Search Results (2,342)

CDK4/6 inhibitors such as palbociclib, ribociclib and abemaciclib are commonly used in the clinical treatment of HR-positive, HER2-negative metastatic or locally advanced breast cancer. Patients with metastatic disease often receive palliative radiotherapy for symptom control of bone metastases and/or local lesions, typically administered in close temporal proximity to CDK4/6 inhibitor therapy, although treatment with the inhibitors may be temporarily paused during the radiotherapy period in some cases. In this study, we investigated the extent to which senescence is induced by CDK4/6 inhibitors, ionizing radiation, and the combination of the two, compared to other types of cell fate. Eight breast cancer cell lines with different molecular subtypes and two healthy cell lines (fibroblasts and keratinocytes) were treated with CDK inhibition using palbociclib, ribociclib or abemaciclib and with or without a single dose of 2 Gy ionizing radiation. Cellular senescence, cell death in form of apoptosis and necrosis, and the cell cycle were analyzed using flow cytometry. We focused mainly on understanding how CDK inhibition can trigger cellular senescence. Our data showed that in many cell lines —but not all—the use of CDK inhibitors induced senescence much more strongly than cell death. Except for one cell line, significantly more cell lines died necrotically than apoptotically. Neither apoptosis nor necrosis was responsible for a major cell fate after CDK inhibition. Combination therapy with irradiation did not show a clear additive effect. In cell lines, senescence is clearly triggered by CDK4/6 inhibitors and even more so when in combination with ionizing radiation, which, when transferred to patients, could lead to less damage caused by cell loss, such as necrotic areas. However, it could also lead to more senescence-specific side effects, such as inflammation-induced tumors and fibrosis. Full article

This paper presents a modular Power Conditioning and Distribution Unit (PCDU) designed for small satellites. The proposed system features a highly adaptable architecture capable of managing a total power throughput of up to 100 W, with specific limits defined by mission-dependent thermal and redundancy configurations. Aligned with the New Space paradigm, the implementation relies on Commercial Off-The-Shelf (COTS) components, a strategy that drastically reduces development and manufacturing costs without compromising reliability. The system has been optimized for operation in harsh environments, including high vacuum, ionizing radiation, and extreme thermal gradients. The design incorporates strict redundancy and fault-tolerance criteria to provide a robust solution for critical subsystems. Comprehensive validation was performed through functional testing, Total Ionizing Dose (TID) radiation campaigns, and Thermal Vacuum (TVAC) cycles. Experimental results demonstrate that the PCDU withstands high-vacuum thermal cycling and cumulative radiation doses exceeding 75 kRad. These findings confirm that the developed unit is a cost-effective, high-reliability solution suitable for both Low Earth Orbit (LEO) and deep-space missions. Full article

Perovskite solar cells (PSCs) have quickly achieved certified energy conversion efficiency reaching a certified record of 27.3% for single-junction cells, while having a low mass, thin-film form factor and high specific power, which are attractive for space energy systems. However, their long-term reliability in extraterrestrial environments is not adequately ensured by terrestrial qualification routes, and standardized space-related test protocols remain insufficiently developed. This review critically summarizes the current understanding of the degradation of PSCs under the influence of key environmental factors in space—ionizing and non-ionizing radiation, thermal vacuum exposure and thermal cycling, and ultraviolet radiation AM0, as well as atmospheric oxygen in low orbits. The central task of the work is to develop and justify the need to create specialized PSCs test protocols for space applications, since existing ground standards do not reflect the multifactorial nature and extreme orbital loads. It has been shown that thermal vacuum accelerates ion migration, interphase reactions, and degassing, while AM0 UV and atomic oxygen introduce additional photochemical and oxidative mechanisms of destruction; at the same time, stressors often act synergistically and are not detected by single-factor tests. Next, the limitations of the current IEC and ISOS are discussed and an approach to their expansion is formulated through the ISOS-T-Space and ISOS-LC-Space protocols, which integrate high vacuum, AM0 lighting, extended temperature ranges and controlled particle irradiation. It is concluded that the development and interlaboratory validation of such space-oriented protocols is a key condition for the correct qualification of PSCs and targeted optimization of materials and interfaces to meet the requirements of space energy. Full article

