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In this work, the heavy-ion irradiation responses of MgO-Nd 2 Zr 2 O 7 (M-NZO) composite ceramics used for inert matrix fuel were experimentally investigated. And the micro and macro radiation damage of M-NZO samples was systemically unveiled after 5 MeV Xe20+ irradiation and quantified by two exposure units, displacements per atom (dpa) and phonons per atom (ppa). The newly ppa represent the number of phonon modes available in the radiated material, which are high relative to thermal properties and the resulting morphological fragmentation after irradiation. In detail, MgO phase mostly retains its pristine structure without extensive amorphization irradiated at high dpa values, meanwhile, Nd 2 Zr 2 O 7 phase also presents satisfactory radiation resistance through the distinctive order-disorder structural transformations that alleviate radiation-induced strain. Besides, MgO grains with lower ppa value dissipate ions energy more efficiently than Nd 2 Zr 2 O 7 , and exhibit higher radiation tolerance at macroscopic morphological scale. Overall, M-NZO composite ceramics have good radiation tolerance under heavy-ion bombardment, in which the lower ppa value and higher thermal conductivity of MgO make itself possess superior resistance to irradiation-induced damage than Nd 2 Zr 2 O 7. [ABSTRACT FROM AUTHOR]

Background: Artemis deficiency is an autosomal recessive disorder characterized by a combined immunodeficiency with increased cellular radiosensitivity. In this review, the clinical and genetic characteristics of 15 patients with DCLRE1C variants are presented. Methods: The demographic, clinical, immunologic, and genetic characteristics of patients with confirmed DCLRE1C variants diagnosed between 2013 and 2023 were collected retrospectively. Three patients were evaluated for radiosensitivity by the Comet assay, compared with age‐ and sex‐matched healthy control. Results: Seven patients who had severe infections in the first 6 months of life were diagnosed with T‐B‐NK+ SCID (severe combined immunodeficiency). Among them, four individuals underwent transplantation, and one of those died due to post‐transplant complications in early life. Eight patients had hypomorphic variants. Half of them were awaiting a suitable donor, while the other half had already undergone transplantation. The majority of patients were born into a consanguineous family (93.3%). Most patients had recurrent sinopulmonary infections (73.3%), and one patient had no other infection than an acute respiratory infection before diagnosis. Two patients (13.3%) had autoimmunity in the form of autoimmune hemolytic anemia. Growth retardation was observed in only one patient (6.6%), and no malignancy was detected in the surviving 11 patients during the median (IQR) of 21.5 (12–45) months of follow‐up. Three patients who had novel variants exhibited increased radiosensitivity and compromised DNA repair, providing a potential vulnerability to malignant transformation. Conclusion: Early diagnosis, radiation avoidance, and careful preparation for transplantation contribute to minimizing complications, enhancing life expectancy, and improving the patient's quality of life. [ABSTRACT FROM AUTHOR]

Our study aims to identify the mechanisms involved in regulating the response of Rhodoendron Chrysanthum Pall. (R.chrysanthum) leaves to UV-B exposure; phosphorylated proteomics and metabolomics for phenolic acids and plant hormones were integrated in this study. The results showed that UV-B stress resulted in the accumulation of salicylic acid and the decrease of auxin, jasmonic acid, abscisic acid, cytokinin and gibberellin in R.chrysanthum. The phosphorylated proteins that changed in plant hormone signal transduction pathway and phenolic acid biosynthesis pathway were screened by comprehensive metabonomics and phosphorylated proteomics. In order to construct the regulatory network of R.chrysanthum leaves under UV-B stress, the relationship between plant hormones and phenolic acid compounds was analyzed. It provides a rationale for elucidating the molecular mechanisms of radiation tolerance in plants. [ABSTRACT FROM AUTHOR]

Background: Quantum Dots (QDs) are fluorescent nanoparticles with exceptional optical and optoelectronic properties, finding widespread utility in diverse industrial applications. Presently, chemically synthesized QDs are employed in solar cells, bioimaging, and various technological domains. However, many applications demand QDs with prolonged lifespans under conditions of high-energy radiation. Over the past decade, microbial biosynthesis of nanomaterials has emerged as a sustainable and cost-effective process. In this context, the utilization of extremophile microorganisms for synthesizing QDs with unique properties has recently been reported. Results: In this study, UV-resistant bacteria were isolated from one of the most extreme environments in Antarctica, Union Glacier at the Ellsworth Mountains. Bacterial isolates, identified through 16 S sequencing, belong to the genera Rhodococcus, Pseudarthrobacter, and Arthrobacter. Notably, Rhodococcus sp. (EXRC-4 A-4), Pseudarthrobacter sp. (RC-2-3), and Arthrobacter sp. (EH-1B-1) tolerate UV-C radiation doses ≥ 120 J/m². Isolated UV-resistant bacteria biosynthesized CdS QDs with fluorescence intensities 4 to 8 times higher than those biosynthesized by E. coli, a mesophilic organism tolerating low doses of UV radiation. Transmission electron microscopy (TEM) analysis determined QD sizes ranging from 6 to 23 nm, and Fourier-transform infrared (FTIR) analysis demonstrated the presence of biomolecules. QDs produced by UV-resistant Antarctic bacteria exhibit high photostability after exposure to UV-B radiation, particularly in comparison to those biosynthesized by E. coli. Interestingly, red fluorescence-emitting QDs biosynthesized by Rhodococcus sp. (EXRC-4 A-4) and Arthrobacter sp. (EH-1B-1) increased their fluorescence emission after irradiation. Analysis of methylene blue degradation after exposure to irradiated QDs biosynthesized by UV-resistant bacteria, indicates that the QDs transfer their electrons to O2 for the formation of reactive oxygen species (ROS) at different levels. Conclusions: UV-resistant Antarctic bacteria represent a novel alternative for the sustainable generation of nanostructures with increased radiation tolerance—two characteristics favoring their potential application in technologies requiring continuous exposure to high-energy radiation. [ABSTRACT FROM AUTHOR]

Objective: Radiotherapy (RT) is a cornerstone of the glioblastoma (GBM) treatment. However, the resistance of tumour cells to radiation results in early recurrence. The mechanisms underlying GBM radioresistance remain unclear. Screening for differentially expressed genes (DEGs) related to radiation might be a potential solution to this problem. Method: RT‐associated DEGs were screened based on the RNA sequencing of 15 paired primary and recurrent GBMs. The mRNA and protein expression of candidate genes were validated in RNA sequencing of The Chinese Genome Atlas (CGGA) dataset and 18 cases of GBM samples. The relationship between the candidate gene and radiation was confirmed in irradiated GBM cells. The association of candidate gene with clinical characteristics and survival was investigated in the CGGA and TCGA dataset. Biological function and pathway analysis were explored by gene ontology analysis. The association of the candidate gene with radiosensitivity was verified using cell counting Kit‐8, comet, and colony formation assays in vitro and subcutaneous tumour xenograft experiments in vivo. Results: Gelsolin (GSN) was selected for further study. GSN expression was significant elevated in recurrent GBM and up‐regulated in irradiated GBM cell lines. High expression of GSN was enriched in malignant phenotype of glioma. Moreover, high expression of GSN was associated with poor prognosis. Further investigation demonstrated that GSN‐knockdown (GSN‐KD) combined with RT significantly inhibited cell proliferation and enhanced radiosensitivity in vivo and in vitro. Mechanistically, GSN‐KD could lead to more serious DNA damage and promotes apoptosis after RT. Conclusion: Radiation induced up‐regulated of GSN. GSN‐KD could enhance the radiosensitivity of GBM. [ABSTRACT FROM AUTHOR]

Background: Interpatient variation of tumor radiosensitivity is rarely considered during the treatment planning process despite its known significance for the therapeutic outcome. Purpose: To apply our mechanistic biophysical model to investigate the biological robustness of carbon ion radiotherapy (CIRT) against DNA damage repair interference (DDRi) associated patient‐to‐patient variability in radiosensitivity and its potential clinical advantages against conventional radiotherapy approaches. Methods and Materials: The "UNIfied and VERSatile bio response Engine" (UNIVERSE) was extended by carbon ions and its predictions were compared to a panel of in vitro and in vivo data including various endpoints and DDRi settings within clinically relevant dose and linear energy transfer (LET) ranges. The implications of UNIVERSE predictions were then assessed in a clinical patient scenario considering DDRi variance. Results: UNIVERSE tests well against the applied benchmarks. While in vitro survival curves were predicted with an R2 > 0.92, deviations from in vivo RBE data were less than 5.6% The conducted paradigmatic patient plan study implies a markedly reduced significance of DDRi based radiosensitivity variability in CIRT (13% change of D50${{D}_{50}}$ in target) compared to conventional radiotherapy (62%) and that boosting the LET within the target further amplifies this robustness of CIRT (8%). In the case of heightened tumor radiosensitivity, a dose de‐escalation strategy for photons allows a reduction of the maximum effective dose within the normal tissue (NT) from a D2${{D}_2}$ of 2.65 to 1.64 Gy, which lies below the level found for CIRT (D2${{D}_2}$ = 2.41 Gy) for the analyzed plan and parameters. However, even after de‐escalation, the integral effective dose in the NT is found to be substantially higher for conventional radiotherapy in comparison to CIRT (Dmean${{D}_{mean}}$ of 0.75, 0.46, and 0.24 Gy for the conventional plan, its de‐escalation and CIRT, respectively). Conclusions: The framework offers adequate predictions of in vitro and in vivo radiation effects of CIRT while allowing the consideration of DRRi based solely on parameters derived from photon data. The results of the patient planning study underline the potential of CIRT to minimize important sources of interpatient divergence in therapy outcome, especially when combined with techniques that allow to maximize the LET within the tumor. Despite the potential of de‐escalation strategies for conventional radiotherapy to reduce the maximum effective dose in the NT, CIRT appears to remain a more favorable option due to its ability to reduce the integral effective dose within the NT. [ABSTRACT FROM AUTHOR]

