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Implementation of a systematic program for galactic cosmic radiation (GCR) countermeasure discovery will require convenient access to ground-based space radiation analogs. The current gold standard approach for GCR simulation is to use a particle accelerator for sequential irradiation with ion beams representing different GCR components. This has limitations, particularly for studies of non-acute responses, strategies that require robotic instrumentation, or implementation of complex in vitro models that are emerging as alternatives to animal experimentation. Here we explore theoretical and practical issues relating to a different approach to provide a high-LET radiation field for space radiation countermeasure discovery, based on use of compact portable sources to generate neutron-induced charged particles. We present modeling studies showing that DD and DT neutron generators, as well as an AmBe radionuclide-based source, generate charged particles with a linear energy transfer (LET) distribution that, within a range of biological interest extending from about 10 to 200 keV/μm, resembles the LET distribution of reference GCR radiation fields experienced in a spacecraft or on the lunar surface. We also demonstrate the feasibility of using DD neutrons to induce 53BP1 DNA double-strand break repair foci in the HBEC3-KT line of human bronchial epithelial cells, which are widely used for studies of lung carcinogenesis. The neutron-induced foci are larger and more persistent than X ray-induced foci, consistent with the induction of complex, difficult-to-repair DNA damage characteristic of exposure to high-LET (10 keV/μm) radiation. We discuss limitations of the neutron approach, including low fluence in the low LET range (10 keV/μm) and the absence of certain long-range features of high charge and energy particle tracks. We present a concept for integration of a compact portable source with a multiplex microfluidic in vitro culture system, and we discuss a pathway for further validation of the use of compact portable sources for countermeasure discovery.

Proneural (PN) to mesenchymal (MES) transition (PMT) is a crucial phenotypic shift in glioblastoma stem cells (GSCs). However, the mechanisms driving this process remain poorly understood. Here, we report that Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key player in regulating PMT. FOSL1 is predominantly expressed in the MES subtype, but not PN subtype, of GSCs. Knocking down FOSL1 expression in MES GSCs leads to the loss of MES features and tumor-initiating ability, whereas ectopic expression of FOSL1 in PN GSCs is able to induce PMT and maintain MES features. Moreover, FOSL1 facilitates ionizing radiation (IR)-induced PMT and radioresistance of PN GSCs. Inhibition of FOSL1 enhances the anti-tumor effects of IR by preventing IR-induced PMT. Mechanistically, we find that FOSL1 promotes UBC9-dependent CYLD SUMOylation, thereby inducing K63-linked polyubiquitination of major nuclear factor κB (NF-κB) intermediaries and subsequent NF-κB activation, which results in PMT induction in GSCs. Our study underscores the importance of FOSL1 in the regulation of PMT and suggests that therapeutic targeting of FOSL1 holds promise to attenuate molecular subtype switching in patients with glioblastomas.

Ionizing radiation is used to create models of accelerated aging because the processes of aging and radiation injury share common elements. In this chapter we review the biological processes of aging and the similarities and impact of ionizing radiation on those processes. The information draws on data from laboratory studies and from epidemiology studies of radiation exposure victims. The chapter reviews the effects of radiation on DNA, cells, and organs systems on aged adults. The science of aging and the effect of radiation on the aging process are areas of active research and our understanding is evolving.

Purpose Cell cycle checkpoints and DNA repair are important for cell survival after exogenous DNA damage. Both rapid blockage of G2 to M phase transition in the cell cycle and the maintenance of relatively slow G2 arrest are critical to protect cells from lethal ionizing radiation (IR). Checkpoint kinase 1 is pivotal in blocking the transition from G2 to M phases in response to IR. The 14-3-3σ protein is important for IR-induced G2 arrest maintenance in which p53-dependent 14-3-3σ transcription is involved. It has been demonstrated that Ring finger protein 126 (RNF126), an E3 ligase, is required to upregulate checkpoint kinase 1 expression. Thus, our goal was to study the role of RNF126 in the G2/M phase checkpoint. Methods and Materials The transition from G2 to M phases and G2 accumulation in response to IR were determined by flow cytometry through staining with phospho-histone H3 (pS10) antibody and propidium iodide, respectively. The interaction of RNF126 and 14-3-3σ was determined by GST-pulldown and coimmunoprecipitation assays. The stability of RNF126 and 14-3-3σ was determined by cycloheximide-based stability assay and ubiquitination detection by coimmunoprecipitation. The sequestering of cyclin-dependent kinase 1 and cyclin B1 from the nucleus was determined by immunofluorescence staining. Results RNF126 knockdown had no impact on the IR-induced transient blockage of G2 to M but impaired IR-induced G2 arrest maintenance in cells with or without wild-type p53. Mechanistically, RNF126 binds 14-3-3σ and prevents both proteins from ubiquitination-mediated degradation. Last, RNF126 is required for enforcing the cytoplasmic sequestration of cyclin B1 and cyclin-dependent kinase 1 proteins in response to IR. Conclusions RNF126 promotes G2 arrest via interaction with 14-3-3σ in response to IR. Our study revealed a novel role for RNF126 in promoting G2 arrest, providing a new target for cancer treatment.

Although the DNA damage response (DDR) is associated with the radioresistance characteristics of lung cancer cells, the specific regulators and underlying mechanisms of the DDR are unclear. Here, we identified the serine proteinase inhibitor clade E member 2 (SERPINE2) as a modulator of radiosensitivity and the DDR in lung cancer. Cells exhibiting radioresistance after ionizing radiation show upregulation of SERPINE2, and SERPINE2 knockdown improves tumor radiosensitivity in vitro and in vivo. Functionally, SERPINE2 deficiency causes a reduction in homologous recombination repair, rapid recovery of cell cycle checkpoints, and suppression of migration and invasion. Mechanistically, SERPINE2 knockdown inhibits the accumulation of p-ATM and the downstream repair protein RAD51 during DNA repair, and RAD51 can restore DNA damage and radioresistance phenotypes in lung cancer cells. Furthermore, SERPINE2 can directly interact with MRE11 and ATM to facilitate its phosphorylation in HR-mediated DSB repair. In addition, high SERPINE2 expression correlates with dismal prognosis in lung adenocarcinoma patients, and a high serum SERPINE2 concentration predicts a poor response to radiotherapy in non-small cell lung cancer patients. In summary, these findings indicate a novel regulatory mechanism by which SERPINE2 modulates the DDR and radioresistance in lung cancer.

The biological damage caused by the environmental factors such as radiation and its control methods are one of the frontiers of life science research that has received widespread attention. Ionizing radiation can directly interact with target molecules (such as DNA, proteins and lipids) or decomposed by radiation from water, leading to changes in oxidative events and biological activities in cells. Liver is a radiation-sensitive organ, and its radiosensitivity is second only to bone marrow, lymph, gastrointestinal tissue, gonads, embryos and kidneys. In addition, as a key organ of mammals, liver performs a series of functions, including the production of bile, the metabolism of nutrients, the elimination of waste, the storage of glycogen, and the synthesis of proteins. Therefore, liver is prone to various pathophysiological changes. In this review, the effects of radiation on liver injury, its pathogenesis, bystander effect and the natural traditional Chinese medicine to protect the radiation induced liver damage are discussed.

As a common treatment of human glioma, ionizing radiation (IR) was reported to result in cell cycle arrest. However, the mechanisms underlying IR-induced abnormal cell cycle remain largely unclear. Here we found that IR caused an elevated expression of B-Myb and cell cycle-related proteins, as well as G2/M phase arrest in U251 cells instead of U87 cells. However, the knockdown of B-Myb by small interfering RNAs ameliorated the increasing of cell cycle-related proteins and G2/M phase arrest induced by IR. Further analysis demonstrated that decreased-B-Myb enhanced the sensitivity of U251 cells to IR. Moreover, the establishment of H1299 cell line proved that B-Myb expression was associated with the status of p53. Immunoprecipitation (IP) and chromatin immunoprecipitation (CHIP) assay results indicated that mutant p53 and SP1 regulated the expression of B-Myb via different mechanisms. This study not only elucidated the role of B-Myb in IR-induced cell cycle alternation, but also provided insight into mechanism of B-Myb expression.

