Radiation Resistance Research Articles

SPIN1 accelerates tumorigenesis and confers radioresistance in non-small cell lung cancer by orchestrating the FOXO3a/FOXM1 axis.

Despite the importance of radiation therapy as a nonsurgical treatment for non-small cell lung cancer (NSCLC), radiation resistance has always been a concern because of poor patient response and outcomes. Therefore, it is crucial to identify novel targets to increase the effectiveness of radiotherapy and investigate the mechanisms underlying radioresistance. Previously, we demonstrated that Spindlin 1 (SPIN1) was related to tumour initiation and progression. In this study, we found that SPIN1 expression was higher in NSCLC tissues and cell lines than in the corresponding controls. SPIN1 overexpression in NSCLC patients was closely correlated with disease progression and poor prognosis. Functionally, SPIN1 depletion inhibited cell proliferation, decreased the percentage of cells in the G2/M phase and suppressed cell migration and invasion. Moreover, SPIN1 knockdown decreased the clonogenic capacity, impaired double-strand break (DSB) repair and increased NSCLC radiosensitivity. Mechanistically, forkhead box M1 (FOXM1) was identified as a key downstream effector of SPIN1 in NSCLC cells. Furthermore, SPIN1 was found to facilitate MDM2-mediated FOXO3a ubiquitination and degradation, leading to FOXM1 upregulation. Moreover, restoration of FOXM1 expression markedly abolished the inhibitory effects and increased radiosensitivity induced by SPIN1 depletion. These results indicate that the SPIN1-MDM2-FOXO3a/FOXM1 signalling axis is essential for NSCLC progression and radioresistance and could serve as a therapeutic target for increasing radiotherapy efficacy.

Long-term outcomes and prognostic factors of short-course radiotherapy (SCRT) in rectal cancer: a monocentric retrospective study.

To evaluate efficacy and tolerance of short-course radiotherapy (SCRT) prior to possible chemotherapy (CHT) and surgery in 64 patients with locally advanced rectal cancer, in terms of acute and early late toxicity and survival outcomes with prognostic factors. Sixty-four patients affected by rectal tumor were treated from 2008 to 2023 radiation therapy, with a total dose of 25Gy in 5 fractions. The Kaplan-Meier method was used to estimate the rates of overall survival (OS), cancer specific survival (CSS), local control (LC), disease free survival (DFS) and metastasis free survival (MFS). Univariate analysis for prognostic factors was performed with the log-rank test, and Cox proportional hazards regression was used to estimate hazard ratios. Toxicity assessment has been considered in acute and in early late for gastrointestinal (GI), genitourinary (GU) districts. Median follow-up was 49.6months. The median OS was 65months with 1-year, 2-year and 5-year OS at 90.6%, 77.7% and 60% respectively. CSS at the 1-year, 2-year and 5-year was 98.3%, 96.2% and 86.2% respectively. LC at 1-year, 2-year and 5-year was 93.4%, 89.4% and 87.2% respectively. DFS at the 1-year, 2-year and 5-year was 93.4%, 89% and 87% respectively. The status of lymph nodes at diagnosis was a prognostic factor in term of LC and DFS. Acute GI toxicity was G1 in 10 (15.6%) patients. Five (7.8%) patients had a G1 acute GU toxicity. Fifteen (23.4%) patients developed chronic GI toxicities. SCRT is an effective treatment in patients with rectal cancer and provides good outcomes with very low rates of toxicity profile.