Radiotherapy with bladder preservation is highly acceptable among patients bearing bladder cancer (BCa), but the occurrence of secondary tolerance (ARR) during treatment is one of the important reasons for the failure of clinical radiotherapy. COX-2 has been frequently reported to be highly expressed and associated with radio-resistance in various cancers. In this study, the feasibility of Taraxasterol (Tara) as a radiosensitizer was investigated, and the target effect of Tara on COX-2 and its underlying mechanism were explored. The toxicity of Tara toward BCa cells was detected with the MTT method and cells in response to IR or Tara + IR were compared by clone formation assay. Next, a small RNA interference system (siRNA) was employed to decrease endogenous COX-2 expression in BCa cells, and the stem cell-like features and motion abilities of BCa cells under different treatments were investigated using microsphere formation and transwell chamber assay, respectively. Meanwhile, the expression of a series of inflammation-related molecules and stem cell characteristic molecules was determined by qRT-PCR, western blot and ELISA method. In vivo studies, BCa cells were subcutaneously injected into the right flank of each male mouse. Those mice were then grouped and exposed to different treatment: Tara, IR, IR + Tara and untreated control. The volumes of each tumor were measured every two days and target proteins were detected with immunohistochemical (IHC) staining. The results show that COX-2 decline, due to COX-2 knocking-down or Tara treatment, could greatly enhance BCa cells' radiosensitivity and significantly decrease their migration, invasion and microsphere formation abilities, companied with the reduce of JAK2, phos-STAT3, MMP2 and MMP9 expression. However, Tara could not further reduce the expression of an above molecule of cells in COX-2-deficient BCa cells. Correspondingly, Tara treatment could not further enhance those siCOX-2 BCa cells response to IR. Our data support that Tara can improve the radiosensitivity of BCa cells by targeting COX-2/PGE2. The mechanism may involve regulating STAT3 phosphorylation, DNA damage response protein activation, and expression of MMP2/MMP9. [ABSTRACT FROM AUTHOR]

DNA damage response (DDR) is the principal mechanism regulating genomic stability and cell cycle checkpoint activation by coordinating DNA repair and apoptotic pathways. Ataxia telangiectasia and Rad3-related protein (ATR) play a significant role in the DDR due to its capability to detect a wide spectrum of DNA damage. Therefore, targeting DDR, specifically ATR, is a promising therapeutic strategy in cancer treatment. Furthermore, the inhibition of ATR sensitizes cancer cells to radiotherapy (RT). Herein, we, for the first time, investigated the synergistic effects of Elimusertib (BAY-1895344) as a highly potent selective ATR inhibitor with RT combination in triple-negative breast cancer (TNBC), in vitro. MDA-MB-231 TNBC cells were firstly treated with different concentrations of Elimusertib for 24 h and then exposed to 4 and 8 Gy of X-ray irradiation. After post-irradiation for 72 h, WST-1, Annexin V, cell cycle, acridine orange/propidium iodide, mitochondria staining and western blot analysis were conducted. Our findings showed that 4 Gy irradiation and lower doses (especially 2 and 4 nM) of Elimusertib combination exerted a considerable anticancer activity at 72 h post-irradiation through apoptotic cell death, marked nuclear and mitochondrial damages and the suppression of ATR-Chk1 based DDR mechanism. ATR inhibition by Elimusertib in combination with RT may be a promising new treatment strategy in the treatment of TNBC. However, further experiments should be performed to elucidate the underlying molecular mechanisms of the therapeutic efficacy of this combination treatment and its association with DNS repair mechanisms in TNBC, in vitro and in vivo. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the effects of PinX1 on non-small cell lung cancer(NSCLC) radiosensitivity and radiotherapy-associated tumor immune microenvironment and its mechanisms. Methods: The effect of PinX1 silencing on radiosensitivity in NSCLC was assessed by colony formation and CCK8 assay, immunofluorescence detection of γ- H2AX and micronucleus assay. Western blot was used to assess the effect of PinX1 silencing on DNA damage repair pathway and cGAS-STING pathway. The nude mouse and Lewis lung cancer mouse model were used to assess the combined efficacy of PinX1 silencing and radiotherapy in vivo. Changes in the tumor immune microenvironment were assessed by flow cytometry for different treatment modalities in the Lewis luuse model. The interaction protein RBM10 was screened by immunoprecipitation-mass spectrometry. Results: Silencing PinX1 enhanced radiosensitivity and activation of the cGAS-STING pathway while attenuating the DNA damage repair pathway. Silencing PinX1 further increases radiotherapy-stimulated CD8+ T cell infiltration and activation, enhances tumor control and improves survival in vivo; Moreover, PinX1 downregulation improves the anti-tumor efficacy of radioimmunotherapy, increases radioimmune-stimulated CD8+ T cell infiltration, and reprograms M2-type macrophages into M1-type macrophages in tumor tissues. The interaction of PinX1 and RBM10 may promote telomere maintenance by assisting telomerase localization to telomeres, thereby inhibiting the immunostimulatory effects of IR. Conclusions: In NSCLC, silencing PinX1 significantly contributed to the radiosensitivity and promoted the efficacy of radioimmunotherapy. Mechanistically, PinX1 may regulate the transport of telomerase to telomeres through interacting with RBM10, which promotes telomere maintenance and DNA stabilization. Our findings reveal that PinX1 is a potential target to enhance the efficacy of radioimmunotherapy in NSCLC patients. [ABSTRACT FROM AUTHOR]

Chalcogenide thin films that undergo reversible phase changes show promise for use in next-generation nanophotonics, microelectronics, and other emerging technologies. One of the many studied compounds, Ge2Sb2Te5, has demonstrated several useful properties and performance characteristics. However, the efficacy of benchmark Ge2Sb2Te5 is restricted by amorphous phase thermal stability below ∼150 °C, limiting its potential use in high-temperature applications. In response, previous studies have added a fourth species (e.g., C) to sputter-deposited Ge2Sb2Te5, demonstrating improved thermal stability. Our current research confirms reported thermal stability enhancements and assesses the effects of carbon on crystalline phase radiation response. Through in situ transmission electron microscope irradiation studies, we examine the effect of C addition on the amorphization behavior of initially cubic and trigonal polycrystalline films irradiated using 2.8 MeV Au to various doses up to 1 × 1015 cm−2. It was found that increased C content reduces radiation tolerance of both cubic and trigonal phases. [ABSTRACT FROM AUTHOR]

Nano-satellites, which are following the CubeSat standard have established for demanding industrial and scientific applications with critical requirements on reliability and radiation tolerance. The employment of commercial off-the-shelf components enables a state-of-the-art performance but requires extensive testing to avoid and mitigate malefunctions due to the space environment. The CubeSat mission CLIMB is representative for future missions with a complex payload, a high power budget and a harsh radiation exposure. For this reason, a comprehensive irradiation study of its on-board-computer was done. The total ionizing dose damage of 50 krad was evaluated at a 60 Co source. As a consequence of this test, specific components were exchanged before performing single event effect studies at the synchrotron accelerator MedAustron. A board-level test revealed that the majority of effects concern the central micro controller wherefore was followed by a component-level test. Those irradiation tests make use of a pencil beam to map the device under test, which provides additional information to localize effects - by the timestamp - at the expense of an increased irradiation time compared to a homogeneous exposure. In this paper, we summarize the major findings of the test campaign and mitigation means and present a procedure for single event effect studies at medical accelerators. [ABSTRACT FROM AUTHOR]

The Japan Aerospace Exploration Agency (JAXA) is planning a Space photovoltaics Demonstration eXperiment (SDX) to reveal the tolerance to the space environment of the next-generation solar cells. One of the next-generation solar cells mounted on SDX is a perovskite solar cell (PSC), which is cost-effective and has the potential for high specific power and radiation tolerance. It is necessary to clarify the long-term stability to analyze the characteristics of PSCs in orbit because SDX will be stored for months before and after launch. Therefore, we conducted three storage tests (in air, nitrogen, and low pressure) using encapsulated PSCs. Their performance was evaluated by Light I–V, Dark I–V, and EQE measurements. As a result, almost no degradation was observed at EOL (after 400 days) under all storage conditions. We found that the encapsulated PSCs mounted on SDX are highly stable. We also found that the slight degradation of P max within 4 % was due to an increase in series resistance. • The Japan Aerospace Exploration Agency is developing perovskite solar cells for use in space. • Perovskite solar cells have an issue with long-term stability; it is still unknown how stable they are in orbit in the subject mission. • We researched the long-term stability (in air, nitrogen, and low pressure) and degradation trend of perovskite solar cells in space. • We found they have high stability after 400 days of storage even though in air, and can be applied to our mission. [ABSTRACT FROM AUTHOR]

