Genome-Wide Profile of Mutations Induced by Carbon Ion Beam Irradiation of Dehulled Rice Seeds.

As a physical mutagen, carbon ion beam (CIB) irradiation can induce high-frequency mutation, which is user-friendly and environment-friendly in plant breeding. In this study, we resequenced eight mutant lines which were screened out from the progeny of the CIB-irradiated dehulled rice seeds. Among these mutants, CIB induced 135,535 variations, which include single base substitutions (SBSs), and small insertion and deletion (InDels). SBSs are the most abundant mutation, and account for 88% of all variations. Single base conversion is the main type of SBS, and the average ratio of transition and transversion is 1.29, and more than half of the InDels are short-segmented mutation (1-2 bp). A total of 69.2% of the SBSs and InDels induced by CIBs occurred in intergenic regions on the genome. Surprisingly, the average mutation frequency in our study is 9.8 × 10-5/bp and much higher than that of the previous studies, which may result from the relatively high irradiation dosage and the dehulling of seeds for irradiation. By analyzing the mutation of every 1 Mb in the genome of each mutant strain, we found some unusual high-frequency (HF) mutation regions, where SBSs and InDels colocalized. This study revealed the mutation mechanism of dehulled rice seeds by CIB irradiation on the genome level, which will enrich our understanding of the mutation mechanism of CIB radiation and improve mutagenesis efficiency.

Evidence of Hexadecapole Deformation in Uranium-238 at the Relativistic Heavy Ion Collider.

State-of-the-art hydrodynamic simulations of the quark-gluon plasma are unable to reproduce the elliptic flow of particles observed at the BNL Relativistic Heavy Ion Collider (RHIC) in relativistic ^{238}U+^{238}U collisions when they rely on information obtained from low-energy experiments for the implementation of deformation in the colliding ^{238}U ions. We show that this is due to an inappropriate treatment of well-deformed nuclei in the modeling of the initial conditions of the quark-gluon plasma. Past studies have identified the deformation of the nuclear surface with that of the nuclear volume, though these are different concepts. In particular, a volume quadrupole moment can be generated by both a surface hexadecapole and a surface quadrupole moment. This feature was so far neglected in the modeling of heavy-ion collisions, and is particularly relevant for nuclei like ^{238}U, which is both quadrupole deformed and hexadecapole deformed. With rigorous input from Skyrme density functional calculations, we show that correcting for such effects in the implementation of nuclear deformations in hydrodynamic simulations restores agreement with BNL RHIC data. This brings consistency to the results of nuclear experiments across energy scales, and demonstrates the impact of the hexadecapole deformation of ^{238}U on high-energy collisions.

Proton radiotherapy in the treatment of IDH-mutant diffuse gliomas: an early experience from shanghai proton and heavy ion center.

PURPOSE: According to the presence or absence of isocitrate dehydrogenase (IDH) mutation, the 2021 WHO classification system bisected diffuse gliomas into IDH-mutant tumors and IDH-wildtype tumors. This study was aimed to evaluate the outcomes of proton radiotherapy treating IDH-mutant diffuse gliomas. PATIENTS AND METHODS: Between May 2015 and May 2022, a total of 52 consecutive patients with IDH-mutant diffuse gliomas were treated at Shanghai Proton and Heavy Ion Center. Tumor histologies were 33 cases of astrocytoma and 19 cases of oligodendroglioma. Tumor classified by WHO grade 2, 3 and 4 were 22, 25, and 5 cases, respectively. All 22 patients with WHO grade 2 tumors and one patient with brain stem WHO grade 4 tumor were irradiated with 54GyE. The other 29 patients with WHO grade 3 and 4 tumors were irradiated with 60GyE. Temozolomide was recommended to all patients, and was eventually conducted in 50 patients. RESULTS: The median follow-up time was 21.7 months. The 12/24-month progression-free survival (PFS) and overall survival (OS) rates for the entire cohort were 97.6%/78.4% and 100%/91.0% group. Examined by both univariate and multivariate analysis, WHO grade of tumor were of the most significant impact for both PFS and OS. No severe acute toxicity (grade 3 or above) was found. In terms of late toxicity, grade 3 radio-necrosis was developed in one case of oligodendroglioma, WHO grade 3. CONCLUSION: Proton radiotherapy produced a favorable outcome with acceptable adverse-effects in patients with IDH-mutant diffuse gliomas.

