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2025
Medulloblastoma (MB) is one of the most common malignant pediatric brain tumors. Current therapy results in a poor prognosis for high-risk SHH/p53-mutated MB, emphasizing the importance of more effective therapeutic strategies. Here, we investigated the potential radiosensitizing effects of the checkpoint kinase inhibitors (Chk-is) prexasertib (Chk1/2) and SAR-020106 (Chk1) in human SHH/p53-mutated MB in vitro and in vivo. UW228 and DAOY cells were treated with Chk-is and irradiation (RT). Metabolic activity, proliferation, and apoptosis were determined at d3, and long-term clonogenicity was determined at d14. DNA damage was assessed after 1, 24, and 72 h. Patient-derived SHH/p53-mutated, luciferase-transfected MB cells were implanted orthotopically into NSG mice (d0). Fractionated therapy (daily, d7–11) was applied. Body weight (BW) was documented daily, tumor growth weekly, and proliferation at d42. In vitro, Chk-is exhibited a dose-dependent reduction in metabolic activity, proliferation, and clonogenicity and increased apoptosis. A combination of Chk-is with RT enhanced these antitumor effects, including proliferation, apoptosis, and clonogenicity, and increased residual DNA damage compared to RT alone. In vivo, tumor growth was delayed by Chk-is alone. Low-dose prexasertib enhanced RT-induced tumor growth inhibition. High-dose prexasertib and SAR-020106 showed opposite effects, at least at later time points (n = 3). BW assessments revealed that the treatment was well tolerated. Our data indicate a potential benefit of Chk-is in combination with RT in SHH/p53-mutated MB. However, high-dose Chk-is may compromise the RT effect, possibly through anti-proliferative activity. Furthermore, we demonstrate, for the first time, the intracranial antitumor activity of the Chk1-specific inhibitor SAR-020106.- Book : 26(6)
- Pub. Date : 2025
- Page : pp.2577-2577
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2025
Cellulosic ethanol has been an attractive biofuel for over a century. Despite the large scientific interest, the first step of treating cellulose before enzymatic hydrolysis is still inadequate, so the scientific community seeks innovative solutions. Among them, plasma treatment of raw cellulose represents an interesting approach. The literature on approaches to treat cellulose with gaseous plasma is surveyed, and the results reported by different authors are interpreted. Reactive gaseous particles like ions, electrons, metastables, and radicals interact chemically with the surface but do not cause significant depolymerization of bulk cellulose. Such depolymerization results from bond scission in the bulk cellulose by energetic plasma species capable of penetrating deep into the cellulose. Among them, photons in the range of vacuum ultraviolet radiation (photon energy above the threshold for bond scission) are the most suitable plasma species for the depolymerization of cellulose and the formation of water-soluble fragments, which are suitable for further treatment by enzymatic hydrolysis.- Book : 17(6)
- Pub. Date : 2025
- Page : pp.782-782
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2025
In this study, we analyze the energetic neutral atom (ENA) observations measured in the lowest energy channel (10–21 eV) of the IBEX-Lo instrument on Interstellar Boundary Explorer (IBEX) during two spring seasons, day of year (DOY) 101–146, 2009, and DOY 88–178, 2013, confirming the existence of outward hydrogen (H) fluxes at 15 eV. The outward H flux decreases slightly with distance, showing an intensity of approximately 106 cm−2 s−1 sr−1 keV−1. Results also suggest that the outward H fluxes are not influenced by solar radio flux. We compute the expected H ENA fluxes at 15 eV using ion flux measurements from the Helium, Oxygen, Proton, and Electron (HOPE) mass spectrometer aboard the Radiation Belt Storm Probes (RBSP) during the corresponding period of the 2013 spring season, combined with a simple exospheric density model (nH=nH0r0/r3, where r0=10 RE). The expected ENA fluxes similarly show a decrease in the intensity with increasing geocentric distance, which is on the order of 105–106 cm-2 s−1 sr−1 keV−1. These consistent features suggest that the outward H fluxes observed by IBEX-Lo are closely related to escaping H ENAs produced within the inner exosphere (<4 RE).- Book : ()
- Pub. Date : 2025
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2025