Studies of the radiation tolerance and electrical behavior of gallium nitride (GaN) based devices are important for the next generation of high-power and high-voltage electronics that may be subjected to harsh environments such as nuclear reactor and fusion facilities, particle accelerators, and post-denotation environments. In this work, we study the behavior of Ga-polar and N-polar GaN Schottky diodes before and after exposure to fast and thermal + fast neutrons. Temperature-dependent current–voltage (I–V) and circular transmission line method (CTLM) measurements were used to study the electrical characteristics. A strong reduction in reverse leakage current and an increase in differential resistance in forward bias were observed after neutron irradiation. Thermionic emission (TE), Frenkel–Poole (FP) emission, and Fowler–Nordheim (FN) tunneling models were used to explain the forward and reverse I–V characteristics pre- and post-irradiation. The study confirms that Ga-polar and N-polar GaN Schottky diodes exhibit different electrical responses to fast and thermal neutron irradiations. The reverse bias characteristics of N-polar diodes are less affected after the fast neutron irradiation compared to Ga-polar diodes, while in the forward bias region, the electrical behavior after fast and thermal neutron irradiations is similar in Ga-polar and N-polar diodes. The results indicate that the role of orientation should be considered in the design of GaN-based radiation-tolerant electronics. [ABSTRACT FROM AUTHOR]

Ultra-thin solar cells are of significant interest for use in space due to their intrinsic radiation tolerance, which may allow them to be used in particularly harsh radiation environments, where thicker cells would degrade rapidly and enable reduction in cover glass thickness to reduce launch mass. In this study, devices with an 80 nm GaAs absorber layer were irradiated with 3 MeV protons. It is shown that integrated light management in these ultra-thin devices offers enhanced efficiency, in addition to extended lifetime through radiation resilience. Time-resolved cathodoluminescence is employed to map the introduction of radiation-induced defects with increasing proton fluence and characterize a decrease in carrier lifetime from 198 ± 5 ps pre-radiation to 6.2 ± 0.6 ps, after irradiation to 2 × 10 14 c m − 2 fluence. Despite the substantial reduction in carrier lifetime, short-circuit current does not degrade up to a proton fluence of 1 × 10 15 cm − 2 , beyond which a collapse in short-circuit current is observed. This exposure correlates with the point at which the carrier lifetime, extrapolated from cathodoluminescence, becomes comparable to the transit time for carriers to cross the ultra-thin device. Variation in current–voltage behavior with carrier lifetime and fluence shows that the recombination statistics are similar to those of a Shockley–Read–Hall single deep-level trap model, but that bimolecular recombination does not fully describe the observed behavior. An implication of these highly radiation tolerant cells for space power systems is shown to offer significant savings in cover glass mass, compared with a thicker cell. [ABSTRACT FROM AUTHOR]

Radiation therapy is a primary treatment for cancer, but radioresistance remains a significant challenge in improving efficacy and reducing toxicity. Accumulating evidence suggests that deubiquitinases (DUBs) play a crucial role in regulating cell sensitivity to ionizing radiation. Traditional small-molecule DUB inhibitors have demonstrated radiosensitization effects, and novel deubiquitinase-targeting chimeras (DUBTACs) provide a promising strategy for radiosensitizer development by harnessing the ubiquitin-proteasome system. This review highlights the mechanisms by which DUBs regulate radiosensitivity, including DNA damage repair, the cell cycle, cell death, and hypoxia. Progress on DUB inhibitors and DUBTACs is summarized, and their potential radiosensitization effects are discussed. Developing drugs targeting DUBs appears to be a promising alternative approach to overcoming radioresistance, warranting further research into their mechanisms. [ABSTRACT FROM AUTHOR]

Despite aggressive multimodal treatment that typically includes definitive or adjuvant radiation therapy (RT), locoregional recurrence rates approach 50% for patients with locally advanced human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC). Thus, more effective therapeutics are needed to improve patient outcomes. We evaluated the radiosensitizing effects of ataxia telangiectasia and RAD3-related (ATR) inhibitor (ATRi) BAY 1895344 in preclinical models of HNSCC. Murine and human HPV-negative HNSCC cells (MOC2, MOC1, JHU-012) were treated with vehicle or ATRi with or without 4 Gy. Checkpoint kinase 1 phosphorylation and DNA damage (γH2AX) were evaluated by Western blot, and ATRi half-maximal inhibitory concentration was determined by MTT assay for HNSCC cells and immortalized murine oral keratinocytes. In vitro radiosensitization was tested by clonogenic assay. Cell cycle distribution and mitotic catastrophe were evaluated by flow cytometry. Mitotic aberrations were quantified by fluorescent microscopy. Tumor growth delay and survival were assessed in mice bearing MOC2 or JHU-012 transplant tumors treated with vehicle, ATRi, RT (10 Gy × 1 or 8 Gy × 3), or combined ATRi + RT. ATRi caused dose-dependent reduction in checkpoint kinase 1 phosphorylation at 1 hour post-RT (4 Gy) and dose-dependent increase in γH2AX at 18 hours post-RT. Addition of RT to ATRi led to decreased BAY 1895344 half-maximal inhibitory concentration in HNSCC cell lines but not in normal tissue surrogate immortalized murine oral keratinocytes. Clonogenic assays demonstrated radiosensitization in the HNSCC cell lines. ATRi abrogated the RT-induced G2/M checkpoint, leading to mitosis with unrepaired DNA damage and increased mitotic aberrations (multinucleated cells, micronuclei, nuclear buds, nucleoplasmic bridges). ATRi and RT significantly delayed tumor growth in MOC2 and JHU-012 in vivo models, with improved overall survival in the MOC2 model. These findings demonstrated that BAY 1895344 increased in vitro and in vivo radiosensitivity in HPV-negative HNSCC preclinical models, suggesting therapeutic potential warranting evaluation in clinical trials for patients with locally advanced or recurrent HPV-negative HNSCC. [ABSTRACT FROM AUTHOR]

Microsclerotia (MS) are considered one of the most promising propagules for use as active ingredients in biopesticides due to their tolerance to abiotic factors and ability to produce infective conidia for the control of pests. Therefore, the objective of this research was to establish the conditions required to induce the formation of microsclerotia in Metarhizium robertsii Mt004 and to study its development process, tolerance to abiotic factors and insecticidal activity of MS-derived conidia. M. robertsii started to form hyphal aggregates after 2 days and looked more compact after 8 days. MS were mature and pigmented after 20 days. The final yield was 2.0 × 103 MS/mL and MS size varied between 356.9 and 1348.4 μm. Ultrastructure analysis revealed that mature MS contained only a few live cells embedded in an extracellular matrix. Mature MS were more tolerance to UV-B radiation, heat and storage trials than conidia from Solid State Fermentation. MS-derived conidia were as virulent as conidia against Diatraea saccharalis larvae. These results showed that MS are promising propagules for the development of more persistent and efficient biopesticides for harsh environmental conditions. Our findings provide a baseline for production and a better understanding of microsclerotia development in M. robertsii strains. • The type and concentration of nitrogen sources are critical for inducing MS formation. • The extracellular matrix content increased during the MS maturation process. • Mature microsclerotia were more tolerant to abiotic factors than aerial conidia. • MS-derived conidia were as virulent as aerial conidia produced on rice. [ABSTRACT FROM AUTHOR]

With the rapid advancement of information technology, microelectronic devices have found widespread applications in critical sectors such as nuclear power plants, aerospace equipment, and satellites. However, these devices are frequently exposed to diverse radiation environments, presenting significant challenges in mitigating radiation-induced damage. Hence, this review aims to delve into the intricate damage mechanisms of microelectronic devices within various radiation environments and highlight the latest advancements in radiation-hardening techniques. The ultimate goal is to bolster the reliability and stability of these devices under extreme conditions. The review initiates by outlining the spectrum of radiation environments that microelectronic devices may confront, encompassing space radiation, nuclear explosion radiation, laboratory radiation, and process radiation. It also delineates the potential damage types that these environments can inflict upon microelectronic devices. Furthermore, the review elaborates on the underlying mechanisms through which different radiation environments impact the performance of microelectronic devices, which includes a detailed analysis of the characteristics and fundamental mechanisms of damage when microelectronic devices are subjected to total ionizing dose effects and single-event effects. In addition, the review delves into the promising application prospects of several key radiation-hardening techniques for enhancing the radiation tolerance of microelectronic devices. [ABSTRACT FROM AUTHOR]

Objective: Non-small cell lung cancer (NSCLC) often exhibits resistance to radiotherapy, posing significant treatment challenges. This study investigates the role of SMAD3 in NSCLC, focusing on its potential in influencing radiosensitivity via the ITGA6/PI3K/Akt pathway. Methods: The study utilized gene expression data from the GEO database to identify differentially expressed genes related to radiotherapy resistance in NSCLC. Using the GSE37745 dataset, prognostic genes were identified through Cox regression and survival analysis. Functional roles of target genes were explored using Gene Set Enrichment Analysis (GSEA) and co-expression analyses. Gene promoter methylation levels were assessed using databases like UALCAN, DNMIVD, and UCSC Xena, while the TISCH database provided insights into the correlation between target genes and CAFs. Experiments included RT-qPCR, Western blot, and immunohistochemistry on NSCLC patient samples, in vitro studies on isolated CAFs cells, and in vivo nude mouse tumor models. Results: Fifteen key genes associated with radiotherapy resistance in NSCLC cells were identified. SMAD3 was recognized as an independent prognostic factor for NSCLC, linked to poor patient outcomes. High expression of SMAD3 was correlated with low DNA methylation in its promoter region and was enriched in CAFs. In vitro and in vivo experiments confirmed that SMAD3 promotes radiotherapy resistance by activating the ITGA6/PI3K/Akt signaling pathway. Conclusion: High expression of SMAD3 in NSCLC tissues, cells, and CAFs is closely associated with poor prognosis and increased radiotherapy resistance. SMAD3 is likely to enhance radiotherapy resistance in NSCLC cells by activating the ITGA6/PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