Particle beam radiotherapy in the treatment of WHO grade 2 and 3 meningiomas: an early experience from Shanghai Proton and Heavy Ion Center.

PURPOSE: To investigate the efficacy and safety of particle beam radiotherapy (PBRT) in the management of patients with WHO grade 2 and 3 meningiomas. METHODS: Thirty-six consecutive and non-selected patients with WHO grade 2 (n = 28) and grade 3 (n = 8) meningiomas were treated at the Shanghai Proton and Heavy Ion Center, from May 2015 to March 2022. The median age of the cohort at PBRT was 48 years. There were 25 and 11 patients treated with PBRT in the setting of newly diagnosed diseases and progressive/recurrent diseases, respectively. PBRT was utilized as re-irradiation in 5 patients. Proton radiotherapy (PRT) and carbon-ion radiotherapy (CIRT), with a median dose of 60 Gy-Equivalent (GyE), were provided to 30 and 6 patients, respectively. RESULTS: With a median follow-up of 23.3 months, the local control rates were 92.0%, 82.0%, and 82.0% at 1, 2, and 3 years for the entire cohort, respectively. Patients with WHO grade 2 meningiomas (100%, 94.1%, 94,1% at 1,2,3 years) had a much better local control than those with WHO grade 3 meningiomas (50%, 25%, 25% at 1,2,3 years; P < 0.001). Three patients, all with WHO grade 3 meningiomas, had deceased at the time of this analysis. Multivariate analyses revealed that WHO grade (grade 2 vs. 3) (p = 0.016) was a significant prognosticator for local control. No severe toxicities (G3 or above) were observed. CONCLUSIONS: Treatment-induced efficacy and toxicities to PBRT in WHO grade 2 and 3 meningiomas were both highly acceptable. Longer follow-up is needed to evaluate the long-term outcome in terms of disease control, survival, as well as potential late effects.

Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias　- Gap Junction and Sympathetic Neural Remodeling.

BACKGROUND: Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1-78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1-44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9-65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group. CONCLUSIONS: Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.

Role of Candida in the bioremediation of pollutants: a review.

The population and modernization of society have increased dramatically from past few decades. In order to meet societal expectations, there has been a massive industrialization and resource exploitation. Anthropogenic practices like disposal of hazardous waste, large carbon footprint release variety of xenobiotic substances into the environment, which endanger the health of the natural ecosystem. Therefore, discovering proper long-term treatment approaches is a global concern. Various physical and chemical approaches are employed to remove contaminants. However, these technologies possess limitations like high cost and low efficacy. Consequently, bioremediation is regarded as one of the most promising remedies to these problems. It creates the option of either totally removing pollutants or transforming them into nonhazardous compounds with the use of natural biological agents. Several microorganisms are being utilized for bioremediation among which yeasts possess benefits such as high biodegradability, ease of cultivation etc. The yeast of Candida genus has the capability to effectively eliminate heavy metal ions, as well as to degrade and emulsify hydrocarbons which makes it a promising candidate for this purpose. The review highlights many potential uses of Candida in various remediation strategies and discusses future directions for research in this field.

New Insights into Radio-Resistance Mechanism Revealed by (Phospho)Proteome Analysis of Deinococcus Radiodurans after Heavy Ion Irradiation.

Deinococcus radiodurans (D. radiodurans) can tolerate various extreme environments including radiation. Protein phosphorylation plays an important role in radiation resistance mechanisms; however, there is currently a lack of systematic research on this topic in D. radiodurans. Based on label-free (phospho)proteomics, we explored the dynamic changes of D. radiodurans under various doses of heavy ion irradiation and at different time points. In total, 2359 proteins and 1110 high-confidence phosphosites were identified, of which 66% and 23% showed significant changes, respectively, with the majority being upregulated. The upregulated proteins at different states (different doses or time points) were distinct, indicating that the radio-resistance mechanism is dose- and stage-dependent. The protein phosphorylation level has a much higher upregulation than protein abundance, suggesting phosphorylation is more sensitive to irradiation. There were four distinct dynamic changing patterns of phosphorylation, most of which were inconsistent with protein levels. Further analysis revealed that pathways related to RNA metabolism and antioxidation were activated after irradiation, indicating their importance in radiation response. We also screened some key hub phosphoproteins and radiation-responsive kinases for further study. Overall, this study provides a landscape of the radiation-induced dynamic change of protein expression and phosphorylation, which provides a basis for subsequent functional and applied studies.

