma cells. In vivo, treatment with A27 resulted in a substantial reduction in melanoma tumour growth, with no observed toxicity in treated animals.Conclusions and ImplicationsAt present, no other Bcl‐3 inhibitors exist for clinical application in the field of oncology, and as a result, our novel findings provide a unique opportunity to develop a highly specific drug against malignant melanoma to meet an urgent clinical need.- Book : ()
- Pub. Date : 2025
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2025
Abstract
Somatostatin, released from δ-cells within pancreatic islets of Langerhans, is one of the most important negative regulators of islet hormone secretion. We find that islet δ-cells are positioned near, and release somatostatin onto, primary cilia of the other islet cell types, including insulin-secreting β-cells. Somatostatin activates ciliary somatostatin receptors, resulting in rapid lowering of the ciliary cAMP concentration which in turn promotes more sustained nuclear translocation of the cilia-dependent transcription factor GLI2 through a mechanism that operates in parallel with the canonical Hedgehog pathway and depends on ciliary Ca2+ signaling. We also find that primary cilia length is reduced in islets from human donors with type-2 diabetes, which is associated with a reduction in interactions between δ-cells and cilia. Our findings show that islet cell primary cilia constitute an important target of somatostatin action, which endows somatostatin with the ability to regulate islet cell function beyond acute suppression of hormone release.- Book : ()
- Pub. Date : 2025
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2025
AbstractThe current understanding of crew health maintenance is founded upon decades of physiological research conducted in terrestrial spaceflight analogues and in low Earth orbit, particularly on the International Space Station. However, as we progress towards the Lunar Gateway and interplanetary missions, it is imperative that the tools employed to maintain crew health are redefined, including the utilisation of exercise countermeasures. The successful implementation of exercise countermeasures for deep space missions must address a number of challenges, including those posed by new environments with elevated levels of cosmic radiation and solar particle events, extended mission durations and constrained space availability. In this Topical Review, the authors address points that are important (and sometimes critical), but often ignored, in order to define future exercise countermeasures for long‐duration space missions. Multi‐organ countermeasures, countermeasure enjoyment, time‐dependent load variability, the relationship between nutrition and the success of exercise countermeasures, and the individual variability in response to a given countermeasure are presented and discussed. The aim of this article is to raise awareness of important aspects that can profoundly influence the efficacy of exercise countermeasures, thereby affecting the health of the crew and the success of the mission during prolonged spaceflight.- Book : ()
- Pub. Date : 2025
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2025
This study analyzes the technology for creating polymer composite materials reinforced with glass fiber. Particular attention is given to their applications in the aerospace industry, where stringent requirements for strength, corrosion resistance, and specific strength render these materials indispensable. The main components of composite materials and their properties are examined. Phenol-formaldehyde resins, widely utilized as a matrix for fiberglass plastics in rocket and space engineering, are studied in detail. The thermomechanical resistance of composites, a critical factor determining their performance under extreme conditions, is highlighted. A significant part of the study focuses on the production and curing processes of composite materials. Various curing methods are analyzed, with a focus on the effectiveness of infrared radiation. The findings establish that infrared heating significantly enhances the physical and mechanical properties of composites while reducing production time.- Book : (1)
- Pub. Date : 2025
- Page : pp.94-102
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2025
