Radiation Damage Research Articles

Hyper-fractionated radiotherapy as a bridging strategy to enhance CAR-T efficacy by regulating T-cell co-stimulatory molecules in relapsed/refractory diffuse large B-cell lymphoma

BackgroundBridging therapy can prevent patients from disease progression while waiting for CAR-T cell preparation. Hyper-fractionated radiotherapy can achieve an effective target dose within a short period, minimize radiation damage, and may modify immune environment compared to conventional radiotherapy.AimsThis study aims to investigate the efficacy and safety of bridging hyper-fractionated radiotherapy in combination with CAR-T therapy for relapsed/refractory diffuse large B-cell lymphoma. The potential mechanisms were explored.MethodsThis is a prospective pilot study. After T-cell collection, the patients underwent hyper-fractionated radiotherapy at lesion sites with 1.5 Gy twice daily for 10 days before CAR-T cell infusion. Peripheral blood immune cell subsets and quantitative serum proteomics were assessed before radiotherapy and after radiotherapy before CAR-T cell infusion.ResultsA total of 13 patients have been enrolled. The median follow-up time was 6 (3–24) months after CAR-T infusion. At 3-month follow-up, 9/13(69%) patients had CR, 1/13(8%) patient had PR, 1/13(8%) patient remained SD, and 2/13(15%) patients died of disease progression. The local recurrence rate was 1/13(8%). Seven patients have been followed up for more than 6 months, and they remain in CR. The median PFS and OS were not reached. No grade 3–4 CRS or ICANS were reported. After hyper-fractionated radiotherapy, peripheral PD1+CD8+T/T ratio significantly decreased while quantitative serum proteomics profiling showed a decrease in sCD28.ConclusionHyper-fractionated radiotherapy can rapidly control tumor progression sites without delaying the infusion time. This approach can improve the ORR and does not increase the incidence of CRS and ICANS. The mechanism may be related to the regulation of T-cell co-stimulatory molecules, which demands further exploration.

A novel small molecule Enpp1 inhibitor improves tumor control following radiation therapy by targeting stromal Enpp1 expression

The uniqueness in each person’s cancer cells and variation in immune infiltrates means that each tumor represents a unique problem, but therapeutic targets can be found among their shared features. Radiation therapy alters the interaction between the cancer cells and the stroma through release of innate adjuvants. The extranuclear DNA that can result from radiation damage of cells can result in production of the second messenger cyclic guanosine monophosphate–adenosine monophosphate (cGAMP) by cyclic GMP-AMP synthase (cGAS). In turn, cGAMP can activate the innate sensor stimulator of interferon genes (STING), resulting in innate immune activation. Ectonucleotide pyrophosphatase/phosphodiesterase 1 (Enpp1) is a phosphodiesterase that can be expressed by cancer cells that can degrade cGAMP, thus can decrease or block STING activation following radiation therapy, impairing the innate immunity that is critical to support adaptive immune control of tumors. We observed that many human and murine cancer cells lack Enpp1 expression, but that Enpp1 is expressed in cells of the tumor stroma where it limits tumor control by radiation therapy. We demonstrate in preclinical models the efficacy of a novel Enpp1 inhibitor and show that this inhibitor improves tumor control by radiation even where the cancer cells lack Enpp1. This mechanism requires STING and type I interferon (IFN) receptor expression by non-cancer cells and is dependent on CD8 T cells as a final effector mechanism of tumor control. This suggests that Enpp1 inhibition may be an effective partner for radiation therapy regardless of whether cancer cells express Enpp1. This broadens the potential patient base for whom Enpp1 inhibitors can be applied to improve innate immune responses following radiation therapy.