Particle radiotherapy and molecular therapies: mechanisms and strategies towards clinical applications.

Immunotherapy and targeted therapy are now commonly used in clinical trials in combination with radiotherapy for several cancers. While results are promising and encouraging, the molecular mechanisms of the interaction between the drugs and radiation remain largely unknown. This is especially important when switching from conventional photon therapy to particle therapy using protons or heavier ions. Different dose deposition patterns and molecular radiobiology can in fact modify the interaction with drugs and their effectiveness. We will show here that whilst the main molecular players are the same after low and high linear energy transfer radiation exposure, significant differences are observed in post-exposure signalling pathways that may lead to different effects of the drugs. We will also emphasise that the problem of the timing between drug administration and radiation and the fractionation regime are critical issues that need to be addressed urgently to achieve optimal results in combined treatments with particle therapy.

iTRAQ-based proteomic analysis of Deinococcus radiodurans in response to 12C6+ heavy ion irradiation.

BACKGROUND: Deinococcus radiodurans (D. radiodurans) is best known for its extreme resistance to diverse environmental stress factors, including ionizing radiation (IR), ultraviolet (UV) irradiation, oxidative stress, and high temperatures. Robust DNA repair system and antioxidant system have been demonstrated to contribute to extreme resistance in D. radiodurans. However, practically all studies on the mechanism underlying D. radiodurans's extraordinary resistance relied on the treated strain during the post-treatment recovery lag phase to identify the key elements involved. The direct gene or protein changes of D. radiodurans after stress have not yet been characterized. RESULTS: In this study, we performed a proteomics profiling on D. radiodurans right after the heavy ion irradiation treatment, to discover the altered proteins that were quickly responsive to IR in D. radiodurans. Our study found that D. radiodurans shown exceptional resistance to 12C6+ heavy ion irradiation, in contrast to Escherichia coli (E.coli) strains. By using iTRAQ (Isobaric Tags for Relative and Absolute Quantitation)-based quantitative mass spectrometry analysis, the kinetics of proteome changes induced by various dosages of 12C6+ heavy ion irradiation were mapped. The results revealed that 452 proteins were differentially expressed under heavy ion irradiation, with the majority of proteins being upregulated, indicating the upregulation of functional categories of translation, TCA cycle (Tricarboxylic Acid cycle), and antioxidation regulation under heavy ion irradiation. CONCLUSIONS: This study shows how D. radiodurans reacts to exposure to 12C6+ heavy ion irradiation in terms of its overall protein expression profile. Most importantly, comparing the proteome profiling of D. radiodurans directly after heavy ion irradiation with research on the post-irradiation recovery phase would potentially provide a better understanding of mechanisms underlying the extreme radioresistance in D. radiodurans.

Predominant contribution of the dose received from constituent heavy-ions in the induction of gastrointestinal tumorigenesis after simulated space radiation exposure.

Gastrointestinal (GI) cancer risk among astronauts after encountering galactic cosmic radiation (GCR) is predicted to exceed safe permissible limits in long duration deep-space missions. Current predictions are based on relative biological effectiveness (RBE) values derived from in-vivo studies using single-ion beams, while GCR is essentially a mixed radiation field composed of protons (H), helium (He), and heavy ions. Therefore, a sequentially delivered proton (H) → Helium (He) → Oxygen (O) → Silicon (Si) beam was designed to simulate simplified-mixed-field GCR (Smf-GCR), and Apc1638N/+ mice were total-body irradiated to sham or γ (157Cs) or Smf-GCR followed by assessment of GI-tumorigenesis at 150 days post-exposure. Further, GI-tumor data from equivalent doses of heavy-ions (i.e., 0.05 Gy of O and Si) in 0.5 Gy of Smf-GCR were compared to understand the contributions of heavy-ions in GI-tumorigenesis. The Smf-GCR-induced tumor and carcinoma count were significantly greater than γ-rays, and male preponderance for GI-tumorigenesis was consistent with our earlier findings. Comparison of tumor data from Smf-GCR and equivalent doses of heavy ions revealed an association between higher GI-tumorigenesis where dose received from heavy-ions contributed to > 95% of the total GI-tumorigenic effect observed after Smf-GCR. This study provides the first experimental evidence that cancer risk after GCR exposure could largely depend on doses received from constituent heavy-ions.