BIOM-38. OPPOSING EFFECTS OF LINKED CX3CR1 GERMLINE VARIANTS ON INCIDENCE, SURVIVAL, AND IMMUNE ACTIVATION IN GLIOMA

Abstract Linkage-disequilibrium connects CX3CR1 V249I and T280M single-nucleotide polymorphisms; V249I occurs as a single-variant (SV) and T280M exclusively as a double-variant (DV) concurrent with V249I. The effect of these combined haplotypes remains unexplored in glioma. We identified CX3CR1 haplotypes in internal LGG and TCGA GBM cohorts and analyzed median overall survival (mOS). The proportion of each haplotype in glioma and normal patients was assessed via meta-analysis. Bulk RNAseq analysis was conducted in TCGA and internal GBM cohorts and scRNAseq in internal IDH mutant gliomas. In LGG, SV improved mOS (n=14, 21.03yrs) by twofold compared to WT (n=45, 9.41yrs) and DV (n=31, 10.49yrs; p=0.037). In TCGA GBM, SV (n=69, 15.65mo) improved mOS over DV (n=106, mOS 11.74mo; p=0.044). In combined meta-analysis, SV patients had increased risk for glioma development (OR 1.11, 1.03-1.19 p = 0.006) and the WT genotype was protective (OR 0.95, p=0.048). Collagen genes associated with increased immunosuppression (COL6A3: log2FC=2.33, p-adj=0.004; COL6A2: log2FC=1.55, p-adj=.059) were reduced in SV. MME, an endopeptidase associated with radiation resistance, was downregulated in SV (log2FC=3.29, p-adj=2.53e-6). MN1, associated with improved glioma survival, was upregulated in SV (log2FC=-1.76, p-adj=0.001). CCL18, an immunosuppressive chemokine associated with M2 macrophage polarization was reduced in SV (log2FC=2.36, p-adj=0.014). Thus, concomitant with its improved survival, SV is biologically distinct from DV and WT. Using scRNAseq, myeloid-derived cells (microglia/macrophages; 7758 cells) were re-clustered, identifying fourteen clusters. Cells clustered by CX3CR1 status, with 58.2% of SV cells in cluster five and 84.9% of DV cells in clusters six or seven. Cluster five over-expressed IL1B (average-log2FC 3.16), a tumor-suppressive M1 macrophage marker. Clusters six and seven were characterized by IFIT genes (IFIT3 average-log2FC 2.72 and 2.16 respectively), which corresponds to glioma associated microglia from recent scRNAseq microglial atlases. We demonstrate that CX3CR1 SV has improved survival and reduced immunosuppression over wildtype and this is lost with in the linked CX3CR1 DV genotype.

Highly Efficient Flexible Antimony Halide Scintillator Films with In Situ Preparation for High‐Resolution X‐Ray Imaging

AbstractFlexible scintillators with high light yield, spatial resolution and low light scattering are ideal for X‐ray imaging application. However, conventional scintillators are always prepared by crystallization of functional layer, grinding and mixing with polymers, resulting in serious light scattering. Herein, an in situ fabrication strategy is proposed to prepare a low light scattering flexible scintillator film based on 0D antimony halide C38H36P2SbCl5 (MTP2SbCl5). The prepared scintillator film exhibits bright yellow emission with an outstanding photoluminescence quantum yield (PLQY) of 99.69%, and it demonstrates linear responsiveness to X‐ray dose, achieving an impressive light yield of 39800 photons MeV−1 and a low detection limitation of 78.4 nGyair s−1. The scintillator film possesses strong radiation hardness and stability. In addition, low light scattering greatly inhibits optical crosstalk during X‐ray detection, effectively improving the spatial resolution of MTP2SbCl5 film from 4.5 to 10.2 lp mm−1. On account of the simple preparation method and high performance, this work provides guidance for the preparation of high‐efficiency, large‐area, low‐scattering and high‐resolution flexible scintillator in the future.

TMIC-25. MICROGLIA IN THE GLIOBLASTOMA MICROENVIRONMENT SECRETE ACETYLATED AMINO ACIDS WHICH ASSIST IN THE REPAIR OF RADIATION INDUCED DNA DAMAGE