Ionizing radiation (IR)-induced excessive reactive oxygen species (ROS) is an important contributor of the injury of hematopoietic system. Grape seed proanthocyanidin extract (GSPE) is a new type of antioxidant, whereas whether it could ameliorate IR-induced hematopoietic injury remains unclear. Here, we show that GSPE treatment improves the survival of irradiated mice and alleviates IR-induced myelosuppression. Meanwhile, the hematopoietic reconstituting ability of hematopoietic stem cells (HSCs) in mice following irradiation exposure is significantly increased after GSPE treatment. Furthermore, GSPE treatment can reduce IR-induced ROS production and relieve DNA damage and apoptosis in hematopoietic stem progenitor cells (HSPCs). Interestingly, we find that a critical antioxidant-associated gene fokhead box transcription factor O1 (Foxo1) is significantly decreased in HSPCs after irradiation. Consistently, hematopoietic specific deletion of Foxo1 increases the radiosensitivity of mice. Further investigations reveal that GSPE treatment specifically upregulates the expression of Foxo1, as well as its target genes superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) and catalase (CAT). Importantly, Foxo1 deficiency largely abolishes the radioprotection of GSPE on HSPCs. Collectively, our data demonstrate that GSPE plays an important role in ameliorating IR-induced HSPC injury via the Foxo1-mediated pathway. Therefore, GSPE may be used as a promising radioprotective agent.

Radiation is widely used for cancer treatment but the radioresistance properties of cancer stem cells (CSCs) pose a significant challenge to the success of cancer therapy. Nuclear factor erythroid-2-related factor 2 (Nrf2) has emerged as a prominent regulator of cellular antioxidant responses and its over-activation is associated with drug resistant in cancer cells. However, the role of Nrf2 signaling in regulating the response of CSCs to irradiation has yet to be defined. Here, we show that exposure of triple-negative breast cancer (TNBC) cells to ionizing radiation (IR) upregulates Nrf2 expression and promotes its nuclear translocation in a reactive oxygen species (ROS)-dependent manner. Ectopic overexpression of Nrf2 attenuates, whereas knockdown of Nrf2 potentiates IR-induced killing of TNBC CSCs. Mechanistically, we found that Nrf2 knockdown increases IR-induced ROS production and impedes DNA repair at least in part via inhibition of DNA-PK. Furthermore, activation of Nrf2 by sulforaphane diminishes, whereas inhibition of Nrf2 by ML385 enhances IR-induced killing of TNBC CSCs. Collectively, these results demonstrate that IR-induced ROS production can activate Nrf2 signaling, which in turn counteracts the killing effect of irradiation. Therefore, pharmacological inhibition of IR-induced Nrf2 activation by ML385 could be a new therapeutic approach to sensitize therapy-resistant CSCs to radiotherapy.

Objectives The objectives of the review were to investigate the legal and sociological basis of justification in society in order to fully assess its relevance to radiation protection. The difference between the justification of practices as distinct from the justification of reasons for the justification of individual activities within a practice and the relevance of cost–benefit analysis to this process are key elements. Key findings Justification of practices as a principle of radiation protection is automatically enshrined within the appropriate legislation once it has been enacted. However, the justification of reasons for justification of activities within a practice are subject to many sociological factors, which are often conflicting and indeterminate and can be subject to political, economic and environmental factors that may change over time. This applies especially to new developments where the primary reason for justification is based upon potential but possibly ill-defined future benefits. Conclusion The primary mechanism whereby society develops a collective consensus on the justification of practices lies within a legal framework. This represents the mechanism by which society defines the accepted standards that must be applied for acceptance of a practice. The justification of reasons for justifying activities that form part of a practice has largely been ignored within the framework of radiation protection. Implications for practice The employment of justification of practices as a fundamental principle of radiation protection should be eliminated since it is already enshrined within the legal framework applicable to applications of ionising radiation. Justification of reasons for pursuing new or modified practices is based upon their perceived benefits to society, which underpins most developments in society.

Radiation enteritis (RE) is the most common radiotherapy complication, and effective RE treatments are lacking. Resveratrol exerts beneficial effects on radiation injury. However, the effect of resveratrol in radiation-induced intestinal injury and the underlying mechanism remain unclear. Here, a C57BL/6 mouse model of RE was established and an intestinal epithelial cell line was used to evaluate the protective effects of resveratrol against radiation-induced intestinal injury and the underlying mechanisms. Resveratrol improved radiation-induced oxidative stress and cell apoptosis via upregulating antioxidant enzymes and downregulating p53 acetylation. In vivo, resveratrol-treated mice exhibited longer survival; longer villi; more intestinal crypt cells; upregulated expression of Ki67, catalase, and superoxide dismutase 2; and fewer inflammatory proteins and apoptotic cells. These protective effects were suppressed by inhibition of SIRT1. These results demonstrate that resveratrol can reduce radiation-induced intestinal injury by inhibiting oxidative stress and apoptosis via the SIRT1/FOXO3a and PI3K/AKT pathways.

The efficacy of radiotherapy depends not only on DNA damage but also on ROS production, both induced by ionizing radiation. Massive ROS production can induce cell death or activate protective pathways such as Keap1/Nrf2 pathway, which regulates intracellular cysteine availability through upregulation of SLC7A11, a subunit of xCT transporter, and subsequently glutathione synthesis, thus improving antioxidative defense. The anti-malaria drug dihydroartemisinin (DHA) shows anti-neoplastic potential. Previous publications suggested that DHA increased ROS production. We intended to enhance oxidative stress with DHA to improve the efficacy of radiotherapy. Therefore, we first analyzed the oxidative response to DHA in HCT116 colorectal and NCI–H460 lung adenocarcinoma cells. In response to DHA, we detected lipid peroxidation and protein oxidation, which resulted in mitochondrial damage and eventually in iron-dependent cell death. Concurrently, DHA activated Keap1/Nrf2 pathway in HCT116 cells, leading to increased SLC7A11 expression and glutathione level. In Keap1-mutant NCI–H460 cells, Nrf2 was constantly activated and responsible for high SLC7A11 and glutathione levels. Pancancer analysis revealed that lung cancer is the tumor entity with the most frequent Keap1 alterations. Although NCI–H460 cells reacted more refractory to DHA-induced cell death than HCT116 cells, eradication of clonogenic cells by DHA was more efficient in both cell lines when Keap1/Nrf2 pathway was inhibited. When applied simultaneously, radiotherapy and DHA more efficiently eradicated clonogenic cells than either therapy alone, but treatment schedule can mitigate the combinatory effect in HCT116 cells. In summary, DHA improved efficacy of radiotherapy, but treatment schedule must be considered with care especially in Keap1-wildtype cells.

In Europe, the male to female ratio at birth (secondary sex ratio: SSR; sex odds: SO) is 1.04-1.06, is influenced by many factors and is declining in industrialized countries. This study was carried out to identify possible impacts of fallout by atomic bomb tests or by the Chernobyl event on SSR in Italy. Italy is a country without commercial nuclear power generation for the last four decades and thus nearly free of radiological confounders. Counts of annual male and female live births in Italy are provided by the World Health Organization (WHO) and by the Italian Istituto Nazionale di Statistica (ISTAT). This study included 57.7 million live births (1940-2019) with overall SSR 1.05829. The Italian SSR trend was modelled with linear and non-linear logistic regression. Trend changes, i.e., periods with level shifts were estimated with Markov Chain Monte Carlo (MCMC). Two distinct idealized level shifts were identified superimposed on a uniform secular downward trend. The first one is seen towards the end of the 1960s with a jump sex odds ratio (SOR) 1.00681, p

Background and purpose Ionising radiation causes mutations in the genomes of tumour cells and serves as a potent treatment for cancer. However, the mutation signatures in the cancer genome following ionising radiation have not been documented. Materials and methods We established an in vitro experimental system to analyse the presence of de novo mutations in the cancer genome of irradiated (60 Gy/20 fr/4 weeks) oesophageal cancer cell lines. Subsequently, we performed whole-genome, chromatin immunoprecipitation, and RNA sequencing using untreated and irradiated samples to assess the damage to the genome caused by radiation and understand the underlying mechanism. Results The irradiated cancer cells exhibited hotspots for the de novo 8502–12966 single nucleotide variants and 954–1,331 indels on the chromosome. These single nucleotide variants primarily originated from double-stranded break repair errors, as determined using mutation signature analysis. The hotspots partially overlapped with the sites of H3K9 trimethylation, which are regions characterised by a weak capacity for double-stranded break repair. Conclusion This study highlights the signature and underlying mechanism of radiation on the cancer genome.

