Pu isotopes in soils collected downwind from Lop Nor: regional fallout vs. global fallout

For the first time, soil core samples from the Jiuquan region have been analyzed for Pu isotopes for radioactive source identification and radiological assessment. The Jiuquan region is in downwind from the Lop Nor Chinese nuclear test (CNT) site. The high Pu inventories (13 to 546 Bq/m2) in most ofthe sampling locations revealed that this region was heterogeneously contaminated by the regional fallout Pu from the CNTs. The contributions of the CNTs to the total Pu in soils were estimated to be more than 40% in most cases. The 240Pu/239Pu atom ratios in the soils ranged from 0.059 to 0.186with an inventory-weighted average of 0.158, slightly lower than that of global fallout. This atom ratio could be considered as a mixed fingerprint of Pu from the CNTs. In addition, Pu in soils of Jiuquan region had a faster downward migration rate compared with other investigated places in China

First determination of Pu isotopes (239Pu, 240Pu and 241Pu) in radioactive particles derived from Fukushima Daiichi Nuclear Power Plant accident

Radioactive particles were released into the environment during the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident. Many studies have been conducted to elucidate the chemical composition of released radioactive particles in order to understand their formation process. However, whether radioactive particles contain nuclear fuel radionuclides remains to be investigated. Here, we report the first determination of Pu isotopes in radioactive particles. To determine the Pu isotopes (239Pu, 240Pu and 241Pu) in radioactive particles derived from the FDNPP accident which were free from the influence of global fallout, radiochemical analysis and inductively coupled plasma-mass spectrometry measurements were conducted. Radioactive particles derived from unit 1 and unit 2 or 3 were analyzed. For the radioactive particles derived from unit 1, activities of 239+240Pu and 241Pu were (1.70-7.06)×10-5 Bq and (4.10-8.10)×10-3 Bq, respectively and atom ratios of 240Pu/239Pu and 241Pu/239Pu were 0.330-0.415 and 0.162-0.178, respectively. These ratios were consistent with the simulation results from ORIGEN code and measurements from various environmental samples. In contrast, Pu was not detected in the radioactive particles derived from unit 2 or 3. The difference in Pu contents is clear evidence towards different formation processes of radioactive particles, and detailed formation processes can be investigated from Pu analysis

Xylitol acts as an anticancer monosaccharide to induce selective cancer death via regulation of the glutathione level

Herbal medicines and their bioactive compounds are increasingly being recognized as useful drugs for cancer treatments. The parasitic fungus Cordyceps militaris is an attractive anticancer herbal since it shows very powerful anticancer activity due to its phytocompound cordycepin. We previously discovered and reported that a high amount of xylitol is present in Cordyceps militaris extract, and that xylitol unexpectedly showed anticancer activity in a cancer-selective manner. We thus hypothesized that xylitol could become a useful supplement to help prevent various cancers, if we can clarify the specific machinery by which xylitol induces cancer cell death. It is also unclear whether xylitol acts on cancer suppression in vivo as well as in vitro. Here we show for the first time that induction of the glutathione-degrading enzyme CHAC1 is the main cause of xylitol-induced apoptotic cell death in cancer cells. The induction of CHAC1 is required for the endoplasmic reticulum (ER) stress that is triggered by xylitol in cancer cells, and is linked to a second induction of oxidative stress in the treated cells, and eventually leads to apoptotic cell death. Our in vivo approach also demonstrated that an intravenous injection of xylitol had a tumor-suppressing effect in mice, to which the xylitol-triggered ER stress also greatly contributed. We also observed that xylitol efficiently sensitized cancer cells to chemotherapeutic drugs. Based on our findings, a chemotherapeutic strategy combined with xylitol might improve the outcomes of patients facing cancer

Novel extracellular role of REIC/Dkk-3 protein in PD-L1 regulation in cancer cells