Ionizing radiation affects enzymes, which are essential for most cellular functions, by inducing chemical alterations in their molecular structures, often resulting in the inhibition of their activities. Unraveling the molecular and kinetic mechanisms driving these effects requires irradiation protocols that ensure accurate dose delivery, spatial homogeneity, and reproducibility. In this study, we established a systematic experimental framework that adapts a medical linear accelerator (LINAC) as a precision source for biochemical irradiation experiments. A rigorous protocol was developed that allows enzyme solutions to be irradiated under strictly defined and verifiable dosimetric conditions. Using this approach, we quantified the radiation-induced modulation of enzyme activity in two representative enzymes: invertase (β-fructofuranosidase) and collagenase. For invertase, a pronounced nonlinear decrease in enzyme activity was observed, with the enzyme retaining approximately only 2.2% of its initial activity at 50 Gy. Conversely, collagenase activity exhibited an exponential dose–response behavior over the dose range 0.1–200 Gy, yielding a global inactivation constant of $K = 0.015 {\mathrm{G}\mathrm{y}}^{-1}$. Complementary SDS–PAGE analysis revealed no detectable radiation-induced protein fragmentation or aggregation under the investigated conditions. These results confirm enzyme-specific radiation sensitivity and demonstrate the efficacy of this LINAC-based methodology for quantitative dose–effect studies. Overall, this work provides a versatile experimental tool for applied radiation research, bridging the gap between clinical medical physics and fundamental biochemistry. Full article

This study presents an investigation of the factors (driven by coupled multi-factor corrosion mechanisms) which contribute to the degradation of the spirally wound armored steel wires used to protect core-structured, unarmored optical-fiber submarine cables. The influences of the physical properties of deep-sea sediments on the durability of unarmored cables, as well as the impact of ionizing radiation on optical fibers, are also assessed. The objective of this paper is to establish a scientific basis for cable longevity by integrating theoretical insights with empirical evidence. Although the steel utilized in armored cables is cost-effective and durable, it remains vulnerable to corrosion. Since the inaugural practical deployment of submarine communication cables between the UK and France in the 1850s, only a small number of studies worldwide have examined the corrosion and durability of cable armor. There is also limited literature examining the physical characteristics of the deep-sea surface sediments that directly affect the service life of the cables’ mechanically fragile polyethylene sheathing. An in-depth analysis of the cable damage and environmental conditions observed during maintenance operations provides valuable insights into the key environmental factors that influence armor corrosion and cable longevity. This research aims to guide future design and support strategies to improve the sustainability and durability of cable systems in marine environments. Full article

Gamma-tocotrienol (GT3) is one of the constituents of vitamin E that demonstrated significant radioprotective efficacy in murine and nonhuman primate (NHP) models. Considering the antioxidant activity of GT3 and its role in terminating lipid peroxidation, we hypothesize that mechanism of radioprotective effect of GT3 may involve the inhibition of irradiation-induced ferroptosis—a form of regulated cell death characterized by excessive, iron-dependent, peroxidation of lipids in cellular membranes. To test this hypothesis, the metabolomic and proteomic data from serum samples of GT3- or vehicle-treated NHPs exposed to 12 Gy (partial- or total-body) radiation was analyzed with focus on lipid peroxidation markers and proteins involved in iron metabolism. Four secondary lipid peroxidation products were identified including 4-oxo-2-nonenal (4-ONE), 4-hydroperoxy-2-nonenal (4-HPNE), 3,4-epoxynonanal (3,4-ENA), and trans-4,5-epoxy-(2E)-decenal (4,5-EDE). In vehicle-treated animals, their concentrations increased significantly as soon as 4 h after irradiation and then gradually declined. GT3 treatment mitigated this radiation-induced increase. In addition to lipid peroxidation products, similar patterns of change were observed for several polyunsaturated, monounsaturated, and saturated fatty acids as well as amino acids such as lysine and its derivatives. Taken together, these metabolomic changes suggest that irradiation induces cellular membrane damage through enhanced lipid peroxidation, while GT3 exerts a protective effect against this process. In addition, GT3 increased serum levels of haptoglobin and hemopexin—two plasma scavenger proteins that play complementary protective roles in iron and heme homeostasis. Although the present study does not conclusively demonstrate that GT3 mediates radioprotection via inhibition of ferroptosis, the data suggest that GT3 limits membrane damage and reduces susceptibility to ferroptosis by enhancing iron and heme scavenging. Further investigation into the interaction between GT3 and key components of ferroptosis following exposure to ionizing radiation is therefore warranted. Full article