In this review, we will specifically address the newest insights on the effect of low doses of ionizing radiations on the hematopoietic stem cells, which are prone to long-term deleterious effects. Impact of high doses of irradiation on hematopoietic cells has been widely studied over the years, in line with the risk of accidental or terrorist exposure to irradiation and with a particular attention to the sensitivity of the hematopoietic system. Recently, more studies have focused on lower doses of irradiation on different tissues, due to the increasing exposure caused by medical imaging, radiotherapy or plane travelling for instance. Hence, we will delineate similarities and discrepancies in HSC response to high and low doses of irradiation from these studies.

The high-throughput analysis of gene expression in ionizing radiation (IR)-exposed human peripheral white blood cells (WBC) has emerged as a novel method for biodosimetry markers detection. We aimed to detect IR-exposure differential expressed genes (DEGs) as potential predictive biomarkers for biodosimetry and radioinduced-response.We performed a meta-analysis of raw data from public microarrays of ex vivo low linear energy transfer-irradiated human peripheral WBC. Functional enrichment and transcription factors (TF) detection from resulting DEGs were assessed. Six selected DEGs among studies were validated by qRT-PCR on mRNA from human peripheral blood samples from nine healthy human donors 24 h after ex vivo X-rays-irradiation.We identified 275 DEGs after IR-exposure (parameters: |lfc| ≥ 0.7, q value0.05), enriched in processes such as regulation after IR-exposure, DNA damage checkpoint, signal transduction by p53 and mitotic cell cycle checkpoint. Among these DEGs, DRAM1, NUDT15, PCNA, PLK2 and TIGAR were selected for qRT-PCR validation. Their expression levels significantly increased at 1-4 Gy respect to non-irradiated controls. Particularly, PCNA increased dose dependently. Curiously, TCF4 (Entrez Gene: 6925), detected as overrepresented TF in the radioinduced DEGs set, significantly decreased post-irradiation.These six DEGs show potential to be proposed as candidates for IR-exposure biomarkers, considering their observed molecular radioinduced-response. Among them, TCF4, bioinformatically detected, was validated herein as an IR-responsive gene.

Summary Epithelial regeneration is critical for barrier maintenance and organ function after intestinal injury, although the repair mechanisms are unclear. Here, we found that Bach2 deficiency promotes intestinal epithelial cell proliferation during homeostasis. Moreover, genetic inactivation of Bach2 in mouse intestinal epithelium facilitated crypt regeneration after irradiation, resulting in a reduction in mortality. RNA-sequencing analysis of isolated crypts revealed that Bach2 deficiency altered the expression of numerous genes, including those regulating double-strand break repair. Mechanistic characterizations indicated that Bach2 deletion facilitated DNA repair in intestinal crypt cells, as evidenced by faster resolution of γ-H2AX and 53BP1 foci in Bach2−/− crypt cells, compared with Bach2+/+ control. Together, our studies highlight that Bach2 deficiency promotes intestinal regeneration by accelerating DNA repair in intestinal stem cells after radiation damage., Graphical Abstract, Highlights • Bach2 deficiency facilitates intestinal recovery after irradiation damage • Bach2 deficiency promotes the regeneration of crypt intestinal stem cells (ISCs) • Bach2 deletion accelerates DNA repair in ISCs, Radiation causes intestinal injury, as occurs in abdominal and pelvic tumor radiotherapy. Intestinal stem cells (ISCs) are critical for epithelial regeneration. In this article, Hua and colleagues show that Bach2 deficiency promotes intestinal epithelial regeneration by accelerating DNA repair in ISCs, resulting in a reduction in mortality during radiation-induced intestine injury.

Radiotherapy combined with chemotherapy is a common modality in abdominal cancer treatment. However, intestinal syndrome induced by radiation is a main factor leading to the poor prognosis of radiotherapy. In this work, we found that miR-378a-3p was markedly up-regulated in the small intestines of mice after total abdominal irradiation. Knocking-down (or overexpression) of miR-378a-3p increased (or decreased) the radiosensitivity of the small intestine cells HIEC and FHs-74-Int. Comet assay and γ-H2AX staining demonstrated that miR-378a-3p exerted its radioprotective function by reducing the accumulation of DNA damage in the cells and tissues of the small intestines. Mechanistically, miR-378a-3p could interact with the 3' UTR of CDK6 through complementary sequences and thus inhibited CDK6 expression in the small intestine cells. Rescue experiments suggested that the repression of miR-378a-3p overexpression on cell radiosensitivity and DNA damage accumulation was abrogated by the forced expression of CDK6. In summary, our results revealed for the first time that miR-378a-3p regulated the radiosensitivity and DNA damage response of small intestines by targeting CDK6. MiR-378a-3p may serve as a promising biomarker and radioprotective target in abdominal cancer.

Amifostine is a cytoprotective agent against the hematopoietic damage induced by ionizing radiation, although the intravenous injection of amifostine is a unique administration method with strict dosing time limitation. Hence, the fields of application of amifostine are greatly limited. Here, we developed an amifostine-loaded armored microneedle (AAMN) with long-term prevention of hematopoietic injury induced by ionizing radiation. First, amifostine-loaded hyaluronic acid microneedles (AMNs) were fabricated, and the AMNs were then dipped in an N-vinyl-2-pyrrolidone (NVP) solution followed by ultraviolet (UV) photocuring to obtain AAMNs. AAMNs were nail-shaped with much higher mechanical strength compared to the conical shape and weak strength of AMNs, which was verified by their in silico simulation. In the in vitro release experiment, more than 55% of amifostine was released from AAMNs within 10 min, and 95% was released in 60 min. Drug skin permeation of AAMNs was also high, at twice that of AMNs. AAMNs provided long-term protection of the hematopoietic system from radiation within 3-7 h pre-radiation compared to the unique amifostine injection 0.5 h pre-radiation because topical application of AAMNs led to the long-term maintenance of the in vivo effective drug concentration. More importantly, AAMNs led to the survival of all irradiated mice due to intravenous amifostine. AAMNs are a promising transdermal delivery system of amifostine for long-term protection against ionizing radiation-induced injury. STATEMENT OF SIGNIFICANCE: An amifostine-loaded dissolving armored microneedle (AAMN) patch is developed for long-term prevention of ionizing radiation-induced injury. High drug loads in microneedles (MNs) with adequate mechanical strength is a challenge. We fabricated armors on the surface of high amifostine-loaded hyaluronic acid microneedles (AMNs) by dipping the tips of AMNs in N-vinyl-2-pyrrolidone (NVP) solutions and then subjecting them to UV irradiation, and high-strength armored AMNs (AAMNs) were obtained. AAMNs show deeper skin insertion and much higher drug permeation than AMNs. The controlled drug release from AAMNs in the mouse skins provides a long-term protection of radiation-induced injury with 3-7 h administration pre-radiation compared to the merely 0.5-h point of amifostine injection.