The primary radiation damage in pure V and TiVTa concentrated solid-solution alloy (CSA) was studied using a molecular dynamics method. We have performed displacement cascade simulations to explore the generation and evolution behavior of irradiation defects. The results demonstrate that the defect accumulation and agglomeration in TiVTa CSA are significantly suppressed compared to pure V. The peak value of Frenkel pairs during cascade collisions in TiVTa CSA is much higher than that in pure V due to the lower formation energy of point defects. Meanwhile, the longer lifetime of the thermal spike relaxation and slow energy dissipation capability of TiVTa CSA can facilitate the recombination of point defects. The defect agglomeration rate in TiVTa CSA is much lower due to the lower binding energy of interstitial clusters and reduced interstitial diffusivity. Furthermore, the occurrence probability of dislocation loops in TiVTa CSA is lower than that in pure V. The reduction in primary radiation damage may enhance the radiation resistance of TiVTa CSA, and the improved radiation tolerance is primarily attributed to the relaxation stage and long-term defect evolution rather than the ballistic stage. These results can provide fundamental insights into irradiation-induced defects evolution in refractory CSAs. [ABSTRACT FROM AUTHOR]

The article discusses the field of radiation biodosimetry, which involves measuring biological responses to estimate the absorbed radiation dose in exposed humans. The article highlights the current biodosimetry tools used, including prodromal signs/symptoms, hematological analysis, cytogenetics, omics, and physical dosimetry. The special issue contains reviews and research articles on various aspects of biodosimetry, including biomarkers, high-throughput automation, and the need for validation and testing of existing tools. The article also emphasizes the importance of considering confounding factors such as age, sex, and genetic predisposition in dose prediction accuracy. The authors hope that this special issue will inspire further research in the field to protect human safety and health from radiation exposures. [Extracted from the article]

There is an increased threat of exposure to ionizing radiation; in the event of such exposure, the availability of medical countermeasures will be vital to ensure the protection of the population. Effective countermeasures should be efficacious across a varied population and most importantly amongst both males and females. Radiation research must be conducted in animal models which act as a surrogate for the human response. Here, we identify differences in survival in male and female C57BL/6 in both a total body irradiation (TBI) model using the Armed Forces Radiobiology Research Institute (AFRRI) 60Co source and a partial body irradiation (PBI) model using the AFRRI Linear Accelerator (LINAC) with 4 MV photons and 2.5% bone marrow shielding. In both models, we observed a higher degree of radioresistance in female animals and a corresponding radiosensitivity in males. One striking difference in male and female rodents is body size/weight and we investigated the role of pre-irradiation body weight on survivability for animals irradiated at the same dose of irradiation (8 Gy TBI, 14 Gy PBI). We found that weight does not influence survival in the TBI model and that heavier males but lighter females have increased survival in the PBI model. This incongruence in survival amongst the sexes should be taken into consideration in the course of developing radiation countermeasures for response to a mass casualty incident. [ABSTRACT FROM AUTHOR]

The present study focuses on investigating the interaction between radiation and biological systems, specifically examining the detrimental effects of radiation. This approach has proven to be effective in determining the optimal tolerance range of radiation on plants, which can lead to the development of beneficial characteristics and help improve the narrow genetic base. The study was conducted on Salvia hispanica L., a medicinally important plant. Inbred seeds of Salvia hispanica L. were subjected to five different doses of gamma rays (50, 100, 150, 200, 250 Gy) using a Co-60 source with a gamma irradiator of 7.247 k rate. The seeds were sown in triplicate, along with a control set. Various characteristics were assessed, including germination percentage, survival percentage, presence of chlorophyll mutants, and plant height. The results indicate that lower doses of gamma irradiation (LD50) have detrimental effects on several plant attributes, such as seed germination, survivability, inflorescence size, and pollen fertility. Chromosomal abnormalities were also observed, with an increase in their occurrence corresponding to higher doses of gamma radiation. Germination percentage and survivability were found to decrease as the dose of gamma radiation increased. The dose of 50 Gy resulted in the highest level of genetic variability. Additionally, compared to the control group, a significant percentage of chromosomal abnormalities, particularly stickiness and scattering, was observed at a dose of 250 Gy. Lower doses of gamma radiation (specifically 50 and 100 Gy) showed statistically significant (p>0.5) positive responses in Salvia plants, including plant height, leaf area, leaf mutants, inflorescence axis, and seed size. On the other hand, higher doses of radiation proved to be fatal for the plants. In summary, this study provides valuable insights into the effects of gamma radiation on Salvia hispanica L., highlighting the optimal dose range for inducing beneficial changes in plant characteristics while also emphasizing the harmful consequences associated with higher doses of radiation. [ABSTRACT FROM AUTHOR]

ZrN films were irradiated with 2 MeV proton and 91.3 MeV Xe ion. Our aim is to demonstrate the radiation damage tolerance of nanostructured ZrN. Uv–visible spectroscopy revealed localized surface plasmon resonance (LSPR) band at 650 nm of ZrN nanoparticles. After irradiation the LSPR band intensity increases and become larger. The band gap decreases, while Urbach energy increases indicating defect formation. It is found a better crystallinity and no swelling or contraction in the studied fluence range. Therefore, nanostructured ZrN can be used in harsh irradiation environments such as neutron reactors and aerospace without altering its structural and plasmonic properties. [ABSTRACT FROM AUTHOR]

Simple Summary: The Oriental fruit fly, Bactrocera dorsalis (Hendel), significantly impacts agriculture in Southeast Asia and some Pacific islands as a major pest. Its widespread distribution, robust invasive ability, and detrimental effects on market access categorize it as a significant threat to numerous countries. Irradiation treatment is recognized as an effective and promising approach, considered as a potential alternative to the traditional phytosanitary treatment method, methyl bromide fumigation. However, the low-oxygen environment can influence the efficacy of irradiation treatment. The aim of this study is to investigate the impact of low-oxygen levels on the phytosanitary irradiation effects against larvae of B. dorsalis. The effects of normoxic (21% O2), hypoxic (5% O2), and super-hypoxic (0.5% O2) conditions on the development and metabolic profile of third-instar larvae of B. dorsalis were evaluated and compared at phytosanitary irradiation dose. Our research emphasizes the importance of lipid metabolism pathways and their associated metabolites in the irradiation tolerance of insects; moreover, neither hypoxic nor super-hypoxic conditions have increased the emergence rate of the evaluated fruit fly species under the current phytosanitary irradiation dose. These findings provide new insights into the mechanisms of radioprotection in insects under low-oxygen environments and advocate for international organizations and regulatory agencies to update guidelines on the application of phytosanitary irradiation under hypoxic conditions. X-ray irradiation and modified atmospheres (MAs) provide eco-friendly, chemical-free methods for pest management. Although a low-oxygen atmospheric treatment improves the performance of some irradiated insects, its influence on the irradiation of quarantine insects and its impacts on pest control efficacy have yet to be investigated. Based on bioassay results, this study employed direct immersion solid-phase microextraction (DI-SPME) combined with gas chromatography-mass spectrometry (GC-MS) to determine metabolic profiles of late third-instar B. dorsalis larvae under normoxia (CON, Air), hypoxia (95% N2 + 5% O2, HY), super-hypoxia (99.5% N2 + 0.5% O2, Sup-HY), irradiation-alone (116 Gy, IR-alone), hypoxia + irradiation (HY + IR) and super-hypoxia + irradiation (Sup-HY + IR). Our findings reveal that, compared to the IR-alone group, the IR treatment under HY and Sup-HY (HY + IR and Sup-HY + IR) increases the larval pupation of B. dorsalis, and weakens the delaying effect of IR on the larval developmental stage. However, these 3 groups further hinder adult emergence under the phytosanitary IR dose of 116 Gy. Moreover, all IR-treated groups, including IR-alone, HY + IR, and Sup-HY + IR, lead to insect death as a coarctate larvae or pupae. Pathway analysis identified changed metabolic pathways across treatment groups. Specifically, changes in lipid metabolism-related pathways were observed: 3 in HY vs. CON, 2 in Sup-HY vs. CON, and 5 each in IR-alone vs. CON, HY + IR vs. CON, and Sup-HY + IR vs. CON. The treatments of IR-alone, HY + IR, and Sup-HY + IR induce comparable modifications in metabolic pathways. However, in the HY + IR, and Sup-HY + IR groups, the third-instar larvae of B. dorsalis demonstrate significantly fewer changes. Our research suggests that a low-oxygen environment (HY and Sup-HY) might enhance the radiation tolerance in B. dorsalis larvae by stabilizing lipid metabolism pathways at biologically feasible levels. Additionally, our findings indicate that the current phytosanitary IR dose contributes to the effective management of B. dorsalis, without being influenced by radioprotective effects. These results hold significant importance for understanding the biological effects of radiation on B. dorsalis and for developing IR-specific regulatory guidelines under MA environments. [ABSTRACT FROM AUTHOR]