The effective treatment of neurodegenerative diseases (NDDs), such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis, remains a critical challenge in modern medicine. Given the limitations of current therapies, alternative strategies to slow neurodegeneration are urgently needed. This study presents a critical review of the current evidence regarding low-dose ionizing radiation (IR) as a promising modality for modulating neurodegenerative processes. This study examines current experimental data on the effects of low-dose IR (LDIR) on cellular protective and compensatory mechanisms, including evidence from in vivo models of NDDs. Our analysis demonstrates that LDIR enhances antioxidant activity and DNA repair, stimulates autophagy and neuroplasticity, and modulates neuroinflammatory signaling. Collectively, these findings support the hypothesis of the neuroprotective potential of LDIR, underscoring its translational viability provided that strict dosimetric guidelines are followed and individual biological responses are rigorously monitored. Full article

Ionizing radiation therapy has undergone a clear paradigm shift in veterinary oncology and inflammatory disease management, moving from mainly palliative use toward structured, curative treatment programs. This review synthesizes current evidence on key modalities used in veterinary practice, including external beam radiotherapy, brachytherapy, systemic targeted radionuclide therapy, stereotactic radiosurgery, stereotactic body radiotherapy, radiosynoviorthesis, and low-dose radiotherapy. Each modality is discussed in relation to its physical and biological basis, major isotopes or beam types, routes of delivery, target species such as dogs, cats, and horses, clinical indications, and global availability. Comparative analysis highlights differences in clinical acceptance, evidence strength, access, and cost. External beam radiotherapy and stereotactic techniques support curative tumor management, whereas radiosynoviorthesis and low-dose radiotherapy are effective for inflammatory and degenerative disorders. Despite ongoing progress, challenges remain in access, dosimetry standardization, and prospective evidence. Companion animals are also emphasized as valuable translational models, guiding future innovation and collaboration internationally. Full article

Glioblastoma (GBM) remains among the most treatment-refractory human malignancies. It is characterized by profound radioresistance and a highly immunosuppressive tumor microenvironment, limiting the durable efficacy of radiotherapy. Beyond direct cytotoxicity, ionizing radiation can induce immunogenic cell death and the release of damage-associated molecular patterns (DAMPs), including surface-exposed calreticulin, HMGB1, extracellular ATP/adenosine, and tumor-derived DNA. These signals engage pattern-recognition receptors and cGAS–STING–type I interferon pathways, transiently promoting antigen presentation and immune activation. In GBM, however, DAMP signaling frequently evolves toward chronic inflammation and immune suppression, characterized by myeloid cell recruitment, adenosine accumulation, and immune checkpoint upregulation, thereby contributing to tumor regrowth and radioresistance. This dual immune-regulatory role of DAMPs highlights the importance of temporal and contextual interpretation of radiation-induced immune responses. In this review, we summarize current mechanistic and translational evidence on DAMP-mediated immunomodulation in GBM radiotherapy; discuss modality-dependent considerations across photon, proton, and high-LET irradiation; and evaluate the emerging potential of DAMPs as dynamic biomarkers of treatment response. We further outline how integration of DAMP profiling with liquid biopsy, imaging, and nanotheranostic platforms may support biologically informed and adaptive radiotherapy strategies for glioblastoma. Full article