Magnetic Nanoparticles as Effective Heavy Ion Adsorbers in Natural Samples.

This paper refers to research based on tests completed on the adsorption of heavy metal ions (Pb2+, Cu2+, Cd2+) from selected natural liquid samples such as apple, tomato, and potato juices using surface-functionalized Mn ferrite nanoparticles (Mn0.2Fe2.8O4). To determine the most efficient adsorption conditions of these heavy metals, the nanoparticles' surfaces were modified with five different ligands (phthalic anhydride, succinic anhydride, acetic anhydride, 3-phosphonopropionic acid, and 16-phosphonohexadecanoic acid). To evaluate the success of the adsorption process, the resultant liquid samples were examined for the amount of residuals using the flame atomic absorption spectroscopy method. The Mn ferrite particles selected for these tests were first characterized physicochemically by the following methods: transmission electron microscopy, scanning electron microscopy, X-ray diffraction, IR spectroscopy, Mössbauer spectroscopy.

Research Progress of Heavy Ion Radiotherapy for Non-Small-Cell Lung Cancer.

Non-small-cell lung cancer (NSCLC) has a high incidence and poses a serious threat to human health. However, the treatment outcomes of concurrent chemoradiotherapy for non-small-cell lung cancer are still unsatisfactory, especially for high grade lesions. As a new cancer treatment, heavy ion radiotherapy has shown promising efficacy and safety in the treatment of non-small-cell lung cancer. This article discusses the clinical progress of heavy ion radiotherapy in the treatment of non-small-cell lung cancer mainly from the different cancer stages, the different doses of heavy ion beams, and the patient's individual factors, and explores the deficiency of heavy ion radiotherapy in the treatment of non-small-cell lung cancer and the directions of future research, in order to provide reference for the wider and better application of heavy ion radiotherapy in the future.

Radiobiological damage by space radiation: extension of the BIANCA model to heavy ions up to iron, and pilot application to cosmic ray exposure.

Space research seems to be object of a renewed interest, also considering that human missions to the Moon, and possibly Mars, are being planned. Among the risks affecting such missions, astronauts' exposure to space radiation is a major concern. In this work, the question of the evaluation of biological damage by Galactic Cosmic Rays (GCR) was addressed by a biophysical model called BIophysical ANalysis of Cell death and chromosome Aberrations (BIANCA), which simulates the induction of cell death and chromosome aberrations by different ions. While previously BIANCA has been validated for calculating cell death along hadrontherapy beams up to oxygen, herein the approach was extended up to Fe ions. Specifically, experimental survival curves available in literature for V79 cells irradiated by Si-, Ne-, Ar- and Fe-ions were reproduced, and a reference radiobiological database describing V79 cell survival as a function of ion type (1 ⩽Z⩽ 26), energy and dose was constructed. Analogous databases were generated for Chinese hamster ovary hamster cells and human skin fibroblasts, finding good agreement between simulations and data. Concerning chromosome aberrations, which are regarded as radiation risk biomarkers, dicentric data in human lymphocytes irradiated by heavy ions up to iron were reproduced, and a radiobiological database allowing calculation of lymphocyte dicentric yields as a function of dose, ion type (1 ⩽Z⩽ 26) and energy was constructed. Following interface between BIANCA and the FLUKA Monte Carlo transport code, a feasibility study was performed to calculate the relative biological effectiveness (RBE) of different GCR spectrum components, for both dicentrics and cell death. Fe-ions, although representing only 10% of the total absorbed dose, were found to be responsible for about 35%-40% of the RBE-weighted dose. Interestingly, the RBE for dicentrics was higher than that for cell survival. More generally, this work shows that BIANCA can calculate RBE values for cell death and lymphocyte dicentrics not only for ion therapy, but also for space radiation.

[Development and Application of the First Carbon Ion Therapy System in China].