Abstract Rapid repair of DNA damage mediates genotoxic therapy resistance and poor prognosis in glioblastoma (GBM). The GBM tumor microenvironment (TME) is heterogenous, and we hypothesized that non-malignant cells support the repair of DNA damage in glioblastoma cells. Consistent with this hypothesis, we found that GBM tumors grown intracranially in mice had rapid DNA repair and were resistant to radiation compared to tumors of identical genotype grown extracranially in mouse flanks. Further interrogation of irradiated intracranial tumors using gamma-H2AX immunofluorescence revealed spatial heterogeneity in DNA damage repair, with spatially separate regions of rapid and slow gamma-H2AX resolution. Paired spatial transcriptomic analysis and gamma-H2AX immunofluorescence showed that tumor regions with rapid DNA repair were rich in microglia. Having nominated microglia from these results, we cocultured GBM cells and microglia in direct contact as well as in transwell coculture. We found that GBM cells cocultured with microglia repair DNA damage faster in a contact-independent manner. We then assessed the supernatant metabolome of microglia and GBM monocultures and cocultures and found that acetylated amino acids are secreted by microglia and consumed by GBM cells. Supplementation with acetylated amino acids promotes radiation resistance by speeding the repair of radiation-induced DNA damage. Mechanistically, acetylated amino acid supplementation allows glioma cells to re-route glucose utilization away from the TCA cycle and towards nucleotide synthesis. Hence, we show that microglia in the GBM microenvironment assist GBM cells to repair radiation induced DNA damage by secreting acetylated amino acids which are consumed by GBM cells and used to fuel the TCA cycle allowing utilization of glucose for nucleotide synthesis, thereby making the GBM cells resistant to radiation therapy.

CNSC-40. GTP SIGNALING PATHWAY PROMOTES NHEJ REPAIR BY INDUCING NUCLEAR ACTIN POLYMERIZATION IN GLIOBLASTOMA

Abstract OBJECTIVES We recently identified that GTP promotes non-homologous end joining (NHEJ) by triggering a GTP-Rac1-PP5-Abi-1/S323 cascade and we sought to define the molecular mechanisms. METHODS Crispr/Cas9, CDNA overexpression and immunoblot were used to modulate and confirm protein levels. Cellular fractionation and immunofluorescence (IF) were used to determine the localization of proteins. Laser micro-irradiation was used to induce DNA damage and monitor the recruitment of DNA repair proteins. RESULTS We found that GTP-activated protein Rac1 and Abi-1, the two key components of the newly identified pathway, shuttled into the nucleus post-RT in glioblastoma (GBM) cells. These effects were further enhanced by the GTP precursor guanosine but blocked by GTP depletion. Furthermore, Abi-1 and Rac1 accumulated in the nucleus of the cells expressing constitutively active Rac1 but not dominant negative Rac1 after RT, which suggests that Rac1/Abi-1 nuclear translocation is Rac1 activity dependent. We previously discovered that GTP-Rac1 promotes DNA repair by facilitating the dephosphorylation of Abi-1 (S323). Here, we discovered that dephosphomimetic Abi-1 (S323A) but not phosphomimetic Abi-1 (S323D) shuttled into nucleus after RT. Because Rac1 canonically binds to Abi-1 and promotes actin polymerization in the cytosol, we next wanted to determine if RT-induced nuclear Rac1/Abi-1/S323A could enhance nuclear actin polymerization, which could enhance NHEJ repair. We found that Abi-1/S323A but not Abi-1/S323D increases nuclear filament actin formation post-RT and activating the GTP-Rac1-Abi-1/S323A axis (through guanosine supplementation, expression of constitutively active Rac1 or expression of dephosphomimetic Abi-1/S323A) enhanced the recruitment and stability of KU80 at sites of DNA damage, which could be blocked by actin polymerization inhibitor cytochalasin D. Furthermore, inhibiting actin polymerization overcame radiation resistance in GBM cells with an active GTP-Rac1-Abi-1/S323A axis. CONCLUSIONS GTP-Rac1-PP5-Abi-1/S323 cascade promotes NHEJ repair by inducing the nuclear assembly of filament actin and disrupting this regulation could improve treatment responses in GBMs.