The increasing utilization of radiation in medicine, industry, and water purification highlights the need for efficient radiation-protection materials. This study investigates lead-free polymer composites based on high-density polyethylene (HDPE) filled with four metallic fillers: tungsten carbide (WC), molybdenum carbide (MoC), tungsten (W), and molybdenum (Mo) at 15 wt%. The objective is to evaluate their potential as alternatives to lead for shielding ionizing radiation. Mechanical performance was examined through tensile testing, while thermal stability was assessed based on the residual mass. Radiation-attenuation behavior was analyzed through linear and mass attenuation coefficients (µ and µₘ), radiation protection efficiency (RPE), half-value layer (HVL), mean free path (MFP), buildup factors (B), and effective atomic number (Z_eff) within the 47.9–248 keV energy range. The HDPE/W composite exhibited the greatest enhancement, with a mass attenuation coefficient (µₘ) 82.5% higher than that of pure HDPE, along with the highest linear attenuation coefficient (µ). Furthermore, tungsten-loaded samples achieved an RPE of 98.05% at 47.9 keV. The increased density, low B, and high Z_eff values collectively contribute to superior shielding performance. These findings indicate that HDPE filled with WC, MoC, W, and Mo are promising lead-free candidates for low-energy X-ray shielding applications. Full article

Endovascular aneurysm repair (EVAR) is a widely used minimally invasive treatment for abdominal aortic aneurysms. However, postoperative type II endoleak (T2EL) remains a relevant complication associated with a risk of aneurysm rupture and the need for repeated imaging follow-up, resulting in exposure to ionizing radiation. Identification of biological factors predisposing to T2EL may improve risk stratification. This pilot study aimed to investigate whether disturbances in hemostasis are associated with early T2EL development after EVAR. A total of 103 patients treated with EVAR for symptomatic or asymptomatic abdominal aortic aneurysms in a tertiary vascular center were prospectively enrolled. Blood samples were collected preoperatively and one month postoperatively to assess fibrinogen, prothrombin fragment F1+2 (F1+2), thrombin–antithrombin complex (TAT), tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor-1 (PAI-1) activity, and platelet activity. Computed tomography angiography (CTA) during follow-up was used to detect endoleaks and calculate their volume. Patients with T2EL had significantly lower levels of prothrombin fragment F1+2 and higher PAI-1 activity compared with patients without endoleak. No significant association was observed between the analyzed biomarkers and endoleak volume. These findings suggest that reduced thrombin generation and impaired fibrinolysis may contribute to endoleak formation after EVAR and warrant further investigation in larger, confirmatory studies. Full article

Some windowless semiconductor photodiodes can detect not only photons but also charged particles, cover a wide spectral range including a part of the ionizing radiation region and, thus, play important roles for synchrotron radiation experiments. To understand the spectral, angular and polarizing properties of semiconductor photodiodes, complex amplitude coefficients of transmittance or reflectance are calculated based on rigorous formulation using Fresnel equations with complex optical constants of the composing materials, whose validity was verified by comparison with experiments. Concrete examples of the behavior on the complex plane are shown as a function of complex optical constants, film thickness, angle of incidence and the wavelength. The results show that the optical properties of the layered system are sensitive to its layer thickness, the angle of incidence and the wavelength in the ultraviolet region where optical indices of the composing materials steeply change. It has been shown that oblique incidence photodiodes are useful as polarization-sensitive devices, and that the graphical technique using the amplitude coefficients expressed on the complex plane is effective and powerful to search for optimal conditions for complex optical constants, film thickness and/or angle of incidence. Full article

Background: Cutaneous radiation injury arises when ionizing radiation disrupts epidermal barrier integrity, triggering persistent DNA damage, oxidative stress, and senescence-associated inflammatory signaling that drive extracellular matrix degradation and impaired regeneration. Clinical burden is rising due to dose-intensified radiotherapy, but also due to an increased use of energy-based aesthetic procedures that elicit radiation-like dermal injury. Dermal fibroblasts exhibit marked sensitivity to ionizing radiation and rapidly acquire senescence-associated secretory phenotypes that suppress collagen biosynthesis and promote chronic inflammation, underpinning the need for regenerative treatments that restore tissue homeostasis and regenerative competence. Mesenchymal stem cell–derived exosomes have emerged as a promising therapeutic strategy in this setting, with increasing preclinical evidence demonstrating their capacity to attenuate oxidative stress, enhance DNA damage-repair pathways, and normalize fibroblast metabolic function. Methods: In this study, we examine the expression profiles for 14 radiation response–associated genes of irradiated human dermal fibroblasts that were treated with bone marrow and umbilical cord MSC-derived exosomes at different timepoints using quantitative RT-PCR analysis. We also explore functional relationships among these genes through interaction network analysis, and outline a framework to organize pathway-level transcriptional responses to irradiation and exosome treatment. Results: MSC-derived exosome treatment was associated with attenuated early damage response signaling at 24 h, followed by increased expression of genes associated with DNA repair and oxidative stress recovery at intermediate timepoints. Exosome-treated cells also exhibited transcriptional changes consistent with modulation of cell-cycle regulatory pathways and reduced expression of pro-inflammatory markers by 5 d. These findings suggest that MSC-derived exosomes influence the temporal organization of the fibroblast transcriptional response to ionizing radiation and may contribute to molecular programs associated with tissue recovery following ionizing radiation exposure. Full article