At present, heavy ion is an ideal radiation for cancer treatment, and carbon ion is used in the treatment of many kinds of cancer due to its higher relative biological effect value. In 2019, Wuwei heavy ion center built the first medical heavy ion accelerator-carbon ion radiotherapy system in China, and obtained the registration license from the National Medical Products Administration, and officially received cancer patients in March 2020. This study introduced the development and application of the first carbon ion radiotherapy system in China.

Application of heavy-ion-beam irradiation to breeding large rotifer.

In larviculture facilities, rotifers are generally used as an initial food source, while a proper size of live feeds to connect rotifer and Artemia associated with fish larval growth is needed. The improper management of feed size and density induces mass mortality and abnormal development of fish larvae. To improve the survival and growth of target larvae, this study applied carbon and argon heavy-ion-beam irradiation in mutation breeding to select rotifer mutants with larger lorica sizes. The optimal irradiation conditions of heavy-ion beam were determined with lethality, reproductivity, mutant frequency, and morphometric characteristics. Among 56 large mutants, TYC78, TYC176, and TYA41 also showed active population growth. In conclusion, (1) heavy-ion-beam irradiation was defined as an efficient tool for mutagenesis of rotifers and (2) the aforementioned 3 lines that have larger lorica length and active population growth may be used as a countermeasure of live feed size gap during fish larviculcure.

Rapid Sorting of Fucoxanthin-Producing Phaeodactylum tricornutum Mutants by Flow Cytometry.

Fucoxanthin, which is widely found in seaweeds and diatoms, has many benefits to human health, such as anti-diabetes, anti-obesity, and anti-inflammatory physiological activities. However, the low content of fucoxanthin in brown algae and diatoms limits the commercialization of this product. In this study, we introduced an excitation light at 488 nm to analyze the emitted fluorescence of Phaeodactylum tricornutum, a diatom model organism rich in fucoxanthin. We observed a unique spectrum peak at 710 nm and found a linear correlation between fucoxanthin content and the mean fluorescence intensity. We subsequently used flow cytometry to screen high-fucoxanthin-content mutants created by heavy ion irradiation. After 20 days of cultivation, the fucoxanthin content of sorted cells was 25.5% higher than in the wild type. This method provides an efficient, rapid, and high-throughput approach to screen fucoxanthin-overproducing mutants.

Low dose of carbon ion irradiation induces early delayed cognitive impairments in mice.

People often encounter various sources of ionizing radiation, both in modern medicine and under various environmental conditions, such as space travel, nuclear power plants or in conditions of man-made disasters that may lead to long-term cognitive impairment. Whilst the effect of exposure to low and high doses of gamma and X-radiation on the central nervous system (CNS) has been well investigated, the consequences of protons and heavy ions irradiation are quite different and poorly understood. As for the assessment of long-term effects of carbon ions on cognitive abilities and neurodegeneration, very few data appeared in the literature. The main object of the research is to investigate the effects of accelerated carbon ions on the cognitive function. Experiments were performed on male SHK mice at an age of two months. Mice were irradiated with a dose of 0.7 Gy of accelerated carbon ions with an energy of 450 meV/n in spread-out Bragg peak (SOBP) on a U-70 particle accelerator (Protvino, Russia). Two months after the irradiation, mice were tested for total activity, spatial learning, as well as long- and short-term hippocampus-dependent memory. One month after the evaluation of cognitive activity, histological analysis of dorsal hippocampus was carried out to assess its morphological state and to reveal late neuronal degeneration. It was found that the mice irradiated with accelerated carbon ions develop an altered behavioral pattern characterized by anxiety and a shortage in hippocampal-dependent memory retention, but not in episodic memory. Nissl staining revealed a reduction in the number of cells in the dorsal hippocampus of irradiated mice, with the most pronounced reduction in cell density observed in the dentate gyrus (DG) hilus. Also, the length of the CA3 field of the dorsal hippocampus was significantly reduced, and the number of cells in it was moderately decreased. Experiments with the use of Fluoro-Jade B (FJB) staining revealed no FJB-positive regions in the dorsal hippocampus of irradiated and control animals 3 months after the irradiation. Thus, no morbid cells were detected in irradiated and control groups. The results obtained indicate that total irradiation with a low dose of carbon ions can produce a cognitive deficit in adult mice without evidence of neurodegenerative pathologic changes.

Carbon ion radiotherapy using fiducial markers for prostate cancer in Osaka HIMAK: Treatment planning.