Optimizing ex vivo penetration tests via quantitative confocal Raman spectroscopy: Impact of incubation time, skin hydration, surfactant treatment and UVA irradiation on caffeine distribution

Ex vivo penetration tests are important tools in cosmetic and pharmaceutical research. However, variability of experimental setups is challenging when reviewing literature. Different skin models, pre-treatments and experimental parameters render comparison difficult. Thus, our aim was to conduct ex vivo penetration tests using caffeine in different setups with varying incubation conditions (ambient vs. Franz cells, infinite vs. finite dose). Additionally, the impact of skin pre-treatment with different aggressors (surfactants, UVA irradiation) should be considered. Possible synergistic barrier damage of surfactants and UVA irradiation should be explored. Analysis was conducted using quantitative confocal Raman spectroscopy. Results showed that incubation time and extensive hydration (20 h in Franz cells) had the greatest impact on penetration behavior. Additional irradiation after pre-treatment with oil-in-water nanoemulsions showed no strong impact on caffeine penetration in general, irrespective of surfactant type. However, in case of sodium lauryl ether sulfate, a trend towards enhanced values was observed due to irradiation (1.3-fold). This suggests cumulative skin barrier damage of irritant surfactants and UVA irradiation, potentially due to stratum corneum alterations. Further studies using different irradiation regimens are planned to confirm this hypothesis.

Corrigendum to “X-Ray Diffraction Line Broadening and Radiation Damage” [Materialia 27C (2023) 101704

Corrigendum to “X-Ray Diffraction Line Broadening and Radiation Damage” [Materialia 27C (2023) 101704

Systematic study of displacement threshold and the near-threshold primary radiation damage model

Radiation damage is a critical concern for materials employed in radiation environments such as space, radiotherapy centers, and nuclear energy systems. Numerous models have been developed to estimate the primary radiation damage. The slightly modified Athermal Recombination-Corrected (mARC)-Displacement per Atom (DPA) model proposes a simple function to describe the atomic displacement near the Threshold Displacement Energy (TDE). The present work systematically investigates the global minimum TDE and the near-TDE mARC-DPA model against experimental electron irradiation damage data for 26 materials. The determined high-accuracy global minimum TDE values are generally consistent with previous studies. The corresponding theoretical calculations agree well with experimental measurements, implying the applicability of the mARC model. Renormalization of certain experimental data is required due to the potential issues related to experimental measurements, the value of resistivity change per Frenkel pair (ρFP), or average TDE (Ed). Nevertheless, while some experimental data are supposed to be adjusted, the analysis shows that the ratio of ρFP/Ed can be definitively determined if assuming the experimental data for the remainders.

Molecular dynamic simulations of displacement cascades in Molybdenum and Molybdenum-Rhenium alloys

Molybdenum-Rhenium (Mo-Re) alloys are considered core materials for advanced nuclear reactor components due to their excellent mechanical properties, machinability, and resistance to irradiation damage. However, irradiation-induced embrittlement and phase precipitation at high temperatures, along with transmutation nuclides, have hindered their broader application. To address this, we developed a Mo-Re interatomic potential using the Finnis-Sinclair formalism, facilitating molecular dynamics simulations to study primary irradiation damage. Systemically primary irradiation damage simulations for Mo and Mo-Re alloys have been performed. It’s found that there were more Frenkel-pair defects produced during the stage of thermal spike in Mo-Re alloys but fewer defects survived at the end of the cascade compared to Mo. In addition, the number of large-size interstitial clusters and dislocation loops was higher in Mo-Re alloys than in pure Mo with the same PKA energy. This is mainly attributed to the fact that Mo-Re alloys have lower thermal conductivity, while the binding energies of interstitial clusters and dislocation loops with sizes less than 100 in Mo-Re alloys are comparable to those of pure Mo, resulting in higher defect composites and larger defect sizes in Mo-Re alloys. These findings provide valuable insights into the primary damage mechanisms in Mo-Re alloys under irradiation, offering a foundation for developing kinetic models to simulate radiation-induced microstructural evolution.

A Brief Review of the Impact of Neutron Irradiation Damage in Tungsten and Its Alloys

Neutron irradiation poses a substantial challenge in the development and application of tungsten (W) and its alloys, predominantly in the framework of nuclear fusion and fission environments. Although W is well-acknowledged for its unique properties like its high melting temperature and higher resistance to sputtering, transmutation products, such as Re and Os, form and impact the alloy properties as a result of neutron irradiation. This transmutation effect accompanied by significant microstructure damage due to neutron irradiation can lead to the significant degradation of mechanical properties. This review surveys the literature focusing on the microstructural modifications post-irradiation and its impacts on the irradiation hardening. This review provides insights into the elaborative understanding on the neutron radiation damage on W and W alloys by exploring the microstructural evolution and hardness changes post-irradiation. The gaps and future opportunities for understanding neutron radiation damage in W are briefly summarized