Radiation mutagenesis, which typically involves gamma rays, is important for generating new rice germplasm resources. Determining the appropriate radiation dose range is critical for the success of radiation mutagenesis. Clarifying the sensitivity and tolerance of genotypically diverse rice varieties to gamma irradiation as well as the radiation-induced changes to reactive oxygen species (ROS) generation and antioxidant enzyme activities is crucial for increasing the utility of radiation mutagenesis in rice breeding programs. The seeds of the following four rice varieties with different genotypes were used as test materials: indica Zhe 1613, glutinous indica Zhe 1708, japonica Zhejing 100, and glutinous japonica Zhenuo 65. Additionally,60Co was used as the source of gamma rays. The rice seeds were irradiated with 14 doses (0, 150, 200, 250, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750 Gy). Non-irradiated seeds were used as the control. The seedling survival rate for each variety was recorded at 3, 7, 14, and 28 days after sowing. Moreover, the median lethal dose (LD50) and critical dose (LD40) were calculated according to the seedling survival rates at 28 days after sowing. The seedling superoxide anion (O2•−), hydrogen peroxide (H2O2), and malondialdehyde (MDA) contents and the superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and ascorbate peroxidase (APX) activities were analyzed at 7 days after sowing. As the radiation dose increased, the seedling survival rate decreased. The seedling survival rate also decreased significantly as the number of days after sowing increased. Among the rice genotypes, the rank-order of the radiation tolerance was as follows: indica Zhe 1613 > glutinous indica Zhe 1708 > japonica Zhejing 100 > glutinous japonica Zhenuo 65. The LD50 values were 426.7 Gy for Zhe 1613, 329.2 Gy for Zhe 1708, 318.3 Gy for Zhejing 100, and 316.6 Gy for Zhenuo 65. Increases in the radiation dose resulted in significant increases in the seedling O2•− and H2O2 contents, but only up to a certain point. Further increases in the radiation dose caused the seedling O2•− and H2O2 contents to decrease. The H2O2 content for each variety peaked when the radiation dose was very close to the LD50. We propose that the radiation dose associated with the highest H2O2 content (±50 Gy) should be used as the recommended dose for the gamma irradiation of rice. The radiation dose that resulted in peak seedling O2•− contents in the analyzed rice varieties was very close to the LD40. In all rice varieties, the MDA content increased as the radiation dose increased. The SOD, CAT, POD, and APX activities increased as the radiation dose increased within a certain range (less than 600 Gy for Zhe 1613 and 400 Gy for the other varieties), but there were slight differences among the rice varieties. Genotypically diverse rice varieties vary regarding their sensitivity to gamma irradiation. Our findings suggest that ROS generation and antioxidant enzyme activities are important factors associated with the radiation mutagenesis of rice. The close relationship between the activities of key antioxidant enzymes, such as SOD, POD, APX, and CAT, and the LD50 and LD40 may be exploited to enhance radiation mutagenesis through the use of plant growth regulators. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the effects of PinX1 on non-small cell lung cancer(NSCLC) radiosensitivity and radiotherapy-associated tumor immune microenvironment and its mechanisms. Methods: The effect of PinX1 silencing on radiosensitivity in NSCLC was assessed by colony formation and CCK8 assay, immunofluorescence detection of γ- H2AX and micronucleus assay. Western blot was used to assess the effect of PinX1 silencing on DNA damage repair pathway and cGAS-STING pathway. The nude mouse and Lewis lung cancer mouse model were used to assess the combined efficacy of PinX1 silencing and radiotherapy in vivo. Changes in the tumor immune microenvironment were assessed by flow cytometry for different treatment modalities in the Lewis luuse model. The interaction protein RBM10 was screened by immunoprecipitation-mass spectrometry. Results: Silencing PinX1 enhanced radiosensitivity and activation of the cGAS-STING pathway while attenuating the DNA damage repair pathway. Silencing PinX1 further increases radiotherapy-stimulated CD8+ T cell infiltration and activation, enhances tumor control and improves survival in vivo; Moreover, PinX1 downregulation improves the anti-tumor efficacy of radioimmunotherapy, increases radioimmune-stimulated CD8+ T cell infiltration, and reprograms M2-type macrophages into M1-type macrophages in tumor tissues. The interaction of PinX1 and RBM10 may promote telomere maintenance by assisting telomerase localization to telomeres, thereby inhibiting the immunostimulatory effects of IR. Conclusions: In NSCLC, silencing PinX1 significantly contributed to the radiosensitivity and promoted the efficacy of radioimmunotherapy. Mechanistically, PinX1 may regulate the transport of telomerase to telomeres through interacting with RBM10, which promotes telomere maintenance and DNA stabilization. Our findings reveal that PinX1 is a potential target to enhance the efficacy of radioimmunotherapy in NSCLC patients. [ABSTRACT FROM AUTHOR]

Ferroptosis, a new type of non-apoptotic cell death which depends on the iron pathway, plays an important role in cancer therapy. There are various ways to induce ferroptosis, among which radiotherapy is one method, but a single radiotherapy method may also have difficulties in patients' drug resistance and radiation resistance, which will affect the therapeutic effect. In this study, we constructed Fenton reaction anti-cancer iron-carrying nano-carbon-dot liposomes (Fe-CDs-PEG) with CDs as the core, which can enhance sensitivity to radiotherapy by inducing ferroptosis in lung cancer cells. Extracellular Fe-CDs-PEG can catalyze H2O2 to produce hydroxyl radicals (˙OH) and consume glutathione (GSH). After Fe-CDs-PEG enters lung cancer cells, it can lead to the occurrence of excess iron, iron metabolism disorder, GSH consumption, and accumulation of reactive oxygen species (ROS), leading to the accumulation of lipid peroxides on the cell membrane, activating the ferroptosis pathway, to achieve sensitization to radiotherapy. This CD-based tool would provide a new idea for an efficient therapy for lung cancer. [ABSTRACT FROM AUTHOR]

Radioresistance is one of the barriers to developing more effective therapies against the most aggressive, triple-negative, breast cancer (TNBC) subtype. In our previous studies, we showed that inhibition of Polo-like Kinase 4 (PLK4) by a novel drug, CFI-400945 significantly enhances the anticancer effects of radiotherapy (RT) compared to single treatment alone. Here we further investigate the role of PLK4 in enhancing radiation effects in TNBC and explore mechanisms of PLK4 inhibition and radiation combinatorial antiproliferative effects. To assess cellular proliferation in response to treatments, we used colony formation assays in TNBC cell lines and patient-derived organoids (PDOs). Downregulation of PLK4 expression was achieved using siRNA silencing in TNBC cell lines. Immunofluorescence against centrin was used to assess the alteration of centriole amplification in response to treatments. We observed that inhibition of PLK4 by CFI-400945 or Centrinone B or its downregulation by siRNA, when combined with RT, resulted in a significant increase in antiproliferative effect in TNBC cells lines and PDOs compared to untreated or single-treated cells. Anticancer synergy was observed using a response matrix in PDOs treated with CFI-400945 and RT. We show that the overamplification of centrioles might be involved in the combined antiproliferative action of RT and PLK4 inhibition. Our data suggest that PLK4 is a promising target for enhancing the anticancer effects of RT in TNBC that, at least in part, is modulated by the overamplification of centrioles. These results support further mechanistic and translational studies of anti-PLK4 agents and RT as an anticancer combination treatment strategy. [ABSTRACT FROM AUTHOR]