The present study illustrates mitochondria-mediated impact of ionizing radiation showing that are paralleled by activation of several pro-adaptive responses in normal human dermal fibroblast cells. Irradiation of cells with X-rays (5 Gy) led to an increase in fragmentation and mitochondrial mass. Distinct temporal changes in cytosolic and mitochondrial reactive oxygen species (ROS) were noted in response to radiation, which was associated with depletion in mitochondrial membrane potential followed by decrease in ATP levels. Long Amplicon-Polymerase Chain Reaction (LA-PCR) analysis showed time-dependent increase in mitochondrial DNA damage that preceded mitochondrial ROS generation. Irradiation of cells led to an initial G2/M arrest at 8 h that persisted till 16 h, with subsequent block at G0/G1 measured at 48 and 72 h time points. Interestingly, cells activated autophagy as a countermeasure against radiation-mediated cellular insults and aided in removal of damaged mitochondria. Blocking autophagy using 3-methyladenine led to cell death via activation of enhanced ROS, PARP-1 and caspase 3 cleavage. Upregulation of mitochondrial biogenesis factors Nrf1/PGC-1α, following irradiation was observed. Irradiated cells exhibited an increase in the phosphorylation of GCN2, PERK and eIF2α that might be responsible for the up-regulation of ATF4 and CHOP thereby regulating autophagy and components of integrated stress response. Apart from this, we measured accumulation of mitochondrial chaperones (HSP60/HSP10) and ATF5 which is a major molecule involved in mitochondrial stress. Taken together, mitochondria are one of the major cytoplasmic targets for ionizing radiation and possibly act as an early indicator of cellular insult. The findings also show that stressed mitochondria might influence endoplasmic reticulum (ER)-related signalling leading to the activation of adaptive mechanisms like cytoprotective autophagy, and molecules responsible for mitochondrial biogenesis and protein quality control in order to replenish mitochondrial pool and maintain cellular homeostasis.

Most of the research in understanding space radiation-induced cancer progression and risk assessment has been performed using mono-energetic single-ion beams. However, the space radiation environment consists of a wide variety of ion species with a various range of energies. Using the fast beam switching technology developed at the NASA Space Radiation Laboratory (NSRL) at Brookhaven National Laboratory (BNL), ion species can be switched rapidly allowing investigators to use multiple ions with different energies to simulate more closely the radiation environment found in space. Here, we exposed a lung cancer susceptible mouse model (K-rasLA-1) to three sequential ion beams: Proton (H) (120 MeV/n) 20 cGy, Helium (He) (250 MeV/n) 5.0 cGy, and Silicon (Si) (300 MeV/n) 5.0 cGy with a dose rate of 0.5 cGy/min. Using three ion beams we performed whole body irradiation with a total dose of 30 cGy in two different orders: 3B-1 (H→He→Si) and 3B-2 (Si→He→H) and used 30 cGy H single-ion beam as a reference. In this study we show that whole-body irradiation with H→He→Si increases the incidence of premalignant lesions and systemic oxidative stress in mice 100 days post-irradiation more than (Si→He→H) and H only irradiation. Additionally, we observed an increase in adenomas with atypia and adenocarcinomas in H→He→Si irradiated mice but not in (Si→He→H) or H (30 cGy) only irradiated mice. When we used the H→He→Si irradiation sequence but skipped a day before exposing the mice to Si, we did not observe the increased incidence of cancer initiation and progression. We also found that a non-toxic anti-inflammatory, anti-oxidative radioprotector (CDDO-EA) reduced H→He→Si induced oxidative stress and cancer initiation almost back to baseline. Thus, exposure to H→He→Si elicits significant changes in lung cancer initiation that can be mitigated using CDDO-EA.

In space, multiple unique environmental factors, particularly microgravity and space radiation, pose a constant threat to astronaut health. MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are functional RNAs that play critical roles in regulating multiple cellular processes. To gain insight into the role of non-coding RNAs in response to radiation and microgravity, we analyzed RNA expression profiles in human lymphoblastoid TK6 cells incubated for 24 h under static or rotating conditions to stimulate microgravity in space, after 2-Gy γ-ray irradiation. The expression of 14 lncRNAs and 17 mRNAs (differentially-expressed genes, DEGs) was found to be significantly downregulated under simulated microgravity conditions. In contrast, irradiation upregulated 55 lncRNAs and 56 DEGs, whereas only one lncRNA, but no DEGs, was downregulated. Furthermore, two miRNAs, 70 lncRNAs, and 87 DEGs showed significantly altered expression in response to simulated microgravity after irradiation, and these changes were independently induced by irradiation and simulated microgravity. GO enrichment and KEGG pathway analyses indicated that the associated target genes showed similar patterns to the noncoding RNAs and were suggested to be involved in the immune/inflammatory response including LPS/TLR, TNF, and NF-κB signaling pathways. However, synergistic effects on RNA expression and cellular responses were also observed with a combination of simulated microgravity and irradiation based on microarray and RT-PCR analysis. Together, our results indicate that simulated microgravity and irradiation additively alter expression patterns but synergistically modulate the expression levels of RNAs and their target genes in human lymphoblastoid cells.

Introduction Informed consent for ionising radiation medical imaging examinations is currently undertaken inconsistently in Australian radiographic practice. There is no uniform informed consent process, and opinions vary about how it should be undertaken, and by whom, if indeed it needs to be undertaken at all. To ensure that patients’ rights are maintained, the informed consent process must be consistent, proactive in the provision of information, and must empower the patient to formulate and ask questions about their care, and to make voluntary decisions. Methods The Delphi technique utilises a group of experts whose individual responses are used to create a collective consensus on a process. This ten-expert (five radiographer, five radiologist) Delphi study examined a basic modelling of the process of informed consent for ionising radiation medical imaging examinations and made recommendations for an ideal process. Results A series of consensus statements were developed, seeking to rectify areas of the process that were inconsistent, unclear, or ethically unsound. These statements were then considered alongside current codes of professional practice, and Australian law on the duty of disclosure. A model of the ideal process was then developed using these consensus statements and adhering to codes of practice. Conclusion The final process model has a continuity of care and a continuity of information provision. The model eliminates the radiographer as a delegatee, and emphasises physician involvement. The referrer and the radiologist have a shared responsibility of providing risk disclosure information. Implications for Practice: For a non-pregnant adult, the ionising radiation dose from conventional radiography is considered insignificant, and does not require risk disclosure, ameliorating the time commitment needed for the process.

The molecular mechanisms underlying exceptional radioresistance in pancreatic cancer remain elusive. In the present study, we established a stable radioresistant pancreatic cancer cell line MIA PaCa-2-R by exposing the parental MIA PaCa-2 cells to fractionated ionizing radiation (IR). Systematic proteomics and bioinformatics analysis of protein expression in MIA PaCa-2 and MIA PaCa-2-R cells revealed that several growth factor-/cytokine-mediated pathways, including the OSM/STAT3, PI3K/AKT, and MAPK/ERK pathways, were activated in the radioresistant cells, leading to inhibition of apoptosis and increased epithelial-mesenchymal plasticity. In addition, the radioresistant cells exhibited enhanced capabilities of DNA repair and antioxidant defense compared with the parental cells. We focused functional analysis on one of the most up-regulated proteins in the radioresistant cells, ecto-5′-nucleotidase (CD73), which is a cell surface protein that is overexpressed in different types of cancer. Ectopic overexpression of CD73 in the parental cells resulted in radioresistance and conferred resistance to IR-induced apoptosis. Knockdown of CD73 re-sensitized the radioresistant cells to IR and IR-induced apoptosis. The effect of CD73 on radioresistance and apoptosis is independent of the enzymatic activity of CD73. Further studies demonstrate that CD73 up-regulation promotes Ser-136 phosphorylation of the proapoptotic protein BAD and is required for maintaining the radioresistant cells in a mesenchymal state. Our findings suggest that expression alterations in the IR-selected pancreatic cancer cells result in hyperactivation of the growth factor/cytokine signaling that promotes epithelial-mesenchymal plasticity and enhancement of DNA repair. Our results also suggest that CD73, potentially a novel downstream factor of the enhanced growth factor/cytokine signaling, confers acquired radioresistance by inactivating proapoptotic protein BAD via phosphorylation of BAD at Ser-136 and by maintaining the radioresistant pancreatic cancer cells in a mesenchymal state.