Observation of biological and emulsion samples by newly developed three-dimensional impedance scanning electron microscopy

Imaging at nanometre-scale resolution is indispensable for many scientific fields such as biology, chemistry, material science and nanotechnology. Scanning electron microscopes (SEM) are widely used as important tools for the nanometre-scale analysis of various samples. However, because of the vacuum inside the SEM, a typical analysis requires fixation of samples, a drying process, and staining with heavy metals. Therefore, there is a need for convenient and minimally invasive methods of observing samples in solution. Recently, we have developed a new type of impedance microscopy, multi-frequency impedance SEM (IP-SEM), which allows nanoscale imaging of various specimens in water with minimal radiation damage. Here, we report a new IP-SEM system equipped with a linear-array terminal, which allows eight tilted images to be observed in a single capture by applying eight frequencies of input signals to each electrode. Furthermore, we developed a three-dimensional (3D) reconstruction method based on the Simulated Annealing (SA) algorithm, which enables us to construct a high-precision 3D model from the 8 tilted images. The method reported here can be easily used for 3D structural analysis of various biological samples, organic materials, and nanoparticles.

Atomistic simulation of chemical short-range order on the irradiation resistance of HfNbTaTiZr high entropy alloy

High entropy alloys (HEAs) have been considered as one of the potential structural material candidates for fourth-generation nuclear reactors and fusion reactors due to their excellent irradiation resistance. Current studies have shown that the chemical short-range order (CSRO) usually exists in HEAs, which has a significant effect on the mechanical properties and irradiation resistance of HEAs. Refractory high entropy alloys (RHEAs), as a new class of HEAs have better mechanical properties at high temperatures than face-centered cubic (FCC) HEAs, and therefore have better prospects of application in the nuclear field. In this study, CSRO and its effect on the irradiation resistance of HfNbTaTiZr are analyzed via molecular dynamics (MD) and Monte Carlo (MC). The primary cascade simulations, multi-cascade simulations and surface bombardment simulations are carried out to simulate the generation and accumulation of irradiation damage. The results of the primary cascade simulations and surface bombardment simulations of CSRO models show that the presence of CSRO induces cascade splitting into subcascades. The presence of subcascades reduces the thermal peak enhancement effect and thus lowers the recombination rate of Frenkel pairs (FPs) in the damage zone when FPs concentrations are low. However, the creation of subcascades increases the size of the damage zone caused by the cascade. Thus, when the concentrations of FPs are high, the larger area of damage zone allows more of the already existing FPs to be included, thus promoting their recombination, i.e., impedes their accumulation when concentrations are high. These subcascades lower the recombination of FPs at low FPs concentrations but inhibit their accumulation at high FPs concentrations. The presence of CSRO is also beneficial in inhibiting the growth of point defect clusters, which further improves the resistance of HfNbTaTiZr to dislocation generation. Furthermore, the presence of CSRO facilitates the irradiation-induced phase transition. But it is found that HfNbTaTiZr shows suppression of HCP cluster growth. And the tendency to break down large HCP clusters into smaller ones is demonstrated in the CSRO model. From our calculations we also find that the irradiation-induced HCP atoms have a higher potential energy relative to the matrix. The potential energy difference between those energetic HCP atoms and the matrix can lead to generating a great number of insurmountable barriers pervading the matrix and largely suppressing the long-term mobility of FPs, thus limiting their aggregation and growth into clusters.