Despite substantial advancements in understanding the pathomechanisms of head and neck squamous cell carcinoma (HNSCC), effective therapy remains challenging. The application of kinase inhibitors (KIs) in HNSCC, specifically mTOR and DNA-PK inhibitors, can increase radiosensitivity and therefore presents a promising strategy when used simultaneously with ionizing radiation (IR) in cancer treatment. Our study focused on the selective DNA-PK-inhibitor AZD7648; the selective mTOR-inhibitor Sapanisertib; and CC-115, a dual inhibitor targeting both mTOR and DNA-PK. The impact of these KIs on HNSCC and normal tissue cells was assessed using various analytical methods including cell death studies, cell cycle analysis, real-time microscopy, colony-forming assays and immunohistochemical staining for γH2AX and downstream mTOR protein p-S6. We detected a strong inhibition of IR-induced DNA double-strand break (DSB) repair, particularly in AZD7648-treated HNSCC, whereas normal tissue cells repaired DNA DSB more efficiently. Additionally, AZD7648 + IR treatment showed a synergistic decline in cell proliferation and clonogenicity, along with an elevated G2/M arrest and cell death in the majority of HNSCC cell lines. CC-115 + IR treatment led to an elevation in G2/M arrest, increased cell death, and a synergistic reduction in cell proliferation, though the effect was notably lower compared to the AZD7648 + IR- treated group. Sapanisertib led to a high cellular toxicity in both HNSCC and normal tissue cells, even in non-irradiated cells. Regarding cell proliferation and the induction of apoptosis and necrosis, Sapanisertib + IR was beneficial only in HPV+ HNSCC. Overall, this study highlights the potential of AZD7648 as a radiosensitizing agent in advanced-stage HPV-positive and negative HNSCC, offering a promising therapeutic strategy. However, the dual mTOR/DNA-PK-I CC-115 did not provide a distinct advantage over the use of selective KIs in our investigations, suggesting limited benefits for its application in KI + IR therapy. Notably, the selective mTOR-inhibitor Sapanisertib was only beneficial in HPV+ HNSCC and should not be applied in HPV− cases. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and hypoxia are associated with radioresistance. The goal of this study is to study the synergy of anti-HER2, trastuzumab, and anti-EGFR, cetuximab, and characterize the tumor microenvironment components that may lead to increased radiation sensitivity with dual anti-HER2/EGFR therapy in head and neck squamous cell carcinoma (HNSCC). Positron emission tomography (PET) imaging ([89Zr]-panitumumab and [89Zr]-pertuzumab) was used to characterize EGFR and HER2 in HNSCC cell line tumors. HNSCC cells were treated with trastuzumab, cetuximab, or combination followed by radiation to assess for viability and radiosensitivity (colony forming assay, immunofluorescence, and flow cytometry). In vivo, [18F]-FMISO-PET imaging was used to quantify changes in oxygenation during treatment. Bliss Test of Synergy was used to identify combination treatment synergy. Quantifying EGFR and HER2 receptor expression revealed a 50% increase in heterogeneity of HER2 relative to EGFR. In vitro, dual trastuzumab-cetuximab therapy shows significant decreases in DNA damage response and increased response to radiation therapy (p < 0.05). In vivo, tumors treated with dual anti-HER2/EGFR demonstrated decreased tumor hypoxia, when compared to single agent therapies. Dual trastuzumab-cetuximab demonstrates synergy and can affect tumor oxygenation in HNSCC. Combination trastuzumab-cetuximab modulates the tumor microenvironment through reductions in tumor hypoxia and induces sustained treatment synergy. [ABSTRACT FROM AUTHOR]

Stress granules (SGs) are cytoplasmic aggregates in which mRNAs and specific proteins are trapped in response to a variety of damaging agents. They participate in the cellular defense mechanisms. Currently, their mechanism of formation in response to ionizing radiation and their role in tumor-cell radiosensitivity remain elusive. The kinetics of SG formation was investigated after the delivery of photon irradiation at different doses to head and neck squamous cell carcinoma cell lines with different radiosensitivities and the HeLa cervical cancer cell line (used as reference). In parallel, the response to a canonical inducer of SGs, sodium arsenite, was also studied. Immunolabeling of SG-specific proteins and mRNA fluorescence in situ hybridization enabled SG detection and quantification. Furthermore, a ribopuromycylation assay was used to assess the cell translational status. To determine whether reactive oxygen species were involved in SG formation, their scavenging or production was induced by pharmacologic pretreatment in both SCC61 and SQ20B cells. Photon irradiation at different doses led to the formation of cytoplasmic foci that were positive for different SG markers. The presence of SGs gradually increased from 30 minutes to 2 hours postexposure in HeLa, SCC61, and Cal60 radiosensitive cells. In turn, the SQ20B and FaDu radioresistant cells did not form SGs. These results indicated a correlation between sensitivity to photon irradiation and SG formation. Moreover, SG formation was significantly reduced by reactive oxygen species scavenging using dimethyl sulfoxide in SCC61 cells, which supported their role in SG formation. However, a reciprocal experiment in SQ20B cells that depleted glutathione using buthionine sulfoximide did not restore SG formation in these cells. SGs are formed in response to irradiation in radiosensitive, but not in radioresistant, head and neck squamous cell carcinoma cells. Interestingly, compared with sodium arsenite–induced SGs, photon-induced SGs exhibited a different morphology and cellular localization. Moreover, photon-induced SGs were not associated with the inhibition of translation; rather, they depended on oxidative stress. [ABSTRACT FROM AUTHOR]

This novel radiolabeled chitosan nanoparticle, facilitated with curcumin, increased doxorubicin cytotoxicity and radiosensitivity to MG-63 osteosarcoma cells in a three-dimensional model. Delivery of the anti-epidermal growth factor receptor (EGFR) targeted carboxymethyl chitosan nanoparticles, directly labeled with Na131I (ICED-N), achieved deep tumor penetration in a three-dimensional model. Of three kinetic models, the Higuchi model more closely matched the experimental curve and release profiles. The anti-EGFR targeting resulted in a 513-fold greater targeting efficacy to MG-63 (EGFR+) cells than the control fibroblast (EGFR−) cells. The curcumin-enhanced ICED-N (4 × 0.925 MBq) fractionated-dose regime achieved an 18.3-fold increase in cell cytotoxicity compared to the single-dose (1 × 3.70 MBq) doxorubicin-loaded nanoparticle, and a 13.6-fold increase in cell cytotoxicity compared to the single-dose Na131I nanoparticle. Moreover, the ICED-N fractionated dose increased cells in the G2/M phase 8.78-fold, indicating the cell cycle arrest in the G2/M phase is associated with DNA fragmentation, and the intracellular damage is unable to be repaired. Overall, the results indicate that the fractionated dose was more efficacious than a single dose, and curcumin substantially increased doxorubicin cytotoxicity and amplified osteosarcoma cell radiosensitivity to Na131I. [ABSTRACT FROM AUTHOR]

This article, published in the Journal of Neurological Surgery, explores the potential use of basal BCL-2-interacting mediator of cell death (BIM) responsiveness as a predictor of radiosensitivity in meningioma. The study used an in vitro model of meningioma to investigate the correlation between BIM-responsiveness and radiosensitivity. The results showed a wide range of radiosensitivities and basal apoptotic sensitivities in the meningioma cells. The study suggests that targeting BCL-XL and MCL-1, which are involved in apoptotic resistance, may enhance radiosensitivity in meningioma. Further research is needed to understand the mechanisms of apoptosis-evasion and radio-resistance in meningioma. [Extracted from the article]

The radiation tolerance of a microcontroller (Raspberry Pi) required for the development of decommissioning robots was investigated. We found that the flash memory needed to boot the microcontroller had particularly low-radiation tolerance, significantly reducing the operation duration of the microcontroller in a radiation environment. We also found that certain high-performance flash memories have high radiation tolerance. Investigation of the process by which flash memory becomes inoperable revealed that internal memory information is rewritten owing to irradiation, leading to limited lifetime for memory. [ABSTRACT FROM AUTHOR]

Localized residual stress and elastic strain concentrations in microelectronic devices often affect the electronic performance, resistance to thermomechanical damage, and, likely, radiation tolerance. A primary challenge for the characterization of these concentrations is that they exist over sub- μ m length-scales, precluding their characterization by more traditional residual stress measurement techniques. Here, we demonstrate the use of synchrotron x-ray-based differential aperture x-ray microscopy (DAXM) as a viable, non-destructive means to characterize these stress and strain concentrations in a depth-resolved manner. DAXM is used to map two-dimensional strain fields between the source and the drain in a gallium nitride (GaN) layer within high electron mobility transistors (HEMTs) with sub- μ m spatial resolution. Strain fields at various positions in both pristine and irradiated HEMT specimens are presented in addition to a preliminary stress analysis to estimate the distribution of various stress components within the GaN layer. γ -irradiation is found to significantly reduce the lattice plane spacing in the GaN along the sample normal direction, which is attributed to radiation damage in transistor components bonded to the GaN during irradiation. [ABSTRACT FROM AUTHOR]

Interstitial atoms usually diffuse much faster than vacancies, which is often the root cause for the ineffective recombination of point defects in metals under irradiation. Here, via ab initio modeling of single-defect diffusion behavior in the equiatomic NiCoCrFe(Pd) alloy, we demonstrate an alloy design strategy that can reduce the diffusivity difference between the two types of point defects. The two diffusivities become almost equal after substituting the NiCoCrFe base alloy with Pd. The underlying mechanism is that Pd, with a much larger atomic size (hence larger compressibility) than the rest of the constituents, not only heightens the activation energy barrier (Ea) for interstitial motion by narrowing the diffusion channels but simultaneously also reduces Ea for vacancies due to less energy penalty required for bond length change between the initial and the saddle states. Our findings have a broad implication that the dynamics of point defects can be manipulated by taking advantage of the atomic size disparity, to facilitate point-defect annihilation that suppresses void formation and swelling, thereby improving radiation tolerance. [ABSTRACT FROM AUTHOR]

Radiation tolerance of semiconductors depends on the dynamic defect annealing efficiency during irradiation. Consequently, it matters at what temperature one keeps the sample during irradiation, so that elevated temperatures typically result in lower remaining disorder. In the present work, we observed an opposite trend for the nitrogen ion implants into zinc oxide. Combining ion channeling technique, x-ray diffraction, and photoluminescence spectroscopy, we demonstrate that the interaction of nitrogen with radiation defects promotes an inverse dynamic annealing process, so that the increase in irradiation temperature leads to a more efficient defect formation. As a result, the residual radiation disorder is maximized at 650 °C and this state is characterized by the appearance of prominent optical signatures associated with zinc interstitials and strongly reduced strain accumulation as compared to the samples implanted at lower temperatures. However, for higher implantation temperatures, the impact of the inverse annealing decreases correlating with the surface degradation and loss of nitrogen. [ABSTRACT FROM AUTHOR]