Several trials have attempted to identify sources of inter-laboratory variability in comet assay results, aiming at achieving more equal responses. Ionising radiation induces a defined level of DNA single-strand breaks (per dose/base pairs) and is used as a reference when comparing comet results but relies on accurately determined radiation doses. In this ring test we studied the significance of dose calibrations and comet assay protocol differences, with the object of identifying causes of variability and how to deal with them. Eight participating laboratories, using either x-ray or gamma radiation units, measured dose rates using alanine pellet dosimeters that were subsequently sent to a specialised laboratory for analysis. We found substantial deviations between calibrated and nominal (uncalibrated) dose rates, with up to 46% difference comparing highest and lowest values. Three additional dosimetry systems were employed in some laboratories: thermoluminescence detectors and two aqueous chemical dosimeters. Fricke’s and Benzoic Acid dosimetry solutions gave reliable quantitative dose estimations using local equipment. Mononuclear cells from fresh human blood or mammalian cell lines were irradiated locally with calibrated (alanine) radiation doses and analysed for DNA damage using a standardised comet assay protocol and a lab-specific protocol. The dose response of eight laboratories, calculated against calibrated radiation doses, was linear with slope variance CV= 29% with the lab-specific protocol, reduced to CV= 16% with the standard protocol. Variation between laboratories indicate post-irradiation repair differences. Intra-laboratory variation was very low judging from the dose response of 8 donors (CV=4%). Electrophoresis conditions were different in the lab-specific protocols explaining some dose response variations which were reduced by systematic corrections for electrophoresis conditions. The study shows that comet assay data obtained in different laboratories can be compared quantitatively using calibrated radiation doses and that systematic corrections for electrophoresis conditions are useful. Several trials have attempted to identify sources of inter-laboratory variability in comet assay results, aiming at achieving more equal responses. Ionising radiation induces a defined level of DNA single-strand breaks (per dose/base pairs) and is used as a reference when comparing comet results but relies on accurately determined radiation doses. In this ring test we studied the significance of dose calibrations and comet assay protocol differences, with the object of identifying causes of variability and how to deal with them. Eight participating laboratories, using either x-ray or gamma radiation units, measured dose rates using alanine pellet dosimeters that were subsequently sent to a specialised laboratory for analysis. We found substantial deviations between calibrated and nominal (uncalibrated) dose rates, with up to 46% difference comparing highest and lowest values. Three additional dosimetry systems were employed in some laboratories: thermoluminescence detectors and two aqueous chemical dosimeters. Fricke's and Benzoic Acid dosimetry solutions gave reliable quantitative dose estimations using local equipment. Mononuclear cells from fresh human blood or mammalian cell lines were irradiated locally with calibrated (alanine) radiation doses and analysed for DNA damage using a standardised comet assay protocol and a lab-specific protocol. The dose response of eight laboratories, calculated against calibrated radiation doses, was linear with slope variance CV= 29% with the lab-specific protocol, reduced to CV= 16% with the standard protocol. Variation between laboratories indicate post-irradiation repair differences. Intra-laboratory variation was very low judging from the dose response of 8 donors (CV=4%). Electrophoresis conditions were different in the lab-specific protocols explaining some dose response variations which were reduced by systematic corrections for electrophoresis conditions. The study shows that comet assay data obtained in different laboratories can be compared quantitatively using calibrated radiation doses and that systematic corrections for electrophoresis conditions are useful.

Ionizing radiation (IR) has found widespread application in modern medicine. As a result, radiotherapy inevitably causes spermatogenic cell injury. Many Chinese herbal prescriptions or natural extracts have the potential to protect against radiation injury.We used GC-2spd cells to investigate the effects and potential mechanisms of YQJD decoction on protecting spermatogenic cells from ionizing radiation injury.Firstly, the GC-2spd cells were irradiated withAfter irradiation withTaken together, the protective effects of YQJD decoction on

Hair follicles (HFs) are stem-cell-rich mammalian mini-organs that can undergo cyclic regenerations over the life span of the organism. The cycle of a HF consists of three consecutive phases: anagen-the active proliferation phase, catagen-the degeneration phase, and telogen-the resting phase. While HFs undergo irreversible degeneration during catagen, recent experimental research on mice shows that when anagen HFs are subject to ionizing radiation (IR), they undergo a transient degeneration, followed by a nearly full regeneration that makes the HFs return to homeostatic state. The mechanisms underlying these IR-induced HF regenerative dynamics and the catagen degenerative dynamics, remain unknown. In this work, we develop an ODE type cell differentiation population model to study the control mechanisms of HF regeneration. The model is built based on current theoretical knowledge in biology and mathematically formulated using feedback mechanisms. Model parameters are calibrated to IR experimental data, and we then provide modeling results with both deterministic ODE simulations and corresponding stochastic simulations. We perform stability and bifurcation analyses on the ODE model, which reveal that for anagen HFs, a low spontaneous apoptosis rate secures the stability of the HF homeostatic steady state, allowing the HF to regenerate even when subject to strong IR. On the other hand, the irreversible degeneration during catagen results from both strong spontaneous apoptosis rate and strong apoptosis feedback. Lastly, we perform sensitivity analysis to identify key parameters in the model to validate these hypotheses.

Advanced imaging techniques such as computed tomography are commonplace in human medicine and increasingly, are being utilized by the veterinary profession as scanners become more available and affordable. The benefit of computed tomography imaging is the provision of detailed cross-sectional imaging and 3D reconstruction, but this incurs higher doses of ionizing radiation to the patient. This paper reviews risks and effects associated with ionizing radiation, making comparisons to human models, and a hypothetical scenario is discussed using the human risk model for age at time of exposure and increased lifetime risk of cancer with a dog to human year's formula. Various issues are considered with respect to dose reduction, training, equipment and the reported "greater need for guidance and the establishment of best practice" which may lead to future guidance from the International Commission on Radiological Protection.

This study has developed a relationship that categorized radiation protection and allows for a proper, clear, and concise review of the different classifications in terms of principles of protection, dose criteria, categories, fundamental tools, exposure situations, applications and control measures. With the groundwork laid, advances of the linear no-threshold (LNT) model which has attracted attention in the field of radiobiology and epidemiology were examined in detail. Various plausible dose-response relationship scenarios were x-rayed under low-dose extrapolation. Intensive review of factors opposing the LNT model involving radiophobia (including misdiagnosis, alternative surgery/imaging, suppression of ionizing radiation (IR) research); radiobiology (including DNA damage repair, apoptosis/necrosis, senescence protection) and cost issues (including-high operating cost of LNT, incorrect prioritization, exaggeration of LNT impact, risk-to-benefit analysis) were performed. On the other hand, factors supporting the use of LNT were equally examined, they include regulatory bodies' endorsement, insufficient statistical significance, partial DNA repair, variability of irradiated bodies, different latency periods for cancer, dynamic nature of threshold and conflicting interests. After considering the gaps in the scientific investigations that either support or counter the scientific paradigm on the use of LNT model, further research and advocacy is recommended that will ultimately lead to the acceptance of an alternative paradigm by the international regulators.

This research was designed to ascertain the effect and mechanism of vinpocetine (VIN) and coenzyme Q10 (CoQ10) combination on cognitive impairment induced by ionizing radiation (IR).Cognitive impairment in mice was induced by 9-Gy IR, and they were intraperitoneally injected with VIN, CoQ10, or VIN + CoQ10. Then novel object recognition and Morris water maze tests were used to detect cognitive function. The number of hippocampal neurons and BrdUIR reduced novel object discrimination index, the time for platform crossing, and the time spent in platform quadrant, in addition to neuron loss, downregulated levels of mitochondrial respiratory complex I, ATP, and MMP, aggravated oxidative stress injury, increased expression of LC3 II/I, Beclin1, PINK1, and parkin, and decreased P62 expression. VIN or CoQ10 treatment mitigated cognitive dysfunction, neurons loss, mitochondrial damage, and oxidative stress injury, and enhanced mitophagy in hippocampal neurons. VIN and CoQ10 combination further protected against IR-induced cognitive dysfunction than VIN or CoQ10 alone.VIN combined with CoQ10 improved neuron damage, promoted mitophagy, and ameliorated cognitive impairment in IR mice.