Therapeutic Potential of Hydrogen as a Radioprotective Agent for the Prevention of Radiation Dermatitis

Radiation dermatitis (RD) is a common side effect in patients receiving radiotherapy. Currently, clinical skincare approaches for acute RD vary widely among institutions and lack consensus. Hydrogen molecules, acting as radioprotective agents by selectively scavenging free radicals, have the potential to protect against RD. In this study, we demonstrate that hydrogen reduces double-strand breaks, mitochondrial depolarization, and inflammatory cytokines induced by irradiation damage in HaCaT cells. Furthermore, in vivo experiments reveal that exposing irradiated skin areas to a hydrogen gas environment alleviates RD. Assessment of skin appearance grade and histology staining revealed that direct transdermal application of hydrogen can prevent radiation-induced follicle damage, dermal thickening, and leukocyte infiltration, thereby reducing the severity of RD. In addition, hydrogen enhances the skin’s antioxidant capacity, leading to a reduction in the Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) ratio, the number of apoptotic cells, and the expression of pro-inflammatory cytokines. Our data demonstrate that hydrogen possesses antioxidant, anti-inflammatory, and anti-apoptotic properties, and could be a preventive strategy for RD.

Proton radiation damage and temperature response mechanism of CMOS image sensor for space high-precision metering

The exoplanet transit telescope uses high-precision CMOS image sensor for planet searching. This device operates at 233 K to reduce dark current and noise interference on the effective signal. This paper examines the effects of space proton radiation on the performance of high-precision CMOS image sensor through proton irradiation and post-irradiation testing at various temperatures. The results indicate that proton irradiation degrades parameters like dark current, dark signal, and fixed pattern noise, with dark current being the most sensitive. As the operating temperature increases, radiation-sensitive parameters degrade rapidly, significantly impairing sensor performance. This indicates that lower temperatures provide better performance. Notably, Dark signal distribution fluctuates with temperature. Compared to before irradiation, the Gaussian mean decreases at 233 K and increases between 243 and 273 K. At low temperature, the ionization damage caused by proton radiation mainly results in the decrease of Gaussian mean, while the displacement damage mainly results in the increase of this. The study concludes that proton-induced displacement damage, which leads to bulk defects, is the primary cause of performance degradation. This provides essential data and foundational support for radiation damage assessment and on-orbit applications.

Diminished Role of Grain Boundaries in Mitigating Irradiation Damage in Multi-Principal Element Alloys

Diminished Role of Grain Boundaries in Mitigating Irradiation Damage in Multi-Principal Element Alloys

General-purpose machine-learned potential for 16 elemental metals and their alloys

Machine-learned potentials (MLPs) have exhibited remarkable accuracy, yet the lack of general-purpose MLPs for a broad spectrum of elements and their alloys limits their applicability. Here, we present a promising approach for constructing a unified general-purpose MLP for numerous elements, demonstrated through a model (UNEP-v1) for 16 elemental metals and their alloys. To achieve a complete representation of the chemical space, we show, via principal component analysis and diverse test datasets, that employing one-component and two-component systems suffices. Our unified UNEP-v1 model exhibits superior performance across various physical properties compared to a widely used embedded-atom method potential, while maintaining remarkable efficiency. We demonstrate our approach’s effectiveness through reproducing experimentally observed chemical order and stable phases, and large-scale simulations of plasticity and primary radiation damage in MoTaVW alloys.

Effect of the surrounding environment on electron beam irradiation damage of enhanced green fluorescent protein

Fluorescent proteins exhibit fluorescence and photoconversion, which are used to study biological phenomena. Among these, enhanced green fluorescent protein (EGFP) emits cathodoluminescence when irradiated with electron beams; this phenomenon has numerous applications in new research tools for biological phenomena. However, bleaching during electron irradiation is a major problem. Generally, the presence of water is important for biological samples, and structural observations are often performed under cryogenic conditions. One of the advantages of cryogenic conditions is the stabilization of the sample due to cooling. However, it is unclear which factor is more effective: the presence of water molecules or cryogenic preservation. To explore the stabilizing factors of the sample structure, we prepared four environments around the sample–dry at room temperature, wet at room temperature, dry at low temperature, and under cryogenic conditions–and investigated the electron beam irradiation damage by measuring the fluorescence emission spectra. Emission intensity from EGFP was attenuated, and the peak was red-shifted by electron beam irradiation; however, the intensity attenuation was fast under dry conditions at low temperature and slow under wet conditions at room temperature. These results imply that sample cooling has no significant effect on the stability of the EGFP chromophore and that the presence of water molecules is extremely important.