PURPOSE: Carbon ion radiotherapy for prostate cancer was performed using two fine needle Gold Anchor (GA) markers for patient position verification in Osaka Heavy Ion Medical Accelerator in Kansai (Osaka HIMAK). The present study examined treatment plans for prostate cases using beam-specific planning target volume (bsPTV) based on the effect of the markers on dose distribution and analysis of target movements. MATERIALS AND METHODS: Gafchromic EBT3 film was used to measure dose perturbations caused by markers. First, the relationships between the irradiated film density and absolute dose with different linear energy transfer distributions within a spread-out Bragg peak (SOBP) were confirmed. Then, to derive the effect of markers, two types of markers, including GA, were placed at the proximal, center, and distal depths within the same SOBP, and dose distributions behind the markers were measured using the films. The amount of internal motion of prostate was derived from irradiation results and analyzed to determine the margins of the bsPTV. RESULTS: The linearity of the film densities against absolute doses was constant within the SOBP and the amount of dose perturbations caused by the markers was quantitatively estimated from the film densities. The dose perturbation close behind the markers was smallest (<10% among depths within the SOBP regardless of types of markers) and increased with depth. The effect of two types of GAs on dose distributions was small and could be ignored in the treatment planning. Based on the analysis results of internal motions of prostate, required margins of the bsPTV were found to be 8, 7, and 7 mm in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions, respectively. CONCLUSION: We evaluated the dose reductions caused by markers and determined the margins of the bsPTV, which was applied to the treatment using fiducial markers, using the analysis results of prostate movements.

Recent Developments on gMicroMC: Transport Simulations of Proton and Heavy Ions and Concurrent Transport of Radicals and DNA.

Mechanistic Monte Carlo (MC) simulation of radiation interaction with water and DNA is important for the understanding of biological responses induced by ionizing radiation. In our previous work, we employed the Graphical Processing Unit (GPU)-based parallel computing technique to develop a novel, highly efficient, and open-source MC simulation tool, gMicroMC, for simulating electron-induced DNA damages. In this work, we reported two new developments in gMicroMC: the transport simulation of protons and heavy ions and the concurrent transport of radicals in the presence of DNA. We modeled these transports based on electromagnetic interactions between charged particles and water molecules and the chemical reactions between radicals and DNA molecules. Various physical properties, such as Linear Energy Transfer (LET) and particle range, from our simulation agreed with data published by NIST or simulation results from other CPU-based MC packages. The simulation results of DNA damage under the concurrent transport of radicals and DNA agreed with those from nBio-Topas simulation in a comprehensive testing case. GPU parallel computing enabled high computational efficiency. It took 41 s to simultaneously transport 100 protons with an initial kinetic energy of 10 MeV in water and 470 s to transport 105 radicals up to 1 µs in the presence of DNA.

Circulating tRNA-Derived Small RNAs as Novel Radiation Biomarkers of Heavy Ion, Proton and X-ray Exposure.

The effective and minimally invasive radiation biomarkers are valuable for exposure scenarios in nuclear accidents or space missions. Recent studies have opened the new sight of circulating small non-coding RNA (sncRNA) as radiation biomarkers. The tRNA-derived small RNA (tsRNA) is a new class of sncRNA. It is more abundant than other kinds of sncRNAs in extracellular vesicles or blood, presenting great potential as promising biomarkers. However, the circulating tsRNAs in response to ionizing radiation have not been reported. In this research, Kunming mice were total-body exposed to 0.05-2 Gy of carbon ions, protons, or X-rays, and the RNA sequencing was performed to profile the expression of sncRNAs in serum. After conditional screening and validation, we firstly identified 5 tsRNAs including 4 tRNA-related fragments (tRFs) and 1 tRNA half (tiRNA) which showed a significant level decrease after exposure to three kinds of radiations. Moreover, the radiation responses of these 5 serum tsRNAs were reproduced in other mouse strains, and the sequences of them could be detected in serum of humans. Furthermore, we developed multi-factor models based on tsRNA biomarkers to indicate the degree of radiation exposure with high sensitivity and specificity. These findings suggest that the circulating tsRNAs can serve as new minimally invasive biomarkers and can make a triage or dose assessment from blood sample collection within 4 h in exposure scenarios.