Antibiotic fermentation residues (AFRs) have been classified as hazardous waste in China. Anaerobic fermentation may be a good approach for AFRs treatment, through which value-added chemicals could be obtained simultaneously. This study firstly explored medium-chain fatty acids (MCFAs) production from AFRs through two-stage anaerobic fermentation, and gamma radiation was adopted for AFRs pretreatment. The results showed that both antibiotics removal and MCFAs production from AFRs were significantly promoted by gamma radiation pretreatment. No residual Cephalosporin C (CEP-C) was detected in gamma radiation treated groups after fermentation. Highest MCFAs concentration of 90.55 mmol C/L was obtained in 50 kGy treated group, which was 2.22 times of the control group. Genera that were positively correlated with MCFAs production were enriched in gamma radiation treated groups, like genus Paraclostridium, Terrisporobacter, Caproiciproducens and Sporanaerobacter, while genera that were negatively correlated with MCFAs production were diminished during the chain elongation process, like genus Bacteroides and NK4A214_group. Enzymes analysis suggested that the promoted MCFAs production was induced by the enrichment of functional enzymes involved in Acetyl-CoA formation and RBO pathway. This work suggested that gamma radiation pretreatment and two-stage anaerobic fermentation could achieve the dual benefits of AFRs treatment and value-added chemicals recovery.

Radiation therapy continues to break down technological barriers to deliver ionizing radiation with exceptional anatomical precision. However, some tumor types and subtypes exhibit intrinsic biological resistance to radiotherapy, which can result in unsuccessful tumor eradication or symptom palliation. Radiation resistance can result from alterations in diverse genetic, epigenetic, and metabolic pathways. Therapeutic targeting of these tumor-specific alterations may provide tumor-selective radiosensitization with relative sparing of adjacent normal tissues. This issue of Seminars in Radiation Oncology presents a series of articles that describe recent progress towards genomically-directed radiosensitization.

Increases in childhood cancer near nuclear facilities in France and in Germany as well as elevated human birth sex ratios after the atmospheric atomic bomb tests and after Chernobyl motivated the inspection of the secondary sex ratio and the corresponding gender-specific birth counts in the vicinity of nuclear facilities. Focus is on which changes in the birth counts go along with significant changes in the sex ratios. Official municipality-specific annual birth counts by sex for all of France and for whole Germany are updated until 2016 and 2017, respectively. Using logistic regression, we determine significant change-points (jumps) after distinct radiological events in sex ratio time-trends in circular areas around pertinent nuclear facilities. With Poisson regression, we quantify the corresponding change-points in the trends of absolute annual birth counts for boys and girls. In the 35-km vicinity of the 'Centre de l'Aube Nuclear Disposal Facility (CSA)' in France in the year 2000, we observe a jump in the sex odds (SO) with sex odds ratio (SOR) 1.101; 95% CI: (1.033, 1.175), p-value 0.0033. This jump in the sex odds can be associated with a drop in boys of 3.44% (-4.02, 10.37), p-value 0.3561, and a drop in girls of 8.44% (1.33, 15.04), p-value 0.0208. In the highly populated area around the nuclear power plant Philippsburg in Germany from 2001 onward, we see a similar effect: SOR 1.027 (1.008, 1.046), p-value 0.0045; drop in boys 5.56% (2.24, 8.76), p-value 0.0012; drop in girls 6.92% (3.62, 10.10), p-value0.0001. The presented findings corroborate and specify earlier observations and call for intensifying bio-physical research in exposure mechanisms and exposure pathways of natural or artificial ionizing radiation including neutron radiation and neutron activation. Reinforced biological and epidemiological research should aim at clarifying the associated genetic and carcinogenic consequences at the population level.

PURPOSE:Quantitative susceptibility mapping (QSM) MRI is a tool that can characterize changes in susceptibility, an intrinsic property which is associated with compositional changes in the tissue. Current QSM estimation of cortical bone is challenging because conventional clinical MRI cannot acquire signal in cortical bone. This study aimed to implement Cones 3D ultrashort echo time MRI (UTE-MRI) for ex vivo QSM measurements in human tibial cortical bone, investigating the correlations of QSM with volumetric intracortical bone mineral density (BMD). MATERIALS AND METHODS:Nine tibial midshaft cortical bone specimens (25 mm long specimens cut at the mid-point of tibial shaft, 67 ± 20 years old, 5 women and 4 men) were scanned on a clinical 3 T MRI scanner for QSM measurement. The specimens were also scanned on a high-resolution micro-computed tomography (μCT) scanner for volumetric BMD estimation. QSM and μCT results were compared at approximately nine regions of interest (ROIs) per specimen. RESULTS:Average 3D UTE-MRI QSM showed significantly strong correlation with volumetric BMD (R = -0.82, P

Objective To assess cumulative radiation doses from computed tomography (CT), patient characteristics, and clinical indications for CT in a population-based sample. Patients and Methods A cohort study using medical records linkage through the Rochester Epidemiology Project was conducted to ascertain all CT examinations in Olmsted County, Minnesota, performed between January 1, 2004, and December 31, 2013, among all adults who were alive for 3 or more years after the end of follow-up (to exclude exposures preceding death). Ten-year cumulative effective ionizing radiation doses were estimated on the basis of typical doses per CT modality. Among patients with high doses (≥100 mSv/10 years), CT scans were reviewed for clinical setting, indications, and results. Results Of 54,447 adults (median age, 44.0 years at inclusion), 26,377 (48.4%) underwent at least one CT. Ten-year radiation doses from CT were 0.1 to 9.9 mSv in 15.8% of the population (8593 patients), 10 to 24.9 mSv in 16.9% (9502), 25 to 99.9 mSv in 13.8% (7492), and 100 mSv or greater in 1.9% (1041). Computed tomography of the abdomen and pelvis accounted for 67.2% of the estimated dose. In multivariable models, doses differed 1.21-fold to 2.16-fold between extreme categories of age, body mass index, education level, smoking status, and by race. Of 600 CTs in 200 patients with high doses, 70.5% were obtained for restaging of solid cancers and lymphoma, abdominal pain, infection, kidney stones, follow-up of nodules or masses, and chest pain/evaluation for pulmonary embolism. Conclusion Exposure to ionizing radiation from CT occurred disproportionally in specific subgroups of the population. A limited number of clinical indications contributed the majority of radiation among adults with high doses.

Background Advanced diagnostic imaging has provided tremendous benefits; however, increased use of ionizing radiation modalities such as cranial computed tomography (CT) may be associated with an increased risk of developing central nervous system tumors. Methods A literature review identified studies published for more than the last 50 years from 1968 to 2018 that explored the association between head CT scans and developing central nervous system tumors in pediatrics. We reviewed seven studies that described and analyzed the risk of brain tumors. Results A positive correlation between exposure to CT scans and developing central nervous system tumors was evident in all cohorts. The strength of the association varied across the studies. Exclusion of patients with predisposing factors to central nervous system tumors was examined in four studies with a decreased risk to develop central nervous system tumors noted in three studies. Two studies reported nonsignificant reduction in the excess relative risk per milliGray of brain dose after adjusting for predisposing factors, whereas the reduction was significant in one study. The frequency of CT exposure was proportional to the risk of developing tumors in two studies although not significantly maintained in two other studies. Gender had no significant effect on the central nervous system tumor risk. The calendar year at the time of imaging showed decreasing risk in those exposed to CT in more recent years compared with prior decades. Conclusions Prospective epidemiologic studies are needed to examine the precise carcinogenic effect of exposure to ionizing radiation and help tailor further preventive measures.