RBIO-08. INVESTIGATING THE EFFICACY AND MECHANISMS OF TUMOR TREATING FIELDS IN RADIATION-RESISTANT GLIOBLASTOMA MODELS

Abstract Glioblastoma (GBM) is an aggressive malignant brain tumor with poor prognosis despite current treatment regimens involving surgical resection, radiation, temozolomide, and the newly approved use of Tumor Treating Fields (TTFields; a noninvasive, transdermal, administration of alternating low-intensity, intermediate-frequency electrical fields). Acquired radiation resistance, thought to be partially driven by brain tumor-initiating cells (BTICs), underscores therapeutic challenges in GBM. While clinical evidence supports the therapeutic benefit of TTFields, its precise mechanisms of action are poorly understood, and TTFields impact on radiation-resistant GBM is unknown. To better understand the effect and mechanism of TTFields in radiation-resistant GBM, we utilized patient-derived xenolines (PDX) and their acquired radio-resistant pairs to assess changes in viability and molecular signaling. PDX were previously developed by subcutaneous implantation of patient GBM cells into immunodeficient (nu/nu) mice. Acquired radiation-resistant PDX were generated through serial in vivo radiation. TTFields were administered with the Novocure inovitroTM device in a cooling incubator to maintain 37oC sample temperature in the ceramic well plates of the device. PDX were cultured on geltrex-coated coverslips under serum-free conditions. Cytotoxicity was quantified 72h post TTFields with crystal violet. Molecular signaling was captured with PamChip peptide-based kinase activity arrays and RayBiotech proteomic arrays. We found that TTFields inhibit cell growth in both parental and acquired radiation-resistant PDX. Differences in molecular signatures between the PDX lines suggest molecular mechanisms of TTFields sensitivity signatures and interactions with acquired radio-resistant PDX. We are currently trying to generate TTFields-resistant PDX lines through serial treatment with plans to examine BTIC populations relative to TTFields efficacy. We also plan to explore targetable TTFields-induced alterations in the future.

TMIC-62. INVESTIGATING THE ROLE OF OSTEOPONTIN IN RADIORESISTANCE OF H3.3-G34R PEDIATRIC HIGH-GRADE GLIOMA

Abstract Pediatric high-grade gliomas (pHGGs) are currently the leading cause of cancer-related deaths in children. Around 15% of pHGGs harbor a glycine to arginine (G34R) mutation in histone H3.3. Gliomas in general, including H3.3-G34R gliomas, contain cell populations that are resistant to chemotherapy and radiation therapy. These resistant cell populations are responsible for tumor recurrence seen in over 90% of patients within two years after treatment. Uncovering molecular mechanisms responsible for radiation resistance is essential for the development of new targeted therapies against glioma. In our lab’s H3.3-G34R mouse model, we have observed mice that are both radioresistant and radiosensitive. In order to investigate potential mechanisms of resistance leading to this phenotype, we performed single-cell RNA sequencing (scRNA-seq) on 3 non-treated (NT) glioma-bearing mice, 3 mice resistant to treatment (R), and 3 mice susceptible to treatment (S). The scRNA-seq data was processed and filtered using FastQC, Cellranger, CellBender, and DoubletFinder before downstream analysis. Ligand-receptor interaction analysis using CellChat in conjunction with differential expression analysis demonstrated differential expression and secretion of a cytokine known as Secreted Phosphoprotein 1 (SPP1)/Osteopontin (OPN) from tumor-associated microglia and macrophages. Current literature on SPP1 has suggested that its expression may play a role in tumor aggressiveness. However, there is conflicting evidence regarding its mechanism of action when secreted from tumor-associated microglia and macrophages. Additionally, its role in radioresistance has yet to be fully explored. We will present data utilizing in vitro and in vivo experimentation to elucidate the role that differential expression of SPP1 may play in the radioresistance of our H3.3-G34R mouse model. Supported by grants from NIH-NINDS, the Pediatric Brain Tumor Foundation, and Ian’s Friends Foundation

Proton irradiation effect mechanism of backside illuminated CMOS image sensors applied to FGS

A study of the mechanism of proton irradiation effects in the in-orbit operation of the backside illuminated CMOS image sensor (BSI CIS) used for imaging by the Fine Guidance Sensor (FGS) is presented in this paper. According to the proton irradiation environment of the Halo L2 orbit where FGS is located and the duration of in orbit operation, proton irradiation experiments were conducted on the BSI CIS, the core imaging device of FGS. Results show that proton irradiation is expected to cause a significant increase in the dark current of the BSI CIS of the FGS after four years of its in orbit, with the peak of the dark signal distribution shift to the right and an exponential trailing of the tail of the dark signal distribution when the proton fluence reached 6.71 × 1010p/cm2. This is the result of a combination of ionization defects and displacement damage defects. In addition, we also report about the device gain, which is of particular interest in space astronomical exploration. We performed a more detailed single pixel gain test of the device gain and found that the degradation of the gain appears to be correlated with the intensity of the ionization defects. The results of this study can provide theoretical basis for the radiation hardening by design of FGS to some extent.