Persistent luminescent nanoprobes with dual effect radiosensitization for precise radiotherapy

Radiotherapy (RT) is a common modality in the clinical management of breast cancer. However, the radiation damage to healthy tissues caused by the high-dose radiation and the limited therapeutic efficacy with DNA damage repair pose significant challenges in RT. In this work, an intelligent responsive nanoplatform with dual effect radiosensitization (mZGSSM-AMD) has been developed to improve the efficacy of RT. The doping of Lu promotes the generation of reactive oxygen species (ROS) under X-ray irradiation, thereby facilitating DNA breakage. To hinder the repair of damaged DNA, NO is loaded into mZGSSM-AMD, enhancing damage of tumor during radiotherapy. Furthermore, persistent luminescence (PersL) recovers with the degradation of MnO2 in tumor microenvironment (TME), which guides precision radiosensitization of tumors. Experimental results indicate that growth of tumors is significantly suppressed by effective radiosensitization of mZGSSM-AMD. The mZGSSM-AMD with dual effect radiosensitization exhibits exceptional antitumor effectiveness, providing promising application prospects for the imaging-guided precise radiosensitization therapy.

Side effects and complications of high dose-rate brachytherapy: literature review and our own observations

Background. Among malignant tumors in men in Russia, prostate cancer is the most common comprising 17 %. Despite the high effectiveness of radiotherapy for prostate cancer in about 20 % of patients, radiation damage of the pelvic organs develops affecting bladder, rectum, and intrapelvic cellular tissue.Aim. To evaluate early and late complications of high dose-rate brachytherapy.Materials and methods. Literature review was performed, and our own results of treatment of 276 patients using high dose-rate brachytherapy as monotherapy with different fractionation regimens: 19 Gy per 1 fraction and 15 Gy per 2 fractions were analyzed.Results. High dose-rate brachytherapy as monotherapy is associated with low complication rate. There were no statistically significant differences between singleand two-fraction regimens. Evaluation of complication severity per the RTOG (Radiation Therapy Oncology Group) classification did not show complication severity above grade III. Early complications were diagnosed in 1.1 %, late in 3.3 % of cases. Between the treatment and comparison groups, no statistically significant differences in the frequency of urinary system organ symptoms per the IPSS (International Prostate Symptom Score) questionnaire were registered. Mean score per the IPSS prior to treatment was 4.0 (3.0–6.0) in the treatment group and 4.0 (3.0–8.5) in the comparison group. Mean follow-up duration in the treatment group was 65.0 (60.0–70.0) months, in the comparison group – 55.0 (49.5–65.0) months. After the treatment, mean IPSS score was 5.0 (4.0–5.0) in the treatment group and 5.0 (3.0–7.0) in the comparison group.Conclusion. High dose-rate brachytherapy as monotherapy and in combination with external beam therapy is a safe and effective treatment method in prostate cancer. Serious and late complications are rare, however toxic effects of severity grades I or II can develop. Careful patient selection for brachytherapy, therapy planning methods, as well as active management of early and late toxicity by a multidisciplinary team with knowledge and experience in treatment of side effects of radiotherapy can help optimize treatment with high dose-rate brachytherapy.

Simulation of displacement damage in Si & SiO2 caused by protons

Nowadays Si & SiO2 have been the most widely used materials in semiconductor devices as CPU and other various integrated circuit chips, utilized in aerospace electronic systems, and at the same time protons are important components of cosmic rays that can cause displacement damage in Si & SiO2. Therefore, it is essential to study the displacement damage of Si & SiO2 caused by protons. The software of Geant4 is adopted in this paper, to simulate transportation process of incident protons with different energy in Si & SiO2. The simulation results indicates that primary knock-on atom (PKA) generated by incident proton in Si & SiO2 is predominant in lower energy range, its spatial distribution increases gradually along the direction of incident proton, and the scattering angle of the PKA is about 90°, following a Gaussian distribution approximately. And in lower energy range, 28Si and 16O generated by elastic scattering are a primary source of radiation damage in Si & SiO2. But as the proton energy increases, the contribution of nuclear inelastic scattering becomes more and more important, but the overall level of induced damage diminishes gradually. Meanwhile, the simulation results indicate that with increasing depth of the material, the non-ionizing energy loss (NIEL) increases gradually, and NIEL caused by elastic scattering is higher near the surface layer of the materials, and as for NIEL caused by nuclear inelastic scattering is also higher near the surface layer of the materials. The simulation results in this paper can provide useful data and theoretical guidance for study on Si & SiO2 displacement damage caused by proton irradiation.