The presence of the ozone hole increases the amount of UV radiation reaching a plant's surface, and UV-B radiation is an abiotic stress capable of affecting plant growth. Rhododendron chrysanthum Pall. (R. chrysanthum) grows in alpine regions, where strong UV-B radiation is present, and has been able to adapt to strong UV-B radiation over a long period of evolution. We investigated the response of R. chrysanthum leaves to UV-B radiation using widely targeted metabolomics and transcriptomics. Although phytohormones have been studied for many years in plant growth and development and adaptation to environmental stresses, this paper is innovative in terms of the species studied and the methods used. Using unique species and the latest research methods, this paper was able to add information to this topic for the species R. chrysanthum. We treated R. chrysanthum grown in a simulated alpine environment, with group M receiving no UV-B radiation and groups N and Q (externally applied abscisic acid treatment) receiving UV-B radiation for 2 days (8 h per day). The results of the MN group showed significant changes in phenolic acid accumulation and differential expression of genes related to phenolic acid synthesis in leaves of R. chrysanthum after UV-B radiation. We combined transcriptomics and metabolomics data to map the metabolic regulatory network of phenolic acids under UV-B stress in order to investigate the response of such secondary metabolites to stress. L-phenylalanine, L-tyrosine and phenylpyruvic acid contents in R. chrysanthum were significantly increased after UV-B radiation. Simultaneously, the levels of 3-hydroxyphenylacetic acid, 2-phenylethanol, anthranilate, 2-hydroxycinnamic acid, 3-hydroxycinnamic acid, α-hydroxycinnamic acid and 2-hydroxy-3-phenylpropanoic acid in this pathway were elevated in response to UV-B stress. In contrast, the study in the NQ group found that externally applied abscisic acid (ABA) in R. chrysanthum had greater tolerance to UV-B radiation, and phenolic acid accumulation under the influence of ABA also showed greater differences. The contents of 2-phenylethanol, 1-o-p-coumaroyl-β-d-glucose, 2-hydroxy-3-phenylpropanoic acid, 3-(4-hydroxyphenyl)-propionic acid and 3-o-feruloylquinic ac-id-o-glucoside were significantly elevated in R. chrysanthum after external application of ABA to protect against UV-B stress. Taken together, these studies of the three groups indicated that ABA can influence phenolic acid production to promote the response of R. chrysanthum to UV-B stress, which provided a theoretical reference for the study of its complex molecular regulatory mechanism. [ABSTRACT FROM AUTHOR]

Hypoxia-induced radioresistance reduces the efficacy of radiotherapy for solid malignancies, including non-small cell lung cancer (NSCLC). Cellular hypoxia can confer radioresistance through cellular and tumor micro-environment adaptations. Until recently, studies evaluating radioresistance secondary to hypoxia were designed to maintain cellular hypoxia only before and during irradiation, while any handling of post-irradiated cells was carried out in standard oxic conditions due to the unavailability of hypoxia workstations. This limited the possibility of simulating in vivo or clinical conditions in vitro. The presence of molecular oxygen is more important for the radiotoxicity of low-linear energy transfer (LET) radiation (e.g., X-rays) than that of high-LET carbon (12C) ions. The mechanisms responsible for 12C ions' potential to overcome hypoxia-induced radioresistance are currently not fully understood. Therefore, the radioresistance of hypoxic A549 NSCLC cells following exposure to X-rays or 12C ions was investigated along with cell cycle progression and gene expression by maintaining hypoxia before, during and after irradiation. A549 cells were incubated under normoxia (20% O2) or hypoxia (1% O2) for 48 h and then irradiated with X-rays (200 kV) or 12C ions (35 MeV/n, LET ~75 keV/µm). Cell survival was evaluated using colony-forming ability (CFA) assays immediately or 24 h after irradiation (late plating). DNA double-strand breaks (DSBs) were analyzed using γH2AX immunofluorescence microscopy. Cell cycle progression was determined by flow cytometry of 4′,6-diamidino-2-phenylindole-stained cells. The global transcription profile post-irradiation was evaluated by RNA sequencing. When hypoxia was maintained before, during and after irradiation, hypoxia-induced radioresistance was observed only in late plating CFA experiments. The killing efficiency of 12C ions was much higher than that of X-rays. Cell survival under hypoxia was affected more strongly by the timepoint of plating in the case of X-rays compared to 12C ions. Cell cycle arrest following irradiation under hypoxia was less pronounced but more prolonged. DSB induction and resolution following irradiation were not significantly different under normoxia and hypoxia. Gene expression response to irradiation primarily comprised cell cycle regulation for both radiation qualities and oxygen conditions. Several PI3K target genes involved in cell migration and cell motility were differentially upregulated in hypoxic cells. Hypoxia-induced radioresistance may be linked to altered cell cycle response to irradiation and PI3K-mediated changes in cell motility and migration in A549 cells rather than less DNA damage or faster repair. [ABSTRACT FROM AUTHOR]

Objective. FLASH radiotherapy (FLASH-RT) with ultra-high dose rate (UHDR) irradiation (i.e. > 40 Gy s−1) spares the function of normal tissues while preserving antitumor efficacy, known as the FLASH effect. The biological effects after conventional dose rate-radiotherapy (CONV-RT) with ≤0.1 Gy s−1 have been well modeled by considering microdosimetry and DNA repair processes, meanwhile modeling of radiosensitivities under UHDR irradiation is insufficient. Here, we developed an integrated microdosimetric-kinetic (IMK) model for UHDR-irradiation enabling the prediction of surviving fraction after UHDR irradiation. Approach. The IMK model for UHDR-irradiation considers the initial DNA damage yields by the modification of indirect effects under UHDR compared to CONV dose rate. The developed model is based on the linear-quadratic (LQ) nature with the dose and dose square coefficients, considering the reduction of DNA damage yields as a function of dose rate. Main results. The estimate by the developed model could successfully reproduce the in vitro experimental dose–response curve for various cell line types and dose rates. Significance. The developed model would be useful for predicting the biological effects under the UHDR irradiation. [ABSTRACT FROM AUTHOR]

Background: MiRNAs are closely related to tumor radiosensitivity. MiR-378a-5p level is down-regulated in colorectal cancer (CRC). Therefore, this study intends to explore the role of miR-378a-5p in CRC, especially radiosensitivity. Methods: The expression of miR-378a-5p was analyzed in CRC samples. CRC cell lines were treated with different doses of X-rays. Bioinformatics analysis, dual-luciferase reporter assay and RT-qPCR were used to detect the expressions and binding relationship of miR-378a-5p and low-density lipoprotein receptorrelated protein 8 (LRP8). MiR-378a-5p inhibitor or/and siLRP8 were transfected into CRC cells with or without irradiation. Subsequently, clonogenic assay, flow cytometry and in vivo experiments including tumorigenesis assay, immunohistochemistry, RT-qPCR and Western blot were performed to clarify the role of miR-378a-5p/LRP8 axis in the radiosensitivity of CRC. Results: The down-regulated expression of miR-378a-5p in CRC is related to histological differentiation and tumor-node-metastasis (TNM) stage. After irradiation, the survival fraction of CRC cells was decreased, while the apoptotic rate and the level of miR-378a-5p were increased. Restrained miR-378a-5p repressed apoptosis and apoptosis-related protein expressions, yet promoted the proliferation and the radioresistance of cells by regulating ß-catenin in CRC cells. LRP8 was highly expressed in CRC, and targeted by miR-378a-5p. SiLRP8 improved radiosensitivity and reversed the effect of miR-378a-5p downregulation on CRC cells. Overexpressed miR-378a-5p and irradiation enhanced the level of miR-378a-5p, yet suppressed the expressions of Ki67 and LRP8 as well as tumorigenesis. Conclusion: MiR-378a-5p may exert a radiosensitizing effect on CRC through the LRP8/ß-catenin axis, which may be a new therapeutic target for CRC radioresistance. [ABSTRACT FROM AUTHOR]

Radiotherapy has long been a main treatment option for nasopharyngeal carcinoma (NPC). However, during clinical treatment, NPC is prone to developing radioresistance, resulting in treatment failure. This study aims to examine the role of histone methylation in the induction of radioresistance. It was found that the radioresistance of NPC cells was related to the increase of the level of histone H3 lysine 27 trimethylation (H3K27me3). Treatment of cells with histone methyltransferase inhibitor GSK126 increased the radiosensitivity of NPC cells by triggering Bcl2 apoptosis regulator/BCL2-associated X, apoptosis regulator (Bcl2/BAX) signaling pathway. Bioinformatics analysis indicated that the expression of 20-50-oligoadenylate synthetase 1 (OAS1) was reduced in the radioresistant cells but increased in the GSK126-treated cells. Chromatin immunoprecipitation assay confirmed that the decrease of OAS1 expression in radioresistant cells was mainly due to the enrichment of H3K27me3 in its promoter region. Furthermore, downregulation of OAS1 reduced apoptosis due to the inhibition of Bcl2/BAX pathway after irradiation, while OAS1 overexpression increased radiosensitivity. Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, the histone methyltransferase inhibitor GSK126 could overcome the radioresistance and thus might be a potential therapeutic strategy for NPC. NEW & NOTEWORTHY: Our findings revealed for the first time that the increase of H3K27me3 level was associated with the decrease of OAS1 expression, leading to the inhibition of apoptosis and ultimately contributing to the radioresistance of NPC cells. Moreover, we demonstrated that the histone methyltransferase inhibitor GSK126 could be a promising therapeutic strategy for NPC by overcoming radioresistance, providing valuable insights into the clinical treatment of NPC. [ABSTRACT FROM AUTHOR]