Background/Objectives: Exposure of cells to ionizing radiation induces isolated DNA lesions, including single-strand breaks, apurinic/apyrimidinic sites, and oxidized bases, as well as clustered damages of different complexity. The latter types of damage are difficult to repair, and the failure to process them accurately and efficiently is related to the induction of mutagenesis, genomic instability, cancer, and aging. Since various types of clustered lesions may occur simultaneously after radiation exposure, leading to a complex architecture of DNA damage, the study of the concomitant formation and the removal kinetics of clustered DNA damage is important to determine the mutagenic and, consequently, the carcinogenic potential of ionizing radiation. Methods: With the aim of capturing real-time coexisting lesion types and assessing the repair kinetics of clustered damages, the simultaneous determination of double-strand breaks, apurinic/apyrimidinic site clusters, and oxypurine clusters induced by γ-irradiation of Saccharomyces cerevisiae yeast cells was performed immediately after exposure and at time intervals during incubation in Liquid Holding Recovery conditions. Results: Ionizing radiation induced lethal and mutagenic events, leading to a dose-dependent linear increase in double-strand breaks, apurinic/apyrimidinic site clusters, and oxypurine clusters. The kinetic study showed that double-strand break frequencies declined during Liquid Holding Recovery, although a transient increase was detected at early time points. At 160 Gy, apurinic/apyrimidinic site clusters repair was evident, whereas at 400 Gy the frequency of damage increased before returning to the initial value at 24 h. In contrast, oxypurine clusters showed no net increase in repaired lesions over 24 h. Conclusions: The complex nature and topological characteristics of ionizing radiation-induced clustered DNA damage may influence lesion processing. Also, ionizing radiation may disrupt redox cellular homeostasis, leading to DNA damage and delayed effects. Full article

Background/Objectives: Canonical microRNAs possess a 5′ phosphate required for Argonaute binding and activity. However, prior work identified an unphosphorylated, inactive nuclear pool of the important radiation-responsive microRNA, miR-34, that is rapidly phosphorylated and activated in response to ionizing radiation (IR). Here, we extend this work and investigate the role of paraspeckles, a phase-separated nuclear sub-compartment, and their association with the localization of unphosphorylated miR-34a. Methods: Mass spectrometry was performed to identify interacting partners of unphosphorylated mir-34. CRISPR-mediated deletion of the paraspeckle NEAT1_2 triple helix motif was performed to create an A549 cell line lacking paraspeckles (dTH). Activity and expression of mir-34a post-irradiation were evaluated by qRT-PCR and luciferase assays comparing dTH and wild-type (WT) A549 cell lines. In situ hybridization (ISH) was performed to evaluate mir-34a localization before and after IR, comparing dTH and WT cell lines. Results: Mass spectrometry identified paraspeckle proteins as significantly enriched interacting partners of unphosphorylated mir-34 mimics. By qRT-PCR and luciferase assays, we found that paraspeckle loss prevented radiation-induced early activation of unphosphorylated mir-34a. We found no difference in radiation-induced transcription of pri-miR-34a, but early processing to pre-miR-34a appeared delayed. ISH confirmed that loss of paraspeckles altered the nuclear localization of miR-34a before and after IR. Conclusions: These data suggest that paraspeckles are associated with nuclear localization and early radiation-responsive activation of unphosphorylated miR-34a. This suggests a coordinated nuclear sequestration of this important miR in its unphosphorylated state to enable an enhanced radiation response. Full article