Nanoscale Mixed-Ligand Metal-Organic Framework for X-ray Stimulated Cancer Therapy.

Concurrent localized radiotherapy and systemic chemotherapy are standards of care for many cancers, but these treatment regimens cause severe adverse effects in many patients. Herein, we report the design of a mixed-ligand nanoscale metal-organic framework (nMOF) with the ability to simultaneously enhance radiotherapeutic effects and trigger the release of a potent chemotherapeutic under X-ray irradiation. We synthesized a new functional quaterphenyl dicarboxylate ligand conjugated with SN38 (H2QP-SN) via a hydroxyl radical-responsive covalent linkage. Because of the similar length of QP-SN and bis(p-benzoato)porphyrin (DBP) ligands, QP-SN was incorporated into Hf-DBP nMOF to afford a novel multifunctional mixed-ligand Hf-DBP-QP-SN nMOF with good biocompatibility. Hf-DBP-QP-SN not only enhances radiation damage to tumors via a unique radiotherapy-radiodynamic therapy (RT-RDT) process but also increases ·OH generation from radiolysis with electron-dense Hf12 secondary building units (SBUs) to release SN38 from Hf-DBP-QP-SN for chemotherapy. Elevated levels of hydrogen peroxide in the tumor microenvironment further stimulate the release of SN38 by enhancing ·OH generation under X-ray irradiation. With low doses of X-ray irradiation, Hf-DBP-QP-SN suppressed the growth of CT26 colon and 4T1 breast tumors by 93.5% and 95.2%, respectively, without any sign of general toxicity. Our study highlights the potential of using ionizing radiation-mediated chemistry for on-demand activation of nanotherapeutics for synergistic radiotherapy and chemotherapy without causing severe adverse effects.

Characterisation of 3D trench silicon pixel sensors irradiated at 1⋅1017 1 MeV neqcm-2

The 3D trench silicon pixel sensors developed by the TimeSPOT collaboration have demonstrated exceptional performance, even after exposure to extreme radiation fluences up to 1⋅1017 1 MeV neq/cm2. This study assesses the radiation tolerance of these sensors using minimum ionizing particles during a beam test campaign. The results indicate that while radiation damage reduces charge collection efficiency and overall detection efficiency, these losses can be mitigated to levels comparable to non-irradiated sensors by increasing the reverse bias voltage. Charge multiplication was observed and characterised for the first time in 3D trench sensors, revealing a distinct operating regime post-irradiation achievable at bias voltages close to 300 V. Additionally, the timing performance of irradiated sensors remains comparable to their non-irradiated counterparts, underscoring their resilience to radiation damage. Currently, 3D trench silicon detectors are among the fastest and most radiation-hard pixel sensors available for vertex detectors in high-energy physics colliders. These findings highlight the potential of these sensors for new 4D tracking systems of future experiments at the Future Circular Hadron Collider (FCC-hh), advancing the capabilities of radiation-hard sensor technology.

Alloying element Ag modifies the behavior of H and defects in Pd alloys

Although alloying can significantly increase the hydrogen permeability of palladium (Pd) and solve the problem of hydrogen embrittlement in service, the intrinsic mechanism has not been revealed. Here, we report intuitive differences in the nucleation, growth and distribution of dislocation loops in Pd and PdAg alloys by in-situ hydrogen irradiation in TEM. The results reveal that alloying element Ag not only modifies the behavior of H, but also induces defects to change from the original long-range one-dimensional (1D) diffusion to short-range three-dimensional (3D) diffusion, which significantly delays the aggregation and growth of dislocation loops and reduces the total irradiation damage and H retention. A new strategy to improve hydrogen embrittlement resistance is proposed, i.e., constructing dense dislocation loop bands (or other sinks that can efficiently trap H) in front of grain boundaries to prevent H from diffusing into the grain boundaries.