A subset of nuclear receptors (NRs) function as permissive heterodimers with retinoid X receptor (RXR), defined by transcriptional activation in response to binding RXR agonist ligands. Permissive NR-RXR activation operates via a classical pharmacological mechanism, where binding of an RXR agonist increases coactivator recruitment to the heterodimer. However, we previously demonstrated that transcriptional activation of permissive Nurr1-RXRα (NR4A2-NR2B1) heterodimers by an RXR ligand set, which included pharmacological RXR agonists and selective Nurr1-RXRα agonists that function as antagonists of RXRα homodimers, occurs via a non-classical mechanism: ligand-binding domain (LBD) heterodimer dissociation (Yu et al., 2023). Here, we extend mechanistic ligand profiling of the same RXR ligand set to Nur77-RXRγ (NR4A1-NR2B3), which is evolutionarily related to Nurr1-RXRα. Biochemical and NMR protein-protein interaction profiling along with cellular transcription studies indicate that the RXR ligand set, which lacks selective Nur77-RXRγ agonists, may influence Nur77-RXRγ transcriptional activation through both classical pharmacological activation and LBD heterodimer dissociation. However, upon reanalyzing our previously published data for Nurr1-RXRα, we found that the inclusion of selective Nurr1-RXRα agonists was essential for elucidating the LBD heterodimer dissociation mechanism. Our findings underscore the need for a more functionally diverse RXR ligand set to explore Nur77-RXRγ activation and unify LBD heterodimer dissociation as a potential targeting mechanism for NR4A-RXR heterodimers in neurodegenerative and inflammatory diseases.- Book : ()
- Pub. Date : 2025
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2025
Abstract
Radioactive cesium was released into the environment from the Fukushima Daiichi Nuclear Power Plant of Tokyo Electric Power Company, which was damaged by the Great East Japan Earthquake. The shiitake industry suffered various damages as a result. One type of damage is contamination by radioactive cesium in the cultivation environment, known as ‘additional contamination’. Additional contamination is assumed to be caused by the transfer of radioactive cesium from the soil to the fruiting bodies via the bed-logs. We conducted a 15-month bed-log cultivation in a glasshouse on soil contaminated with radioactive cesium to verify the transfer of radioactive cesium from the soil to the fruiting body. The transfer was verified mainly using stable cesium, but no transfer of radioactive cesium from soil to the fruiting body was observed. This result indicates that additional contamination is caused by other factors.- Book : 71(1)
- Pub. Date : 2025
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2025
- Book : 25(1)
- Pub. Date : 2025
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2025
- Book : 1075()
- Pub. Date : 2025
- Page : pp.170461-170461
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2025
- Book : ()
- Pub. Date : 2025
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2025
AbstractPurposeThe response of various detectors in small fields from a variety of treatment machines has been studied and is summarized in IAEA TRS‐483. However, data for the novel RefleXion system remains largely unexplored. This study measured the output correction factors of multiple detectors in small fields for a clinical RefleXion unit.MethodsThe RefleXion machine consists of a binary multi‐leaf collimator and two pairs of Y‐jaws with clinical openings of 1 and 2 cm. The reference dosimetry is applied to the 10 × 2 cm2 clinical‐reference field, and the output factors of different fields are presented relative to the clinical‐reference field. The responses of detectors Edge, Razor, Micro‐Diamond, A14SL, CC01 and CC03 in rectangular fields from 1.25 × 1 to 20 × 2 cm2 on the RefleXion unit was studied at a depth of 10 cm in an IBA Blue‐Phantom‐Helix with a 85 cm source‐to‐surface distance. Gafchromic EBT4 film data in a solid‐water phantom were used as the reference to obtain correction factors for the detectors.ResultsIn the fields of the 2 cm jaw, all 6 detectors showed similar responses to the film reference within around 0.5% except at the first field width (1.25 cm), where the Edge and Micro‐Diamond exhibited over‐response and the CC13 showed the volume effect of ion chambers. In the fields of the 1 cm jaw, the Edge and Micro‐Diamond had responses close to the film and the same over‐response at small field‐widths. Significant deviations of the CC13 (∼4%) and the A14SL (∼2.5%) from the film were present over the whole range of field widths.ConclusionsThe small field output correction factors of 6 kinds of detectors were determined for a RefleXion system, conforming to the formalism in TRS‐483. All detectors except CC13 fulfil the 5% correction limit recommended by the TRS‐483 for output factor measurement.- Book : ()
- Pub. Date : 2025
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2025
- Book : ()
- Pub. Date : 2025
- Page : pp.100745-100745
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