Radioresistance remains the most challenging issue leading to radiotherapy failure in the treatment of non-small cell lung cancer (NSCLC). The nuclear factor IA (NFIA) is associated with tumor response to treatments in many cancers, but its role in NSCLC radioresistance remains unclear. Here, we established two radioresistant NSCLC cell lines, H226R and H460R, by dose-gradient irradiation to investigate the function of NFIA in NSCLC radioresistance. The results showed a dramatically reduced expression of NFIA in radioresistant cells accompanied with elevated phosphorylation of AKT and ERK, when compared with their parental cells. Overexpression of NFIA restored the sensitivity of radioresistant cells to radiation through increased ionizing radiation (IR)-induced apoptosis and DNA damage by downregulating p-AKT and p-ERK, whereas knockdown of NFIA promoted radioresistance of the parental cells. Our findings suggested that NFIA enhanced cell radiosensitivity by downregulating p-AKT and p-ERK in NSCLC. Our study fills a gap in the field of NFIA and radioresistance, and establishes a mechanistic foundation to improve radiotherapy efficiency in NSCLC patients.

Ionizing radiation (IR) causes severe damage to the hematopoietic system; thus, it is necessary to explore agents or compounds that can reduce this damage. SS31 is a mitochondria-targeted peptide that can scavenge cellular reactive oxygen species (ROS) and inhibit the production of mitochondrial ROS. Therefore, in this study, we discuss the protective effect of SS31 on IR-induced hematopoietic system damage. Our results showed that treatment with 6 mg/kg SS31 elevated the survival rate of lethally irradiated mice and increased the numbers of white blood cells, red blood cells, hemoglobin and platelets in mice exposed to 4 Gy whole-body irradiation. In addition, SS31 administration improved the number of hematopoietic stem/progenitor cells (HSPCs) and the self-renewal and reconstitution abilities of these cells in irradiated mice. The elevation of ROS levels is the main cause of IR-induced hematopoietic system damage, and SS31 can effectively reduce the ROS level in HSPCs. The above results suggest that SS31 can protect the hematopoietic system from radiation-induced damage by reducing cellular ROS levels.

Ecosystem response to gamma radiation exposure depends on the different species sensitivities and the multitude of direct and indirect pathways by which individual organisms can be affected, including the potential for complex interactions across multiple trophic levels. In this study, multi-species microcosms were used to investigate effects of ionizing radiation in a model freshwater ecosystem, including endpoints at both structural and functional levels and ecological interactions. Microcosms were exposed for 22 days to a gradient of gamma radiation with four dose rates from 0.72 to 19 mGy h−1, which are within the range of those seen at contaminated sites. Results showed significant dose related effects on photosynthetic parameters for all macrophyte species. No significant effects of radiation were observed for the consumers in the microcosms, however trends indicate the potential for longer-term effects. We also witnessed a different response of Daphnia magna and Lemna minor compared to previous single-species studies, illustrating the importance of multispecies studies, which aim to encompass systems more realistic to natural ecosystems. Microcosms allowed us to isolate specific relationships between interacting species in an ecosystem and test the effects, both direct and indirect, of radiation on them. In addition, the ecological pathways and processes, and the experimental design itself, was central to understanding the results we witnessed. This type of study is important for radioecology research that has been very much limited to high dose rates and single species studies. This approach to radioecology has been strongly promoted in recent decades and, to our knowledge, this is the first microcosm study performed at dose rates similar to those at contaminated field sites.

The study of effects of ionizing radiation (IR) on plants is important in relation to several problems: (I) the existence of zones where background radiation - either natural or technogenic - is increased; (II) the problems of space biology; (III) the use of IR in agricultural selection; (IV) general biological problems related to the fundamental patterns and specifics of the effects of IR on various living organisms. By now, researchers have accumulated and systematized a large body of data on the effects of IR on the growth and reproduction of plants, as well as on the changes induced by IR at the genetic level. At the same time, there is a large gap in understanding the mechanisms of IR influence on the biochemical and physiological processes - despite the fact that these processes form the basis determining the manifestation of IR effects at the level of the whole organism. On the one hand, the activity of physiological processes determines the growth of plants; on the other, it is determined by changes at the genetic level. Thus, it is the study of IR effects at the physiological and biochemical levels that can give the most detailed and complex picture of IR action in plants. The review focuses on the effects of radiation on the essential physiological processes, including photosynthesis, respiration, long-distance transport, the functioning of the hormonal system, and various biosynthetic processes. On the basis of a large body of experimental data, we analyze dose and time dependences of the IR-induced effects - which are qualitatively similar - on various physiological and biochemical processes. We also consider the sequence of stages in the development of those effects and discuss their mechanisms, as well as the cause-effect relationships between them. The primary IR-induced physicochemical reactions include the formation of various forms of reactive oxygen species (ROS) and are the cause of the observed changes in the functional activity of plants. The review emphasizes the role of hydrogen peroxide, a long-lived ROS, not only as a damaging agent, but also as a mediator - a universal intracellular messenger, which provides for the mechanism of long-distance signaling. A supposition is made that IR affects physiological processes mainly by violating the regulation of their activity. The violation seems to become possible due to the fact that there exists a crosstalk between different signaling systems of plants, such as ROS, calcium, hormonal and electrical systems. As a result of both acute and chronic irradiation, an increase in the level of ROS can influence the activity of a wide range of physiological processes - by regulating them both at the genetic and physiological levels. To understand the ways, by which IR affects plant growth and development, one needs detailed knowledge about the mechanisms of the processes that occur at the (i) genetic and (ii) physiological levels, as well as their interplay and (iii) knowledge about regulation of these processes at different levels.

Sulfamethoxazole (SMX) is a widespread and persistent antibiotic pollutant in the aquatic environment. In this paper, SMX was degraded by gamma irradiation, and various influencing factors were explored. The experimental results revealed that after 1.5 kGy irradiation, 20 mg/L SMX could be completely decomposed. Kinetics studies suggested that the radiation-induced degradation process of SMX conformed first-order kinetic. The pH value had influence on the decomposition efficiency through changing the species of reactive radicals and the existing form of SMX molecules and their distribution. Additionally, the effect of inorganic anions (CO32−, HCO3−, NO3−, SO42−, Cl−, HPO42−) and organic matters (peptone, glucose, humic acid) on SMX degradation was evaluated, which had negative influence on SMX degradation. The degradation efficiency of SMX decreased in the effluent water of WWTP in comparison with that in deionized water, suggesting that the components in the effluent inhibited the radiation-induced decomposition of SMX. The mineralization of SMX by ionizing radiation was also evaluated. These results revealed that ionizing radiation is a promising technology to degrade SMX in aqueous solution as well as in wastewater.

S. cerevisiae-derived-beta- d -glucan (S. cerevisiae-BG) is a natural polysaccharide with various biological effects. The present study was to investigate the protective effect of S. cerevisiae-BG on the injury induced by high linear-energy-transfer (LET) carbon ion irradiation and to reveal the protective mechanisms. Female mice were orally administrated with S. cerevisiae-BG before irradiation. 30-day survival of 6 Gy irradiated-mice was monitored. The damage and recovery of hematopoietic system were evaluated after 2 Gy irradiation, cytokines in plasma were detected, transcriptomics of bone marrow mononuclear cells (BMMNCs) were detected and analyzed. The mortality results showed that S. cerevisiae-BG could prolong the survival of mice exposed to 6 Gy. The results of BMMNCs injury analysis showed that S. cerevisiae-BG could reduce the ROS level, mitigate DNA damage and apoptosis. S. cerevisiae-BG increased the plasma radioprotective cytokines level in irradiated mice. Transcriptomics analysis revealed that S. cerevisiae-BG modulated the gene expression in BMMNCs of irradiated mice, 256 genes were significantly up-regulated and 97 genes were significantly down-regulated. Gene function and Gene Ontology analysis indicated the key genes related to hematopoiesis and immunity. Pathway analysis revealed that these up-regulated genes mainly focus on PI3K-Akt pathway and down-regulated genes mainly focus on MAPK pathway. These data contribute to understanding the molecular mechanisms of the radioprotective effect of S. cerevisiae-BG.

