Searching for actinide decorporation agents with advantages of high decorporation efficiency, minimal biological toxicity, and high oral efficiency is crucial for nuclear safety and the sustainable development of nuclear energy. Removing actinides deposited in bones after intake is one of the most significant challenges remaining in this field because of the instantaneous formation of highly stable actinide phosphate complexes upon contact with hydroxyapatite. Here we report a hydroxypyridinone-based ligand (5LIO-1-Cm-3,2-HOPO) exhibiting stronger affinity for U(VI) compared with the reported tetradentate hydroxypyridinone ligands. This is further revealed by the first principles calculation analysis on bonding between the ligand and uranium. Both in vitro uranium removal assay and in vivo decorporation experiments with mice show that 5LIO-1-Cm-3,2-HOPO can remove uranium from kidneys and bones with high efficiencies, while the decorporation efficiency is nearly independent of the treatment time. Moreover, this ligand shows a high oral decorporation efficiency, making it attractive for practical applications.
Deferiprone (3-hydroxy-1,2-dimethyl-4(1H)-pyridone, DFP), which is a drug clinically used for removing heavy metals in vivo, was explored for its removal efficiency towards uranium. The reaction of uranyl nitrate hexahydrate with DFP at room temperature yielded the compound [(UO2)(H2O)(C7NO2H8)2]·4H2O (1), which crystallizes from a mixed solution of methanol and water (pH = 7.0). X-ray diffraction shows that the stable complexation of uranyl occurs from the coordination of two bidentate DFP ligands perpendicular to the O[double bond, length as m-dash]U[double bond, length as m-dash]O unit with a fifth coordinating oxygen atom coming from one water molecule, resulting in a pentagonal bipyramidal geometry. The formation constants of uranyl and DFP complexes were measured and the species distribution diagram illustrates that UO2L2 (94.6%) is the dominant uranyl-DFP complex in 0.1 M KCl solution at physiological pH = 7.4. The results from both crystallographic and potentiometric studies imply that the metal : ligand ratio is 1 : 2. The effectiveness of using DFP to remove uranium was examined at the cellular level, and the results suggest that it can significantly reduce the cellular uptake and increase the cellular release of U(vi) in renal proximal tubular epithelial cells (NRK-52E).
3,4-Hydroxypyridinone-modified carbon quantum dots were prepared via a post-modification approach by introducing a specific molecule into the CQD surface, and applied to the field of rapid detection of uranyl ions.
Brachytherapy
has been clinically used for the treatment of malignant
solid tumors. However, the classic therapeutic radioactive 125I seed must be surgically implanted directly into tumors. To avoid
the surgery and prevent irrational radioactive distribution, radioiodine-loaded
nanomaterials are ever-developing for brachytherapy. Hence, it is
still a notable challenge to obtain an advanced material that simultaneously
incorporates features of high radiolabeling rate, short labeling time,
good radiolabeling stability, and long tumor retention time. Covalent
organic frameworks (COFs), which are crystalline polymers with ordered
pores, are widely applied in guest delivery of drugs based on their
high porosity and modifiable skeleton. Herein, we developed a functionalized
nanoscale PEG-COF-Ag material, which could rapidly capture radioiodine
reaching a 94% radiolabeling yield in 30 s. In addition, more than
95% 125I was maintained after 24 h in PBS (phosphate-buffered
saline) as well as in serum and over 90% for nearly 1 week. PEG-COF-Ag-125I (125I-COF) demonstrated excellent cancer cell
killing performance in vitro, and further experiments in vivo revealed
a long tumor retention time and effective tumor treatment during the
radiotherapy. The results indicate that radioiodine-labeled PEG-COF-Ag
could be potentially applied in brachytherapy with a promising therapeutic
effect.
Multiple instance learning algorithms have been increasingly utilized in computer aided detection and diagnosis field. In this study, we propose a novel multiple instance learning method for the identification of tumor invasion depth of gastric cancer with dual-energy CT imaging. In the proposed scheme, two level features, bag-level features and instance-level features are extracted for subsequent processing and classification work. For instance-level features, there is some ambiguity in assigning labels to selected patches. An improved Citation-KNN method is presented to solve this problem. Compared with benchmarking state-of-the-art multiple instance learning algorithms using the same clinical dataset, the proposed algorithm can achieve improved results. The experimental evaluation is performed using leave-one-out cross validation with the total accuracy of 0.7692. The proposed multiple instance learning algorithm serves as an alternative method for computer aided diagnosis and identification of tumor invasion depth of gastric cancer with dual-energy CT imaging techniques.
Uranium poses a threat for severe
renal and bone damage in vivo. With the rapid development
of nuclear industry,
it is more urgent than ever to search for potential in vivo uranium chelators. In this work, 3-hydroxy-2-pyrrolidinone (HPD)
is investigated as a new potential uranium decorporation ligand. The
potentiometric titration measurements were carried out, and the stability
constants were determined to be log β110 = 10.5(7),
log β120 = 20.7(9), and log β130 = 28.2(4). The species distribution diagram shows that nearly all
uranyl is complexed by HPD at pH 7.4 under the defined condition.
A single crystal of uranyl and HPD complexes, [(UO2)3O(H2O)3(C4H6NO2)3]·NO3·12H2O (uranyl-HPD), was obtained via an evaporation method. The
overall structure of uranyl-HPD is a trimer that consists of three
uranyl units and three HPD ligands. The uranyl unit is equatorially
coordinated by three oxygen atoms from two HPD agents, one coordinated
water molecule, and one μ3-O atom that is shared
by three uranyl units. The results of the cytotoxicity assay indicate
that the ligand is less toxic than the chelators used clinically (i.e.,
DTPA-ZnNa3 and 3-hydroxy-1,2-dimethyl-4(1H)-pyridone (DFP)). The results of the uranium removal assay using
the NRK-52E cell show that it could reduce as much as 58% of the uranium
content at the cellular level. Furthermore, the in vivo uranium decorporation assays demonstrate that HPD can remove 52%
of uranium deposited in the kidney but shows poor uranium removal
efficacy in the bone.
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