Tardigrada is an ecdysozoan lineage famed for its resilience. Tardigrades can tolerate high doses of radiation, low-oxygen environments, desiccation, and both high and low temperatures under a dormant state called "anhydrobiosis", which is a reversible halt of metabolism upon almost complete desiccation. A large amount of research has focused on the genetic pathways related to these capabilities, and a number of genes have been identified and linked to the extremotolerant response of tardigrades. However, the history of these genes is unclear, and the origins and history of extremotolerant genes within Tardigrada remain a mystery. Here, we generate the first phylogenies of six separate protein families linked with desiccation and radiation tolerance in Tardigrada: cytosolic abundant heat-soluble protein, mitochondrial abundant heat-soluble protein, secretory abundant heat-soluble protein, meiotic recombination 11 homolog, and the newly discovered Echiniscus testudo abundant heat-soluble proteins (alpha and beta). The high number of independent gene duplications found amongst the six gene families studied suggests that tardigrades have a complex history with numerous independent adaptations to cope with aridity within the limnoterrestrial environment. Our results suggest that tardigrades likely transitioned from a marine environment to a limnoterrestrial environment only twice, once in stem Eutardigrada and once in Heterotardigrada, which explains the unique adaptations to anhydrobiosis present in both classes. [ABSTRACT FROM AUTHOR]

Objective: Non‐small cell lung cancer (NSCLC) occupies 85% of lung cancer. Long non‐coding RNAs (LncRNAs) can regulate the radiosensitivity of cancers. This study explored the mechanism of lncRNA TRERNA1 in the radiosensitivity of NSCLC cells. Methods: LncRNA TRERNA1 level in NSCLC cell lines was determined. NSCLC cell radiation tolerance was measured. TRERNA1 expression was silenced or overexpressed in A549/HCC827 cells with the highest/lowest radiation tolerance, respectively. The contents of γ‐H2AX and SA‐β‐gal in NSCLC cells after radiation induction were detected. The targeted binding of TRERNA1 to miR‐22‐3p and miR‐22‐3p to SP1 were verified by dual‐luciferase assay. SP1 expression were detected. Functional rescue experiments were implemented to confirm the roles of miR‐22‐3p and SP1 in the regulatory mechanism of TRERNA1. Results: TRERNA1 was upregulated in NSCLC cells. TRERNA1 silencing enhanced radiosensitivity of NSCLC cells. TRERNA1 silencing elevated the contents of γ‐H2AX and SA‐β‐gal in A549 cells after radiation induction, while TRERNA1 overexpression showed an opposite trend in HCC827 cells. There were targeting relationships between TRERNA1 and miR‐22‐3p, and miR‐22‐3p and SP1. miR‐22‐3p repression or SP1 overexpression abolished the effects of TRERNA1 silencing. Conclusion: TRERNA1 silencing enhanced radiosensitivity of NSCLC cells via the miR‐22‐3p/SP1 axis. This study may offer new targets for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Tissue radiosensitivity plays a critical role in the overall outcome of radiation therapy. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data have suggested a difference in male and female radiotherapy outcomes. Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity. In this manuscript, we demonstrated sex-specific differences in intestinal epithelial radiosensitivity. In a mouse model of abdominal irradiation, we observed a significant increase in oxidative stress and injury in males compared to females. Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation-induced toxicity. However, sex-specific differences in intestinal radiosensitivity were not dependent on sex hormones, as we demonstrated similar sex-specific radiosensitivity differences in pre-pubescent mice. In an ex vivo study, we found that patient-derived intestinal organoid (PID) from males showed higher sensitivity to radiation compared to females as evident from loss of budding crypts, organoid size, and membrane integrity. Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation-induced upregulation of mitochondrial oxidative metabolism in males compared to females, a possible mechanism for radiosensitivity differences. [ABSTRACT FROM AUTHOR]

Background: Cancer is a highly heterogeneous disease, driven by frequent genetic alterations which have significant effects on radiosensitivity. However, radiotherapy for a given cancer type is typically given with a standard dose determined from population‐level trials. As a result, a proportion of patients are under‐ or over‐dosed, reducing the clinical benefit of radiotherapy. Biological optimization would not only allow individual dose prescription but also a more efficient allocation of limited resources, such as proton and carbon ion therapy. Proton and ion radiotherapy offer an advantage over photons due to their elevated Relative Biological Effectiveness (RBE) resulting from their elevated Linear Energy Transfer (LET). Despite significant interest in optimizing LET by tailoring radiotherapy plans, RBE's genetic dependence remains unclear. Purpose: The aim of this study is to better define the RBE/LET relationship in a panel of cell lines with different defects in DSB repair pathways, but otherwise identical biological features and genetic background to isolate these effects. Methods: Normal human cells (RPE1), genetically modified to introduce defects in DNA double‐strand break (DSB) repair genes, ATM, BRCA1, DCLRE1C, LIG4, PRKDC and TP53, were used to map the RBE‐LET relationship. Cell survival was measured with clonogenic assays after exposure to photons, protons (LET 1 and 12 keV/µm) and alpha particles (129 keV/µm). Gene knockout sensitizer enhancement ratio (SER) values were calculated as the ratio of the mean inactivation dose (MID) of wild‐type cells to repair‐deficient cells, and RBE values were calculated as the ratio of the MID of X‐ray and particle irradiated cells. 53BP1 foci were used to quantify radiation‐induced DSBs and their repair following irradiation. Results: Deletion of NHEJ genes had the greatest impact on photon sensitivity (ATM−/− SER = 2.0 and Lig4−/− SER = 1.8), with genes associated with HR having smaller effects (BRCA1−/− SER = 1.2). Wild‐type cells showed RBEs of 1.1, 1.3, 5.0 for low‐ and high‐LET protons and alpha particles respectively. SERs for different genes were independent of LET, apart from NHEJ knockouts which proved to be markedly hypersensitive across all tested LETs. Due to this hypersensitivity, the impact of high LET was reduced in cell models lacking the NHEJ repair pathway. HR‐defective cells had moderately increased sensitivity across all tested LETs, but, notably, the contribution of HR pathway to survival appeared independent of LET. Analysis of 53BP1 foci shows that NHEJ‐defective cells had the least DSB repair capacity after low LET exposure, and no visible repair after high LET exposure. HR‐defective cells also had slower repair kinetics, but the impact of HR defects is not as severe as NHEJ defects. Conclusions: DSB repair defects, particularly in NHEJ, conferred significant radiosensitivity across all LETs. This sensitization appeared independent of LET, suggesting that the contribution of different DNA repair pathways to survival does not depend on radiation quality. [ABSTRACT FROM AUTHOR]

Background: Ultra‐high dose rate (FLASH) radiation has been reported to efficiently suppress tumor growth while sparing normal tissue; however, the mechanism of the differential tissue sparing effect is still not known. Oxygen has long been known to profoundly impact radiobiological responses, and radiolytic oxygen depletion has been considered to be a possible cause or contributor to the FLASH phenomenon. Purpose: This work investigates the impact of tissue pO2 profiles, oxygen depletion per unit dose (g), and the oxygen concentration yielding half‐maximum radiosensitization (the average of its maximum value and one) (k) in tumor and normal tissue. Methods: We developed a model that considers the dependent relationship between oxygen depletion and change of radiosensitivity by FLASH irradiation. The model assumed that FLASH irradiation depletes intracellular oxygen more rapidly than it diffuses into the cell from the extracellular environment. Cell survival was calculated based on the linear quadratic‐linear model and the radiosensitivity related parameters were adjusted in 1 Gy increments of the administered dose. The model reproduced published experimental data that were obtained with different cell lines and oxygen concentrations, and was used to analyze the impact of parameter uncertainties on the radiobiological responses. This study expands the oxygen depletion analysis of FLASH to normal human tissue and tumor based on clinically determined aggregate and individual patient pO2 profiles. Results: The results show that the pO2 profile is the most essential factor that affects biological response and analyses based on the median pO2 rather than the full pO2 profile can be unreliable and misleading. Additionally, the presence of a small fraction of cells on the threshold of radiobiologic hypoxia substantially alters biological response due to FLASH oxygen depletion. We found that an increment in the k value is generally more protective of tumor than normal tissue due to a higher frequency of lower pO2 values in tumors. Variation in the g value affects the dose at which oxygen depletion impacts response, but does not alter the dose‐dependent response trends, if the g value is identical in both tumor and normal tissue. Conclusions: The therapeutic efficacy of FLASH oxygen depletion is likely patient and tissue‐dependent. For breast cancer, FLASH is beneficial in a minority of cases; however, in a subset of well oxygenated tumors, a therapeutic gain may be realized due to induced normal tissue hypoxia. [ABSTRACT FROM AUTHOR]

This article discusses the surgical technique of extradural anterior clinoidectomy for the resection of clinoidal meningiomas (CMs). CMs are challenging tumors due to their involvement of neurovascular structures and their growth into the optic canal and cavernous sinus. The article presents a case study of a 45-year-old patient who underwent the procedure, detailing the surgical steps and outcomes. The authors argue that the skull-base approach with clinoidectomy allows for better tumor devascularization, control of neurovascular structures, and oncological control. However, they acknowledge that this approach is technically demanding and has a steep learning curve. [Extracted from the article]