ABSTRACTRegulation of protein synthesis is central to maintaining skeletal muscle integrity and its understanding is important for the treatment of muscular and neuromuscular pathologies. The eIF3f subunit of the translation initiation factor eIF3 has a key role, as it stands at the crossroad between protein-synthesis-associated hypertrophy and MAFbx/atrogin-1-dependent. To decipher the molecular mechanisms underpinning the role of eIF3f in regulating muscle mass, we established a cellular model that enables interrogation of eIF3f functionality via identification of proximal interactors. Using CRISPR-Cas9 molecular scissors, we generated single cell clones of immortalised human muscle cells expressing eIF3f fused to the BirA biotin ligase (eIF3f-BioID1 chimera) from the endogenousEIF3Flocus. Biotinylated proteins, representing interactors of eIF3f in nanometer range distance, were identified by streptavidin pull-downs and mass spectrometry. In both proliferating and differentiated muscle cells, the eIF3f-BioID1 chimera co-sedimented with ribosomal complexes in polysome profiles and interacted mainly with components of the eIF3 complex, and with the eIF4E, eIF4G, and eIF5 initiation factors. Surprisingly, we identified several nucleus-localised interactors of eIF3f, and the immunofluorescence analyses revealed a previously unknown nuclear localization of eIF3f in both myoblasts and myotubes. We also identified novel cytoplasmic partners of eIF3f, responsible for the maintenance of skeletal muscle ultrastructure (sarcomeric/Z-disc (SYNPO2) bound proteins) and proteins of the lysosomal compartment (LAMP1). The established tagging system should be useful to further advance studies of eIF3f function in hypertrophic and atrophic conditions in skeletal muscle.- Book : ()
- Pub. Date : 2025
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2025
Background: According to the 8th edition of the American Joint Committee on Cancer (AJCC), involvement of the masticator space and infratemporal fossa (ITF) in oral cancers indicates advanced disease (T4b), which is often considered unresectable. Previous studies have shown that the extent of ITF involvement influences management and outcomes. Therefore, to optimize management, T4b disease should be subclassified based on ITF involvement. Notably, infranotch disease has a more favorable prognosis compared to supranotch disease. Our study also observed that certain subsets of high anterior retroantral ITF involvement may be operable with favorable clinical outcomes. This study aims to derive a new image-based compartmentalization of high ITF involvement and assess its impact on the management and outcomes of oral head and neck squamous cell carcinoma (HNSCC) patients with high ITF involvement. Materials and Methods: This retrospective observational study included 154 non-metastatic, upfront unresectable locally advanced HNSCC patients who were fit for induction neoadjuvant chemotherapy (NACT). ITF involvement was classified into distinct compartments, and detailed staging of the primary tumor (T) and regional nodes (Ns) was performed. Clinical data, including patient demographics, treatment received, and follow-up notes, were documented. Prognosis was assessed using survival metrics: event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). The ITF was categorized into the following compartments: compartment 1 (low ITF: medial pterygoid), compartment 2 (anterior high ITF: retroantral fat), compartment 3 (posterior high ITF), including 3a (paramandibular compartment: paramandibular fat/temporalis), 3b (muscle compartment: lateral pterygoid), and 3c (Perineural compartment: pterygopalatine fossa and pterygomaxillary fissure). Results: Of the 154 cases, 142 (92%) were classified as T4b, with 63 (40.9%) having high ITF involvement and 79 (55.6%) having low ITF involvement. Twelve cases had T4a disease, which was deemed unresectable due to extensive nodal involvement. Subcompartmentalization of the 63 high ITF cases revealed 26 (41.2%) with compartment 2 involvement, 17 (26.9%) with compartment 3a involvement, 11 (17.4%) with compartment 3b involvement, and 9 (14%) with compartment 3c involvement. Disease progression following NACT was significantly higher in compartment 3c, which showed a poor response (p = 0.007). Univariate analysis for PFS revealed similar outcomes for compartments 1 and 2 (p = 0.692), while compartment 3 demonstrated poorer outcomes (p = 0.033). Among thosehigh ITF involvement, compartment 3c had the worst PFS outcome (p = 0.03). Conclusions: Baseline imaging plays a critical role in guiding individualized treatment and predicting clinical outcomes. Low ITF involvement and disease limited to the high retroantral fat compartment exhibit similar clinical outcomes. Among the posterior high ITF compartments, involvement of the pterygopalatine fossa and pterygomaxillary fissure (compartment 3c) is associated with the worst prognosis and poor response to chemotherapy. Subcompartmentalization of ITF involvement provides valuable prognostic information to tailor treatment strategies.- Book : 32(2)
- Pub. Date : 2025
- Page : pp.99-99
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