Design and Performance of an InAs Quantum Dot Scintillator with Integrated Photodetector

A new scintillation material composed of InAs quantum dots (QDs) hosted within a GaAs matrix was developed, and its performance with different types of radiation is evaluated. A methodology for designing an integrated photodetector (PD) with a low defect density and that is optically matched to the QD’s emission spectrum is introduced, utilizing an engineered epitaxial InAlGaAs metamorphic buffer layer. The photoluminescence (PL) collection efficiency of the integrated PD is examined using two-dimensional scanning laser excitation. The detector response to 5.5 MeV α-particles and 122 keV photons is presented. Yields of 13 electrons/keV for α-particles and 30–60 electrons/keV for photons were observed. The energy resolution of 12% observed with α-particles was mainly limited by noise- and geometry-related optical losses. The radiation hardness of an InAs QDs hosted within GaAs and a wider band gap AlGaAs ternary alloy was studied under a 1 MeV proton implantation up to a 1014 cm−2 dose. The integrated PL responses were compared to evaluate PL quenching due to non-radiative defects. The QDs embedded in the AlGaAs demonstrated improved radiation hardness compared to QDs in the GaAs matrix and in the InGaAs quantum wells.

Measuring the radiation hardness of terahertz devices for space applications

The application of terahertz technology in space is frontier for the development of 6G technologies. Terahertz transceiver devices based on gallium arsenide Schottky barrier diodes (GaAs SBDs) have the characteristics of small size, light weight and low power consumption, making them suitable for application on spacecraft. However, there is currently a lack of experimental assessments on their space adaptability. Here, we study the radiation hardness of terahertz devices to determine their adaptability in complex space environments. We exposed GaAs SBDs and terahertz multipliers as typical terahertz devices to gamma rays and protons. The experimental results showed that the terahertz devices exhibited good tolerance to protons, but prolonged exposure to gamma rays could significantly increase the leakage current of the GaAs SBDs and alter its C-V characteristics, leading to the failure of the terahertz multiplier. Nevertheless, the terahertz devices maintained a good level of radiation hardness, making them highly suitable for use in Low Earth Orbit (LEO) satellites. The comparison between the results of proton and gamma ray tests indicated that the terahertz devices exhibited high inherent radiation hardness against displacement damage but were more sensitive to ionization damage, requiring higher shielding requirements.

Shape Memory Polyurethane Foams With Tunable Mechanical Properties and Radiation Tolerance for Breast Repair and Reconstruction.

This study developed a shape memory polyurethane foam (SM-PUF) with tunable mechanical properties and exceptional radiation tolerance for potentially implanting tissue defects after mastectomy. The PUFs were synthesized via an insitu foaming strategy using water as a foaming agent, incorporating 4,4'-diphenylmethane diisocyanate (MDI) as the rigid segment and both polyoxytetramethylene glycol and polycaprolactone as the soft segment. The resultant PUFs possess an open-cell structure with a pore size of 30 ~ 800 μm, which achieves a compressive stress of 0.04 MPa under 70% compression strain and a tensile elongation of 667.9%. PUFs exhibit body temperature (37°C)-responsive softening and shape memory abilities, with recovery and fixation ratios reaching 88% and 98%, respectively. It was verified that PUFs can resist 40 Gy radiotherapy without changing their mechanical properties and biocompatibility. This study introduces an innovative approach to produce customizable foam for the reconstruction of implant prostheses for the breast.

Experience of rescue therapy with [177Lu]Lu-rhPSMA-10.1 in patients with primary or acquired resistance to [177Lu]Lu-PSMA-I&T.

Radioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T. Ten patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application. Despite progression with [177Lu]Lu-PSMA-I&T, after the first cycle of [177Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [177Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [177Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [177Lu]Lu-PSMA-I&T therapy but showed an immediate response to [177Lu]Lu-rhPSMA-10.1. The additional treatment with [177Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients. Patients showing tumour progression while receiving [177Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [177Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [177Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.

State primary standard for units of absorbed dose and absorbed dose rate of photon, electron, proton radiation and in carbon ion beams, quantity, fuence, fux density and energy of particles in proton beams and heavy charged particles GET 38-2024

The problem of ensuring the accuracy and traceability of the measurement results of the absorbed dose in carbon ion beams, as well as the measurement results of the amount, fluence, flux density and energy of particles in proton and heavy charged particles beams is considered. Until now, in practice, these values have been measured only by indirect methods. The lack of approved measuring instruments for the quantities under consideration and the metrological traceability of measurement results of these quantities to standards did not allow achieving consistency of measurement methods used in practice and confirming the reliability of the results obtained. To solve this problem, three measuring complexes have been developed and created, which are included in the State Primary Standard of units of absorbed dose and absorbed dose rate of photon, electron, proton radiation and in carbon ion beams, quantity, fluence, flux density and energy of particles in proton and heavy charged particles beams GET 38-2024. The measuring complex for reproducing the unit of absorbed dose in carbon ion beams consists of an adiabatic calorimeter, a thermostating system, a data collection and processing system and a vacuum pumping station. To reproduce the unit of energy of protons and heavy charged particles, a complex has been implemented, which includes a total absorption calorimeter, a data collection and processing system, a vacuum pumping station and a particle count determination system based on the use of a Faraday cup. To reproduce the units of fluence and particle flux density in proton and heavy charged particles beams, a measuring complex has been created containing a Faraday cup, a set of collimators and a low current meter. The schemes, the principles and the results of studies of the metrological characteristics of the developed measuring complexes are described. The results are relevant for the field of radiation therapy and radiation resistance tests of the electronic component base used in the space industry.

Radiation Resistivity of Ti-5331 Alloy with Different Microstructures

Titanium alloys have promising potential for applications in marine nuclear power systems owing to their exceptional mechanical and corrosion properties. Nevertheless, their radiation resistivity is a determining factor for their extensive use as structural materials in nuclear energy systems. In this study, the radiation resistivity of Ti-5Al-3V-3Zr-Cr (Ti-5331) alloys with three different microstructures was examined using a combination of characterization techniques including positron annihilation Doppler broadening spectroscopy (DBS), Elastic Recoil Detection Analysis (ERDA), Transmission Electron Microscope (TEM), Small-Angle X-ray scattering (SAXS) and nanoindentation. The results reveal that the equiaxed structure, bimodal structure, and Widmanstatten structure of Ti-5331 alloy obtained through different annealing processes exhibit differences in the number of interfaces and the content of the β phase. The α/β interfaces can significantly enhance the radiation resistance of titanium alloys by inhibiting the diffusion of helium atoms after helium ion irradiation. Notably, the alloy with a bimodal structure exhibited the best overall radiation resistivity, showing small defect size, low hardening effect, and low swelling rate of 0.003%. Moreover, the size of helium bubbles of the bimodal structure is half of that in the equiaxed structure and Widmanstatten structure. Thus, the bimodal structure of the Ti-5331 alloy possesses superior radiation resistivity.

Design and evaluation of UKRI-MPW0: a monolithic HV-CMOS pixel sensor with backside biasing

High-Voltage CMOS (HV-CMOS) pixel sensor technology is the most promising route for achieving thin, monolithic pixel detectors with excellent radiation tolerance, as required by future tracking applications in physics experiments, such as the High Luminosity LHC. This paper introduces a U.K. Research and Innovation funded Multi-Project Wafer prototype chip UKRI-MPW0, which is an HV-CMOS pixel sensor designed to push the performance parameters of these detectors. Having a novel sensor cross-section optimised for backside biasing to unprecedented high voltages, UKRI-MPW0 demonstrates the capability to withstand bias voltages of up to 600 V, surpassing the current state-of-the-art and promising enhanced radiation tolerance. The paper provides a detailed description of the design and performance evaluation results of UKRI-MPW0.