The adenovirus-REIC/Dkk-3 expression vector (Ad-REIC) has been the focus of numerous clinical studies due to its potential for the quenching of cancers. The cancer-suppressing mechanisms of the REIC/DKK-3 gene depend on multiple pathways that exert both direct and indirect effects on cancers. The direct effect is triggered by REIC/Dkk-3-mediated ER stress that causes cancer-selective apoptosis, and the indirect effect can be classified in two ways: (i) induction, by Ad-REIC-mis-infected cancer-associated fibroblasts, of the production of IL-7, an important activator of T cells and NK cells, and (ii) promotion, by the secretory REIC/Dkk-3 protein, of dendritic cell polarization from monocytes. These unique features allow Ad-REIC to exert effective and selective cancer-preventative effects in the manner of an anticancer vaccine. However, the question of how the REIC/Dkk-3 protein leverages anticancer immunity has remained to be answered. We herein report a novel function of the extracellular REIC/Dkk-3—namely, regulation of an immune checkpoint via modulation of PD-L1 on the cancer-cell surface. First, we identified novel interactions of REIC/Dkk-3 with the membrane proteins C5aR, CXCR2, CXCR6, and CMTM6. These proteins all functioned to stabilize PD-L1 on the cell surface. Due to the dominant expression of CMTM6 among the proteins in cancer cells, we next focused on CMTM6 and observed that REIC/Dkk-3 competed with CMTM6 for PD-L1, thereby liberating PD-L1 from its complexation with CMTM6. The released PD-L1 immediately underwent endocytosis-mediated degradation. These results will enhance our understanding of not only the physiological nature of the extracellular REIC/Dkk-3 protein but also the Ad-REIC-mediated anticancer effects

Neuroplastinβ-mediated upregulation of solute carrier family 22 member 18 antisense (SLC22A18AS) plays a crucial role in the epithelial-mesenchymal transition, leading to lung cancer cells' enhanced motility

Our recent study revealed an important role of the neuroplastin (NPTN)β downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTNβ is a serial activation of the key molecules we identified: tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF). The question of how dissemination is controlled by SPDEF under the activated NPTNβ has not been answered. Here, we show that the NPTNβ-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTNβ pathway in lung cancer cells. In vitro, the induced EMT is linked to the acquisition of active cellular motility but not growth, and this is correlated with highly disseminative tumor progression in vivo. The publicly available data also show the poor survival of SLC22A18AS-overexpressing lung cancer patients. Taken together, these data highlight a crucial role of SLC22A18AS in lung cancer dissemination, which provides novel input of this molecule to the signal cascade of NPTNβ. Our findings contribute to a better understanding of NPTNβ-mediated lung cancer metastasis

Histidine-Rich Glycoprotein Suppresses the S100A8/A9-Mediated Organotropic Metastasis of Melanoma Cells

The dissection of the complex multistep process of metastasis exposes vulnerabilities that could be exploited to prevent metastasis. To search for possible factors that favor metastatic outgrowth, we have been focusing on secretory S100A8/A9. A heterodimer complex of the S100A8 and S100A9 proteins, S100A8/A9 functions as a strong chemoattractant, growth factor, and immune suppressor, both promoting the cancer milieu at the cancer-onset site and cultivating remote, premetastatic cancer sites. We previously reported that melanoma cells show lung-tropic metastasis owing to the abundant expression of S100A8/A9 in the lung. In the present study, we addressed the question of why melanoma cells are not metastasized into the brain at significant levels in mice despite the marked induction of S100A8/A9 in the brain. We discovered the presence of plasma histidine-rich glycoprotein (HRG), a brain-metastasis suppression factor against S100A8/A9. Using S100A8/A9 as an affinity ligand, we searched for and purified the binding plasma proteins of S100A8/A9 and identified HRG as the major protein on mass spectrometric analysis. HRG prevents the binding of S100A8/A9 to the B16-BL6 melanoma cell surface via the formation of the S100A8/A9 complex. HRG also inhibited the S100A8/A9-induced migration and invasion of A375 melanoma cells. When we knocked down HRG in mice bearing skin melanoma, metastasis to both the brain and lungs was significantly enhanced. The clinical examination of plasma S100A8/A9 and HRG levels showed that lung cancer patients with brain metastasis had higher S100A8/A9 and lower HRG levels than nonmetastatic patients. These results suggest that the plasma protein HRG strongly protects the brain and lungs from the threat of melanoma metastasis

Sources and Variability of Plutonium in Chinese Soils: A Statistical Perspective with Moving Average