Radon is widely recognized as a human carcinogen and findings from epidemiologic studies support a causal association between residential radon exposure and lung cancer risk. Our aim was to derive population attributable risks (PAR) to estimate the numbers of incident lung cancer due to residential radon exposure in Canada in 2015. Potential impact fractions for 2042 were estimated based on a series of counterfactuals. A meta-analysis was conducted to estimate the relative risk of lung cancer per 100 Becquerels (Bq)/m3 increase in residential radon exposure, with a pooled estimate of 1.16 (95% CI: 1.07–1.24). The population distribution of annual residential radon exposure was estimated based on a national survey with adjustment for changes in the population distribution over time, the proportion of Canadians living in high-rise buildings, and to reflect annual rather than winter levels. An estimated 6.9% of lung cancer cases in 2015 were attributable to exposure to residential radon, accounting for 1741 attributable cases. If mitigation efforts were to reduce all residential radon exposures that are above current Canadian policy guidelines of 200 Bq/m3 (3% of Canadians) to 50 Bq/m3, 293 cases could be prevented in 2042, and 2322 cumulative cases could be prevented between 2016 and 2042. Our results show that mitigation that exclusively targets Canadian homes with radon exposures above current Canadian guidelines may not greatly alleviate the future projected lung cancer burden. Mitigation of residential radon levels below current guidelines may be required to substantially reduce the overall lung cancer burden in the Canadian population.

Introduction Healthcare professionals must sufficiently understand ionising radiation and the associated protection measures to avoid unnecessarily exposing patients and staff to ionising radiation. Hence, a proper safety culture is important to lowering health risks. The development and establishment of an instrument that can indicate healthcare professionals' understanding/knowledge of radiation protection concepts can greatly contribute to a good safety culture. The purpose of the present study was to develop and psychometrically test the Healthcare Professional Knowledge of Radiation Protection (HPKRP) self-evaluation scale, which was designed to measure the knowledge level of radiation protection by healthcare professionals working with ionising radiation in a clinical environment. Methods The presented research employed a cross-sectional study design. Data were collected from eight Finnish hospitals in 2017. A total of 252 eligible nurses responded to the newly developed HPKRP scale. The face and content validity were tested with the Content Validity Index (CVI). Explorative factor analysis was used to test construct validity, whereas reliability was tested with Cronbach's alpha. Results Overall S-CVI for the HPKRP scale was 0.83. Exploratory factor analysis revealed a three-factor model for the HcPCRP scale containing 33 items. The first factor was defined by Radiation physics and principles of radiation usage, the second factor by Radiation protection, and the third factor by Guidelines of safe ionising radiation usage. These three factors explained 72% of the total variance. Cronbach's alpha coefficient for the scale ranged from 0.93 to 0.96. Conclusion The results provide strong evidence for the validity and reliability of the HPKRP scale. Additionally, educators can use the scale to evaluate healthcare students' understanding in radiation safety before and after education.

Cellulose nanocrystals (CNCs) reinforced chitosan based antifungal films were prepared by encapsulating essential oils (EOs) nanoemulsion. Vapor phase assays of the chitosan-based nanocomposite films loaded with thyme-oregano, thyme-tea tree and thyme-peppermint EO mixtures showed significant antifungal activity against Aspergillus niger, Aspergillus flavus, Aspergillus parasiticus, and Penicillium chrysogenum, reducing their growth by 51-77%. Combining the bioactive chitosan films loaded with thyme and oregano EOs produced ~2 log reduction in fungal growth in inoculated rice during 8 weeks of storage at 28 °C. The bioactive films showed a slow release (26%) of volatile components over 12 weeks of storage. Sensorial evaluation of rice samples packed with the bioactive films showed no significant change in odor, taste, color and general appreciation compared with untreated rice. Incorporation of cellulose nanocrystals (CNCs) with the chitosan matrix played an important role in stabilizing the physicochemical and release properties of the nanocomposite films. In addition, combining the bioactive chitosan films with a dose of 750 Gy of ionizing radiation showed significantly higher antifungal and mechanical properties than treatment with the bioactive film or irradiation alone.

Fluoroscopy-guided procedures constitute a major part in the practice of cardiology. These procedures are also a source of human-made ionizing radiation. Although the benefits of performing the procedure surpass the radiogenic risks in most cases, the risks are not negligible. Exposure to ionizing radiation may lead to tissue injuries and potential increase in risk of cancer. Both patients and operating physicians are exposed to these risks in variable degrees. The institution of radiation safety practices alone significantly reduces radiation exposure. Beyond the interventional laboratory, increasing physicians’ awareness to health-related risks of ionizing radiation is crucial in reducing unnecessary testing and increases receptiveness to patient risks. Incorporating the radiogenic risks of a future procedure in patient-informed consent also increases patients’ awareness to potential consequences. Innovation in imaging technology resulted in a plethora of alternate modalities. Electroanatomical mapping, magnetic navigation systems, robotic and magnetic resonance imaging (MRI)-assisted techniques are examples of clinically used modalities that limit the exposure of patients and operating physicians to radiation. Documentation of patients’ exposure in their medical records is essential. Tracking of patients’ cumulative exposure can be implemented at an institutional level. Identifying patients with the highest exposure would help shed light on a blind spot in our current practice, as the implications are unclear.

High affinity natural killer cells (haNKs) are a cell therapy product capable of mediating both direct and antibody-dependent cell-mediated cytotoxicity (ADCC). These cells may be particularly useful in tumors that escape T-cell anti-tumor immunity by harboring antigen processing and presentation defects. Here, we demonstrated that haNKs directly kill both HPV-positive and negative head and neck squamous cell carcinoma cells. Variable tumor cell sensitivity to haNK direct cytotoxicity did not correlated with MHC class I chain-related protein A or B (MICA or MICB) expression. Importantly, haNK killing was significantly enhanced via ADCC mediated by cetuximab or avelumab in cells with higher baseline EGFR or PD-L1 expression, respectively. The ability of IFNγ to induce tumor cell PD-L1 expression correlated with enhanced PD-L1-specific ADCC. IFNγ induced neither tumor cell EGFR expression nor EGFR-specific ADCC. Although a single dose of 8 Gy IR did not appear to directly enhance susceptibility to haNK killing alone, enhanced PD-L1- and EGFR-mediated ADCC after IR correlated with increased PD-L1 and EGFR expression in one of four models. This pre-clinical evidence supports the investigation of haNK cellular therapy in combination with ADCC-mediating mAbs, with or without IR, in the clinical trial setting for patients with advanced HNSCCs. Given the MHC-unrestricted nature of this treatment, it may represent an opportunity to treat patients with non-T-cell inflamed tumors.

Ectomycorrhizal (EM) fungi form symbioses with dominant tree families in boreal, temperate and tropical ecosystems and are important drivers of ecosystem function. EM fungal hyphae extend over a large area making them susceptible to enhanced radiation levels from naturally occurring or anthropogenically originating radioisotopes in the rhizosphere. In this study, the in-vitro effects of ionizing radiation on the growth and biomass of EM fungi Suillus luteus, S. bovinus and Rhizopogon luteolus were investigated. EM fungal cultures were exposed to gamma radiation from a 137Cs source for 137 h in darkness at 21 °C at dose rates of 404, 108.5 and 54.9 mGy h−1 resulting in total absorbed doses of 55.21, 14.82 and 7.50 Gy respectively. Cultures grown in the dark at 21 °C but not exposed to the 137Cs source served as the control. Our results show that EM fungi vary in their sensitivity to ionizing radiation. EM fungi used in this study produced melanin and reactive oxygen species scavenging enzymes such as catalase and superoxide dismutase as a response to ionizing radiation.