Achieving strength-ductility synergy of ODS-FeCrAl alloys via heterostructured strategy

Oxide dispersion strengthened (ODS)-FeCrAl alloys are candidate structural materials for advanced nuclear reactor applications, which have excellent strength and radiation tolerance but low ductility. In this study, a novel ODS-FeCrAl heterostructured composite, reinforced with FCC-structured ODS-CoCrFeNiMn high-entropy particles, was prepared by using mechanical alloying and spark plasma sintering to achieve the strength-ductility synergy. The effect of different reinforcement contents (0, 10, 15 and 20 wt.%, designated as RC-0, RC-10, RC-15, and RC-20, respectively) on the microstructure and mechanical properties of the composites was investigated. The results showed that the unreinforced reference alloy, RC-0, consists of BCC-structured ODS-FeCrAl matrix and high-density oxides. In the RC-10, RC-15, and RC-20 composites, in addition to the ODS-FeCrAl matrix and nanoscale oxides, FCC-structured ODS-CoCrFeNiMn high-entropy reinforcement with ultrafine grain size and FCC transition layer with gradient grain size are observed. As the reinforcement content increases, the thickness of transition region increases. The composites show an increase in ultimate compressive strength and compressive strain with increasing reinforcement content in the following order: 2951 MPa/33.6%, 3169 MPa/40.0%, 3290 MPa/43.2%, and 3489 MPa/48.8%. And the compressive yield strength exhibits an initial increase and subsequent decrease, i.e. 1523 MPa (RC-0), 1680 MPa (RC-10), 1635 MPa (RC-15), and 1355 MPa (RC-20), respectively. The increase in yield strength is mainly attributed to hetero-deformation induced (HDI) strengthening and reinforcement hardening. The improvement in ductility is mainly attributed to the HDI work hardening and the suppression of microcrack formation and propagation at prior powder boundaries.

Environment-friendly glass with high refractive index and radiation resistance

Environment-friendly glass with high refractive index and radiation resistance

Cancer Stem Cells and Treatment of Cancer: An Update and Future Perspectives.

Cancer stem cells (CSCs) play an essential role in tumour progression and metastasis. Stem cell ability of self-renewal enables it to persist over time, thereby contributing to cancer relapse or recurrence and also resistance to current therapies. Therefore, targeting CSCs emerged as a promising strategy of cancer treatment. CSCs exhibit differentiation, self-renewal, and plasticity, they contribute to formation of malignant tumours, also favors, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Coventional cancer treatments predominantly target cancer cells that are not CSCs, CSCs frequently survive, eventually leading to relapse. This article focuses on the development of novel therapeutic strategies that combine conventional treatments and CSC inhibitors to eradicate cancer cells and CSCs, for the better and permanent treatment. However, the diversity of CSCs is a significant obstacle in the development of CSC-targeted therapies, necessitating extensive research for a better understanding and exploration of therapeutic approaches. Future development of CSC-targeted therapies will rely heavily on overcoming this obstacle.

Molecular dynamics simulations on the evolution of irradiation-induced dislocation loops in FeCoNiCrCu high-entropy alloy

High-entropy alloys (HEAs) have received extensive attention due to their excellent irradiation resistance. In this work, the displacement cascade simulations were performed by using the molecular dynamics (MD) method to study the dislocation loop evolution in FeCoNiCrCu HEA. The simulation results showed the dislocation loops evolution in pure Ni were dominated by Frank loops with larger size but lower density, which was caused by the absorption of prismatic dislocation loops by Frank loops. In contrast, prismatic dislocation loops were more prevailing in FeCoNiCrCu HEA with smaller size but higher density, since the interactions between dislocation loops were suppressed in HEA. To figure out the influence of HEA on dislocation loop evolution, the formation energy, interaction energy and mobility were analyzed. It was found that formation energy and interaction energy were basically the same, while the mobility of prismatic dislocation loop in HEA was much lower than that in pure Ni, which was considered as the main reason why the irradiation-induced dislocation loops were more difficult to interact and grow in HEA. The current work provides new insights into understanding the irradiation resistance from micro-mechanism in FeCoNiCrCu HEAs.