We investigated the different sources and their corresponding impact areas of Pu in Chinese surface soils to illustrate the state-of-the-art of the sources, levels and distributions of 240Pu/239Pu atom ratios as well as 239+240Pu activity concentrations in China. For the first time a moving average strategy in combination with statistical analysis was employed to partition geographic areas in China based on the reported 240Pu/239Pu atom ratio and 239+240Pu concentration data from public literature. During the partitioning, the median (MED) of the dataset was basically employed as a criteria in place of the commonly used arithmetic average (AM). Concisely, three areas were partitioned according to the different influences of Pu from the Lop Nor (LNTS) and Semipalatinsk (STS) test sites and the global fallout. The partitioned Ternary area (80° E–105° E, 35° N–50° N) was supposed to have multiple sources of Pu including the STS and LNTS besides the global fallout, which was characterized with slightly lower 240Pu/239Pu atom ratios (MED = 0.174) as well as elevated 239+240Pu concentrations (MED = 0.416 mBq/g). Meanwhile, the Binary area (35° N–45° N, 100° E–115° E) was considered to have received the extra contribution from the high-yield nuclear tests at the LNTS besides the global fallout, resulting in the highest 240Pu/239Pu atom ratios (MED = 0.200) across China. The remaining area was marked as the Unitary area, where it only received the exclusive contribution of global fallout. Furthermore, through the statistical analysis of the 240Pu/239Pu data in the Unitary area, we recommended a value of 0.186 ± 0.021 (AM ± SD) as a representative or area-specific 240Pu/239Pu atom ratio baseline to characterize the global fallout derived Pu in Chinese soils

The Key Role of Isotopic Analysis in Tracing the Fukushima Nuclear Accident-Released Pu and Radiocesium Isotopes in the Environment. In: Steinhauser G., Koizumi A., Shozugawa K. (eds) Nuclear Emergencies. Current Topics in Environmental Health and Preventive Medicine. Springer, Singapore

The actinide plutonium (Pu) isotopes and the fission product radiocesium isotopes released in the Fukushima Daiichi Nuclear Power Plant (FDNPP) nuclear accident have drawn scientific attention in post-accident studies. In this review, studies were summarized that trace the Pu and radiocesium isotopes released in the FDNPP accident after they entered the environment to ensure better nuclear emergency preparedness for the future. The characteristic 240Pu/239Pu, 241Pu/239Pu and 135Cs/137Cs atom ratios of the FDNPP accident were determined to be 0.323-0.330, 0.128-0.135 and 0.333-0.343, respectively, which were distinctive from those of global fallout. While Pu and radiocesium isotopic signatures from the accident were detected in the terrestrial environment, the release of Pu to the marine environment, if any, was negligible. And no data for 135Cs in the marine environment have been reported yet

Development of low-temperature fusion using ammonium hydrogen fluoride for rapid determination of actinides in environmental and nuclear decommissioning samples

In this study, a green and rapid analytical method was developed for determination of 237Np and Pu isotopes in environmental and nuclear decommissioning samples, such as soil, marine sediment and concrete samples. The methods consisted of NH4HF2 fusion incorporated with procedure for CaF2/LaF3 co-precipitation, extraction chromatography or anion-exchange chromatography and ICP-MS measurement. ICP-MS, as an atom-counting approach that counts the atoms themselves, irrespective of their decay mode, specific activity, or half-life, is gradually replacing/has replaced conventional radiometric methods, for ultra-sensitive analysis of actinides. The fusion procedure was done at 250oC on a portable hot plate instead of in a cumbersome muffle furnace and took only 15 min. Chemical recoveries of 237Np and Pu after completing the NH4HF2 fusion method and chromatographic separation for 0.5-1 g sample were approximately 70-90%. The NH4HF2 fusion was capable of completely releasing actinides from samples that were pre-ignited at temperatures over 450 oC to 1000 oC, which was comparable to releases obtained by the hazardous and time-consuming HNO3-HF digestion. Additionally, because HF is not used in any procedure of the NH4HF2 fusion, a safer and greener alternative to HNO3-HF digestion is realized for rapid 237Np and Pu isotopes determination in soil, marine sediment and concrete samples. It takes approximately one day for 10 sample analysis (NH4HF2 fusion and sample transferring, 0.5 h; CaF2/LaF3 coprecipitation and filtration, 1.5 h; chromatographic separation and sample preparation, 5.5 h; ICP-MS measurement, 0.5 h) which is less than the conventional acid digestion methods.日本分析化学会第６８年